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Geraint Thomas 'will be very happy going to the Tour de France as a support rider ', says Ineos Grenadiers ' Rod Ellingworth | Geraint Thomas will be satisfied to race this summer's Tour de France as a domestique, according to Ineos Grenadiers ' deputy team principal Rod Ellingworth.
Many expected the Welshman, who won the Tour in 2018, would be the British team's leader at July's race in the aftermath of Egan Bernal's January crash, but in recent weeks it has became apparent that the 35-year-old faces a fight to be even selected for the race. Adam Yates is now expected to lead Ineos.
After starting his season at the Volta ao Algarve in February, Thomas made his return to racing on Tuesday at the Coppi e Bartali, revealing that a shoulder operation and a bout of Covid had resulted in a `` slow winter '', adding to CyclingProNet that `` the main goal of the season is always the Tour de France. ''
But speaking to Cycling Weekly at the Volta a Catalunya, Ellingworth could not promise that Thomas would be on the startline in Copenhagen, although stressed that there remains three months until final selections are made.
`` It’ s like anything, we have a lot of good quality bike riders, and as I always say it’ s about putting the best bike riders on the line when we can, and let’ s see what happens between now and then, '' he said.
`` There’ s a long way to go, and I think Geraint is pretty clear what he’ s doing within the team at the minute - he’ s playing a support role, and he’ s building.
`` Who knows what will happen, but I do also think Geraint will be very happy going and doing a support role if he has to go as a support rider. Who better to have than to have Geraint alongside you? ''
Put to him that Thomas has made no secret of his desire to win the Tour once again, Ellingworth responded: `` He’ s still hungry, he wants to win, of course he does, whatever that is.
`` Geraint goes into every race wanting to win, whether that’ s him winning or the team winning. That’ s just Geraint, he’ s got that bite about him that is quite unique. ''
Discounting three national championship successes, Ineos have won five races so far this year, Filippo Ganna accounting for a hat-trick of those via time trials.
It's the same return as they had posted 12 months ago, but last spring they went on to win three smaller stage races and the Giro d'Italia, a string of success that looks less likely to be repeated this time around with the slow progression of Thomas, the injury of Bernal, the struggling form of Richard Carapaz, and illness affecting Richie Porte.
There has, however, been impressive results from Dani Martínez ( third at both the Volta ao Algarve and Paris-Nice) and Carlos Rodriguez ( third at the Volta a la Comunitat Valenciana and fourth at the Ruta del Sol).
While confessing that big wins haven't been forthcoming so far, Ellingworth was calm about the team's chances in the coming months.
`` I don’ t think there is a reason except a bit of bad luck, '' the Briton said. `` It's just things happening, illnesses like a lot of teams have had - I can’ t really put a finger on it. We’ re not having much luck at this minute.
`` The competition is really good at the minute and there’ s a lot of really good young guys across the teams. I think, cycling has its ups and downs, and you have to take the knocks.
`` I think there’ s been a lot of good performances among the team, but we’ ve just had a bit of bad luck along the way and it maybe shows with the results.
`` The group in general is building well and there’ s some good morale in the team, and they’ re looking forward to some of the races coming up. We’ ll keep plugging away, keep going.
`` We’ re definitely moving these young guys on a bit which is great to see. If you look at how how the riders rode at GP Denain, the performances were fantastic but the results didn’ t really come, but that’ s how bike racing goes.
`` Carlos today [ on stage two of Catalunya ], the guy is on good form, super motivation, but he punctured at the wrong time. That’ s life. '' | general |
Support Enforcement Program - Justice and Public Safety | Warning: It seems JavaScript is either disabled or not supported by your browser. Please enable JavaScript to improve your experience.
Payors who have lost their job due to the COVID-19 pandemic are expected to continue paying support. Please call 709-637-2608 to speak to the officer assigned to your file and allow two business days for your call to be returned.
For up-to-date information on account balances, payments and enforcement please use the web portal. We thank you for your continued patience during these extraordinary times.
For secure on-line access to your account with Support Enforcement, please log in:
If you are not signed up, or for more information, Read our brochure ( 795 KB).
The Support Enforcement Division performs a number of services related to the collection and distribution of court-ordered funds for support, maintenance or alimony. The authority for the establishment of the agency lies under the Support Orders Enforcement Act, 2006.
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When payments are not made on court orders or agreements registered with the Support Enforcement Program ( SEP), collection action ( s) will be taken. SEP has many collection tools available and may use one or more of these tools to achieve compliance on an order. The following is a list of these actions:
Note: The above are presented for information purposes only and may not be able to be used in all cases. If there are any discrepancies between the Act and the information above, the Act will prevail.
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Support Enforcement Web Portal:
The web portal is located at the following link https: //sea-remote.justice.gov.nl.ca/ and can provide you with account balance and payments information as well as details of who your case worker is; their contact information, the current order being enforced and the current order terms. It also allows you to text message your case worker and provides direct access to account statements. To sign up for this service you will need a Personal Identification Number ( PIN) which we will send to you on request. This service is available 24/7 so we encourage you all to contact us to get set up. If you don’ t have internet you may contact your case worker to obtain your PIN. Our contact information is:
Email: Seps @ gov.nl.ca Toll free: 1.855.637.2608 Local: 637.2608 Fax: 709.634.9518
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Payment Options ( 10 KB)
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Please be advised that the Child Support Recalculation Service remains operational during the COVID-19 situation. At this time, all deadlines for the recalculation of support orders and the filing of income information, and the filing of Notice of Objections remain unchanged.
If you have an immediate concern regarding the enforcement of your support order or agreement, please contact the Support Enforcement Agency at seps @ gov.nl.ca or the secure web portal at https: //sea-remote.justice.gov.nl.ca.
Stay safe and healthy.
The Child Support Recalculation Office helps maintain a fair standard of support for children. This service is provided when child support is ordered by a court, or set out in an agreement that has been filed with a court. The monthly amount of child support payable is reviewed annually and updated if there has been a change in the income of the person who is paying child support.
The Recalculation Office operates as part of the services provided under the Support Enforcement Program. The authority for its operations lies under the Administrative Recalculation of Child Support Regulations, made pursuant to the Family Law Act.
Please note that this overview is intended as general information only. It does not contain a complete statement of the law. If you require legal advice regarding a specific situation, you should contact a lawyer.
An information pamphlet is provided at the link below:
Recalculation Information Brochure ( 100 KB)
The Recalculation Office conducts an administrative recalculation of child support in cases where the court order or child support agreement has been filed with a court and contains a “ recalculation clause ” that requires the recalculation of child support. This allows the parties to update child support annually without having to go back to court to seek a variation when there has been a change in a party’ s income. It also ensures the level of financial support paid for the benefit of the children reflects the updated income. There is no fee for this service.
The Recalculation Office does not recalculate the following:
Parties must notify the Recalculation Office of any changes to their contact information ( mailing address, phone number, e-mail address, etc.) within ten days of the change.
What is the Recalculation process?
1. The party who is required to pay child support must provide the Recalculation Office with their updated income information on an annual basis. This information is used to recalculate the monthly amount of child support. If the Office receives satisfactory income information, then the Office will change the child support amount to reflect the child support table amount that corresponds to the updated income. If the change in child support is greater than $ 5.00 per month, the parties are notified of the recalculated amount in a Recalculation Notice.
2. Where the Recalculation Office determines that there will be no change in the child support amount ( i.e.: the change is less than $ 5.00 per month), a letter will be sent to both parties notifying them that there will be no change to the child support amount that year.
3. If the party required to pay child support does not provide satisfactory income information to the Recalculation Office within the required time frame, the Recalculation Office will calculate the gross annual income of the payer to be the income amount on which the most recent child support order, agreement, or recalculation notice was based, plus either:
( a) 10% of that income where the court order or agreement was filed before March 1, 2018; or ( b) 20% of that income where the court order or agreement was filed on or after March 1, 2018.
4. If a party wishes to dispute the recalculated amount of child support, they must file a Notice of Objection with the court and the Recalculation Office within the time frame set out in the Recalculation Notice. The Notice of Objection should set out the reason ( s) why they are objecting to the new amount of child support. The court will advise both parties of a hearing date. The judge will then determine what amount of child support is appropriate.
5. If no Notice of Objection is filed with the Court within the required time frame, then the new child support amount stated in the Recalculation Notice will come into effect on the date set out in the Recalculation Notice.
CONTACT INFORMATION FOR RECALCULATION OFFICE
Child Support Recalculation Office 9th Floor, Sir Richard Squires Building P.O. Box 2006 Corner Brook, NL A2H 6J8
Telephone: ( 709) 634-4172
Fax: ( 709) 634-4155
E-mail: recalculation @ gov.nl.ca
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Employers are a very important part of the enforcement of child support orders. Employers garnish wages in accordance with the “ Notice of Garnishment ” provisions and forward money to the program for the benefit of Newfoundland and Labrador children. To assist employers with executing the requirements of a garnishment order, the following document is offered to assist.
Garnishment Instruction Sheet ( 17 KB)
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Problem Review Process:
If you have identified a problem with how your case is being handled, you should follow the process as outlined below:
Director of Support Enforcement Re: Problem Review Process P.O. Box 2006 Corner Brook, NL A2H 6J8
If a written communication is received an acknowledgement of receipt will follow. Within 30 days of receipt of your letter you will receive a response from the Director. Because of the high volume of mail received each day it is very important that the address be marked exactly as shown so that your letter is properly directed.
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Contact Information for the Support Enforcement Division.
Telephone Listings Last Updated: March 23, 2022
Please note that, due to the volume of calls received, we can not guarantee that you will be able to speak to someone immediately. Utilize the Enforcement Officers voice messaging system and your call will be returned within two business days.
Business Hours:
Summer
Winter
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The Interjurisdictional Support Orders Act ( ISO) is used to obtain or vary an order for support or to request registration and enforcement of an order where one of the parties does not live in the same jurisdiction within Canada, the United States or any other reciprocating country.
The applicant, whether applying under the Divorce Act or Family Law Act, must complete an ISO application and send it to the Designated Authority who then transfers the application to the Designated Authority in the jurisdiction where the respondent lives. The respondent will be served a copy of the application and will be required to appear in court at a later date. Once the hearing is complete an order will be made.
Applications for respondents who reside in Quebec
If the respondent resides in Quebec and your court order was granted under the Divorce Act, you would complete the ISO application as described above. If your order was granted under Family Law, you would have to apply under the REMO Act ( Reciprocal Enforcement of Maintenance Orders Act. This means that you must apply to the court here in Newfoundland and Labrador for a provisional hearing. Once a provisional order has been made, the order together with the transcripts of the hearing is forwarded to the Designated Authority who then transfers them to the Designated Authority in the jurisdiction where the respondent resides. After a court hearing in that jurisdiction takes place a confirmation order may be made or made with changes.
APPLICATION
The link below will take you to the ISO FORMS SELECT WEB PAGE where you can access the forms that you will need to include with your ISO application.
ISO Application Forms and frequently asked questions
Once the application has been completed and notarized it should be forwarded to the “ Designated Authority ” for Newfoundland and Labrador.
The address of the Designated Authority is as follows
ISO and the USA
To establish/vary an order in the United States, the following US forms are available or if you wish to use the ISO forms, attach the US Petition and Transmittal form to ensure the application is recognized. These forms are as follows and are in PDF format. | general |
Has Covid changed celebrity gossip? Plus: the return of the cringe it couple – with Who? Weekly | This week, Steph Harmon and Michael Sun are joined by Bobby Finger and Lindsey Weber of the US podcast Who? Weekly ( no: not the Australian magazine), for a slightly unhinged chat about D-list celebrity culture in Australia and beyond. Also: the tabloid couples who were doing the absolute most in lockdown.
How to listen to podcasts: everything you need to know
Presented by Michael Sun and Steph Harmon with Bobby Finger and Lindsey Weber. Produced by Miles Herbert, Joe Koning, and Jake Morcom. Executive producers Steph Harmon and Miles Martignoni
Wed 23 Mar 2022 05.00 GMT Last modified on Wed 23 Mar 2022 05.52 GMT
The Guardian is editorially independent. And we want to keep our journalism open and accessible to all. But we increasingly need our readers to fund our work. | general |
How pandemics end and what they leave behind | Two years after the first UK coronavirus lockdown, Laura Spinney reflects on what the years after the 1918 Spanish flu pandemic looked like, and what we might expect in a post-Covid era
How to listen to podcasts: everything you need to know
Presented by Hannah Moore with Laura Spinney; produced by Tom Glasser and Axel Kacoutié; executive producers Mythili Rao and Phil Maynard
Wed 23 Mar 2022 03.00 GMT
On 23 March 2020 – two years ago today – the first Covid lockdown was announced in the UK, upending life for everybody. It marked the start of a new era– one that has not entirely come to an end.
Science writer Laura Spinney says pandemics don’ t conclude neatly, and that the after-effects can be seen for years to come. While researching her book Pale Rider, a history of the 1918 Spanish flu pandemic, she read countless pandemic diaries. She tells Hannah Moore that those accounts, as well as public records, paint a rich picture of how that pandemic changed society – and we can already see how Covid-19 has reshaped our world.
The Guardian is editorially independent. And we want to keep our journalism open and accessible to all. But we increasingly need our readers to fund our work. | general |
China searches for victims from plane crash with cause still unclear | WUZHOU, China – Rescuers in southern China searched for victims from a China Eastern Airlines jet on Tuesday after it crashed with 132 people on board and authorities said severe damage to the aircraft would make it difficult to establish the cause of the crash.
Flight MU5735 was headed on Monday for the port city of Guangzhou from Kunming, capital of the southwestern province of Yunnan, when it plunged from cruising altitude to crash in the mountains of Guangxi less than an hour before landing time.
The jet appeared to dive to the ground at an angle of about 35 degrees from the vertical in video images from a vehicle’ s dashboard camera, according to Chinese media. Reuters could not immediately verify the footage.
No survivors have been found, said Zhu Tao, director of aviation safety at the Civil Aviation Administration of China ( CAAC), told reporters.
“ The jet was seriously damaged during the crash, and investigations will face a very high level of difficulty, ” Zhu said at the first government briefing on the disaster.
“ Given the information currently available, we still do not have a clear assessment of the cause for the crash, ” he said, adding that the aircraft did not respond to repeated calls from air controllers during its rapid descent.
On Tuesday, rescuers combed heavily forested mountain slopes in southern China, using shovels and torches in their search for victims and flight recorders from the jet.
About 600 soldiers, firefighters and police marched to the crash site, a patch of about 1 square kilometer in a location hemmed in by mountains on three sides, after excavators cleared a path, state television said.
It added that the search for the recorders, or “ black boxes, ” of the Boeing 737-800 involved in China’ s first crash of a commercial jetliner since 2010, would be carried out in grid-by-grid fashion, probably through the night.
Si, 64, a villager near the crash site who declined to give his first name, said he heard a “ bang, bang ” at the time of the crash.
State television has shown images of plane debris strewn among trees charred by fire. Burnt remains of identity cards and wallets were also seen.
Police set up a checkpoint at Lu village, on the approach to the site, and barred journalists from entering. Several people gathered for a small Buddhist ceremony nearby to pray for the victims.
The last commercial jetliner to crash in China was in 2010, when an Embraer E-190 regional jet flown by Henan Airlines went down, killing 44 of the 96 aboard.
Highlighting the top-level concern, Vice Premier Liu He went to Guangxi on Monday night to oversee search and rescue operations. An official of the same rank was similarly sent to the site of the 2010 crash in northeast China.
“ That B737-800 jet met airworthiness standards before taking off and technical conditions were stable, ” Sun Shiying, a China Eastern official, said at the briefing.
“ The crew members were in good health, and their flying experience was in line with regulatory requirements, ” he said.
The disaster comes as Boeing seeks to rebound from several crises, notably the impact of the coronavirus pandemic on air travel and safety concerns over its 737 MAX model following two deadly crashes.
“ Accidents that start at cruise altitude are usually caused by weather, deliberate sabotage, or pilot error, ” said Dan Elwell, a former head of U.S. regulator the Federal Aviation Administration.
Elwell, who led the FAA during the 737 MAX crisis, said mechanical failures in modern commercial jets were rare at cruise altitude.
The 737-800 was delivered on June 22, 2015, and accumulated 18,239 hours of flight time after 8,986 flights, said Zhu.
Chinese investigators are leading the probe because the crash took place there, but U.S. authorities will provide aid because the plane was U.S.-made.
The U.S. National Transportation Safety Board ( NTSB) said on Tuesday it was in touch with CAAC’ s investigator-in-charge and would support the investigation with technical advisers from the Federal Aviation Administration, Boeing and engine manufacturer CFM in all ways necessary.
China has strict quarantine policies due to the pandemic. No decision has been made yet about whether U.S. authorities will travel there for the investigation, a NTSB spokesperson said.
On Monday, China Eastern and two subsidiaries grounded its fleet of 737-800 planes. The group has 225 of the aircraft, data from British aviation consultancy IBA shows. | tech |
WTO takes “ major step forward ” on Covid-19 vaccine restrictions | Trade experts have welcomed a preliminary agreement by four influential World Trade Organization ( WTO) members that would allow companies to produce and export Covid-19 vaccines without falling foul of patent laws. An internal WTO document leaked last week revealed that the EU, India, South Africa and US had agreed to let countries waive intellectual property... | general |
Yuan expected to weaken as COVID resurgence threatens China growth | The yuan is setting a course for depreciation this year as risks to economic growth put an end to two straight years of gains.
The resurgence of COVID-19 lockdowns and surging commodity prices are spurring doubts over China’ s 5.5% growth target for the year. And the prospect of further monetary easing as global central banks hike rates is set to accelerate outflows and further undermine the yuan.
Tolerance at the People’ s Bank of China ( PBOC) for yuan strength also is wearing thin: Through fixings last week it made a push to weaken the currency.
While a weaker yuan could help boost exports, a sharp decline could trigger panic about financial stability and take the shine off Chinese assets — although some strategists see that as a boon for the nation’ s bonds.
A global exodus from Chinese markets last week prompted a swath of promises of support from policymakers.
“ The renminbi has passed an inflection point, ” said Hao Hong, head of research and chief strategist at BOCOM International Holdings Co. It will continue to weaken, but the pace will be controlled by the PBOC, he said, adding that a weaker yuan will spread recovery costs onto China’ s trading partners and neighbors.
The yuan has fallen 0.9% in March so far, and is set for its biggest decline since May 2021. It still remains Asia’ s best-performing currency this year with the smallest loss against the greenback, which is getting bolstered by bets that the Federal Reserve could hike rates by half a percentage point at its next meeting, if needed.
In contrast, a median of forecasts from economists surveyed by Bloomberg shows the PBOC may cut banks’ reserve requirement ratio by 100 basis points, to 10.5%, by the first quarter of next year.
UBS Group AG cut its growth forecast for China this year to 5% from 5.4%. Morgan Stanley now forecasts a 5.1% gain, down from 5.3% as COVID-19 curbs weigh on the economy.
“ This round of COVID-19 resurgence is likely to not only hurt services, but also industrial production and trade growth, ” said Jingyang Chen, Asian FX strategist at HSBC. The yuan is likely to be on the back foot over the near term and may fall to 6.45 per dollar by year-end, she said.
The dollar-onshore yuan option implied volatility indicates a 70% probability it will fall to 6.5 to the dollar by the end of the year. It dropped 0.1% to 6.37 per dollar Tuesday while the offshore yuan was little changed at 6.38 per dollar Wednesday.
The yuan jumped the most since December on March 16, on the back of a historic surge in Chinese shares as the top financial policy committee, led by Vice Premier Liu He, pledged to stabilize battered financial markets and stimulate the economy.
A report that Saudi Arabia is seeking to price some of its oil exports in yuan also helped the advance.
However, the currency pared those gains as the average of the gap between the People’ s Bank of China’ s daily yuan reference rate and market estimates widened to 68 basis points last week, the highest on record since Bloomberg started the survey with analysts and traders in 2018.
The PBOC’ s weaker fixings could also be aimed at correcting the divergence in the onshore and offshore yuan, which widened last week to the most since June, a former State Administration of Foreign Exchange official said. The onshore unit is being supported by dollar selling by exporters, whereas the offshore rate is weighed by stock outflows, said Guan Tao, a member of China FX Committee, in an interview.
“ China’ s export growth is likely to slow more notably in the second half, and a step-by-step partial border reopening — likely to begin later this year — could lead to an increase in the service trade deficit, ” said Ju Wang head of Greater China FX and rates strategy at BNP Paribas SA. Wang sees the yuan falling to 6.60 to the dollar by year-end.
Portfolio investment from banks’ clients turned to a deficit of $ 32 billion in February, surpassing the previous record set in March 2020 at the onset of the pandemic, monthly cross-border flow data released Friday shows. That was partly driven by a record retreat by bond investors from Chinese debt.
While HSBC’ s Chen sees the yuan’ s “ overvaluation and reduced yield advantage ” weighing on the hedging behavior of corporates and portfolio investors, Australia & New Zealand Banking Group ( ANZ) expects the real yield differential between the U.S. and China to support the yuan.
“ Although the strong trade surpluses will ease later in the year, we see portfolio inflows remaining robust, ” wrote Khoon Goh, head of Asia research, in a note. The foreign bond outflows in February and the sell-off in the onshore equity markets are temporary, he said. | tech |
Gymnast Hitomi Hatakeda quits over injury and motivation struggles | Gymnast Hitomi Hatakeda has announced she will retire at 21 after suffering a spinal injury at last year’ s world championships and struggling with motivation during the coronavirus pandemic.
Hatakeda was diagnosed with damage to her central spinal cord and bruising of the cervical vertebrae after falling off the uneven bars during practice in October last year.
She was discharged from hospital one week later but said in an Instagram post on Tuesday that she has still not completely recovered, citing the injury as one of her reasons for quitting.
She also said she has found it “ difficult to stay motivated ” with competitions being canceled or postponed because of the pandemic.
Next month’ s national championships in Tokyo will be her final competition before retiring, she added.
She said her injury will prevent her from competing on all apparatus but she will “ try to do as much as I can so that I can give something back to people, even if it’ s just a little. ”
“ I’ ve had so many great experiences that I would have never thought possible when I started out in gymnastics, and that’ s down to the people who have supported me, who I have nothing but gratitude for, ” she wrote.
Hatakeda was part of the Japan women’ s team that finished fifth at last year’ s Tokyo Olympics.
Her father Yoshiaki is a former gymnast who won bronze in the men’ s team event at the 1992 Barcelona Olympics. Her younger sister Chiaki is also a gymnast. | tech |
Lack of recycled resin could challenge company sustainability goals | Many brands have plans to increase recycled content in their packaging by 2025. But supply will likely outstrip demand.
Plenty of brands have already announced their 2025 goals for increasing recycled content in their packaging, but supply of postconsumer recycled resin will likely fall short of the 2025 demand, said speakers at the Plastics Recycling Conference.
Experts weighed in on how to remedy these supply and demand issues. They urged rapid mobilization to improve recycling collection while building consensus among stakeholders through complex policies such as extended producer responsibility ( EPR), container deposit bills, and postconsumer recycled content laws.
The conference, hosted by Resource Recycling and the Association of Plastic Recyclers, was held March 7-9 in Oxon Hill, Maryland.
Top of mind at the conference was the huge demand for recycled resin spurred by recent brand and policy moves. Big brands have pledged to integrate recycled resin into their plastic packaging, with many setting goals for using specific proportions of recycled resin by 2025. At the same time, states including New Jersey, Washington and California have passed laws requiring certain plastic products to contain more recycled content, and conference speakers expect more states will take that action in the coming years.
Current U.S. recycling rates are unable to match projected demand, said Resa Dimino, managing partner at consulting firm Signalfire Group, during a policy discussion session. Though the United States has been reliably recycling high density polyethylene ( HDPE) and polyethylene terephthalate ( PET) for about 30 years, recycling rates are stagnant at between 25% and 30%, while plastics in less mature markets, such as polypropylene ( PP), are at even lower recycling rates. “ We have a big hill to climb to meet these targets, ” she said.
The U.S will need to double collection of most plastic resin types to meet the projected demand for products with a 25% recycled content composition, and “ for polypropylene, the amount is greater than that, ” she said of the growth needed. Dimino estimated collection for most resins will need to triple to be able to supply enough to meet 50% PCR goals.
Chemical recycling technology may be able to help meet the “ astronomical ” demand, said Emily Friedman, recycled plastics senior market editor for the Independent Commodity Intelligence Services ( ICIS). For that to work, the U.S. would need to build at least another 145 mechanical recycling plants to meet 2025 targets. To reach the 2030 targets, the industry would need a 45% compounded annual growth rate, she said.
Some speakers expressed concern about relying on chemical recycling to generate the recycled feedstock needed as a strategy for handling and processing plastic in coming years. Kaitlyn Trent, a plastics campaigner for Greenpeace, cited a report that it could be 2050 before chemical recycling facilities are producing the level of recycled resin the market needs. `` We don’ t have time to wait until 2050 because plastic pollution won’ t wait until then, '' she said.
Dave Andrew, vice president of new market development for ExxonMobil, said that the company plans to process one billion pounds of plastic per year via chemical recycling within five years.
Complicating the supply issue is the growing demand for resins approved for food-contact applications, which must meet U.S. Food and Drug Administration standards. Further, brand owners in the market for widely-recycled PET face another complicating factor is that highly-recycled PET faces competition from other consumers markets other than those making major brand commitments, such as the fiber industry, Friedman said.
`` What's really tying us up, and I think we all agree, is the supply side of things, the feedstock into this market, '' she said.
Those concerned about limited recycled resin supply said it’ s more important than ever for stakeholders to communicate better with each other to reach consensus on policies that could improve and streamline recycled plastic collection. During the policy panel discussion, speakers noted how EPR and bottle bill provisions are still divisive in many states, but attitudes are beginning to change, in part because of volatile commodity markets and plastics supply pressures.
`` We 've seen bale prices shoot up over the last year. Every time prices shoot up, supply stays the same. We see that price does not drive supply, so we need policy to drive supply, '' Dimino said.
Craig Cookson, the American Chemistry Council’ s senior director of plastics sustainability, said the organization sees EPR as a driver to help fund local recycling systems and kick-start more collection, as long as the model `` doesn’ t disrupt business partnerships in the end markets or innovation on the back end — let's have a full free market that can compete. ''
Cookson said he sees `` opportunities '' in the EPR provisions of the federal Break Free From Plastic Pollution Act, a bill ACC has opposed due to a provision that would temporarily suspend permits on new resin plant construction. Though ACC still does not support the whole bill, `` I think we all agree that supply is an issue. I think we all agree that we need strong end markets and that recycled plastic targets are a good idea, '' he said.
Bree Dietly, principal for Breezeway Consulting, speaking as a representative of American Beverage, said consensus-building is key to building strong bills. The beverage industry’ s long-stated goal is to collect as many beverage containers as possible to turn them into new beverage containers, but `` we're agnostic on policy, '' Dietly said. `` We acknowledge that deposits make sense in some places, that EPR makes sense in some places, that minimum content makes sense in some places. ''
Though speakers agreed stakeholders were getting better about collaborating more closely on recycling policies, they still don’ t always agree on which style of EPR works best. Dietly said the beverage industry considers Maine’ s newly-approved EPR for packaging bill to be `` lousy '' because it gives too much control to the state government, but it supported the EPR bill in Washington, which died before the state’ s legislative session ended.
`` Program design matters. Just because it has EPR on it doesn’ t mean it's a good bill, '' she said.
And while municipalities could end up with more funding from EPR laws to help beef up collection rates and provide recycling education, many local governments are wary of policies that could strip them of local control of their recycling systems, said David Biderman, CEO of the Solid Waste Association of North America.
`` Local governments are responsible by law to set up and support these systems, '' he said, adding that they may be on the hook if private companies walk away from future systems after deciding the investment wasn’ t worth the effort.
Minimum recycled content policies are another area where stakeholders are beginning to coalesce, partly because some see state laws as a more stable driver for recycled content supply and demand than brands’ voluntary commitments, Dimino said.
Kate Davenport, co-president of Eureka Recycling, a nonprofit MRF operator in Minneapolis, said recycled content policies will strengthen and stabilize demand, but they must be coupled with other policy drivers, such as bottle deposit laws.
“ Brands, you called me and asked for [ recycled ] content, then disappeared three months later when the price of virgin went really low, ” she said.
Yet some brands represented at the conference said they’ re committed to their recycled content goals, noting that consumers are more savvy than ever about greenwashing and want to see real data behind brand recycling claims. Numerous signatories to the U.S. Plastics Pact attended the conference to outline their recycled content and packaging commitments. In 2020, 6 million metric tons of plastic packaging placed on the U.S. market was produced by U.S. pact activators, according to the pact’ s baseline report released during the conference.
Brands can also invest in recycling infrastructure improvements to better the entire system, said John Caturano, national recycling manager for Nestle's North American procurement division. In 2020, the company invested $ 30 million into one of Closed Loop Partners’ private equity funds to help upgrade U.S. recycling infrastructure and give the company better access to food-grade recycled plastics. “ We’ re getting much more integrated into the market infrastructure, ” he said.
Topics covered: logistics, freight, operations, procurement, regulation, technology, risk/resilience and more.
The retailer's acquisition of a middle- and final-mile carrier as the COVID-19 pandemic took hold has allowed it to take more control over its delivery process.
The launch of Connect Local gives smaller businesses access to the same offering USPS has provided to larger shippers, an agency executive said.
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Topics covered: logistics, freight, operations, procurement, regulation, technology, risk/resilience and more.
Topics covered: logistics, freight, operations, procurement, regulation, technology, risk/resilience and more.
Topics covered: logistics, freight, operations, procurement, regulation, technology, risk/resilience and more.
The retailer's acquisition of a middle- and final-mile carrier as the COVID-19 pandemic took hold has allowed it to take more control over its delivery process.
The launch of Connect Local gives smaller businesses access to the same offering USPS has provided to larger shippers, an agency executive said.
Topics covered: logistics, freight, operations, procurement, regulation, technology, risk/resilience and more. | general |
Unknown symbols written by the lost 'painted people ' of Scotland unearthed | Live Science is supported by its audience. When you purchase through links on our site, we may earn an affiliate commission. Learn more
By Laura Geggel published 23 March 22
The symbols may represent a naming system.
Archaeologists in Scotland shed `` genuine tears '' upon discovering a stone covered with geometric carvings that the Picts, the Indigenous people of the region, designed about 1,500 years ago.
The team unexpectedly found the 5.5-foot-long ( 1.7 meters) carved stone while doing a geophysical survey in Aberlemno, a village with Pictish roots. The stone has several geometric shapes showing abstract Pictish symbols, such as triple ovals, a comb and mirror, a crescent and double discs. Some of the carved symbols overlap, suggesting that they were carved in different time periods, the researchers said.
It's unclear what all of the symbols mean, but the `` best guess is that they are a naming system representing Pictish names, '' Gordon Noble, excavation leader and a professor of archaeology at the University of Aberdeen, told Live Science in an email.
`` It's the find of a lifetime, genuinely, '' James O'Driscoll, an archaeologist at the University of Aberdeen in Scotland who helped excavate the stone, said in a university video.
Related: In photos: Stone monument discovered in Scotland
The Picts — possibly named after the Latin word for painted, or `` picti, '' — were fierce people who lived in ancient and medieval times in parts of what is now Scotland. They are partly the reason why the Roman Empire never conquered Scotland.
The new finding is one of only about 200 such stones known to archaeologists. Other stones with Pictish symbols are also from Aberlemno, which is known for its unique standing stones, including a slab that may depict scenes from the Battle of Nechtansmere, a Pictish victory over the Anglo-Saxon kingdom of Northumbria in 685 A.D. that is tied to the creation of what would become Scotland.
The discovery happened in early 2020, when archaeologists were surveying the area as a part of the Comparative Kingship project, a five-year investigation into the early medieval kingdoms of northern Britain and Ireland. While moving imaging equipment across the grass, the team noticed anomalies suggesting that the remains of a settlement lay underground.
To learn more, the archaeologists dug a small pit to see what was hidden beneath their feet. To their astonishment, they found the carved Pictish stone. `` I just brushed my hand, and there was a symbol, '' Zack Hinckley, an archaeologist at the University of Aberdeen who took part in the excavation, said in the video. `` And we had a freakout. ''
The team hoped to immediately excavate and study the stone, but COVID-19 lockdowns meant they had to put their plans on hold. Finally, after months of waiting, they were able to remove and examine the stone, dating the carvings to the fifth or sixth century A.D.
It's rare to find carved Pictish stones. `` They are occasionally dug up by farmers ploughing fields or during the course of road building, but by the time we get to analyse them, much of what surrounds them has already been disturbed, '' Noble said in a statement.
—Photos: Gilded Bronze Age weaponry from Scotland
—In photos: Scotland's cave of the dead
—Photos: Giant sauropods plodded along in Scottish lagoon
`` To come across something like this while digging one small test pit is absolutely remarkable, and none of us could quite believe our luck, '' Noble added. Because they found the rock undisturbed in the ground, they were able to `` examine and date the layers underneath it and extract much more detailed information without losing vital evidence, '' he said.
The slab was later repurposed as a paver in a building dating to the 11th or 12th century, according to radiocarbon dating, and placed next to other pavers, including some with Bronze Age rock art. The building `` dates to after the Pictish period — in the era of the Kingdom of Alba, the forerunner of medieval Scotland, '' Noble told Live Science.
The stone is now in the Graciela Ainsworth conservation lab in Edinburgh, where scientists plan to investigate the artifact further.
Originally published on Live Science. | general |
JB Hunt, BNSF partner to boost intermodal capacity | As shippers contend with congestion and high rates in the trucking industry, J.B. Hunt sees `` tremendous pent-up demand to convert highway freight to intermodal, '' Shelley Simpson, chief commerical officer and executive vice president of people and HR, said on the company's Q4 earnings call.
But disrupted rail service has put pressure on capacity, offsetting improvements in truck equipment turn times.
`` Over the past few years, intermodal has been disrupted by increased demand and tight capacity, resulting in poor container velocity and long dwell times, '' John Roberts, president and CEO of J.B. Hunt, said in a statement. `` Together, J.B. Hunt and BNSF will enhance their work to bring back the consistency and reliability customers expect with intermodal services and further embrace intermodal conversion and transloading services. ''
The two companies have already begun collaborating on how to optimize flows and manage capacity using BNSF or J.B. Hunt-owned properties near key facilities in Southern California and Chicago. The work in those areas `` will serve as a framework for systemwide optimization efforts, '' BNSF spokesperson Ben Wilemon said in an emailed statement.
BNSF also plans to expand intermodal facilities this year as part of an effort to grow parking availability and maximize capacity. The railroad will add 1,100 parking stalls at its Alliance Intermodal Facility in North Texas and 400 additional parking stalls at its Cicero Intermodal Facility in Chicago. The railroad also plans to bring an additional 1,250 double-stacked cars into service this year capable of handling around 2,500 containers.
`` At this point, we are in position to move several thousand more units per week than are currently being loaded directly at the ports on to rail, so we believe increasing rail use should be a key part of the nation’ s greater logistics solution, '' Wilemon said.
The collaboration shows the two companies are deepening their relationship after J.B. Hunt competitor Schneider announced in January that it would move its primary intermodal business in the western U.S. from BNSF to Union Pacific. The partnership will give Schneider the largest drayage fleet with company drivers of any intermodal carrier hauling with Union Pacific, according to a statement.
Topics covered: logistics, freight, operations, procurement, regulation, technology, risk/resilience and more.
The retailer's acquisition of a middle- and final-mile carrier as the COVID-19 pandemic took hold has allowed it to take more control over its delivery process.
Heightened demand put Amazon's distribution buildout into overdrive. To speed up delivery and limit costs, it will have to invest more.
Topics covered: logistics, freight, operations, procurement, regulation, technology, risk/resilience and more.
Topics covered: logistics, freight, operations, procurement, regulation, technology, risk/resilience and more.
Low capacity and vessel delays are here to stay, industry insiders said at the TPM22 conference in Long Beach, California.
Both retailers leaned on their scale to get goods on shelves and keep prices low, at least relative to the industry.
Topics covered: logistics, freight, operations, procurement, regulation, technology, risk/resilience and more. | general |
' I am spent ': World No. 1 Barty goes out on top | Melbourne – Ashleigh Barty dropped a bombshell on the tennis world on Wednesday, as the 25-year-old announced her retirement at the peak of her game and just two months after claiming a third Grand Slam title at the Australian Open.
Citing the fulfilment of her tennis goals and fatigue with life on the WTA Tour, the world No. 1 walks away with 15 titles to her name, the last coming at Melbourne Park where she ended Australia's 44-year wait for a home champion.
`` I know how much work it takes to bring the best out of yourself … I don't have that in me anymore, '' she said in video posted on her Instagram account on Wednesday.
`` I don't have the physical drive, the emotional want and everything it takes to challenge yourself at the very top level any more. I am spent. ''
It marks Barty's second retirement from the sport, having walked away from the game as a teenager in late-2014 after becoming disaffected by the Tour.
She returned in 2016 and rose rapidly up the rankings, earning global acclaim for her tennis and fans ' affection for her sportsmanship and laid-back demeanor.
Spending 121 weeks as world No. 1, Barty won the 2019 French Open and Wimbledon in 2021 and appeared well set for more Grand Slam success to take her place among the game's greats.
However, she never made any secret of her dislike for the touring life and her battles with homesickness.
She said realizing her `` one true dream '' by winning Wimbledon last year had changed her perspective.
`` Ash Barty the person has so many dreams she wants to chase after that don't necessarily involve traveling the world, being away from my family, being away from my home, which is where I 've always wanted to be, '' she said in the video, interviewed by her close friend and former doubles partner Casey Dellacqua.
`` I 'll never, ever stop loving tennis, it's been a massive part of my life, but I think it's important that I get to enjoy the next part of my life as Ash Barty the person, not Ash Barty the athlete. ''
Barty suffered depression on the Tour after turning professional as a teenager, leading her to quit and briefly reinvent herself as a professional cricketer in her home state of Queensland.
When COVID-19 halted tennis in 2020 she took nearly a year off to stay home with family rather than rejoin the circuit when it resumed.
As players battled at the delayed 2020 French Open, Barty was spotted in the crowd at an Australian Rules football match in Brisbane, cheering her beloved Richmond Tigers with a cup of beer in her hand.
Wearing a simple blue sports top and with her hair pulled back in her trademark bun, Barty wiped away tears during the interview with Dellacqua.
`` I know I 've done this before, but in a different feeling, '' she said.
`` I 'm so grateful for tennis, it's given me all of my dreams, plus more, but I know the time is right now for me to step away and chase other dreams and to put the rackets down. ''
She bows out with almost $ 24 million in career prize money and as a national hero by beating American Danielle Collins in the Australian Open in the final in January.
As the second Aboriginal Australian to win a Grand Slam title, following in the footsteps of the great Evonne Goolagong Cawley, Barty has also become an idol for her country's Indigenous population.
Prime Minister Scott Morrison thanked Barty for `` inspiring a generation of young people and particularly a generation of young Indigenous people '' in Australia.
`` You are all class, your commitment to excellence in your chosen field in tennis … I’ m sure anything you turn your hand to you are going to be a great success, '' he added.
Barty's bombshell triggered tributes from players and officials.
`` Happy for @ ashbarty, gutted for tennis, '' said Briton Andy Murray, former men's world No. 1. `` What a player. ''
WTA boss Steve Simon said Barty led by example through her professionalism and sportsmanship in every match.
`` With her accomplishments at the Grand Slams, WTA Finals, and reaching the pinnacle ranking of No. 1 in the world, she has clearly established herself as one the great champions of the WTA. ''
Her retirement echoes Justine Henin's decision to quit in 2008 as a 25-year-old world No. 1 with seven Grand Slam titles. Henin came out of retirement in 2010, inspired by fellow Belgian Kim Clijsters ' comeback.
Clijsters, the 2005 U.S. Open champion, retired in 2007 at the age of 23 but returned after a two-year hiatus to claim another three Grand Slam titles.
Women's tennis will have a new world No. 1 in Poland's Iga Swiatek.
Australia will hope Barty's second retirement ends up like her first, broken by another comeback and more Grand Slam silverware. | tech |
Russian Oil Seeps Into Global Market, Easing Supply Fears for Now | Millions of barrels of Russian oil are still finding a way to buyers almost a month after the country first invaded Ukraine, tempering concerns that a sanctions backlash would all but choke off supply and cause the market for physical cargoes to overheat.
India’ s oil refiners grabbed multiple cargoes of Russia’ s flagship Urals crude this month, potentially supplanting the Middle Eastern varieties they normally purchase from Abu Dhabi and Iraq. Meanwhile, China’ s private processors are still thought to be targeting their favored cargoes from the east of Russia — likely at knock-down prices.
Since Russia invaded Ukraine late last month, the market has been twisting on two vital questions: how much crude will Moscow end up selling, and where? There’ s been a buyers’ strike across swaths of Europe in response to the invasion, but what’ s less clear is how much other regions — especially Asia, the top demand center — will purchase.
“ Russian barrels must look tempting, ” said John Driscoll, chief strategist at JTD Energy Services Pte., adding that his view is that measures against the country will nonetheless curb buying of its crude over time. “ Resourceful traders may explore ways to move cargoes — the Chinese won’ t be intimidated by U.S. sanctions, and will remain the largest importer of Russian crude. India is the next one to watch. ”
At least for now, what’ s going on with the buying and selling of non-Russian oil suggests traders are becoming less fraught about the threat of supply shortages, even if trading the nation’ s barrels isn’ t risk-free, and spreads on Brent oil point to a market that remains incredibly tight by historical standards.
At the moment, there are no sanctions directly prohibiting purchases but there are worries about what steps might ultimately be taken if the war drags on. Financing, insuring and shipping of Russian petroleum have also become much more complicated by the measures that the west has taken.
European officials are debating the idea of an embargo on Russian oil sales, although the bloc is divided on the idea and Germany opposes such a step. European Union and NATO leaders are poised to gather in Brussels on Thursday to beef up their response to the crisis.
For now, though, traders appear to be taking the view that the flow of Russian oil indicates that the market won’ t be as tight as first thought.
A flurry of offers for Middle Eastern barrels took place in the Asian spot market this week, according to traders. Importantly, that comes together with a slowdown in Chinese demand amid COVID-19 lockdowns, and wild price gyrations that’ s kept many buyers on the sidelines.
The differentials at which Middle Eastern barrels sell, a key indicator of demand for them, have dipped after starting off strongly early this month. Abu Dhabi’ s Upper Zakum crude for May loading was purchased by Thailand’ s PTT Pcl at about $ 7.50 a barrel more than the Dubai benchmark this week. That compares with a premium of over $ 10 two weeks ago.
Crude cargoes from the Persian Gulf were thought to be a natural choice for Asian buyers in the absence of Russian cargoes.
Shortly after the invasion, more and more buyers became wary of Russian cargoes despite record discounts after the U.S. banned Russian oil imports and Shell Plc came under heavy criticism due to a purchase of Urals. The major, along with TotalEnergies SE and BP Plc, were among a swath of European buyers that stepped back.
While it’ s still early in the trading and shipping process to gauge the volume of Russian crude that will ultimately flow to Asia in the coming months, the International Energy Agency said in a report last week that the nation’ s oil production is forecast to slump by about a quarter next month, inflicting the biggest supply shock in decades.
Still, some deliveries to Asia are likely to stay, at least for now.
May shipments of Sokol crude — another variety from the Russian Far East — are being organized to some customers in northeast Asia who have committed volumes under long-term contracts and equity agreements, according to traders who sell and buy the grade.
May-loading cargoes of ESPO from eastern Russia were being offered at discounts to the Dubai marker against which they trade, compared with premiums for comparative grades from the Middle East. Chinese independent refiners were seen as most likely buyers, although no transaction has yet been heard this month amid a reduction in market transparency, traders said.
What’ s adding to the slowness in spot transactions is lackluster demand from Chinese refiners including independent processors that have reduced operating rates amid a Covid resurgence that’ s led to lockdowns.
The private plants, known as teapots, make up a quarter of the nation’ s processing capacity. They are running at a five-year low, according to industry consultant OilChem. At least two of them sold back cargoes of crude from West Africa and Latin America in a rare move earlier this month.
Diminished appetite from Chinese buyers has also hindered purchases of West African cargoes, dragging down offer levels for crude from producers like Angola, traders said. A handful of Angolan cargoes for April loading are still left unsold even after the release of program for May, they said.
In Europe, traders said the impact of missing barrels of Urals hasn’ t been as profound in terms of market tightness as they had previously expected, with most European refiners already having secured their required cargoes through the middle of next month.
European buyers are more likely to secure cargoes from the North Sea such as Johan Sverdrup to replace their Urals, and Iraq’ s Basrah Medium is another variety that could be picked up as an alternative to the Russian grade, the traders added.
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Kerbedanz CEO: “ Today, In The Watch Market, Nobody Is Expecting A New Brand. ” | Guillain Maspetiol is a man who likes a challenge. After a career spanning more than 20 years across multiple continents, companies, and roles, his latest project has meant taking over the helm of Kerbebanz, an independent watchmaking brand nestled in the heart of Switzerland that was seeking a leader to elevate its business and help build the foundations for the next step in its expansion.
The trouble was, Kerbedanz’ s plans for expansion came at a time when many watch brands had been hit hard by the global COVID-19 pandemic. Where customers would have previously flown to Switzerland to commission creations or have bespoke watch models made for them, travel restrictions made it almost impossible for customers to enjoy the same experience the brand once offered. Meaning, it needed to adapt to the changes in the market and it needed to rethink its business model for the digital age.
Enter Maspetiol, a luxury veteran who has worked at Cartier, Girard-Perregaux, and Jaeger-LeCoultre, and whose experience proved invaluable when it came to repositioning the company for the new era of growth and expansion.
“ The positioning of the brand was extremely exclusive, and also very intimate, ” said Maspetiol, on what drew him to the company. “ Every single piece was designed in collaboration with the artistic director and its clients, to create specific timepieces and specific designs unique to each customer. ”
“ But it was also limited, ” he added. “ Those types of watches are not the first purchase of a watch collector or even the second. They were the purchase of collectors and enthusiasts that perhaps would consider the brand as a fifth or sixth purchase. ”
However, during times of crisis, luxury consumers tend to lean towards bigger, well-known names as clearly seen through the successful results of luxury conglomerates like LVMH and Richemont. And selling bespoke watches – particularly at a time when Swiss watch exports were sluggish and where there is no shortage of watch brands on the market aimed at meeting the most discerning customers’ needs – is not an easy task for a brand whose prices ranged from around $ 37,000 to around $ 857,000.
The end result was the decision to undergo a full brand overhaul, working from a blank page to come up with new product categories and a new positioning centered around the idea of Crafting Your Singularity to refocus the company’ s aims of reaching new customers in new markets.
Focusing on their communication and branding was key, which is why they chose to partner with DLG, a leading independent digital agency for luxury brands and the publisher of Luxury Society, to define their brand territory and develop a new image to broaden out its appeal.
“ It was a drastic decision to shift from a very niche and exclusive mono-product offering to a more universal luxury brand. Focusing towards a totally different offer that not only includes timepieces but also accessories and leather goods was a huge undertaking and a big challenge for a company as small as ours, ” said Maspetiol, who is also considering adding jewellery, writing instruments, and accessories to its product ranges in the future.
And while Kerbedanz has lowered the points of entry to its brand, starting from $ 165 for a small leather good, it also plans to introduce three limited-edition timepieces with a price tag of around $ 3.2 million each.
“ Every year, we want to come up with these limited edition pieces that are highly complicated and one of a kind, ” said Maspetiol. Marrying the two ends of the luxury market may not be a simple task, but Maspetiol believes that by focusing on the brand’ s core values of craftsmanship, authenticity, and transparency, it’ s a task that can be managed well.
“ We want a genuine relationship with our customers, ” he said. “ But the idea is also to be very approachable. In today's world, you have to be reachable, you have to be faithful to your values and you have to have un fil rouge that you follow. ”
The company also plans to expand its global footprint, focusing on the United States, China and the Middle East as its three key regions of future growth in the coming years.
“ We want to explore new territories, ” said Maspetiol. “ And we are planning to go from three doors to 30 doors. By the end of 2022, we aim to have between six to 10 doors.
Kerbedanz’ s latest campaign. Credit: DLG.
But partnering with retailers isn’ t the only path forward for Kerbedanz. Maspetiol added that there are also plans in the future to open its own branded stores, to help elevate the customer experience of Kerbedanz.
“ We don't want to have a retail concept which is what everybody else does, ” noted Maspetiol. “ We want to go beyond that. Our slogan is Crafting Your Singularity, which can be a challenge because you have to be singularly innovative with new products, new packaging, in your events and communication. ”
“ Today, nobody is expecting a new brand, ” he continued. “ But I think, for me, it’ s the utmost luxury when you grant customers the opportunity to sit at the inner circle of the table. We have the freedom to think outside the box, and not have to adhere to historical codes or untouchable iconic products. And we want to give that freedom to our customers, to our retailers. ”
Freedom in Maspetiol’ s mind means being able to meet the designer, craft their own timepiece, change an existing timepiece and involve his customers in the process of design and certain processes of construction.
“ We have to really define something which is singular, in the way we welcome our clients, in the way we host events, the way we provide our services because you can be very creative but it can also be a struggle, ” he noted.
“ These kinds of experiences where you can be a part of assembling a portion of the movement, or inviting to the testing of the watch, makes the experience of owning that timepiece so much more personable because you have had a hand in it, ” he added. “ It carries more emotional content. ” | general |
China Eastern crash could set back Boeing's China recovery and return of MAX | The deadly crash of a China Eastern Airlines 737-800 could set back Boeing’ s efforts to regain ground in the world’ s biggest aircraft market and deliver more than 140 of their 737 MAX jets already constructed for Chinese customers.
The 737-800 that crashed on Monday does not have the equipment that led to 737 MAX crashes more than three years ago, but that may not make a difference to Chinese passengers and a national regulator known for scrupulous safety requirements.
China Eastern said the cause of the crash was under investigation. Such accidents typically involve multiple factors, and experts warned it was far too early to draw any conclusions on the potential causes, especially in light of the scarce information available.
China was the first country to ground the 737 MAX after fatal crashes in Indonesia and Ethiopia more than three years ago, and it is the only major market where the MAX has not resumed commercial flights.
A 737 MAX built for China Eastern subsidiary Shanghai Airlines took off from Seattle bound for Boeing’ s completion plant in Zhoushan last week, industry sources said, in a sign the model’ s return to service in China was close.
The plane landed in Guam on March 15 as part of a multi-leg journey and has not moved in the week since, according to flight tracking website FlightRadar24. Boeing declined to comment.
Robert Spingarn, a managing director at Melius Research who focuses on the aerospace sector, said the MAX’ s return in China could be delayed until authorities there had some answers on the cause of the China Eastern crash. China’ s aviation regulator is known for being very thorough on safety issues.
Plane debris at the site where a China Eastern Airlines Boeing 737-800 plane flying from Kunming to Guangzhou crashed, in Wuzhou, China, on Monday. | REUTERS
Chinese airlines do not need new MAX planes because demand is down following the country’ s biggest COVID-19 outbreaks in two years, industry sources said. But the U.S. manufacturer has more than 140 MAX jets already built for Chinese customers waiting to be delivered once the jet returns to commercial service there, a person familiar with the matter said.
Boeing’ s shares closed 3.6% lower on Monday. Boeing declined to comment on whether the crash could delay a business recovery in China, while China’ s aviation regulator did not respond immediately to a request for comment.
The 737-800 that crashed is an earlier model with a strong safety record and there are nearly 1,200 in service in China, making it the world’ s largest market for the plane, according to aviation consulting firm IBA.
More than 4,200 737-800s are in service globally, data from aviation firm Cirium shows.
China Eastern and two of its subsidiaries on Monday grounded its fleet of 737-800 planes. The group has 225 of the aircraft, data from British aviation consultancy IBA shows.
Other Chinese carriers are continuing to fly the jets, according to data from Chinese aviation data provider Flight Master.
Jefferies analysts said China’ s aviation regulator was unlikely to ground the 737-800 fleet unless it specifically suspected a technical failure as the root cause because of the operational consequences of grounding more than 1,000 planes in the world’ s second-biggest domestic aviation market.
However, there are concerns the Chinese public could look to avoid flying on 737-800s until the cause of the crash is determined, given the broader reputational issues with the 737 family caused by the MAX, Cowen analyst Cai von Rumohr said in a note.
“ Hence, isolating the cause of the crash will be critical, ” he added, noting the leading causes of commercial air transport crashes tend to be maintenance issues, pilot error or sabotage, rather than manufacturing or design issues.
Boeing cancelled a meeting of its senior executives scheduled for this week in Miami to focus its attention on assisting the investigation and China Eastern, a second person familiar with the matter told Reuters.
“ We have been in close communication with our customer and regulatory authorities since the accident, and have offered the full support of our technical experts to the investigation, ” Boeing CEO Dave Calhoun said in a memo to employees, which was seen by Reuters. | tech |
CR2/IBS Intelligence Latest Market Insight Report Looks at the Importance of Digital Onboarding for Banks Today | The latest IBS Intelligence report, in partnership with CR2 ( www.cr2.com), looks at how critical digital onboarding is for banks and other financial institutions to retain their current customers while also attracting new ones. As a result, banks are attempting to create an easy, tailored, and frictionless end-to-end digital buying and contracting experience. Having the capability to digitally onboard customers simplifies and streamlines the very first user experience that a customer has with the bank as well as significantly reducing the cost of customer onboarding.
Due to the COVID-19 pandemic, banks and financial services providers have faced unanticipated challenges. As clients shift online to receive essential services, the financial industry needs to rethink the future of digital banking through quick adaption methods and a deeper focus on banks’ digital presence. Digital customer onboarding has become the buzzword in the industry as business leaders begin to recognise the enormous potential of digitisation.
The benefits and drivers of digital onboarding for banks are abundant, including higher efficiency and cost optimisation. IBS Intelligence’ s 4S framework sheds light on the essentials of digital onboarding. For a digital onboarding platform to provide the imagined benefits, it must have the following characteristics: Speed, Smart, Secure, Seamless.
In the Banking and Financial Services sector, digital onboarding addresses some of the long-standing issues with traditional onboarding models. It helps businesses onboard new clients remotely and quickly through integrated customer journeys.
Digital onboarding is the start of a customer’ s digital banking journey. A holistic digital transformation must supplement a seamless digital onboarding experience, and a solid digital ecosystem is required to cater to higher customer expectations. Both digital banks and traditional financial institutions will need to develop strategies and solutions tailored to their specific environments.
To download the report ‘ Why Digital Onboarding is Imperative for Banking Today’ click the following link: https: //knowledge.cr2.com/why-digital-onboarding-is-imperative-for-banking-today
If you would like more information or would like to arrange an interview with a representative from CR2, please contact Nigel Sutton: nige @ seventeen59pr.com
View source version on businesswire.com: https: //www.businesswire.com/news/home/20220322005731/en/ | general |
China builds makeshift hospitals to help cope with COVID-19 | China’ s provinces should set up at least two to three temporary hospitals each to treat COVID-19 patients, Beijing said Tuesday, a potential sign the country is anticipating an increase in cases as it battles an omicron outbreak and ponders how to exit its isolationist virus strategy.
The order from the National Health Commission came after China updated its COVID-19 treatment guidelines last week to reserve actual hospitals for those with severe COVID-19 conditions. Patients with mild or no symptoms will now be sent to the makeshift facilities to isolate so as to avoid overwhelming the medical system.
China still isolates all cases, regardless of severity, as part of its “ COVID zero ” policy — an approach that has kept deaths low but is now being challenged as more contagious variants emerge and the rest of the world opens up. The country has 31 provinces and territories, meaning at least 62 temporary sites could be constructed, a mammoth undertaking.
Some 33 makeshift hospitals have already been built, or are currently under construction, providing 35,000 beds, Jiao Yahui, an official with National Health Commission, said at a briefing Tuesday. Local governments are required to come up with plans to ensure the facilities can be put to use within two days when needed.
China first started building temporary facilities at the start of the pandemic, when they famously constructed two makeshift hospitals in the original epicenter, Wuhan, in 10 days. The hospitals are typically made with prefab-style buildings that in some cases resemble shipping containers, and thousands of workers are brought in to construct them quickly. In Wuhan, they were key to the eventual containment of the outbreak there, stifling community transmission by removing the source.
Around 95% of the cases in China’ s current outbreak have mild symptoms or are asymptomatic, which would mean significant pressure on the under-resourced permanent medical system if cases were to swell.
The country of 1.4 billion saw 4,594 new locally-acquired infections on Tuesday, low by global standards but the most significant outbreak China has seen since the Wuhan days. China would see a “ colossal outbreak ” with as many as 630,000 new infections a day if it were to remove restrictions like border curbs, compulsory quarantines and mandatory isolation of cases, like countries from the U.S. to Singapore have done, modeling by Peking University in November showed.
A delivery worker waits to deliver food over barriers blocking a residential area, which have been built to separate buildings from a street, amid the COVID-19 pandemic, in Shanghai on Tuesday. | REUTERS Strategy tweaked
China should stick to the zero-tolerance approach, with not “ one iota of relaxation ” said Liang Wannian, a seasoned epidemiologist who has overseen China’ s COVID-19 response since the beginning of the pandemic and was recently sent to Hong Kong to guide efforts to contain its worst ever outbreak.
The remarks, made to the state-run Xinhua news agency, came as Hong Kong moves to ease some incoming travel curbs and laid out a timeline for relaxing internal social-distancing rules.
Still, there are concrete signs China is at least adjusting COVID zero, after Chinese President Xi Jinping said last week the country needed to reduce its impact on the economy and business.
While lockdowns are still being imposed — yet another city, Tangshan, near Beijing was subject to such restrictions late Tuesday — other places are taking a more targeted approach.
The tech hub of Shenzhen was allowed to let factories resume during its recent lockdown under certain constraints, and Shanghai, which is currently seeing more than 900 new cases a day, is taking a more targeted approach, locking down individual buildings for short periods to test residents.
The lockdown on the northeastern province of Jilin, however, was tightened even further Tuesday, with residents banned from even leaving their homes for four days and grocery stores in apartment complexes closed so that authorities can choke off the outbreak. The province remains the single biggest virus hotspot in the country, with cases holding around 3,000 a day.
A key tool in China’ s COVID zero arsenal has been mass testing early in an outbreak. Sometimes conducted over multiple rounds so as to root out all infections, the process has led to disruptions, with Toyota Motor Corp. and Volkswagen AG factories in the city of Tinjian having to shut down for about two weeks in January because workers were being constantly tested.
Mandated testing in targeted regions will need to be completed within 24 hours, the official Jiao said Tuesday. The time requirement will help officials keep up with the spread of omicron, he said. | tech |
Key4Women Members Create TheWMarketplace: A Business Supporting Women-Owned Businesses | Originally published at key.com. KeyBank ranked No. 23 on The DiversityInc Top 50 Companies for Diversity list in 2021.
When you read the story of TheWMarketplace, you’ re going to ask yourself, “ Why didn’ t I think of that? ” Because that’ s what we do when we learn about a brilliant startup. Check out the talent, tenacity and daring of the two women behind this successful-out-of-the-gate eCommerce company.
It started with an unremarkable question posed by a friend who had just moved to the States from Europe: “ Why doesn’ t the U.S. celebrate International Women’ s Day ( IWD) like many other countries do? ”
“ Great question, ” thought Kate Isler, who had recently left a post at Microsoft and was wrestling with the many challenges of her digital health startup business. “ Why don’ t we celebrate? We should do that. ”
IWD has been observed on March 8 since the early 1900s and is an official holiday in more than 25 countries. But, until Isler came along, it’ s gone by mostly unnoticed in the United States for decades.
With six weeks to plan, Kate decided to host an event. “ We had 80 people. It was fun. Then the next summer and fall, people started saying, ‘ Well, what are you going to do this year?’ ” So Isler and her team found themselves in the IWD event business, interacting with crowds of more than 500 women at Seattle Symphony Hall.
That is until the global pandemic stopped gatherings and celebrations altogether. Then came the stark realization that there was so much more to do to acknowledge, support and celebrate women.
“ Everyone was shopping online. We needed to figure out a way to put money directly into women’ s pockets, ” Isler said. “ We need to create an eCommerce site for women. ” The first thing she did was share the idea with a friend in hopes of recruiting a business partner.
“ I told Kate I would love something positive to work on, ” said Susan Gates, co-founder of TheWMarketplace. “ It was clear that my job was about to come to an end due to the impact of COVID-19 on the coffee industry. I’ ve always been a gender equality advocate and I was ready to do something different. What better time to start a business than during a pandemic? Let’ s go for it. ”
With that, TheWMarketplace was born.
Isler and Gates both work in Seattle, but remote from each other. Team members also work remotely. “ With eCommerce, you can work anywhere. Our tech partner is a woman-owned firm in Jacksonville, Florida, ” Isler commented.
In addition to TheWMarketplace, Isler remains the leader of Be Bold Now, a nonprofit organization that supports International Women’ s Day.
“ We opened up TheWMarketplace to women-owned brands on September 29, 2020, ” said Isler. “ And by July of 2021, we had 425 sellers offering more than 2,800 products and services. ” The company is proud of its focus on diversity, already tracking and building its Black, Asian, Latina, veteran and LGBTQIA+ sellers and consumers.
Products range from artwork, clothing and jewelry to custom invitations, cake toppers and tea. Services include tax advice, logo development, website overhauls, tutoring, stationery design, estate planning, yoga and every kind of coach imaginable.
Isler brings more than 20 years of international executive leadership experience with Fortune 100 companies to TheWMarketplace. Gates adds two decades of global sales and sponsorship experience. Both have a passion for helping women and working toward a more gender-balanced economy. Isler’ s new book, Breaking Borders, tells the story of her journey from launching her career, to global executive, to entrepreneur of her dream company. She also discusses the many hurdles she jumped along the way.
One of Isler and Gate’ s secrets to success is developing partnerships. “ We partner with organizations like LeadHERship Global, Take the Lead Women, many Small Business Administration offices, the Washington Center for Women in Business, Association of Women Accountants and, of course, Key4Women, ” Gates said. “ We are proactive in our outreach. ”
Isler and Gates specialize in connecting women to other women, so women can buy, sell and research products and services they need. “ We’ ve created an ecosystem of support that is growing businesses. The amazing organizations we partner with do a lot of mentoring and networking. ”
With respect to how they reach shoppers, Gates acknowledged that social media gets the lion’ s share of their marketing resources.
“ Women are shopping their values, ” Isler noted. “ Women doing business with women will change the world. ” This — changing the world — is what Kate calls her “ latest strategy. ”
“ In celebrating International Women’ s Day, we learned what the gaps were in the U.S. and the developed world. We think we are very far along in closing the gender gap, but we are not, ” Isler said. “ When we shine a light on that — and then take action to change it — it will be powerful. That’ s where our heart is as a company. ”
“ One of the things we’ re clear on is that we want to continue to create a space that is accommodating to women and redefines ‘ normal. ' ”
“ Many women who have engaged with TheWMarketplace have ( or had) brick and mortar stores. Many have dreams and are making them come alive through a side hustle. We can help women in both these situations. ”
Gates added, “ Rarely do you meet a woman whose career is single-dimensional. We are listening and evolving our business to accommodate that. Our business model today is vastly different than it was nine months ago when we started. ”
An example of this was a deliberate recasting of their target market. Initially they thought they would focus on the millennial demographic and a specific income level, but they learned quickly they needed to go broader.
“ We have such a variety of sellers ranging in age from 13 to early 70s, ” Susan said. Teen and senior entrepreneurs are key segments TheWMarketplace has expanded to accommodate.
“ We also thought our goal was 300 products in 12 months, ” said Isler. “ We thought that would give us a viable product. ” Instead, the two savvy business owners secured 2,800 products in nine months. “ We like to laugh about that, ” said Isler.
TheWMarketplace owners raised a round of seed capital in three days last winter and intend to do more fundraising in the fall.
“ We see the need to provide business support and skill development on the platform. That is a focus area for us, ” Isler explained. “ We also see a huge push for digital-first transformation in B2B businesses, and we want to help our sellers with fulfillment, supply chain, creative — whatever they need. ”
“ Kate and I make a great team, ” Gates said. “ Kate has the vision and drive and is admittedly a little impatient. I like to plan. Neither of us is new to business, ” Gates added. “ When people say, ‘ Oh my gosh, how did you do that,’ we remind them of all of our combined experiences. We made mistakes in the past, and we now know how to avoid them. ”
Both women say they “ show up every day excited to do this work ” — which almost feels like an understatement after you meet them. Their smiles and enthusiasm alone will change the world.
As the saying goes, the news never stops — but there’ s a lot of it out there, and all of it doesn’ t always pertain to our readers. In this weekly news roundup, we’ ll cover the top news stories that matter most to our diversity focused audience. 1. Ketanji Brown Jackson…
Originally published at corporate.dow.com. Dow ranked No. 19 on The DiversityInc Top 50 Companies for Diversity list in 2021. Dow announced a new partnership with Teach For All to fund Science, Technology, Engineering and Math ( STEM) teacher recruitment, professional development and placement in underserved schools in Lagos, Nigeria; Bahía Blanca, Argentina; …
Originally published at about.att.com. Melissa Arnoldi is the Executive Vice President and Chief Customer Officer at AT & T Consumer. AT & T is a Hall of Fame company. My Path to AT & T I often think about the legacy I hope to leave behind; one where my career journey creates an easier path…
For the eighth consecutive year, U.S. Bank has been named one of the World’ s Most Ethical Companies by the Ethisphere Institute, a global leader in defining and advancing the standards of ethical business practices. “ Our employees have gone above and beyond to support our communities and customers, ” said Andy Cecere, chairman, president and chief…
This article was updated on March 24, 2022. In anticipation of the potential historic appointment of the first Black woman to the U.S. Supreme Court, the nation has its eye on Ketanji Brown Jackson’ s confirmation hearing for Supreme Court Justice this week. As the three days of public questioning came…
Originally published at home.kpmg. KPMG ranked No. 16 on The DiversityInc Top 50 Companies for Diversity list in 2021. KPMG International published an update of its progress towards a broad set of ESG commitments, first published in 2021. KPMG: Our Impact Plan outlines how the entire global organization is coming…
Originally published at jnj.com. Johnson & Johnson is a Hall of Fame company. 1908. That’ s the year Johnson & Johnson hired its first female scientist — no small feat during an era in which fewer than 3% of women attended college. Then again, this is hardly surprising for a company…
Originally published at newsroom.accenture.com. Accenture ranked No. 2 on The DiversityInc Top 50 Companies for Diversity list in 2021. Ecopetrol SA, Accenture and Amazon Web Services, Inc. ( AWS) announced a first-of-its-kind solution for water intelligence and management to help advance sustainability and operational efficiencies for energy companies. The availability of…
Originally published at basf.com. BASF ranked No. 12 on The DiversityInc Top 50 Companies for Diversity list in 2021. BASF, a leading supplier and innovator in the global personal care industry, announced its collaboration with StitchCrew, an organization serving early-stage entrepreneurs, to launch the Inclusive Beauty Accelerator. The program will…
Originally published at southerncompany.mediaroom.com. Southern Company ranked No. 20 on The DiversityInc Top 50 Companies for Diversity list in 2021. Georgia Power announced a new education equity initiative in partnership with four Georgia school districts, designed to support impactful local programs in communities of color and facilitate holistic generational change. The…
@ EY announced the launch of the 2022 Better Working World Data Challenge. The global competition is part of the EY’ … https: //t.co/FSEKJZjBND 15 hours ago
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Would an extra day off help professionals with work-life balance? https: //t.co/ibkpEndW14 March 20, 2022 | general |
Sekiwake Wakatakakage seizes share of lead in Osaka | Osaka – New sekiwake Wakatakakage ended No. 7 maegashira Takayasu’ s unbeaten run in the ongoing basho, forcing him out of the ring to seize a share of the Spring Grand Sumo Tournament lead on Wednesday.
Wakatakakage improved to 6-2 in his career against former ozeki Takayasu and both have 10-1 records after 11 days of the 15-day meet at Edion Arena Osaka.
Seeking his first career championship, Takayasu was undone by the sekiwake’ s combination of speed and strength. Wakatakakage came straight on, the top of his head impacting Takayasu’ s cheek bone and slowing him slightly.
Takayasu squeezed his opponent’ s arms together as tightly as he could to avoid surrendering a belt hold, but Wakatakakage persevered, latched on to the back of the maegashira’ s belt and wrestled him over the straw.
In the day’ s final bout, ozeki Takakeisho survived an opening-charge misfire against No. 6 Kotonowaka ( 9-2) to improve to 8-3 and secure his position at sumo’ s second highest rank for the next tournament.
Wrestling as a demotion-threatened kadoban ozeki after withdrawing hurt and failing to win eight bouts in January, Takakeisho put himself at the disadvantage when Kotonowaka easily evaded his charge.
Kotonowaka pivoted, and with the ozeki’ s back to the straw bales, geared up to ram Takakeisho from the ring, but missed. Takakeisho stepped to one side and gave his opponent a hand as Kotonowaka propelled himself out of the ring.
The loss cost Kotonowaka a share of the tournament lead and left him tied with new ozeki Mitakeumi at 9-2, one win back of the leaders.
Mitakeumi withstood a series of shoves to his face and throat, pressed new sekiwake Abi ( 6-5) back to the straw and yanked him down when the sekiwake leaned too far forward.
Abi had won 12 bouts in each of his two tournaments since returning to the top-flight makuuchi division from a suspension for breaking coronavirus rules, but fell to 2-9 against Mitakeumi in his career.
Shodai ( 6-5) took another step toward securing his rank for the next grand tournament. Like Takakeisho, Shodai entered the tourney needing eight wins to avoid being relegated to sekiwake, sumo’ s third highest rank.
The ozeki won just one of his first six bouts here, but has now won five straight with a tsukiotoshi victory over No. 5 Takarafuji ( 3-8), against whom he is now 16-3 in his career.
New komusubi Hoshoryu was gifted a quick fifth win. The nephew of former yokozuna Asashoryu made a strong start, but the bout ended prematurely when No. 1 Daieisho’ s left knee buckled, and he slumped to his sixth defeat.
Fellow komusubi Takanosho’ s struggles continued. The former sekiwake fell to a 2-9 record following a shove-out defeat at the hands of No. 3 Onosho ( 5-6).
No. 15 Tochinoshin, a former ozeki, improved to 8-3 for his first kachikoshi winning record since November 2020. The Georgian finished off No. 11 Terutsuyoshi by hoisting him in the air and carrying him over the straw, a move that was one of his signatures during the height of his career. | tech |
Six players to watch in the 2022 Central League | The pennant races are set to begin anew as NPB prepares to kick off another season. As Japan’ s 12 clubs prepare to chase the pennant, here are six players from the Central League to keep an eye on.
Shiomi is one of NPB’ s most exciting players with all-around talent and speed that helps him create havoc on the basepaths and track down balls in center field.
An injury derailed him in 2020 before he burst onto the scene last year, hitting.278 and stealing 21 bases in 140 games. Shiomi also hit 14 home runs, including one on Sept. 18, when he hit for the cycle against the Giants. The 28-year-old also finished tied for the NPB lead with seven triples.
Shiomi was a big piece of last season’ s run to the Central League and Japan Series crowns. While he is not a force of nature like teammates Munetaka Murakami and Tetsuto Yamada, he’ s a superstar in his role and only getting started.
Rojas’ considerable success in the Korea Baseball Organization, where he was the league MVP in 2020, did not translate into a similar performance in his first NPB season.
He arrived in Japan over a week after opening day last season due to COVID-19 travel restrictions and had to quarantine before joining the team. He finally made his top team debut in May, but things never seemed to click. Rojas batted.217 and hit eight home runs in 60 games.
Rojas was in spring camp on time this year and should start this season on sturdier footing. If that, plus a year of NPB experience, helps Rojas hit the way he did in KBO, then having him alongside Teruaki Sato will get the Tigers roaring at the plate.
Hanshin let go of Justin Bour after one season, and Jerry Sands only lasted two, so the pressure may be on for Rojas. If he delivers for a team sorely in need of another bat to step up — it was Yusuke Oyama in 2020 and Sato for half of 2021 — he’ ll live up to the expectations that preceded his arrival.
Sho Nakata is preparing for his second season in the Central League with the Giants. Nakata hit just.154 in 34 games with the club last season. | KYODO
Nakata’ s 2021 included a suspension for a violent act against a teammate while with the Hokkaido Nippon Ham Fighters, eventually being kicked to the curb by the team and landing in the Central League with an thud after the Giants’ perplexing decision to acquire him in a midseason trade. Nakata managed just a paltry.177 average and seven home runs in 73 games through it all last year.
Despite Nakata’ s baggage, it has been proven over and over that as long as you have talent, teams will keep doling out second chances. Nakata will likely enter this year motivated to be on his best behavior, and the Giants stand to benefit.
Nakata reported for camp heavier than in recent years but has said he’ s mostly at his ideal playing weight. He batted.325 with three doubles and three home runs in 40 at-bats in the preseason and even made a few nifty plays with his glove at first base. He gets to hit in the CL full time this year, which is another positive for a player trying to get back on track.
The Giants need offense and Nakata has the potential to be a game-changer if he can stay on the straight and narrow and hit the way once did for the Fighters.
Ugusa spent part of his offseason training with Seiya Suzuki and tried to learn as much as could from the now-former Carp superstar.
Suzuki leaving for the majors — he signed with the Chicago Cubs — leaves a gaping hole in the Carp roster but gives some of the team’ s other players a chance to prove themselves. Ugusa is one of them, and the 24-year-old will be trying to nail down a regular spot in manager Shinji Sasaoka’ s lineup.
Shogo Sakakura and Kaito Kozono made the most of their playing time in 2021, and Ugusa’ s time could be now. He spent most of the year on the farm team, hitting.256 with six home runs, 26 RBIs and five stolen bases. He played in 41 games on the top squad and hit.291 with four homers, seven doubles and a triple in 148 at-bats.
Ugusa could carve out a place for himself at the top of the order if he stretched out that performance across an entire season while also providing value with his glove in the outfield.
Kinoshita played in over 100 games for the first time in his career last year and produced his best season.
He was the Dragons’ second-best hitter, putting up a.270 average and.748 on-base plus slugging percentage while hitting 11 home runs. He might have also been the best fielding catcher in Japan and was the bane of would-be base stealers.
Kinoshita looks primed to again be of the few shining lights amid the darkness that is the Chunichi offense. He hit.353 with a pair of home runs during the spring and it will be interesting to see if he can improve on his 2021 campaign.
Kinoshita’ s offensive prowess on a team mostly bereft of consistent run production and his skills as a catcher makes him perhaps the team’ s most important player. Catching is a grueling business, though, and Kinoshita’ s availability may be his most important ability this season.
BayStars pitcher Katsuki Azuma ( right) poses with manager Daisuke Miura after being named the team’ s opening day starter on March 10. | KYODO
Azuma was injured before fans could see how he followed up his CL Rookie of the Year campaign in 2018, when he was 11-5 with a 2.45 ERA and 155 strikeouts. He then missed most of the next two seasons after needing Tommy John surgery.
Azuma will not have to wait long to take the mound this year, as manager Daisuke Miura named the lefty as his opening day starter. Azuma enters the season with some momentum after allowing one run and striking 11 over 13⅔ innings in the preseason.
The Baystars’ pitching staff was the worst in the league last season, so Azuma has the chance to be a potentially huge addition. If he pitches the way he did in 2018, his presence helps address one of the club’ s glaring weaknesses from a year ago. Azuma looked like a rising star back in 2018. He finally has a clean bill of health and can continue on that path this season. | tech |
Ukraine war and pandemic force nations to retreat from globalization | WASHINGTON – When the Cold War ended, governments and companies believed that stronger global economic ties would lead to greater stability. But the Ukraine war and the pandemic are pushing the world in the opposite direction and upending those ideas.
Important parts of the integrated economy are unwinding. U.S. and European officials are now using sanctions to sever major parts of the Russian economy — the 11th largest in the world — from global commerce, and hundreds of Western companies have halted operations in Russia on their own. Amid the pandemic, companies are reorganizing how they obtain their goods because of soaring costs and unpredictable delays in global supply chains.
Western officials and executives are also rethinking how they do business with China, the world’ s second-largest economy, as geopolitical tensions and the Chinese Communist Party’ s human rights abuses and use of advanced technology to reinforce autocratic control make corporate dealings more fraught.
The moves reverse core tenets of post-Cold War economic and foreign policies forged by the United States and its allies that were even adopted by rivals like Russia and China.
“ What we’ re headed toward is a more divided world economically that will mirror what is clearly a more divided world politically, ” said Edward Alden, a senior fellow at the Council on Foreign Relations. “ I don’ t think economic integration survives a period of political disintegration. ”
“ Does globalization and economic interdependence reduce conflict? ” he added. “ I think the answer is yes, until it doesn’ t. ”
Opposition to globalization gained momentum with the administration of former U.S. President Donald Trump’ s trade policies and “ America First ” drive, and as the progressive left became more powerful. But the pandemic and Russian President Vladimir Putin’ s invasion of Ukraine have brought into sharp relief the uncertainty of the existing economic order.
Former U.S. President Donald Trump tosses out MAGA hats and greets attendees during a ‘ Save America’ Rally at the Lorain County Fairgrounds in Wellington, Ohio, U.S., on Saturday, June 26, 2021. | BLOOMBERG
U.S. President Joe Biden warned President Xi Jinping of China on Friday that there would be “ consequences ” if Beijing gave material aid to Russia for the war in Ukraine, an implicit threat of sanctions. China has criticized sanctions on Russia, and Le Yucheng, the vice foreign minister, said in a speech on Saturday that “ globalization should not be weaponized. ” Yet China increasingly has imposed economic punishments — Lithuania, Norway, Australia, Japan and South Korea have been among the targets.
The result of all the disruptions may well be a fracturing of the world into economic blocs, as countries and companies gravitate to ideological corners with distinct markets and pools of labor, as they did in much of the 20th century.
Biden already frames his foreign policy in ideological terms, as a mission of unifying democracies against autocracies. Biden also says he is enacting a foreign policy for middle-class Americans, and central to that is getting companies to move critical supply chains and manufacturing out of China.
The goal is given urgency by the hobbling of those global links over two years of the pandemic, which has brought about a realization among the world’ s most powerful companies that they need to focus on not just efficiency and cost, but also resiliency. This month, lockdowns China imposed to contain COVID-19 outbreaks have once again threatened to stall global supply chains.
The economic impact of such a change is highly uncertain. The emergence of new economic blocs could accelerate a massive reorganization in financial flows and supply chains, potentially slowing growth, leading to some shortages and raising prices for consumers in the short term. But the longer-term effects on global growth, worker wages and supplies of goods are harder to assess.
The war has set in motion “ deglobalization forces that could have profound and unpredictable effects, ” said Laurence Boone, the chief economist of the Organisation for Economic Co-operation and Development ( OECD).
For decades, executives have pushed for globalization to expand their markets and to exploit cheap labor and lax environmental standards. China especially has benefited from this, while Russia profits from its exports of minerals and energy. They tap into enormous economies: The Group of 7 industrialized nations make up more than 50% of the global economy, while China and Russia together account for about 20%.
A view of a closed Starbucks coffee shop in Moscow on March 10. McDonald’ s, Coca-Cola and Starbucks on March 8, bowed to public pressure and suspended their operations in Russia, joining the international corporate chorus of outrage over Moscow’ s invasion of Ukraine. | AFP-JIJI
Trade and business ties between the United States and China are still robust, despite steadily worsening relations. But with the new Western sanctions on Russia, many nations that are not staunch partners of America are now more aware of the perils of being economically tied to the United States and its allies.
If Xi and Putin organize their own economic coalition, they could bring in other nations seeking to shield themselves from Western sanctions — a tool that all recent U.S. presidents have used.
“ Your interdependence can be weaponized against you, ” said Dani Rodrik, a professor of international political economy at Harvard Kennedy School. “ That’ s a lesson that I imagine many countries are beginning to internalize. ”
The Ukraine war, he added, has “ probably put a nail in the coffin of hyperglobalization. ”
China and, increasingly, Russia have taken steps to wall off their societies, including erecting strict censorship mechanisms on their internet networks, which have cut off their citizens from foreign perspectives and some commerce. China is on a drive to make critical industries self-sufficient, including for technologies like semiconductors.
And China has been in talks with Saudi Arabia to pay for some oil purchases in China’ s currency, the renminbi, The Wall Street Journal reported; Russia was in similar discussions with India. The efforts show a desire by those governments to move away from dollar-based transactions, a foundation of American global economic power.
For decades, prominent U.S. officials and strategists asserted that a globalized economy was a pillar of what they call the rules-based international order, and that trade and financial ties would prevent major powers from going to war. The United States helped usher China into the World Trade Organization in 2001 in a bid to bring its economic behavior — and, some officials hoped, its political system — more in line with the West. Russia joined the organization in 2012.
A resident undergoes a nucleic acid test for the COVID-19 coronavirus in Shenyang, in China’ s northeastern Liaoning province on March 14. | AFP-JIJI
But Putin’ s war and China’ s recent aggressive actions in Asia have challenged those notions.
“ The whole idea of the liberal international order was that economic interdependence would prevent conflict of this kind, ” said Alina Polyakova, president of the Center for European Policy Analysis, a research group in Washington. “ If you tie yourselves to each other, which was the European model after the Second World War, the disincentives would be so painful if you went to war that no one in their right mind would do it. Well, we’ ve seen now that has proven to be false. ”
“ Putin’ s actions have shown us that might have been the world we’ ve been living in, but that’ s not the world he or China have been living in, ” she said.
The United States and its partners have blocked Russia from much of the international financial system by banning transactions with the Russian central bank. They have also cut Russia off from the global bank messaging system called SWIFT, frozen the assets of Russian leaders and oligarchs, and banned the export from the United States and other nations of advanced technology to Russia. Russia has answered with its own export bans on food, cars and timber.
The penalties can lead to odd decouplings: British and European sanctions on Roman Abramovich, the Russian oligarch who owns the Chelsea soccer team in Britain, prevent the club from selling tickets or merchandise.
About 400 companies have chosen to suspend or withdraw operations from Russia, including iconic brands of global consumerism such as Apple, Ikea and Rolex.
While many countries remain dependent on Russian energy exports, governments are strategizing how to wean themselves. Washington and London have announced plans to end imports of Russian oil.
The outstanding question is whether any of the U.S.-led penalties would one day be extended to China, which is a far bigger and more integral part of the global economy than Russia.
Even outside the Ukraine war, Biden has continued many Trump administration policies aimed at delinking parts of the American economy from that of China and punishing Beijing for its commercial practices.
U.S. President Joe Biden listens while meeting virtually with Xi Jinping, China’ s president, in the Roosevelt Room of the White House in Washington, D.C., U.S., on Monday, Nov. 15, 2021. | BLOOMBERG
Officials have kept the tariffs imposed by Trump, which covered about two-thirds of Chinese imports. The Treasury Department has continued to impose investment bans on Chinese companies with ties to the country’ s military. And in June, a law will go into effect in the United States barring many goods made in whole or in part in the region of Xinjiang.
Despite all that, demand for Chinese-made goods has surged through the pandemic, as Americans splurge on online purchases. The overall U.S. trade deficit soared to record levels last year, pushed up by a widening deficit with China, and foreign investments into China actually accelerated last year.
Some economists have called for more global integration, not less. Speaking at a virtual conference on Monday, Ngozi Okonjo-Iweala, director-general of the World Trade Organization, urged a move toward “ re-globalization, ” saying, “ Deeper, more diversified international markets remain our best bet for supply resilience.
But those economic ties will be further strained if U.S.-China relations worsen, and especially if China gives substantial aid to Russia.
Besides recent warnings to China from Biden and Secretary of State Antony Blinken, Commerce Secretary Gina Raimondo has said her agency would ban the sale of critical American technology to Chinese companies if China tried to supply forbidden technology to Russia.
In the meantime, the uncertainty has left the U.S.-China relationship in flux. While many major Chinese banks and private companies have suspended their interactions with Russia to comply with sanctions, foreign asset managers appear to have also begun moving their money out of China in recent weeks, possibly in anticipation of sanctions.
Mary Lovely, a senior fellow at the Peterson Institute for International Economics, said she did not expect China to “ throw all in ” with Russia, but that the war could still strain economic ties by worsening U.S.-China relations.
“ Right now, there is great uncertainty as to how the U.S. and China will respond to the challenges posed by Russia’ s increasingly urgent need for assistance, ” she said. “ That policy uncertainty is another push to multinationals who were already rethinking supply chains. ” | tech |
Toyota plans ¥100 billion buyback with shares trending down | Toyota Motor Corp. announced a ¥100 billion ( $ 826 million) stock buyback on Wednesday, delivering on a promise to flexibly repurchase shares and pay out stable dividends to shareholders.
With Toyota shares trading more than 10% off recent highs, the Japanese automaker said it was taking the current stock price into account and being “ more flexible ” than ever in its implementation of buybacks, according to a statement to the Tokyo Stock Exchange.
The buyback announcement comes as the top-selling automaker’ s shares have taken a hit in recent months as it faces a windfall of disruptions. Toyota’ s factories have been halted recently due to a cyberattack on one of its suppliers, a powerful earthquake in Japan and a COVID-19 outbreak in the Chinese city of Changchun. Toyota’ s shares closed in Tokyo on Wednesday almost 12% off a record close in January.
Toyota’ s decision came at “ bargain timing ” given current stock prices, said Bloomberg Intelligence analyst Tatsuo Yoshida. While the size of the buyback may be small relative to the company’ s market capitalization, it’ s a “ positive ” for Toyota’ s shares, and a sign that the company is “ steadily doing what it says it’ ll do ” in terms of flexibly acquiring shares and paying steady dividends, Yoshida said.
Buybacks have been on investors’ minds this week in Asia, after shares in Alibaba Group Holding Ltd. surged following its announcement of an expanded $ 25 billion repurchase. Investors are betting that Tencent Holdings Ltd. could be next to jump on the bandwagon.
Toyota will repurchase the shares from Thursday through May 10, around the time the carmaker typically announces full-year earnings. | tech |
Russian oil seeps into global market to ease supply fears for now | Millions of barrels of Russian oil are still finding a way to buyers almost a month after the country first invaded Ukraine, tempering concerns that a sanctions backlash would all but choke off supply and cause the market for physical cargoes to overheat.
India’ s oil refiners grabbed multiple cargoes of Russia’ s flagship Urals crude this month, potentially supplanting the Middle Eastern varieties they normally purchase from Abu Dhabi and Iraq. Meanwhile, China’ s private processors are still thought to be targeting their favored cargoes from the east of Russia — likely at knock-down prices.
Since Russia invaded Ukraine late last month, the market has been twisting on two vital questions: how much crude will Moscow end up selling, and where? There’ s been a buyers’ strike across swaths of Europe in response to the invasion, but what’ s less clear is how much other regions — especially Asia, the top demand center — will purchase.
“ Russian barrels must look tempting, ” said John Driscoll, chief strategist at JTD Energy Services Pte., adding that his view is that measures against the country will nonetheless curb buying of its crude over time. “ Resourceful traders may explore ways to move cargoes — the Chinese won’ t be intimidated by U.S. sanctions, and will remain the largest importer of Russian crude. India is the next one to watch. ”
At least for now, what’ s going on with the buying and selling of non-Russian oil suggests traders are becoming less fraught about the threat of supply shortages, even if trading the nation’ s barrels isn’ t risk-free, and spreads on Brent oil point to a market that remains incredibly tight by historical standards.
At the moment, there are no sanctions directly prohibiting purchases but there are worries about what steps might ultimately be taken if the war drags on. Financing, insuring and shipping of Russian petroleum have also become much more complicated by the measures that the west has taken.
European officials are debating the idea of an embargo on Russian oil sales, although the bloc is divided on the idea and Germany opposes such a step. European Union and NATO leaders are poised to gather in Brussels on Thursday to beef up their response to the crisis.
For now, though, traders appear to be taking the view that the flow of Russian oil indicates that the market won’ t be as tight as first thought.
A flurry of offers for Middle Eastern barrels took place in the Asian spot market this week, according to traders. Importantly, that comes together with a slowdown in Chinese demand amid COVID-19 lockdowns, and wild price gyrations that’ s kept many buyers on the sidelines.
The differentials at which Middle Eastern barrels sell, a key indicator of demand for them, have dipped after starting off strongly early this month. Abu Dhabi’ s Upper Zakum crude for May loading was purchased by Thailand’ s PTT Pcl at about $ 7.50 a barrel more than the Dubai benchmark this week. That compares with a premium of over $ 10 two weeks ago.
Storage tanks at the Valero Energy Corp. oil refinery in Memphis, Tennessee, on Feb. 16. Millions of barrels of Russian oil are still finding a way to buyers almost a month after the country first invaded Ukraine. | BLOOMBERG
Crude cargoes from the Persian Gulf were thought to be a natural choice for Asian buyers in the absence of Russian cargoes.
Shortly after the invasion, more and more buyers became wary of Russian cargoes despite record discounts after the U.S. banned Russian oil imports and Shell PLC came under heavy criticism due to a purchase of Urals. The major, along with TotalEnergies SE and BP PLC, were among a swath of European buyers that stepped back.
While it’ s still early in the trading and shipping process to gauge the volume of Russian crude that will ultimately flow to Asia in the coming months, the International Energy Agency said in a report last week that the nation’ s oil production is forecast to slump by about a quarter next month, inflicting the biggest supply shock in decades.
Still, some deliveries to Asia are likely to stay, at least for now.
May shipments of Sokol crude — another variety from the Russian Far East — are being organized to some customers in northeast Asia who have committed volumes under long-term contracts and equity agreements, according to traders who sell and buy the grade.
May-loading cargoes of ESPO from eastern Russia were being offered at discounts to the Dubai marker against which they trade, compared with premiums for comparative grades from the Middle East. Chinese independent refiners were seen as most likely buyers, although no transaction has yet been heard this month amid a reduction in market transparency, traders said.
What’ s adding to the slowness in spot transactions is lackluster demand from Chinese refiners including independent processors that have reduced operating rates amid a COVID-19 resurgence that’ s led to lockdowns.
The private plants, known as teapots, make up a quarter of the nation’ s processing capacity. They are running at a five-year low, according to industry consultant OilChem. At least two of them sold back cargoes of crude from West Africa and Latin America in a rare move earlier this month.
Diminished appetite from Chinese buyers has also hindered purchases of West African cargoes, dragging down offer levels for crude from producers like Angola, traders said. A handful of Angolan cargoes for April loading are still left unsold even after the release of program for May, they said.
In Europe, traders said the impact of missing barrels of Urals hasn’ t been as profound in terms of market tightness as they had previously expected, with most European refiners already having secured their required cargoes through the middle of next month.
European buyers are more likely to secure cargoes from the North Sea such as Johan Sverdrup to replace their Urals, and Iraq’ s Basrah Medium is another variety that could be picked up as an alternative to the Russian grade, the traders added. | tech |
Looking at the state of the freight railroad market with Tony Hatch, ABH Consulting | In this podcast, Hatch offered up his views on various aspects of the freight railroad and intermodal sectors, including: market conditions, service levels, capital expenditures, the impact of inflation on railroads, and policy matters, among other topics.
A nationally-known freight railroad and intermodal expert, Hatch also examined the impact of the ongoing COVID-19 pandemic on the freight railroad and intermodal sectors, the impact of the incoming Biden Administration on the sectors, and Peak Season, among other topics.
Tony Hatch has nearly three decades of experience in the freight railroad and transportation sectors, primarily as an analyst. As principal of New York-based ABH Consulting, Hatch has been focused on the freight transportation segment, particularly surface transportation. And he is well-known for his knowledge of the intermodal area, where the various modes of freight transport converge, on which he has held several dozen specialized conferences.
Prior to launching ABH Consulting, Hatch was an analyst for Salomon brothers; proceeding to Argus, Painewebber, and most recently at NatWest Markets ( USA) prior to starting his independent analyst/consultancy in 1999.
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New Type of UV Light Makes Indoor Air As Safe as Outdoors – Variant Proof & Effective Against COVID, Flu | Using far-UVC light in places where people gather indoors could help prevent the next pandemic.
A new type of ultraviolet light that is safe for people took less than five minutes to reduce the level of indoor airborne microbes by more than 98%, a joint study by scientists at Columbia University Vagelos College of Physicians and Surgeons and in the U.K. has found. Even as microbes continued to be sprayed into the room, the level remained very low as long as the lights were on.
The study suggests that far-UVC light from lamps installed in the ceiling could be a highly effective passive technology for reducing person-to-person transmission of airborne-mediated diseases such as COVID and influenza indoors, and lowering the risk of the next pandemic.
“ Far-UVC rapidly reduces the amount of active microbes in the indoor air to almost zero, making indoor air essentially as safe as outdoor air, ” says David Brenner, PhD, director of the Center for Radiological Research at Columbia University Vagelos College of Physicians and Surgeons and co-author of the study. “ Using this technology in locations where people gather together indoors could prevent the next potential pandemic. ”
The study was published March 23 in the journal Scientific Reports, a Nature journal.
“ Far-UVC light is simple to install, it’ s inexpensive, it doesn’ t need people to change their behavior, and above all it’ s a safe way to prevent the transmission of any virus, including the COVID virus and its variants, as well as influenza and also any potential future pandemic viruses, ” Brenner says.
Disinfecting indoor air with far-UVC light is a new approach to safely and efficiently destroy airborne viruses in occupied spaces, including the viruses that cause COVID and influenza.
Scientists have known for decades that a type of ultraviolet light known as UVC light rapidly kills microbes, including bacteria and viruses. But conventional germicidal UVC light can not be used directly to destroy airborne viruses in occupied indoor spaces because it is a potential health hazard to the skin and eyes.
About a decade ago, Columbia University scientists proposed that a different type of UVC light, known as far-UVC light, would be just as efficient at destroying bacteria and viruses but without the safety concerns of conventional germicidal UVC.
Far-UVC light is safe for people because it has a shorter wavelength than conventional germicidal UVC, so it can’ t penetrate into living human skin cells or eye cells. But it is equally efficient at killing bacteria and viruses, which are much smaller than human cells.
In the past decade, many studies around the world have shown that far-UVC is both efficient at destroying airborne bacteria and viruses and safe for use around people. But until now these studies had only been conducted in small experimental chambers, not in full-sized rooms mimicking real-world conditions.
In the current study, scientists at the University of St. Andrews, University of Dundee, University of Leeds, and Columbia University tested the efficacy of far-UVC light in a large room-sized chamber with the same ventilation rate as a typical home or office ( about three air changes per hour).
During the experiment, a sprayer continuously emitted an aerosol mist of S. aureus bacteria into the room. ( This microbe was chosen because it is slightly less sensitive to far-UVC light than coronaviruses, providing the researchers with an appropriately conservative model.) When the concentration of microbes in the room stabilized, the researchers turned on commercially available overhead far-UVC lamps.
At an intensity based on the current regulatory limit on far-UVC light exposure, set by the American Conference of Governmental Industrial Hygienists, the far-UVC lamps inactivated more than 98% of the airborne microbes in just five minutes. The low level of viable microbes was maintained over time, even though microbes continued to be sprayed into the room.
The efficacy of different approaches to reducing indoor virus levels is usually measured in terms of equivalent air changes per hour. In this study, far-UVC lamps produced the equivalent of 184 equivalent air exchanges per hour. This surpasses any other approach to disinfecting occupied indoor spaces, where five to 20 equivalent air changes per hour is the best that can be achieved practically.
“ Our trials produced spectacular results, far exceeding what is possible with ventilation alone, ” says Kenneth Wood, PhD, lecturer in the School of Physics and Astronomy at the University of St. Andrews and senior author of the study. “ In terms of preventing airborne disease transmission, far-UVC lights could make indoor places as safe as being outside on the golf course on a breezy day at St. Andrews. ”
“ Previous studies have shown that far-UVC light can kill the COVID virus, other human coronaviruses, influenza, and drug-resistant bacteria, ” Brenner says. “ What’ s particularly attractive about far-UVC technology as a practical method of preventing indoor disease transmission is that it will be equally good at inactivating all future COVID variants, as well as new infectious viruses that have yet to emerge, while retaining efficacy against ‘ old fashioned’ viruses like influenza and measles. ”
Finally, because of the way ultraviolet light kills microbes, viruses and bacteria can not develop resistance as they do with vaccines and drug treatments.
The study, titled “ Far-UVC ( 222 nm) efficiently inactivates an airborne pathogen in a room-sized chamber, ” was published in Scientific Reports on March 23.
The authors are Ewan Eadie ( Ninewells Hospital, Dundee, Scotland), Waseem Hiwar ( University of Leeds, England), Louise Fletcher ( University of Leeds), Emma Tidswell ( University of Leeds), Paul O’ Mahoney ( University of Dundee), Manuela Buonanno ( Columbia University), David Welch ( Columbia University), Catherine Adamson ( St. Andrews University, Scotland), David Brenner ( Columbia University), Catherine Noakes ( University of Leeds), and Kenneth Woods ( University of St. Andrews).
The study was supported by grants from the U.K. Health Security Agency.
David J. Brenner and co-inventors have been granted a U.S. patent titled “ Apparatus, method and system for selectively affecting and/or killing a virus ” ( US1078019B2). Columbia University has licensed aspects of filtered UV light technology to USHIO Inc. and has received a research gift from LumenLabs, a company producing far-UVC sources. Other disclosures are noted in the paper.
Reference: “ Far-UVC ( 222 nm) efficiently inactivates an airborne pathogen in a room-sized chamber ” 23 March 2022, Scientific Reports. DOI: 10.1038/s41598-022-08462-z | tech |
'What have we done wrong? ' Afghan school girls forced home | Hi, what are you looking for?
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Atiya Azimi was up all night packing and repacking her bag, feverish at returning to school for the first time since the Taliban seized control of Afghanistan.
The joy was shockingly brief.
In the middle of a lesson, just hours after the school reopened, she learned the hardline Islamists had revoked permission for girls to study.
“ Suddenly we were told to leave until another order is issued, ” said Azimi, who was returning to grade 12 at Zarghona Girls School in the capital Kabul.
“ What have we done wrong? Why should women and girls face this situation? I ask the Islamic Emirate to start our classes. ”
“ I did not sleep the whole night thinking about going back to school again, ” she told AFP.
Secondary school age girls have been out of education for around a year in many provinces.
Schools were first closed under the previous US-backed government as a result of the Covid-19 outbreak, and after the Taliban took power the new rulers reopened all schools for boys.
But girls were allowed to return only to primary schools and were banned from secondary institutions in most areas.
The Islamists claimed that schools needed to be adapted so girls and boys could be segregated, despite the vast majority in conservative Afghanistan already operating separate classrooms.
The Taliban’ s education ministry days ago announced that girls’ secondary schools would reopen for the start of the new academic year on Wednesday.
But an 11th hour U-turn by the Taliban leadership was a devastating blow for students, parents and even teachers.
“ Our hopes were high but now they are shattered, ” said Muthahera Arefi, 17, turning around from a Kabul school to head home.
Amina Haidari, a mother of four daughters, was frustrated with how events unfolded.
“ I think for girls living in the shadow of the Taliban, it is a total mess and waste of time, ” said Haidari, who herself lost her job in the election commission which was scrapped by the Taliban soon after they stormed back to power.
“ All the statements that the Taliban make are just propaganda… We don’ t believe this government will reopen schools. ”
Across the country, groups of jubilant girls had arrived at schools on Wednesday morning carrying their bags and books, greeting their former classmates with grins and chatter.
Teacher Alia Hakimi, at Tajwar Sultana Girls School in Kabul, said the decision will leave “ students weak and stressed. ”
At Kabul’ s Rabia Balkhi, one of the largest in the country, girls were not able to even make it through the school gates.
“ They denied us entry into the school. It’ s heartbreaking for my girls, ” said a mother who asked not to be named.
One of her two daughters, both with a hijab covering their hair, was brimming with tears.
“ I was looking forward to meeting my friends again, to be together again, ” said the girl, who also asked not to be named.
Some girls even pleaded to the guards to allow them entry into the premises.
“ We are ready to fulfil all conditions of the Taliban, including wearing hijabs or anything but we urge them not to stop our education, ” said a girl from class 11.
With 2,400 staff representing 100 different nationalities, AFP covers the world as a leading global news agency. AFP provides fast, comprehensive and verified coverage of the issues affecting our daily lives.
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UK confronts cost of living crisis with inflation-fighting budget | Hi, what are you looking for?
British finance minister launched plans to ease a cost of living crisis, with inflation set to spike.
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British finance minister Rishi Sunak on Wednesday launched plans to ease a cost of living crisis, with UK inflation set to spike to a 40-year high on Ukraine fallout.
In a budget update, Chancellor of the Exchequer Sunak unveiled measures to help household finances, including a cut on fuel duty and easing the tax burden for the lowest earners.
Britain’ s economy will grow far slower than expected this year owing to the Ukraine war and soaring global inflation, he told parliament.
The UK economy was set to grow 3.8 percent in 2022, down from an official estimate of six percent made in October.
– ‘ Prepare for worse’ –
Sunak said that the Office for Budget Responsibility ( OBR) — the government’ s official economic forecaster — “ has not accounted for the full impacts of the war in Ukraine and we should be prepared for the economy and public finances to worsen, potentially significantly ”.
“ Their initial view, combined with high global inflation and continuing supply chain pressures means ” the UK economy is forecast to grow significantly slower than thought.
Gross domestic product was estimated to expand a further 1.8 percent next year, down from an official prediction of 2.1 percent.
The OBR warned that should “ wholesale energy prices remain as high as markets expect, energy bills are set to rise… pushing inflation to a 40-year high of 8.7 percent in the fourth quarter ”.
UK annual inflation accelerated to a 30-year high at 6.2 percent in February, official data showed Wednesday.
Countries across the world are battling surging inflation fuelled by rocketing commodity prices over the Ukraine war and after nations exited pandemic lockdowns.
Sunak last month unveiled a package worth £9 billion ( $ 11.9 billion, 11 billion euros) targeted at helping 28 million poorer and middle-income households with energy bills in particular.
Household incomes are set to shrink further in April owing to a planned tax hike on all UK workers and businesses to fund care for the elderly.
The same month, a cap on domestic gas and electricity bills will be increased, in line with rebounding wholesale energy costs.
“ Higher inflation will erode real incomes and consumption, ” the OBR said Wednesday.
It said that “ with inflation outpacing growth in nominal earnings and net taxes due to rise in April ”, real living standards are set to fall by a record amount this year.
– Rate hikes –
Spiking global inflation has forced central banks around the world to lift interest rates, including the Bank of England which last week lifted borrowing costs to 0.75 percent.
Rising interest rates are significantly increasing governments’ debt repayments, which ballooned over the past two years on vast pandemic costs.
Britain’ s economy rebounded by a record 7.5-percent last year on easing Covid curbs after a pandemic-driven collapse.
The record UK expansion followed an all-time slump of 9.4 percent in 2020.
Sunak has also been comforted by news that the UK unemployment rate has fallen to its pre-pandemic level.
However, rising wages are being eroded at the fastest pace in eight years as inflation soars.
With 2,400 staff representing 100 different nationalities, AFP covers the world as a leading global news agency. AFP provides fast, comprehensive and verified coverage of the issues affecting our daily lives.
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Amazon faces rising union push in United States | Hi, what are you looking for?
The e-commerce behemoth, one of the biggest employers in the United States, so far has kept itself union-free in its home market.
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Christian Smalls no longer works at Amazon’ s JFK8 warehouse in New York, but he still sees former colleagues every day at the bus stop as they head into work.
His mission: To convince the workers to form a union.
The e-commerce behemoth, one of the biggest employers in the United States, so far has kept itself union-free in its home market.
But Amazon faces imminent votes at three US facilities that could establish a union toehold, something labor experts think could spur on campaigns at other venues.
At JFK8, in the city’ s Staten Island borough, 5,000 workers will be able to cast their ballots on the union bid from March 25 to 30, and the counting is scheduled to commence on March 31.
A vote at a second Staten Island venue, a sorting center employing 1,500 people, is scheduled to begin April 25.
In the southern state of Alabama, more than 6,000 workers at a warehouse in Bessemer have another opportunity to form a union. They have until March 25 to vote by mail, and the counting there will start March 28 and could take up to two weeks.
A large majority of workers at the Bessemer facility last year voted against unionizing, but US labor officials overseeing the process threw out the result, citing “ interference ” by Amazon.
– Need for change –
Smalls, 33, was fired in March 2020 just after organizing a protest for personal protective equipment amid the surge of the first major Covid-19 outbreak in New York.
Rather than go away quietly, Smalls spoke out about his experience and continued to clamor for more support for essential workers.
Shortly after the first vote in Bessemer, Smalls together with current and former Amazon workers created the Amazon Labor Union.
“ I know I am on the right side of this fight, ” Smalls told AFP earlier this month during a phone-banking event at which about 20 volunteers gathered to call employees one-by-one in order to tout the potential of a union to boost wages, working conditions, benefits and job security.
Isaiah Thomas, 20, who is working at Bessemer in order to finance his studies, is using essentially the same arguments to convince his fellow Amazon workers.
After last year’ s setback, the Retail, Wholesale and Department Store Union, which backs the Alabama campaign, has redoubled its efforts to speak with workers, going door-to-door and during breaks.
“ The moment that I stepped through the doors on my first day on the job, I realized that we needed to have change at Amazon, ” said Thomas, who pointed to safety hazards, unreasonable workloads over a long day and limited break times.
Thomas joined the effort following outreach from union supporters.
Before then, “ I didn’ t really know how a union operated, ” he said.
– Uphill fight –
Amazon has adopted a similar approach in both New York and Alabama, discouraging the workers from supporting unions at mandatory meetings, and through signs and other literature at the work site.
The company argues that forming a union will mar the company’ s direct relationship with workers and represent a jump into the unknown, with no guarantee workers will wind up with better wages or job security.
“ Our employees have the choice of whether or not to join a union, ” said Amazon spokesperson Kelly Nantel. “ As a company, we don’ t think unions are the best answer for our employees.
“ Our focus remains on working directly with our team to continue making Amazon a great place to work. ”
Nantel touted company benefits that include health care and financing college tuition after three months of work. The company also pays competitively, including at Bessemer, where the $ 15.80 an-hour floor is more than twice the federal minimum wage.
Ruth Milkman, a sociologist of labor movements at City University of New York, said US labor law stacks the odds in favor of the company, so a union win would be significant.
“ If either of these campaigns at Amazon were to be successful, it would be huge and that would be very inspiring to other people working at Amazon, ” Milkman said.
However, “ I’ m not optimistic, ” she said, noting that the New York campaign is not affiliated with an established union that could commit financial resources to support the effort to organize.
In Bessemer, meanwhile, workers have few alternatives in terms of jobs that pay as well as Amazon.
“ You can be intimidated by employer propaganda, ” Milkman said, adding that workers will “ think twice ” about rocking the boat.
With 2,400 staff representing 100 different nationalities, AFP covers the world as a leading global news agency. AFP provides fast, comprehensive and verified coverage of the issues affecting our daily lives.
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How Indonesian politicians misuse the term 'big data ' to delay the next presidential election | Indonesian politicians backing President Joko “ Jokowi ” Widodo have come up with the idea to postpone the next presidential election, slated to be held in 2024, and enable the president to serve a third term.
The politicians, all affiliated with the ruling coalition, and Indonesia’ s Coordinating Minister for Maritime Affairs and Investment, Luhut Binsar Pandjaitan, claimed that there were big data containing aspirations from social media users who demand the election postponement.
The term big data now has become a buzzword used by many people in the country.
With the rapid development in communication and information technology, politicians and government officials often misuse the term big data to push their political agendas, including those that violate the Constitution.
Many politicians use the term Big Data to look up-to-date and technologically savvy to the public without understanding its concept.
Many assume that Big Data is only about the size of the data, as if when I have a massive amount of data, then I have Big Data.
In some cases, that might be true, but not in most cases.
The term Big Data generally refers to large and complex datasets in various formats, either structured, unstructured, or semi-structured ones.
IT experts and data scientists typically define Big Data by using 3V: Volume, Velocity, and Variety.
Volume relates to the data size ( in Tera or Zettabyte sizes) collected from various devices and applications. Velocity refers to how fast the data is produced and processed to extract meaningful information. Meanwhile, Variety deals with the kinds of data formats, whether structured data ( e.g. relational databases) or unstructured data ( e.g. videos, texts, or posts in social media).
In recent years, many scientists have agreed to add more Vs to be able to define big data properly. Thus, many have used 5Vs ( or even 6Vs, and so on), with two important factors included: Value and Veracity.
Value deals with how information, knowledge, and patterns in the data can be extracted to accelerate business processes, while Veracity deals with the accuracy and trustworthiness of the data.
If we talk about data in social media, Veracity appears as the most fundamental factor to consider, because it deals with the trustworthiness, accuracy, authenticity, and accountability of the data. While in fact, in social media, everyone can write, post, and share any information without thorough verification.
Creating an account on social media is very easy. People can make multiple accounts and share the same information numerous times. Consequently, conclusions made from data distributed in social media can be full of bias or partisan.
There are at least four reasons Indonesia should not base its election planning on big data.
First, analysis of big data, especially when it is taken from conversations on social media, has been widely used to predict election results. Yet, the results have not consistently matched the voting results, as what happened in India, Malaysia, and Pakistan.
Second, many conversations on social media in Indonesia are driven by cyber troops who spread pro-government propaganda. During the 2019 general election, many cyber troops spread fake news to amplify political taglines and hashtags.
Therefore, analysing conversations on social media is not only about collecting the data but also about “ cleaning ” and ensuring its integrity.
Third, and most importantly, conversations on social media are dominated by government-led narratives.
My research about the narratives of COVID-19 pandemic in Southeast Asian countries has shown that in Indonesia, narratives about the pandemic are dominated by the government authorities from various levels.
In Indonesia, posts from government accounts, such as the Facebook pages of President Jokowi, ministries, state bodies, and regional leaders, got the most engagements from social media users. The entire top 70 posts were from government-controlled accounts.
But the engagements obtained by the accounts were only in passive forms, such as through likes or reactions. Thus, such a predominance does not necessarily mean that the public really gets information from the government. Passive engagements usually come from ads placement on Facebook.
Compared to civil society organisations, government institutions certainly have larger resources to advertise their content on social media.
Fourth, although many policy designs and implementations are concluded from big data analysis, the policies still have to reflect public values.
The idea to postpone the 2024 election based on people’ s aspirations on social media has denied the participation of people who do not have access to social media and, thus, undermines public values of trust, equality, and fairness.
Therefore, people should be more careful before making conclusions from what appears on social media. We need to ensure whether the data are genuine, accurate and trustworthy – which can be done using the 5V formula.
We should not use any term to follow a trend or be seen as technology-savvy without truly understanding its meaning. | business |
The importance of Indigenous storytelling in tales of post-apocalyptic survival | With many provinces across Canada lifting vaccine and mask mandates, anxieties are high. If COVID-19 is becoming endemic, we must search for what philosopher Jonathan Lear calls “ radical hope. ”
However, alongside trauma and particularly in times of pandemics throughout history, hope can take the form of stories about resilience. And for Indigenous people in particular, who have disproportionately experienced the effects of the pandemic, what better way to find hope than to turn to Indigenous survivors in post-apocalyptic narratives?
Métis author Cherie Dimaline provides us the opportunity to do just this. Dimaline is best known for The Marrow Thieves, which won the Governor General’ s Literary Award and the Kirkus Prize. The Marrow Thieves is listed as one of TIME magazine’ s Best YA Books of All Time.
The novel was written in response to the suicide epidemic within Indigenous communities. During her work with Indigenous youth, Dimaline wanted to show them a viable future where they could be the heroes.
The Marrow Thieves and its sequel, Hunting by Stars, follow Métis protagonist Frenchie and his found family of other Indigenous survivors as they roam a post-apocalyptic wasteland ravaged by climate change. In this new world, everyone except Indigenous people have lost the ability to dream. Without dreams, people go mad — killing others and committing suicide.
Governments respond by establishing schools inspired by the residential school system, and characters called “ recruiters ” search for Indigenous survivors to bring back to the schools to be “ harvested. ” The marrow within the bones of Indigenous people contains dreams, and by harvesting and consuming the marrow, non-Indigenous survivors can finally dream.
“ …medical masks hanging from their ears like hand-me-down jewelry. They had the plague. Trash cans at the end of each driveway were heaped with syringes, so many vaccinations and cures thrown out because none would work. The people stumbled into one another, knocking over cans and crunching through needles. They had that look, the one that let you know they were dreamless. ”
In Dimaline’ s novels, there is the Story: as Indigenous survivors tell their stories, the overarching Story changes slightly to include these new voices. Story, with a capital “ s, ” is comprised of a “ shared oral history, ” produced by the various characters’ narratives.
Miigwans, the Elder figure in the novel is responsible for telling Story to ensure the younger Indigenous survivors in the novel remember their history. Therefore, his telling of Story ensures that it will never be forgotten. However, Story is not just the history of the Indigenous characters in the novel; Story is the history of everyone living in Canada, both Indigenous and non-Indigenous peoples.
Story includes climate change, pipelines, colonialism, Treaties and the residential school system.
Dimaline admits that stories are how she understands herself and her community.
Given that Dimaline’ s original inspiration was to bring hope to Indigenous youth amidst rising suicide rates, the relationship between Story and hope can not be overlooked.
Dimaline’ s novels resonate in today’ s world. The re-introduction of residential schools in the world of Dimaline’ s novels is timely, given recent confirmations of unmarked burial sites at former residential school locations throughout Canada.
Story plays a similar role in Mi'kmaq director Jeff Barnaby’ s 2019 zombie film, Blood Quantum. In Blood Quantum, a zombie-producing plague has ravaged the world, but Indigenous people find themselves immune to the virus. They establish a safe zone on the fictional Red Crow Reservation and protect both Indigenous and non-Indigenous survivors. However, the inclusion of the latter is a point of contention for some characters.
In the film, there are a few animated scenes that represent Story. In the final animated scene, an elder named Gisigu appears to perish beneath a mass of zombies. However, the scene changes to animation, and Gisigu emerges victorious. Gisigu may have perished in the material world, but in Story, he lives on. When animated Gisigu emerges from beneath the mass, he vows never to let the zombies pass, protecting the future of his surviving Indigenous family.
For many Indigenous people, storytelling is a form of reclamation — what Anishnaabe writer Gerald Vizenor would call “ survivance, ” a portmanteau of survival and resistance. The concept relies on the use of stories to ensure the continued presence of Indigenous people.
In response to the recent confirmations of unmarked burial sites at residential schools, survivors are recounting stories about those who unfortunately did not survive. Doing so is survivance — these stories bring lost Indigenous children into the present and give those who survived as well as those who unfortunately did not, voice and agency.
As a third-generation residential school survivor, I can not possibly understand what my grandmother experienced inside the schools. I can, however, read Story and begin to understand my own part in Story. Therefore, we can all learn a little something about ourselves and our world from Indigenous survival stories. | business |
New Zealand to ease domestic virus restrictions | Hi, what are you looking for?
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New Zealand will relax its strict Covid-19 rules this week because case numbers have peaked and the population has high levels of immunity, Prime Minister Jacinda Ardern said Wednesday.
Ardern said limits on outdoor crowd numbers would be scrapped late Friday, allowing sporting events and concerts to take place with unrestricted crowds.
She said vaccine passes and scanning codes would no longer be compulsory from April 4 and most vaccine mandates — requiring employees to be immunised or face the sack — would be dropped.
“ This is not the end, but in some ways it is also a new beginning, ” Ardern told reporters, saying the changes acknowledged that “ Covid is here to stay ”.
“ To date, we’ ve had more than 500,000 reported cases of Covid-19 and expert modellers say there have probably been 1.7 million actual infections, ” she said.
“ That figure, coupled with 95 percent of New Zealanders being fully vaccinated, means we now have a high level of collective immunity. ”
The announcement comes a week after Ardern outlined plans to open New Zealand’ s borders earlier than originally scheduled.
New Zealand was widely praised for keeping Covid-19 out of the community for extended periods during the pandemic but it is currently experiencing a wave of Omicron-variant infections, with almost 21,000 new cases recorded on Tuesday.
However, the population is highly vaccinated and there have been just 177 coronavirus-related deaths in a population of five million.
“ While we’ ve been successful, it’ s also been bloody hard, ” Ardern said.
“ I want to start by thanking New Zealanders for the enormous sacrifices they’ ve made over the past two years. ”
Ardern said vaccine mandates for the police, military and education sector would be dropped, although they would remain for healthcare and border workers.
She denied the move was linked to protests in Wellington which ended in rioting early this month as police removed a camp of anti-vaccine demonstrators that occupied the grounds outside parliament for three weeks.
“ ( We’ re acting) because it’ s safe to do so, not because anyone arrived on the front lawn of parliament, ” she said.
With 2,400 staff representing 100 different nationalities, AFP covers the world as a leading global news agency. AFP provides fast, comprehensive and verified coverage of the issues affecting our daily lives.
The big issue facing Russia’ s military is the future. If the present is godawful, the future could be truly, fatally, disastrous.
One billboard depicts Russian President Vladimir Putin's face in the dirt under a boot emblazoned with the Ukrainian trident - Copyright AFP DALE DE...
Hong Kong used strict travel curbs to keep the virus at bay for two years but these left Asia's world city increasingly isolated.
Mykolaiv residents are determined to stay and defend the city despite incessant bombardment - Copyright AFP TED ALJIBESelim SAHEB ETTABAUkraine’ s strategic city of Mykolaiv...
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Key Antiviral Treatment for COVID-19 Still Effective Against the Newest Variants Despite Resistance Fears | Antiviral drug Paxlovid used to treat SARS-CoV-2 remains effective against the newest variants of the evolving virus.
Rutgers study also finds signs of emerging mutations, indicating urgent need for new drugs.
An antiviral drug used to treat SARS-CoV-2 remains effective against the newest variants of the evolving virus, according to Rutgers researchers.
The study, published in the journal Cell Research, is one of the first to explore the full extent of SARS-CoV-2 mutations.
Researchers concluded that the Pfizer antiviral drug Paxlovid still quashes COVID by jamming the cell machinery of a key protein, known as the “ main protease ” or Mpro, involved in replicating the virus.
As COVID’ s Omicron variant spreads rapidly throughout the world, with recent severe outbreaks in Asia, authorities have watched to see whether the virus evolves “ resistance, ” evading the defenses provided by current medicines. With only a few drugs that are available to treat COVID, physicians are counting on treatments like Paxlovid to stem the spread.
But the Rutgers study also conveyed a warning – scientists discovered through genetic analysis that the virus is beginning to evolve in ways that may produce strains that can evade present treatments.
“ There is hope, at least for now, ” said study author Jun Wang, an associate professor in the Department of Medicinal Chemistry at Rutgers Ernest Mario School of Pharmacy. “ At this point, Omicron is still new enough so that treatments are still working. But as more people take Paxlovid, we will expect drug resistance to emerge. ”
The scientists accessed a public database known as GISAID, studying the Mpro sequences of all strains of COVID detected so far. The protein is central to the reproduction of the virus and the target of the antiviral Paxlovid.
Comparing more recent strains with earlier strains collected by physicians around the world, the scientists searched for mutations in genetic sequences of Mpro that occur when a virus replicates. Mutations can lead to possible new structures of Mpro, which are generally correlated with drug resistance.
“ We wanted to pick out if there is a mutation in the protease that’ s a ‘ red flag,’ ” Wang said. “ We did that because, generally speaking, as we have seen in the past, this would be the first sign of the development of resistance. ”
The researchers found the top 25 most common new mutations in the main protease of many Omicron strains, a discovery Wang characterized as “ concerning, ” with the most common one called P132H. When they tested Paxlovid against the Mpro with the P132H mutation, the antiviral remained effective. This was further confirmed by the X-ray crystallography, showing that the P132H did not change the Mpro structure significantly.
“ Although this mutation does not cause drug resistance to Paxlovid, this implies that the virus can still evolve to create additional mutations that might cause drug resistance, ” Wang said. “ When a drug gets widespread use, it is just a matter of time before resistance appears. ”
Wang’ s lab is working to develop new antivirals against COVID by targeting the Mpro and another key protein known as the papain-like protease. The best approach, he said, is to employ a strategy that has been highly successful with the treatment of HIV/AIDS and HCV – creating a “ cocktail ” containing multiple antivirals to thwart resistance.
“ The idea, ” Wang said, “ is to always be one step ahead of the virus. ”
Reference: “ The P132H mutation in the main protease of Omicron SARS-CoV-2 decreases thermal stability without compromising catalysis or small-molecule drug inhibition ” by Michael Dominic Sacco, Yanmei Hu, Maura Verenice Gongora, Flora Meilleur, Michael Trent Kemp, Xiujun Zhang, Jun Wang and Yu Chen, 15 March 2022, Cell Research. DOI: 10.1038/s41422-022-00640-y
Yanmei Hu, a Rutgers post-doctoral student, is another co-author on the paper. The research is funded by the National Institutes of Health’ s National Institute of Allergy and Infectious Diseases. | tech |
Moderna, with new data, to seek clearance for COVID-19 vaccine in young children | Study results showed two shots led to similar immune responses as has been observed in young adults, although protection against omicron was modest.
Moderna on Wednesday said its COVID-19 vaccine spurred strong immune responses in a large study testing the shot in children as young as 6 months old, results that the biotech will use to seek regulatory clearance in the U.S. Yet study data showed weaker protection against infection, which, while expected versus the omicron variant, could make Moderna's case more difficult.
In a late stage study known as KidCove, two doses of Moderna's vaccine, spaced four weeks apart and administered to children aged 6 months to 6 years old, generated similar antibody levels to what was observed in young adults given a higher dose. That kind of response has been associated with protection against COVID-19 and a lasting defense against the disease's more serious effects.
Moderna said there were no serious safety concerns reported in the study. The company also didn't find any instances of heart inflammation that has been associated with its vaccine in rare cases. Side effects, such as fever, were mostly mild to moderate and more frequently observed after the second dose.
Moderna plans to submit the results to regulators in the U.S., Europe and elsewhere in the `` coming weeks. '' No vaccine is currently cleared for use in children under five years of age in the U.S., although the Food and Drug Administration is currently reviewing data for Pfizer and BioNTech's shot.
Still, Moderna's findings, which were described in a press release Wednesday, leave several questions unanswered for drug regulators. None of the infants and young children in the study developed severe COVID-19, meaning the company could not measure how well the shot might protect against the disease's worst effects in younger age groups.
The trial also took place in the U.S. as the omicron variant, which can partially evade vaccine protection, was surging. Moderna found two shots were only about 44% protective against symptomatic COVID-19 in children between 6 months and 2 years old, and 38% protective in kids aged between 2 and 6 years — numbers below what the FDA has previously set as a minimum bar for vaccines in adults.
The FDA recently delayed its review of Pfizer's vaccine in children under 5, reportedly because two doses weren't working well against omicron and the regulator wanted to see the effects of a third shot. Moderna also intends to study boosters, which have provided adults with stronger protection against omicron, but filed for authorization in young children with the data it has in hand.
That could make for a tough decision for regulators. With Pfizer's shot delayed, the roughly 19 million children under 5 remain ineligible to receive vaccines in the U.S. While kids are less likely than adults to become hospitalized or die from COVID-19, infections among young children spiked during the omicron surge, according to the American Academy of Pediatrics. COVID-19 hospitalization rates among children 4 years old or younger were five times higher during omicron's January peak than they were during delta's surge last summer, according to the Centers for Disease Control and Prevention.
Mild infections can also lead to longer-lasting symptoms, spark outbreaks in daycare facilities and communities and disrupt work for parents.
The FDA has been willing to authorize COVID-19 vaccines in younger age groups based on a clinical trial process known as `` immunobridging, '' in which the levels of immune response are compared to those in older adults. That strategy is an inexact science, as researchers still don't know the precise levels of coronavirus antibodies needed to protect people from infections and disease. But it's meant to broaden use of a vaccine more quickly and has worked to make shots available for adolescents.
`` Given the need for a vaccine against COVID-19 in infants and young children we are working with the U.S. FDA and regulators globally to submit these data as soon as possible, '' Moderna CEO Stephen Bancel said in a statement.
Fevers of over 100 degrees Fahrenheit occurred in 17% of vaccinated infants and about 15% of kids between 2 and 6, a rate that Moderna said is similar to what's typically seen with other commonly used and recommended kids ' vaccines. Fevers higher than 104 degrees were observed in about 0.2% of each group. Pfizer, which is using a much lower dose than Moderna, reduced its dosing in infants and young children to reduce the likelihood of high fevers.
While Moderna didn't observe any cases of heart inflammation, or myocarditis, in its study, the trial was likely too small to detect such a rare side effect. Moderna's shot has generally been associated with higher myocarditis rates than Pfizer's, one reason its vaccine isn't yet authorized for adolescents in the U.S.
Moderna said in its Wednesday announcement that it has begun authorization filings for kids between 6 to 11 years old and submitted more data to the FDA in adolescents.
Topics covered: Pharma, biotech, FDA, gene therapy, clinical trials, drug pricing and much more.
As record levels of money pour into gene therapy research, biotechs are under increased pressure to address issues related to safety, delivery and overlapping pipelines.
Despite tumbling biotech valuations, however, several said they still prefer smaller-sized `` bolt-on '' deals to larger, potentially more disruptive, transactions.
Topics covered: Pharma, biotech, FDA, gene therapy, clinical trials, drug pricing and much more.
Topics covered: Pharma, biotech, FDA, gene therapy, clinical trials, drug pricing and much more.
As record levels of money pour into gene therapy research, biotechs are under increased pressure to address issues related to safety, delivery and overlapping pipelines.
Despite tumbling biotech valuations, however, several said they still prefer smaller-sized `` bolt-on '' deals to larger, potentially more disruptive, transactions.
Topics covered: Pharma, biotech, FDA, gene therapy, clinical trials, drug pricing and much more. | tech |
US eases tariffs on UK steel and aluminum | The agreement with the U.K. comes after the U.S. struck similar deals to ease steel and aluminum tariffs with Japan and the European Union.
The U.K. will be able to export 500,000 metric tons of finished steel and 900,000 metric tons of aluminum before tariffs take effect. That's far less than the quotas set for the European Union and Japan.
The deal also requires U.K.-based steel producers owned by companies in China to undergo a financial audit to evaluate whether there are any market distorting practices that `` would materially contribute to non-market excess capacity of steel, '' according to a statement.
Aluminum shipments are subject to novel `` smelt and cast '' provisions, and producers must prove that products contain no aluminum from China, Russia or Belarus.
`` Today’ s historic deal is a testament to that ambitious goal and will benefit America’ s steel and aluminum industries and workers by protecting manufacturing, as well as consumers by easing inflationary pressures in the U.S., '' Commerce Secretary Gina Raimondo said in a statement. `` By allowing for a flow of duty-free steel and aluminum from the UK, we further ease the gap between supply and demand for these products in the United States. ''
The deal also lifts tariffs the U.K. placed on U.S. imports of products such as jeans, whiskey and motorcycles. The Distilled Spirits Council of the United States estimated that whiskey exports to the U.K. have declined 42% since tariffs were enacted.
The U.K. is the fourth largest market for whiskey exports, according to the trade group, and the value of exports dropped to $ 88 million in 2021 from $ 150 million in 2018.
`` Distillers throughout the United States are cheering the end of this long tariff nightmare, '' Distilled Spirits Council CEO and President Chris Swonger said in a statement. `` We toast the Biden administration for its resolve in bringing a stop to these punitive tariffs on American Whiskeys and securing the return to duty-free trade in spirits across the Atlantic. ''
Topics covered: logistics, freight, operations, procurement, regulation, technology, risk/resilience and more.
The retailer's acquisition of a middle- and final-mile carrier as the COVID-19 pandemic took hold has allowed it to take more control over its delivery process.
Retail supply chains have transformed into a complex web of goods movement and technology, with more touchpoints to the consumer than ever before.
Topics covered: logistics, freight, operations, procurement, regulation, technology, risk/resilience and more.
Topics covered: logistics, freight, operations, procurement, regulation, technology, risk/resilience and more.
The retailer's acquisition of a middle- and final-mile carrier as the COVID-19 pandemic took hold has allowed it to take more control over its delivery process.
Retail supply chains have transformed into a complex web of goods movement and technology, with more touchpoints to the consumer than ever before.
Topics covered: logistics, freight, operations, procurement, regulation, technology, risk/resilience and more. | general |
Coal to help solve EU energy crisis as trade patterns shift: shippers | In this week’ s highlights: Prospects of a modest oil price recovery in the coming months are growing...
Coal will help solve the European Union's current energy price squeeze, even while the Russia-Ukraine crisis is expected overall to speed up actions towards the energy transition, participants in a shipping panel at the FT Commodities Global Summit said March 23.
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`` The only commodity that can help solve the energy crisis in Europe in the short term is coal, '' said Sveinung Stohle, deputy CEO of Greek-based shipping company Angelicoussis Group. `` Like it or not, coal will play a very important role. ''
CO2 emissions are set to hit a record high in 2022, growing 2.5% over 2021, despite greater focus on climate and the continuing impact of the COVID-19 pandemic, S & P Global Commodity Insights Analytics said in a bulletin distributed this week. This follows a rise in CO2 emissions already last year on higher coal usage and growing energy demand as economies recovered from the pandemic.
Stohle noted that while the iron ore dry bulk trade has remained relatively steady since Russia invaded Ukraine on Feb. 24, and should continue to do so, coal trade has increased. This is `` definitely helping the ( shipping) market, '' particularly as coal is now being shipped for longer distances, creating more freight miles per ton of coal, he said.
There is backfilling of Russia coal orders with coal coming from as far afield as Australia to Europe, he said.
Angelicoussis Group CEO Maria Angelicoussis said that coal has become a `` swing factor '' in freight markets, with trade patterns again shifting following China's ban on imports of coal from Australia in late 2020. The company won't lift Russian coal cargoes, she said.
Coal is needed to enable European power stations to reduce usage of gas from Russia, which will be phased out under new EU directives and sanctions.
`` Europe's gas dependency is much, much higher than in most Asian economies, '' Stolhe said. `` Gas represents at least 30-40% of total energy demand in most European countries, compared to possibly 6-7% in China, of which maybe half is LNG. ''
More coal will be needed in Europe until more LNG production comes on stream, while Asia will continue to burn coal or oil as necessary, he indicated.
China's seaborne coal demand is likely to increase in the near term as domestic buyers look to stock up ahead of summer and railway maintenance that is expected to hamper the supply chain in April, market sources told S & P Global Commodity Insights March 23.
Expectations of a rise in thermal coal demand come at a time when domestic production has been impacted by COVID-19-induced lockdowns and movement restrictions. More than 20 provinces and cities have imposed travel bans and lockdowns as the number of positive cases surged.
The price of Indonesian 4,200 kcal/kg GAR has risen to $ 108.05/mt FOB March 23 from $ 65.45/mt FOB on Jan. 3, S & P Global data showed.
In the coking coal market, Asia delivered prices to China weakened March 23 as China's domestic market softened amid a worsening COVID-19 situation, with major steelmaking region Tangshan in Hebei province entering a temporary lockdown late March 22. FOB prices also continued a downwards momentum.
Premium Low Vol was down $ 8.00/mt at $ 590/mt FOB Australia, and CFR China down $ 8.00/mt at $ 440/mt CFR China March 23, according to the Platts assessment from S & P Global Commodity Insights. However, prices remained close to recent peak levels.
Ghigo Ravano, co-CEO at independent brokerage IFCHOR, said that in the dry bulk market generally, uncertainties are high but fundamentals remain good with a growing orderbook which is `` benign '' to the sector as oversupply is not foreseen.
Ulrik Uhrenfeldt Andersen, CEO of shipper Golden Ocean Management, said he believes the capesize market is set for a relatively good year, although there are some markers that are not as positive as 12 months ago. `` China has clearly been going down a gear with its steel production in the preparation for the Olympics... we saw warning shots fired in the real estate and construction sector with Evergrande and an increasing coal production in response to the energy crisis, although most of this may now be behind us and we're coming into a season that may be much more active, '' he said. Industrial activity statistics just published in China show the biggest rate of growth since June 2021, he added.
Angelicoussis ' CEO said that the shipping industry's decarbonization drive would be considerably aided by introduction of a global carbon tax which could create a level playing field in the sector. Regional carbon tax mechanisms `` will make it very complicated, fragment things, will be hard to enforce and will skew trade. As shipowners we need to take a very long-term view, 15-20 years when we are designing future ships, '' she said.
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Rwanda turns to event hosting for economic boost | Hi, what are you looking for?
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Blue, yellow, green: As night falls, the dome of the Kigali conference centre lights up, resplendent in the colours of Rwanda’ s flag as it aims to attract all eyes on the capital, and beyond.
In less than a decade, the small, landlocked nation has established itself as a destination for conferences, sports tournaments and other events, billing itself as “ Africa’ s Singapore ” in a bid to boost business and the economy.
“ Rwanda is one of the most stable countries in East Africa. So… people feel comfortable and safe when they come to these kinds of meetings, ” Senegalese agricultural expert Ghislain Kanfany told AFP as he arrived for a conference of African plant producers.
Although rights groups regularly accuse President Paul Kagame’ s government of crushing dissent and keeping an iron grip on power, Kigali’ s clean, well-paved streets and modern infrastructure make a positive first impression on many visitors.
Organisers say that low levels of bureaucracy and effective management of the Covid-19 pandemic also make it easier to hold large-scale events in the country.
“ There is not much red tape, ” said South African Kuben Pillay of the International Cricket Council, in town for a qualifying tournament.
Prior to the pandemic, conference revenues had jumped nearly 40 percent between 2016 and 2019, according to government figures, with Kigali second only to Cape Town in terms of the number of events hosted on the African continent, the International Conferences and Conventions Association said.
– Building boom –
The mushrooming of new infrastructure over the last six years — including the Kigali Convention Centre, whose dome is inspired by Rwanda’ s beehive-shaped palaces, the Gahanga Cricket Stadium, or the 10,000-seater Kigali Arena, East Africa’ s biggest indoor venue — has helped develop the nascent sector.
Hotel owners have also sensed an opportunity, with major international hotel chain setting up shop next to the convention centre.
The authorities are pumping in funds to expand the national airline RwandAir and build a new international airport on the outskirts of the capital.
“ The government of Rwanda has ( put) a lot of effort into making sure people can feel safe having their event ( here), ” said Janet Karemera, deputy director of the Rwanda Convention Bureau ( RCB), the public agency promoting the sector.
But the success of the fast-growing sector has raised concerns among activists, who have previously accused Rwandan authorities of rounding up street vendors, homeless people and sex workers ahead of high-profile events such as the Commonwealth Heads of Government Meeting ( CHOGM).
“ Rwanda’ s strategy to promote Kigali as a hub for meetings and conferences often means continued abuse of the capital’ s poorest and most marginalised residents, ” Lewis Mudge, Central Africa director at Human Rights Watch, said last September after the CHOGM event was rescheduled due to the pandemic.
“ Rwanda’ s Commonwealth partners have a choice: either speak up for the rights of the victims or be silent as the crackdown is carried out in their name, ” he said.
Government spokeswoman Yolande Makolo told AFP the claims were “ fabricated reports… specifically calculated to harm a strategic sector of our economy. ”
– ‘ Domino effect’ –
With the promise of bringing in foreign exchange, authorities hope the sector will offer an economic boost to the landlocked nation which relies on expensive imports.
Heavy investment in infrastructure has contributed to Rwanda’ s debt, up from 15 percent of GDP in 2010 to nearly 54 percent in 2019, according to a report last year by the French Development Agency.
Conversely, conference revenues remain low for the time being -– around one percent of GDP, according to the RCB.
But the government is counting on a “ domino effect ” to yield dividends, Karemera told AFP.
Trevor Ward, managing director of Lagos-based consulting firm W Hospitality Group, said the “ MICE ” industry ( “ Meetings, Incentives, Conferences and Exhibitions ”) brings many direct and indirect economic benefits.
“ The obvious one is job creation, then you got the linkages to support industries: catering, audiovisual, drivers, cleaners, flowers etc, ” he told AFP.
The sector is still reeling from the pandemic: Revenues collapsed from $ 65 million ( 57 million euros) in 2019 to $ 5.4 million in 2020, according to government figures.
But Karemera remains optimistic, pointing out that Rwanda’ s 2022 calendar includes some major events including CHOGM which is now scheduled for June, followed by the world cycling championships in 2025 — a first for the African continent.
With 2,400 staff representing 100 different nationalities, AFP covers the world as a leading global news agency. AFP provides fast, comprehensive and verified coverage of the issues affecting our daily lives.
That’ s the real danger. Nobody trusts Russian judgment anymore.
The UN refugee agency UNHCR says 4,656,509 Ukrainians have fled since Russia invaded on February 24 - Copyright AFP FARJANA K. GODHULYRobin MILLARDMore than...
President Joe Biden for the first time accused Vladimir Putin's forces of committing genocide in Ukraine.
AI, facial recognition, and biometrics can help the world get back to work.
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Putin intends to participate in G20 Summit, says Russian envoy | Jakarta – President Vladimir Putin plans to attend the G20 Summit later this year in Indonesia, one of Moscow’ s envoys said on Wednesday, dismissing suggestions Russia could be excluded from the group over the war in Ukraine.
A day earlier, the United States indicated it would consult allies over Russia’ s membership in international forums to increase pressure over the invasion of Ukraine, which has prompted a refugee crisis in Europe and roiled global markets.
Russian Ambassador to Indonesia Lyudmila Vorobieva said that G20 host Jakarta had invited Putin to the November heads of state summit in Bali.
“ It will depend on many things, including the COVID situation that is getting better. But, so far yes, the intention is ( for Putin) to come, ” she told reporters on Wednesday.
Vorobieva said there have been attempts by western countries to expel Russia from many world organizations, including the Group of 20 major economies, calling it a “ disproportionate ” reaction.
Russia, she added, appreciates Indonesia’ s “ firm position, ” after Jakarta repeatedly said the forum was for resolving economic situations.
Indonesia, which currently holds the rotating presidency of the G20, has said it will keep the forum focused on the initial objectives, implying it was planning to keep Russia’ s invasion of Ukraine largely off the agenda.
“ Of course, the expulsion of Russia from this kind of forum will not help these economic problems to be resolved. On the contrary, without Russia, it will be difficult, ” said Vorobieva.
“ We really hope that the Indonesian government will not give in to the horrible pressure that is being applied to not only Indonesia, but so many countries in the world by the West. ”
White House National Security Advisor Jake Sullivan had said Washington would consult with allies about Russia’ s G20 membership.
“ We believe that it can not be business as usual for Russia in international institutions and in the international community, ” he said at a press briefing on Tuesday.
Russia was previously indefinitely suspended from the smaller Group of Eight major economies in 2014 over the annexation of Crimea from Ukraine. The grouping was renamed the G7. | tech |
Pfizer Issues Recall for Blood Pressure Medications Containing Nitrosamine | Pfizer issued a statement on Monday regarding a voluntary recall of three of its products due to high levels of nitrosamine ( N-nitroso-quinapril). The recall affects eleven lots of hypertension medication in total: six lots of Accuretic ( quinapril HCl/hydrochlorothiazide), one lot of generic quinapril HCl, and four lots of a generic formulation of quinapril HCl/hydrochlorothiazide.
These lots, listed in detail in Pfizer’ s press release, appear to be different than the lots BioSpace previously reported as recalled for the same reasoning, which were distributed in Canadian markets and approved by Health Canada. While distributors and sales markets have been instructed to hold affected lots from public consumption, patients have been reassured that there is no immediate risk to taking this medication. Pfizer also reports that there are no current reported adverse events related to the products recalled, per the Food and Drug Administration ( FDA)’ s MedWatch Adverse Event Reporting program.
Nitrosamines are present in everyday foods, such as produce and dairy products, but the levels present in the lots being recalled exceeded the Accepted Daily Intake ( ADI) limitations set by U.S. FDA regulations. At high intake levels such as this, nitrosamines act as a carcinogen, increasing risk of developing cancer when taken over a long period of time.
The FDA directly addresses this by stating, “ A person taking a drug that contains nitrosamines at or below the acceptable daily intake limits every day for 70 years is not expected to have an increased risk of cancer. “
Hypertension medication regimens are often strict- physicians encourage routine use to maintain stable blood pressure. The U.S. Centers for Disease Control and Prevention ( CDC) reports that nearly half of the population ( 24%) has hypertension, but only a fraction of this statistic manages their condition effectively ( 24%). Hypertension places a substantial $ 131 billion burden on the U.S. healthcare system, averaged from 2003 to 2014.
BioSpace reported findings regarding the biopharmaceutical industry from the Transparency Market Research early this year, which analyzed the demand of hypertension medications to predict trends. Quinapril prescription is expected to outperform competitors, such as cilazapril and ramipril. The market for quinapril prescriptions is supported by various generic formulations that have been approved by the U.S. FDA’ s Office of Generic Drugs, such as the one marketed by Ranbaxy.
Pfizer has been featured heavily in pharmaceutical news, particularly since the onset of the COVID-19 pandemic, for which it developed one of the most commonly administered prevention vaccines. The company received emergency use authorization for the vaccine and skyrocketed its stock market valuation. | general |
Telehealth can effectively manage COVID-19 at home, study finds | A University of Iowa study published this month in the Journal of Telemedicine and Telecare found that an at-home telemonitoring program was an effective and sustainable way to manage COVID-19 for patients.
The goals of the program, as outlined in the study, were to avoid unnecessary hospitalizations, identify declining patients, escalate care when needed, and provide support to patients and families.
`` Despite the low intensity of the intervention, our results support the use of telehealth to effectively monitor patients with COVID-19 at home, '' wrote researchers.
As researchers explained, 1,128 University of Iowa Hospitals and Clinics patients who had been diagnosed with COVID-19 met the criteria for the home-monitoring program, or HMP.
Enrolled patients were risk-stratified based on age and underlying comorbidities.
High-risk patients were given a monitoring kit that included a pulse oximeter, an automated blood pressure cuff, vital signs and symptoms log sheet, contact information to report worsening symptoms, and instructions in English, Spanish and French.
A call line was established for patients to use outside regular business hours, and patients were instructed to call if they developed oxygen saturation under 92%, new shortness of breath, decrease in systolic blood pressure or other worsening symptoms.
Most patients, researchers found, did well with the system. Only 6.2% required hospitalization and 1.2% a stay in the intensive care unit from the time of HMP enrollment. One patient, who had been in an emergency department beforehand, died while being monitored.
Hospitalizations were much more frequent for high-risk patients.
`` Our observed rates of hospitalization and mortality were very low compared with national and regional averages at the time of this study, '' said researchers.
Although the patient population was racially and ethnically diverse, the study team noted that the mean patient age was lower than what is described in similar studies, and the majority of patients had zero or one risk factors for severe illness.
`` It is not clear whether similar interventions would be sufficient in these settings where the rate of patient adverse outcomes would be much higher, '' said the study.
Health systems have been strategizing throughout the pandemic about the best ways to keep patients out of the hospital, given COVID-19's strain on resources.
Research published in December 2020 found that remote patient-monitoring ( RPM) capabilities contributed to favorable COVID-19 patient outcomes at the Mayo Clinic.
But the potential for RPM goes beyond acute conditions. For instance, Dr. Waqaas Al-Siddiq, chairman, CEO and founder of Biotricity, told Healthcare IT News earlier this month that telehealth can help patients with chronic disease, as well.
`` When you have a chronic condition, you need to maintain contact with providers to stay on track. And the added stress of living in a pandemic is enough to worsen a chronic condition, which has been reported. Patients need more care, not less, '' said Al-Siddiq.
The University of Iowa researchers concluded that their `` study highlights a novel method of providing healthcare in a technology-driven world, reducing the utilization of hospital resources, while also allowing timely identification of disease progression and rapid escalation to inpatient care when necessary. ''
`` It is also important to know that, in the event of a future pandemic, we have a tested method of risk-assessing patients and providing healthcare while minimizing healthcare worker exposures, '' they said.
Kat Jercich is senior editor of Healthcare IT News.Twitter: @ kjercichEmail: kjercich @ himss.orgHealthcare IT News is a HIMSS Media publication. | tech |
Daily Update: March 23, 2022 | You're one step closer to unlocking our suite of comprehensive and robust tools.
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On February 28, 2022, S & P Global completed its merger with IHS Markit, the next step in delivering data, technology and expertise that accelerates progress.
As great as last year was for our company, in many ways 2022 is shaping up to be even better. In February, we closed a transformative merger with IHS Markit. We believe combining our two companies will create substantial long-term value for all our stakeholders.
The S & P Global Foundation is about much more than philanthropy—we are about making a difference by finding and developing essential connections between the knowledge- and skill-driven work of S & P Global and the needs of society.
Following the unprecedented market and policy momentum behind ESG in 2021, investors, corporate boards, and government leaders have raised expectations for progress on climate pledges in 2022.
With a full scale invasion of Ukraine now under way, stock markets, global trade, energy markets, and commodities markets are all registering the impact of a new geo-political reality.
While much of the world is rebounding from the COVID-19 crisis’ economic downturn, global supply chains are facing continuing pressures from pandemic-prompted changes in consumption patterns, surging demand for goods, shortages of workers, and pre-existing political pressures—leading to high shipping volumes and freight costs. Analysts expect disruptions to persist through 2022.
Start every business day with our analyses of the most pressing developments affecting markets today, alongside a curated selection of our latest and most important insights on the global economy.
The Russia-Ukraine conflict is bringing the good, the bad, and the ugly perceptions of cryptocurrencies into the spotlight.
Some observers have suggested that Russian entities and individuals may be converting their capital into cryptocurrencies to evade sanctions on financial institutions and bypass money transfers via banks to finance deals. Others believe cryptocurrencies haven’ t proven their value as safe haven assets to hedge against the market volatility spurred by the conflict—as popular decentralized assets like Bitcoin and Ethereum plunged within hours after Russia invaded Ukraine, before recovering losses later on. Overall, the Russia-Ukraine conflict may simply represent an extraordinary event for these decentralized assets that prompts more widespread regulatory oversight.
“ Demand for cryptocurrencies by Russian residents has surged as sanctions threaten to severely restrict the country from access to the global financial system. This will likely further accelerate the pace of regulatory scrutiny. However, S & P Global Ratings doesn't believe cryptocurrency use has reached a scale that could blunt the likely severe consequences of sanctions on the Russian economy, ” S & P Global Ratings said in a recent report. “ In our view, the surge of interest in Bitcoin is primarily attributable to customers trying to protect savings against a weaker domestic currency along with other local asset depreciation. Under extreme circumstances such as war and severe sanctions, Bitcoin may be viewed as a way to safeguard wealth and bridge access to reserve currencies. ”
Due to the traceable nature of crypto exchanges and their lack of scalability as an alternative form of payments, S & P Global Ratings doesn’ t believe cryptocurrencies are being used broadly to evade sanctions on Russian corporations or certain nationals.
Nonetheless, the potential for crypto to be used as a tool for evading sanctions could result in regulatory action. The U.S. Treasury Department warned in October that digital currencies posed a threat to its sanctions program. Just yesterday, the leader of the European Central Bank indicated that it sees cryptocurrencies as a current tool for Russian entities to evade international sanctions.
“ When you see the volumes of rubles into stable [ coins ], into cryptos, at the moment it is the highest level that we have seen since maybe 2021, ” ECB President Christine Lagarde said yesterday at a Bank for International Settlements virtual event. Because decentralized finance assets “ are certainly being used, as we speak, as a way to try to circumvent the sanctions that have been decided by many countries around the world against Russia, ” she added that the ECB has “ taken steps to clearly signal to all those who are exchanging, transacting, offering services in relation to crypto assets that they are being accomplices to circumvent sanctions. ”
Today is Wednesday, March 23, 2022, and here is today’ s essential intelligence.
How can Europe help its 25 million small and medium-sized enterprises better access finance and grow? These companies account for 99% of all EU businesses, half of its GDP, and two jobs out of three. However, SMEs can find it difficult to access finance given their smaller size, opacity, and somewhat weaker profitability than large firms. They therefore live on bank loans, credit lines, and leasing—their main three sources of financing. What's more, they have generally refrained from accessing capital market funding by issuing bonds or other securities.
Hina Shoeb and Sandeep Chana are joined by Winston Chang, Chief Analytical Officer - Structured Finance, where they discuss direct and indirect impact of the geopolitical crisis and how some sectors are more impacted than others.
Potential export restrictions and panic buying could push agriculture prices further higher as the market grapples with growing uncertainty owing to Russia's invasion of Ukraine, Joseph Glauber, senior research fellow at International Food Policy Research Institute said in an interview with S & P Global Commodity Insights. Glauber, who was formerly the chief economist with the U.S. Department of Agriculture, said that the biggest risk that he sees emerging from Russia's invasion of Ukraine is that countries will try to regulate exports to keep prices low internally.
Listen: Tracking Upstream Emissions With U.S. Oil Supply On The Rise
U.S. oil supply is expected to increase this year, and new tools tracking upstream emissions will bring interesting new insights. Deb Ryan, head of low-carbon market analytics for S & P Global Commodity Insights, explains her team's monthly carbon-intensity estimates, which rank upstream emissions from 104 oil fields around the world. She's watching what will happen in the Permian Basin as drillers potentially respond to higher prices but face challenges with gas takeaway capacity. The U.S. Energy Information Administration estimates U.S. oil supply growth at 850,000 b/d in 2022, and S & P Global raised its outlook to 930,000 b/d to account for higher sustained prices.
The number of countries that have proposed or adopted long-term blending targets for sustainable aviation fuel, or SAF, continues to increase. But with supply limitations potentially constraining growth to 2050, many countries may fall short of their blending targets. Based on current and announced commercial commitments, S & P Global Commodity Insights projects that SAF demand by 2050 could climb to 5.8% of global jet fuel demand, with country-level demands concentrated in Europe and the U.S.
The conflict in Ukraine is having dire humanitarian consequences and is creating economic disruption. The impacts that many expected in the cyber realm have been more muted. Scott Crawford and Johan Vermij return to discuss what this means for the evolution of the attacker community and what organizations should be considering with host Eric Hanselman. Alignments between state actors and some criminal groups may not be as tight many expected, but it’ s clear that we’ re in a very new situation. | business |
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The technology used to help with mRNA development is always improving. Develop your understanding of the best technologies and what works most effectively to help with manufacturing and other stages of mRNA development. Get one-step ahead of the competition with insights on the advancement of mRNA technology from key technology providers in the field, with speakers from BIA Separations and CRB Group.
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Whether you're increasing your company profile, launching a new product or focusing on new business development opportunities, collaborate with us to identify custom solutions to help you reach your goals. Get in touch with us to discover how you can leverage your company's offering to thought-leaders and key buyers within the mRNA field.
Contact Michael Dunnet: MDunnet @ informaconnectls.com | +1 ( 617) 960-6173 | tech |
China's seaborne thermal coal demand seen set to rebound on summer stockpiling, rail maintenance | Ira Joseph, directora de gas y electricidad de Platts Analytics, y Ryan Ouwerkerk, director de...
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China's seaborne coal demand is likely to increase in the near term as domestic buyers look to stock up ahead of summer and railway maintenance that is expected to hamper the supply chain in April, market sources told S & P Global Commodity Insights March 23.
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The expectations of a rise in thermal coal demand come at a time when domestic production has been impacted by COVID-induced lockdowns and movement restrictions. More than 20 provinces and cities have imposed travel bans and lockdowns as the number of positive cases surged.
Sources said railway line maintenance scheduled to begin April 8 may lead to supplies from Qinhuangdao port being affected during the month. Therefore, buyers want to stock up before the maintenance begins.
The announcement of the maintenance comes around the same time as buyers traditionally look to increase their stockpiles ahead of summer, when demand for cooling increases, sources said.
`` Summer is coming soon so stockpiles would be needed, and if they are not having enough domestic coal production, that demand should come to the import market, '' an Indonesia-based producer said.
Market sources said the rise in COVID-19 cases and the restrictions in place to contain the spread have affected production capacity, with restrictions imposed on the number of workers allowed at mine sites and the increased testing delaying transportation and other logistics.
The price of Indonesian 4,200 kcal/kg GAR has risen to $ 108.05/mt FOB March 23 from $ 65.45/mt FOB on Jan. 3, S & P Global data showed.
While the period witnessed firm demand from buyers in Japan and South Korea, as well as from Europe amid concerns of gas supply disruptions following Russia's invasion of Ukraine, China opted to stay out of the market, waiting for prices to soften.
Spot offers for Qinhuangdao 5,500 kcal/kg NAR were at Yuan 1,700/mt [ $ 266.65/mt ] March 23, sources said.
China's top economic body National Development and Reform Commission has said that it believes the stable price is Yuan 770/mt. However, production levels so far have been unable to match the requirements to meet this price cap guidance, sources said.
China produced 690 million mt coal over January-February, up around 10% year on year, National Bureau of Statistics data showed. The country imported 35.39 million mt over the same period, down 14% on the year.
A South Korea-based source said that city lockdowns and lower factory output in China could be a factor for lower demand, but buyers may want to stockpile ahead of the railway line repairs.
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How Russia's war in Ukraine rocked the global economy | Hi, what are you looking for?
In a month of conflict in Ukraine, global oil prices have soared, foreign companies have exited Russia and Moscow faces the spectre of default.
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In a month of conflict in Ukraine, global oil prices have soared, foreign companies have exited Russia and Moscow faces the spectre of default.
Here is a look at the economic fallout from Russia’ s February 24 invasion of its neighbour:
– Commodities soar –
Oil and gas prices have surged over supply fears as Russia is one of the world’ s biggest producers and exporters of the fossil fuels.
Brent North Sea crude, the international benchmark, stood at around $ 90 in February. On March 7, it jumped to $ 139.13, close to a 14-year high and prices remain highly volatile.
Prices have risen at the pump, too, prompting governments to take measures to ease the financial pain for consumers: A lower VAT in Sweden, a price cap in Hungary, or a discount in France.
Gas prices have also skyrocketed, with Europe reference Dutch TTF leaping to an all-time high at 345 euros on March 7.
The United States, Canada and Britain have announced Russian oil bans.
The European Union has avoided sanctions on Russia’ s energy sector as countries such as Germany rely heavily on Moscow’ s gas supplies.
Other commodities massively produced in Russia have soared, including nickel and aluminium.
Auto industry supply chains face disruptions as key parts come from Ukraine.
– Food threat –
UN chief Antonio Guterres has warned that the conflict could reverberate far beyond Ukraine, causing a “ hurricane of hunger and a meltdown of the global food system ”.
Russia and Ukraine are breadbaskets for the world, accounting together for 30 percent of global wheat exports.
Prices of cereals and cooking oils have risen.
The UN’ s Food and Agriculture Organization says the number of undernourished people could increase by eight to 13 million people over the course of this year and next.
Ships are not leaving Ukraine and there are concerns about the upcoming sowing season in the country.
The United States, India and Europe could cover wheat shortages. But it could be more complicated to replace sunflower oil and corn, of which Ukraine is the world’ s number one and number four exporter, respectively.
– Markets rattled –
Stock markets had started off 2022 on a good note as economies recovered from the Covid pandemic and companies posted healthy results.
But the war has brought volatility to the markets while Moscow’ s stock exchange closed for three weeks and only partially reopened on Monday.
Western sanctions have paralysed the Russian banking sector and financial system, while the ruble has collapsed.
The measures include efforts to freeze $ 300 billion of Russia’ s foreign currency reserves held abroad.
Russia now faces the risk of defaulting on debt for the first time in decades.
Moscow paid interest on two dollar-denominated bonds last week, giving the government some breathing room until the next debt payments in the coming weeks.
– Firms flee –
Hundreds of Western firms have closed shops and offices in Russia since the war started — due to the sanctions, political pressure or public opinion.
The list includes famous names such as Ikea, Coca-Cola and MacDonald’ s.
Russian President Vladimir Putin has raised the threat of nationalising foreign-owned companies.
Some companies have chosen to stay in Russia, citing their social responsibility to not abandon their local employees and deprive the population of essential goods.
– Slower growth –
The war threatens to be a drag on the global economic recovery from the Covid pandemic.
The OECD has warned that the conflict could inflict a one-percentage-point hit on global growth.
The IMF is expected to lower its growth forecast, which currently stands at 4.4 percent for 2022.
“ The entire global economy will feel the effects of the crisis through slower growth, trade disruptions, and steeper inflation, harming especially the poorest and most vulnerable, ” the IMF, World Bank and European Bank for Reconstruction and Development ( EBRD) warned in a joint statement.
With inflation soaring, analysts fear economies could face a period of stagflation — a toxic mix of rising prices and weak growth.
“ Even if the war stopped today, the consequences of this conflict would be felt for months to come, and that would work through commodity prices, ” the EBRD’ s chief economist, Beata Javorcik, told AFP.
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Daily Update: March 24, 2022 | You're one step closer to unlocking our suite of comprehensive and robust tools.
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At this time we are unable to offer free trials or product demonstrations directly to students. If you discover that our solutions are not available to you, we encourage you to advocate at your university for a best-in-class learning experience that will help you long after you 've completed your degree. We apologize for any inconvenience this may cause.
On February 28, 2022, S & P Global completed its merger with IHS Markit, the next step in delivering data, technology and expertise that accelerates progress.
As great as last year was for our company, in many ways 2022 is shaping up to be even better. In February, we closed a transformative merger with IHS Markit. We believe combining our two companies will create substantial long-term value for all our stakeholders.
The S & P Global Foundation is about much more than philanthropy—we are about making a difference by finding and developing essential connections between the knowledge- and skill-driven work of S & P Global and the needs of society.
Following the unprecedented market and policy momentum behind ESG in 2021, investors, corporate boards, and government leaders have raised expectations for progress on climate pledges in 2022.
With a full scale invasion of Ukraine now under way, stock markets, global trade, energy markets, and commodities markets are all registering the impact of a new geo-political reality.
While much of the world is rebounding from the COVID-19 crisis’ economic downturn, global supply chains are facing continuing pressures from pandemic-prompted changes in consumption patterns, surging demand for goods, shortages of workers, and pre-existing political pressures—leading to high shipping volumes and freight costs. Analysts expect disruptions to persist through 2022.
Start every business day with our analyses of the most pressing developments affecting markets today, alongside a curated selection of our latest and most important insights on the global economy.
As the global economy experiences the ripple effects of the Russia-Ukraine conflict, international banks are disclosing their exposure to Russia and weighing the implications of sanctions on their operations.
The sanctions implemented by the U.S., EU, and other major economies on the Central Bank of the Russian Federation and those removing Russia’ s major lenders from the Society for Worldwide Interbank Financial Telecommunications ( SWIFT) messaging service on March 2—and market participants’ subsequent concern about their exposure—has effectively cut the country off from the global financial system. While the direct effects of the SWIFT sanctions will likely be limited and manageable for foreign banks, S & P Global Ratings believes that banks outside of Russia may be unwilling to risk their compliance and operational standing by interacting with those banks sanctioned from SWIFT.
Some foreign banks with operations in Russia have expedited efforts to de-risk their operations and are confronting the possibility of losing their investments in the country, while Russian lenders face the risk of a liquidity squeeze due to the Russian central bank’ s lacking access to its foreign exchange reserves, according to S & P Global Market Intelligence. While some European banks have notable exposure to Russian entities, others—and banks elsewhere in world—have limited direct exposure.
“ Thus far, we have taken negative rating actions mainly on financial institutions in Russia, Ukraine, and Belarus, with many of them linked to our downgrades of the sovereigns and our view of the deteriorated operating environment, ” S & P Global Ratings said in a report yesterday. “ We continue to closely monitor any potential rating effects on these [ European and global ] institutions, but we remain mindful of the modest materiality in terms of the groups ' total exposure and the ample local deposit funding of the subsidiaries, which historically has held up well in previous times of stress. ”
Austria-based but majority-owned by the Russian government Sberbank Europe failed due to deteriorating liquidity on Feb. 28, a consequence of the sanctions implemented on its parent company and resulting loss of depositor confidence. Large institutional investors worldwide may now face billions of dollars in stock losses due to its collapse of its parent, Sberbank, according to S & P Global Market Intelligence data.
Four European banks rated by S & P Global Ratings—Austria’ s Raiffeisen Banking Group, Hungary’ s OTP Bank, France’ s Société Générale, and the Italian banking group UniCredit—have sizable but varying Russian and Ukrainian exposures, and all are expected to be resilient during this period of uncertainty and volatility, according to S & P Global Ratings. Still, major European banks are unlikely to reserve significant provisions in the near-term due to the conflict.
An S & P Global Market Intelligence analysis found that as of late last year U.S. banks ' collective exposure to Russia was smaller than to countries like Finland. Similarly, another S & P Global Market Intelligence analysis showed that Latin American banks also have little to no exposure to Russian firms and financial instructions.
“ The modest direct linkages are a legacy of a Russian economy that had become increasingly isolated even before the most recent hostilities, as sanctions imposed on Russia in 2014 after its annexation of Crimea forced foreign banks to pull back and Russia used trade surpluses to build up an enormous, defensive stockpile of foreign reserves, ” S & P Global Market Intelligence said in a recent report.
Still, S & P Global Market Intelligence data showed that Japanese megabanks—namely Mitsubishi UFJ, Sumitomo Mitsui, and Mizuho—had cumulative direct loan exposure to Russia of approximately US $ 4 billion as of Sept. 30, 2021, equivalent to nearly 20% of the lenders ' own estimated net profit of ¥2.25 trillion combined for the current fiscal year.
`` In my experience, the moment some Russian banks are sanctioned, and the moment you have two, three, or more sets of sanctions regimes which are similar but different, the reaction of, at the very least, the Western European and American banking system will be, 'we will not touch Russian banks full stop, and we will not touch Russian trade full stop, ' '' Nigel Kushner, chief executive of the law firm W Legal, told S & P Global Market Intelligence.
Some of Wall Street’ s biggest banks—namely the investment banking multinational Goldman Sachs and largest U.S. bank JPMorgan Chase—announced earlier this month that they are “ winding down ” their businesses in Russia in compliance with regulatory requirements. Deutsche Bank announced similar action, reversing course on its previous plans to maintain operations in Russia.
Today is Thursday, March 24, 2022, and here is today’ s essential intelligence.
Listen: Ep. 25: Ray Dalio on Economic Cycles, Career Advice, Crypto, & ESG
Ray Dalio, co-chairman and co-CIO of Bridgewater Associates, and Martina Cheung, president at S & P Global Ratings, joined Joe Cass on this edition of Fixed Income in 15. In a wide-ranging discussion, conversation touched on markets, Sustainable Finance, diversity in societies, Ray’ s new book, life and work role models, Joe’ s job at McDonalds, and career advice.
In this month's episode of Capital Markets View, Taron and Chris discuss the impact that the Russia-Ukraine conflict continues to have on the leveraged finance market, including secondary market trading activity, the limitations on primary market activity, and what pricing and leverage might look like when the market reopens as there is still a large pipeline of deals waiting syndication in the forward calendar.
The Russian invasion of Ukraine and the related economic sanctions represent a threat to a scenario of mild recovery of global light-vehicle production in 2022. The economic consequences of the war in Ukraine are adding to ongoing supply-side risks related to the shortage of semiconductors, which intensified for the global auto industry in the second half of 2021. S & P Global Ratings now sees a material threat to its previous base case for moderate growth in sales and production this year and has revised its estimates downward. S & P Global Ratings projects global sales will decline by up to 2% in 2022 on last year compared to its projection in October last year of a sales rise of between 4% and 6% for 2022.
The rapid expansion of soybean farming in Brazil over the past decade has catapulted the South American nation to being the world's biggest producer and exporter of the oilseed. According to the Ministry of Agriculture, Livestock and Supply in crop year 2011-12 ( September-August), Brazil produced 66.5 million mt of beans, well behind 84.3 million mt of the U.S. By 2017-18, Brazil surpassed the U.S. and became world's premier beans producer at 123.4 million mt. In just the last decade, soybean acreage in Brazil expanded from roughly 25 million hectares in 2011-12 to nearly 40 million hectares in 2021-22, an astounding growth rate of 60%. Most analysts attribute the surging soybean prices as the primary factor in the beans acreage expansion in Brazil.
Big Tech dominates the corporate renewable energy space as contracted capacity approaches 60 GW. The evolution of the top 10 U.S. corporations by cumulative capacity, which account for nearly 60%, or 34.9 GW, of the total tracked by S & P Global Commodity Insights, shows Google ( Alphabet Inc.) long occupying the top spot, before relinquishing the corporate-tied renewable energy crown to Amazon.com Inc. after 2021. This analysis relies on partnering developments ' actual and expected online years, not when inventoried agreements were signed. For instance, Amazon's contracted renewable energy capacity comes in at a cumulative 1.5 GW via projects that came online through 2020.
Media, Telco Capital Offerings Raise $ 5.71B In February
Capital markets activity in publicly traded media and telecom companies in the U.S., Canada, and Bermuda brought in a total of $ 5.71 billion in February 2022, according to S & P Global Market Intelligence data. Senior debt offerings accounted for the majority of the raise, at about $ 5.70 billion, while common equity offerings brought in $ 11.6 million. That compared to a total raise of about $ 1.21 billion in January. Telecom companies took over the top two spots for the largest capital raises for the combined sectors year-to-date, with Charter Communications Inc. unit CCO Holdings LLC raising $ 1.2 billion from an offering of its senior unsecured notes and Verizon Communications Inc. bringing in $ 1.0 billion from a senior debt offering. | business |
Latin America's IT brain drain a regional challenge | Hi, what are you looking for?
Software engineer Ribeiro used to work remotely and had no intention of emigrating, but a harrowing incident changed his mind.
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Safety concerns at home in Rio de Janeiro and a bumper pay packet convinced Bruno Ribeiro to join the burgeoning ranks of Latin Americans moving to California to work in IT.
Software engineer Ribeiro used to work remotely and had no intention of emigrating, but a harrowing incident changed his mind.
“ It was one night that my wife and I witnessed four robberies. We didn’ t want to see that violence so close to our children, ” he told AFP from his home in Los Angeles, where he works for entertainment giant Disney.
In Latin America, like elsewhere, demand for software engineers, developers and programmers has exploded.
In 2021, the Latin American IT market grew by 8.5 percent, according to specialists IDC, who expect it to grow by another 9.4 percent this year.
But companies face an “ enormous ” deficit in skilled IT professionals, according to Diego Bertolini, human resources director at the digital marketing agency Raccoon.Monks.
International companies “ are being extremely aggressive in terms of salaries and benefits ” to capture Latin American talent, Bertolini told AFP, providing the region’ s firms with “ a great challenge. ”
This appetite for digital talent has reshaped the labor market, blurring traditional boundaries and accelerating the switch to remote employment.
International consultancy PageGroup says the upshot is that by the end of 2022, Latin America will have 48 percent fewer IT specialists than demand requires.
– Paid like a government minister –
One of the impacts of the coronavirus pandemic was the devaluation of Latin American currencies, which made international work opportunities that pay in dollars or euros more attractive.
At the same time, companies hiring remote workers found they could save costs.
“ It suits everyone … I’ m happy and they’ re happy, ” said Bolivian Adriana Zegarra, a self-taught programmer who works for a Canadian firm from her home in La Paz.
Widespread crime is just one of the reasons Latin American IT professionals are increasingly moving abroad. — © AFP
“ Contracts for international consultants in my post are between $ 2,000 and $ 3,000 a month, ” Zegarra told AFP.
“ Here there are ministers that earn that! ”
She said she would earn “ three times less ” if she worked for a Bolivian company.
But while this appears to be a win-win situation, the losers in the story are the thousands of small and medium-sized startups in the region that struggle to attract or retain staff.
Jhon Montevilla, 39, wanted to launch an online marketplace in Bolivia, but his application “ never saw the light of day. ”
“ When you need to invest in marketing, you’ ve already spent your funds on salaries in an attempt to be competitive, ” he said.
Faced with this problem, Latin American firms often opt to train staff with little or no experience.
“ We make a big internal effort to get them to what we need ” but even “ while we’ re still training them and they are becoming ready, a better proposal arrives, ” said Bertolini.
“ They don’ t think twice before accepting. ”
– Lack of training –
Uruguayan Guzman Freigedo, 31, has just been hired by a Dutch online supermarket as a network engineer.
In his previous job, “ they needed someone more senior and with more experience, and in the first year, they practically trained me for everything I would need to do afterwards, ” he said.
However, he left three years later.
In Amsterdam, he will earn “ three to four times ” what he was paid in Montevideo, although he insists that he left “ to have another experience ” in a more international environment.
Local governments and higher institutions are starting to react.
Although some criticise the lack of university training and public policies promoting IT in Latin America, its IT workforce has grown twice as fast as the United States’ over the last five years, says PageGroup.
Colombia, for example, has put in place a plan to train 100,000 young people.
But they have a long way to go.
Uruguay has a deficit of 5,000 IT technicians, which “ has increased recently, ” Matias Boix, vice-president of the People Talent Commission at Uruguay’ s Chamber of Information Technology, told AFP.
Brazil trains 53,000 people a year in IT, but the industry needs 159,000 new professionals a year, according to Brasscom, a company that promotes the IT sector.
pr-ms-raa-ll/bc/jh/cwl
With 2,400 staff representing 100 different nationalities, AFP covers the world as a leading global news agency. AFP provides fast, comprehensive and verified coverage of the issues affecting our daily lives.
The dangers facing America's homeless were highlighted earlier this month when a man murdered two homeless men.
Kyiv is a ghost town - Copyright AFP Pascal POCHARD-CASABIANCAHervé BARFilled with mountains of sandbags and weapons at the ready, Kyiv is waiting. On...
Philippine social media has exploded with support for presidential election favourite Ferdinand Marcos Junior, driven by a misinformation campaign.
The timing of the new variant is interesting in a black humor sort of way.
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Biden heads to Europe to bolster West's unity, toughen Russia sanctions | Hi, what are you looking for?
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President Joe Biden leaves Wednesday for Europe on a mission to bolster Western unity, ramp up unprecedented sanctions against Russia over its invasion of Ukraine and attempt to upset the post-Cold War balance of power.
The conflict with Russian President Vladimir Putin is redefining Biden’ s 14-month old presidency as he pivots from domestic woes to leading the transatlantic alliance in the most serious crisis in Europe for decades.
After four years of Donald Trump, who treated European nations as economic competitors and scorned the traditional US role as senior partner in NATO, Biden has put the accent on unity. At back-to-back summits in Brussels on Thursday, he’ ll be pushing for more.
White House National Security Advisor Jake Sullivan told reporters that Biden will seek to “ reinforce the incredible unity we built with allies and partners. ”
Sullivan also said that economic sanctions, imposed by a global network of Western allies to cripple Russia’ s finances, will be deepened.
A further package will be “ rolled out in conjunction with our allies on Thursday, ” Sullivan said. He gave no details, other than to say the package “ will focus not just on adding new sanctions but on ensuring that there is joint effort to crack down on evasion on sanctions. ”
On Thursday, Biden will attend summits with NATO, the G7 group and the European Council. He flies Friday to Poland, which neighbors Ukraine and is now the frontline in what some call a new Cold War, and on Saturday he meets President Andrzej Duda.
The intense diplomacy marks a crucial moment in the dangerous standoff with Putin, who seeks to force Ukraine from its pro-Western path. After a month of fighting, Russian forces have laid waste to swaths of the country but have made few significant military gains, while Ukraine continues to resist.
– China question –
Sullivan noted Ukraine’ s success, which has been assisted by large-scale Western arms shipments, but he warned against any presumption of a quick end to the war or a climbdown by Moscow.
“ There will be hard days ahead in Ukraine, hardest for the Ukrainian troops on the frontlines and the civilians under Russian bombardment, ” Sullivan said. “ This war will not end easily or rapidly. ”
If the conflict does drag on, Russia’ s ability to weather military losses and the crushing Western economic sanctions may partly depend on the position taken by its authoritarian partner China.
Beijing has refused to condemn Putin’ s war, but Washington hopes at least to dissuade China from actively helping the Kremlin, either by bailing out the Russian economy or sending weapons.
Sullivan said there was no sign that China was providing military assistance in the wake of a nearly two-hour phone call between President Xi Jinping and Biden last Friday.
“ This is something we are monitoring closely, ” he said.
“ The president will certainly consult on the question of China’ s potential participation in the conflict of Ukraine while he’ s in Brussels. He’ ll do so at NATO, ” Sullivan said.
“ He’ ll also do so when he addresses the 27 leaders of the European Union, because on April 1st, the European Union is having a summit with China, ” he added.
“ We believe we’ re very much on the same page with our European partners. ”
In a wrinkle for Biden’ s travel plans, his chief spokeswoman, Jen Psaki, will have to stay home because of a positive Covid-19 test announced Tuesday.
With 2,400 staff representing 100 different nationalities, AFP covers the world as a leading global news agency. AFP provides fast, comprehensive and verified coverage of the issues affecting our daily lives.
The big issue facing Russia’ s military is the future. If the present is godawful, the future could be truly, fatally, disastrous.
One billboard depicts Russian President Vladimir Putin's face in the dirt under a boot emblazoned with the Ukrainian trident - Copyright AFP DALE DE...
Hong Kong used strict travel curbs to keep the virus at bay for two years but these left Asia's world city increasingly isolated.
Mykolaiv residents are determined to stay and defend the city despite incessant bombardment - Copyright AFP TED ALJIBESelim SAHEB ETTABAUkraine’ s strategic city of Mykolaiv...
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Spotlight: The Limitations of Biometric Verification | Persona is an identity infrastructure that enables companies to verify their customers are who they say they are and carry an individual’ s identity across an entire business. The idea for Persona came to CEO Rick Song while working at Square as an engineer. Rick saw how challenging it was for the payments leader to manage customer identities across their growing portfolio of products. That’ s when the market opportunity became clear.
To share more of his insights into identity verification, its application in the fintech industry and how challenging bias can be, we sat down with Persona CEO Rick Song to learn more.
What problem is Persona trying to solve?
We create trust in the online world by enabling every business to verify that each user is who they claim to be throughout the customer lifecycle. Our customer Coursera must ensure that every recipient of a degree is actually the student who completed the course. In financial services, BlockFi uses Persona to protect customers from fraudulent withdrawals by bad actors.
But most companies today still treat identity as an isolated issue. They still use manual, time-consuming, and error-prone methods to confirm identities. They verify user identity for one use case, attach that person to a set of credentials for future interactions, and call it a day.
That’ s why we built the industry’ s first true identity infrastructure platform that can be customised for all use cases and types of businesses—from payment platforms to e-commerce companies to marketplaces.
What are the opportunities that biometric verification presents in fintech?
Biometric verification offers convenience—it’ s often easier than passwords, and always ready to use because we take our face, eyes, and fingerprints everywhere. And while biometrics were previously more expensive than other verification methods, the price differential is evaporating and now there is almost parity, cost-wise, with SMS. SMS isn’ t foolproof, as there are ploys and techniques for stealing SMS authorisation codes, enabling accounts to be stolen or hijacked.
Biometrics also make it much harder for unauthorised users to access your accounts and services. When your kids in college hitchhike on your Netflix, it’ s probably no issue, but a stowaway in your stock brokerage account is a major problem—and illegal.
What are the limitations of biometric verification in fintech?
Accessibility is an issue for biometric verification because it requires equipment. If your laptop or phone camera doesn’ t work, you might not be able to access your account if that’ s the only medium a company allows you to use to log in. Also, the hardware must be of high enough quality. Not everyone will have the right equipment, so it’ s important for financial institutions to allow for backup verification options—or they could risk losing legitimate customers.
Deepfakes are another problem for facial recognition, which is why financial institutions should not depend exclusively on biometric selfies to verify identities. Then there’ s theft. Your fingerprints, once lost or stolen, are permanently compromised. You can not change your fingerprint and shrug off the loss. Eventually, it may return as a targeted attack and compromise your accounts.
Every security technology has its limitations. The key with biometrics is to apply them as part of a holistic solution. For example, banks can use Persona for biometric selfies, but combine this verification method with other signals that can pick up on suspicious users. They can also step up scrutiny—and apply multi-factor authentication—on specific user activity.
What are the challenges for biometric verification?
Environmental factors can interfere. Good lighting is important for accuracy in facial matching. Background noise and masks can impede voice matching—so can the flu, actually. If your hands are wet, the fingerprint reader may not work properly. On the other hand, a password is good all the time—as long as you’ re the only one who knows it.
Biometrics have also become more spoofable with time. Five years ago, deepfakes were unheard of. It takes ongoing investment to keep up with evolving fraud techniques.
Biometric data is also tougher to handle and store than passwords. It’ s dense, and storing it securely and compliantly requires knowing what and when to delete. Because over time, a lot of biometric data may be—is likely to be—breached and stolen, multifactor security should be the framework for biometrics.
What happens when biometrics gets it wrong?
False positives occur from time to time—some people look alike, so an intruder may have a chance to fake their way in if they happen to be an identical twin. However, a random iPhone thief from the population at large has only the remotest chance of defeating the Face ID system.
There are also issues with certain methods like voice as it provides relatively weak security compared to other biometrics. Yes, it shows you are alive, but voice verification requires consistent conditions. A sore throat, poor microphone quality, or COVID mask could foil correct matching. It can be difficult to obtain the best control data for voice mapping, and good control data is always an important requirement for biometrics.
That’ s why it’ s critical to have a broad set of verification methods, so if one fails, you have other ways of verifying the user in question.
How much do bias issues factor into facial recognition tech?
Biometric verification depends on AI, and AI accuracy depends on the data used to train the model. If a system rejects legitimate users who have darker skin colour, it’ s likely because the training data lacked sufficient representation of the diverse user population. As a result, the model’ s training is incomplete.
We’ ve dug deep into the challenges of face verification. We audited our own facial verification results. With better data, and directions for users to ensure the necessary lighting, we achieved 30% higher accuracy—meaning much less bias. We continue working on data quality so the system is less and less likely to give a false non-match for anyone.
How can we solve these issues? What are the challenges involved?
While AI may never be perfect, there are ways to address the bias in facial recognition: better lighting, cameras that adjust for facial shots, and most importantly, better—more representative—training of AI systems. We can also guide users to improve lighting settings on their phone before they snap the selfie required for verification.
What is the future of biometric IDV in the financial sector?
We’ re working toward the day when you can prove who you are online without needing to give away so much personal data. Our mission is to make that a reality by becoming the identity layer of the Internet. We help companies store and manage data within a secure infrastructure to limit how much sensitive personal information they have to ingest into their platforms.
Final thoughts?
In the financial industry, which includes physical and online banks as well as stock brokerages, lenders, and insurance, bad actors have almost unlimited motivation to impersonate someone else in order to gain access and steal or defraud.
And the victims aren’ t just the individuals fraudsters are attacking — these attacks can damage companies’ reputations and make it hard to attract and retain customers. According to Twilio, 86% of consumers said they’ d stop using a business if their account was compromised.
Identity verification is a powerful way to help protect businesses and customers — and build trust. But while biometric verification is useful, it’ s not foolproof. Instead, it needs to be part of a holistic set of signals businesses use to know their customers.
At Persona, we give businesses the building blocks they need to design and build the ideal identity experience for their specific industry, use case, and customers. Organisations can easily switch up verification methods or add more friction for extra assurance. This is increasingly important to make things unpredictable for hackers, who never, ever rest. With our holistic set of verification options and ability to dynamically step-up or step-down friction based on risk signals, businesses can ultimately make identity verification painful for fraudsters and painless for customers — in essence, mitigating fraud without hurting conversion.
Polly is a journalist, content creator and general opinion holder from North Wales. She has written for a number of publications, usually hovering around the topics of fintech, tech, lifestyle and body positivity.
The Fintech Times is the world’ s first and only newspaper dedicated to fintech.
Published Bimonthly, the Fintech Times explores the explosive world of financial technology, blending first hand insight, opinion and expertise with observational journalism to provide a balanced and comprehensive perspective of this rapidly evolving industry.
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Preclinical Data Suggest PTGDR Antagonist Could Help Aging Immune Systems | BioAge Labs presented new data in Nature this week demonstrating how its drug candidate BGE-175 ( asapiprant) is uniquely poised to tackle age-related immune system decline that leads to disease progression. As the COVID-19 pandemic evolved to include multiple variants of concern, researchers at BioAge Labs sought to find a way to counter the immune system weakening seen in older patient populations as a way to prevent morbidity and mortality.
BGE-175 is currently being evaluated in Phase II trials to assess efficacy, safety and tolerability for patients over the age of 50 who are hospitalized with COVID-19.
In an interview with BioSpace, BioAge Labs Co-founder and CEO Kristen Fortney, Ph.D. described the pharmacokinetics of BGE-175 as a two-part mechanism that protects from lethal infection and decreases the viral load to enhance immune response. Digging further into the drug’ s mechanism, the published data elaborates that BGE-175 works within the PLA2G2D-PGD2/PTGDR pathway as a PTGDR antagonist. To correct and reverse the effects that aging has on the immune system, the drug inhibits the PGD2 DP1 protein within this pathway, a target found through BioAge’ s extensive age-related biomarker research.
The preclinical trial results involve 8-12-month-old mice that have been infected with a typically lethal, genetically-altered dose of COVID-19 virus derived from mouse lung tissue. This adapted version of the virus showed mutations that also arose as variants of concern in humans. It is also highly virulent, contributing to ideal research conditions.
The mice were treated with BGE-175 two days after infection. The waiting period allowed for the mice to incubate the virus, which mirrors the average treatment timeline of humans. With BGE-175 treatment, death was prevented in 90% of mouse subjects, whereas all control non-treated mice died.
The Phase II trial is geared toward COVID-19 patients over the age of 50 who are “ at risk for respiratory failure. '' NCT04705597, a multicenter, randomized, double-blind, placebo-controlled study, is currently recruiting in the U.S. The primary endpoint is the proportion of participants that are able to avoid respiratory failure, which requires secondary ventilation efforts. Secondary endpoints sought are the proportion of participants that experience adverse events, oxygen saturation, quantifiable viral load amounts, oxygen supplementation, time under hospitalization, clinical improvement and overall survival. Additional clinical trials are being conducted internationally to capture a diverse data set.
The U.S. Centers for Disease Control and Prevention ( CDC) reported statistics from May through August 2020 showing that 78% of fatalities linked to COVID-19 were for people 65 years old and over. A more generalized statement issued by the CDC advises that “ immune function and defense against infection is impaired with aging. ” This is attributed to “ suboptimal T cell response, which resulted from a delayed migration of respiratory dendritic cells ( rDCs) to draining lymph nodes ”. BioAge hypothesizes this decreased immune response is linked to an age-related increase in PGD2, a prostaglandin that accumulates when infection occurs.
Although previous empirical data from 18 clinical studies in the U.S., UK and France support BGE-175 as a treatment for common allergies and asthma, further research sets the candidate up as a treatment for any disease or condition that would benefit from a proactive or reactive immune system boost.
The potential of BGE-175 extends far beyond COVID-19. Fortney proposes BGE-175 as a potential prophylactic candidate for pandemic preparedness, saying, “ Imagine if everyone over the age of 50 had the immune system of a 20-year-old. That would have been a very different pandemic. ”
In stark contrast to some of the antiviral and experimental treatments that are formulated when a novel virus panics the global population, she continued, “ It’ s one pill that they take every day… that’ s something that would be easy to stockpile. ”
The feature in Nature, co-authored by Stanley Perlman, M.D, Ph.D., pediatric infectious physician and professor of microbiology and immunology at the University of Iowa, supports BGE-175 as a preventative drug with broad implications, citing advantages over traditional antiviral medications.
Fortney said that BioAge’ s unique research and discovery platform is based partly upon blood banks with which it has an exclusive agreement to receive data on healthy patients for up to 50 years. She went on to explain that each sample allowed for the use of machine learning and artificial intelligence to scan for age-related biological markers and establish correlations that could then go on to become topics of research. This was the case in identifying BGE-175’ s therapeutic target. | general |
With Robust Results, Moderna to Request Vaccine EUA for Kids Under 6 | Moderna reported positive interim results from the Phase II/III KidCOVE trial of its mRNA COVID-19 vaccine for children six months to under two years and two to six years of age. The data showed a “ robust neutralizing antibody response ” in both cohorts. The doses were lower, a 25-microgram, two-shot series, than the 100 microgram doses used in adults.
Based on the results, the company plans to submit a request for an Emergency Use Authorization to the U.S. Food and Drug Administration for those age groups, as well as to the European Medicines Agency and other global regulators.
“ We believe these latest results from the KidCOVE study are good news for parents of children under six years of age, ” said Stephane Bancel, Moderna’ s chief executive officer. “ We now have clinical data on the performance of our vaccine from six months of age through older adults. ”
He went on to say, “ Given the need for a vaccine against COVID-19 in infants and young children we are working with the U.S. FDA and regulators globally to submit these data as soon as possible. Additionally, after consultation with the U.S. FDA, we have initiated a submission for emergency use authorization of our COVID-19 vaccine in children ages six to 11 years old and are updating our submission to the FDA for emergency use authorization of mRNA-1273 in adolescents ages 12 to 17 years with additional follow-up data. ”
In the six months to two years and two years to six years groups, the safety and tolerability profile of the vaccine was consistent with what was seen in children six to 12 and adolescents 12 to 17 and in adults. Most adverse events were mild or moderate, being more common after the second dose.
The immunogenicity of the 25 microgram doses was similar to those observed with the 100-microgram two-dose shots in adults 17 to 25 years. Omicron ( BA.1) was the dominant variant in the United States during the study period. As expected, the secondary endpoint of vaccine efficacy against Omicron was statistically significant but lower than what was seen against earlier variants, including Delta.
In children six months to two years, efficacy was 43.7% and in two years to six years, it was 37.5% against infection. Any infections seen were mild, with no severe cases observed. There were zero incidents of severe disease, hospitalizations or death.
No cases of myocarditis, a rare form of heart inflammation that has been associated with the vaccines, were observed.
According to the U.S. Centers for Disease Control and Prevention, during the Omicron surge beginning in late Dec. 2021, the hospitalization rate for infants and children up to the age of four was approximately five times the rate during the Delta surge in the summer and fall of 2021.
Most children in this age group are not eligible for a COVID-19 vaccine. The Pfizer-BioNTech vaccine has been authorized in people in the U.S. starting at the age of five, while Moderna’ s is only authorized for adults.
In February, Pfizer and BioNTech indicated they were postponing their rolling application to the FDA for children under five after finding the two-shot regimen didn’ t create a strong-enough immune response in the two-to-four-years age group. The Pfizer-BioNTech shots for youngest kids were very low, 3 micrograms, compared to Moderna’ s 25 microgram shots. | general |
High gasoline prices may dent Japan's demand recovery after pandemic restrictions end | In this week’ s highlights: All eyes are set on the IEA as it weighs long-term scenarios for global...
澳大利亚于3月20日表示，其将立即禁止向俄罗斯出口铝矿石（包括铝土矿）及氧化铝。 澳大利亚外交部在一项声明中表示，该禁令将限制俄罗斯生产铝的能力，而 “ 铝是俄罗斯的主要出口产品 ” 。...
Japan's domestic gasoline demand is expected to rise after the government lifted COVID-19-led movement restrictions in all 18 prefectures March 21, but surging retail prices are a worry and could dent some of that growth, market sources said March 23.
The country's new COVID-19 cases slumped 81% from a peak on Feb. 5 to 20,231 March 22, according to Japanese public broadcaster NHK. This is the first time that Japan has not been under any pandemic-related curbs since early January.
`` With the lifting of the priority measures, gasoline demand will recover gradually but as retail prices remain high, demand will not increase significantly, '' a refiner source said.
Japan's gasoline demand in March is expected to fall 7% year on year and remain 6% below the pre-pandemic level, the country's largest refiner ENEOS Holdings Chairman Tsutomu Sugimori said March 22.
`` After all, [ consumers ] would refrain from buying [ gasoline ] from rising prices, generally speaking, '' Sugimori said.
The Japanese government began providing fuel subsidies, covering gasoline, kerosene, gasoil, and fuel oil, to refiners and oil product importers from end-January, as part of its efforts to alleviate the effect of rising oil prices on economic recovery from the pandemic.
Spot and retail gasoline prices have surged in the wake of the Russia-Ukraine war, dulling the effect of the subsidies.
`` The current spot prices are still higher compared to last year, and this situation is expected to continue, though government's subsidies have been provided, '' a trader based in Tokyo said. `` It will be difficult for gasoline demand in April to exceed the results for the same month of the previous year. ''
Japan's domestic spot average rack price for gasoline in Chiba soared to Yen 80,966/kl, or $ 106.3/b, in the month through March 22, up from an average of Yen 59,213/kl, or $ 77.8/b, in March 2021, data from S & P Global Commodity Insights showed.
The country's national average retail price of regular gasoline increased for the 10th straight week to Yen 175.2/liter ( $ 1.48/liter) March 14, reaching the highest level in 13 years after rising Yen 0.6/liter week on week, the Oil Information Center said March 16.
`` It is true that subsidies have curbed retail price hikes. However, gasoline demand will continue to be curtailed, as consumers are less likely to feel the benefits of the subsidies, '' a trader based in Osaka said.
Refiners use the government's subsidies to curb increases in weekly wholesale prices of gasoline, kerosene, gasoil, and fuel oil, while trading houses deduct subsidies from the selling prices of imported oil products. | business |
Socioeconomic Trends in the UK Analysed in UK Payments Regulation Review | This industry report explores the impact of regulation and outlines how industry, lawmakers and regulators can work together to strengthen and enhance the country’ s payments infrastructure and regulatory and supervisory frameworks, following both Brexit and in light of the expanding digitalisation of the economy.
With commerce and day-to-day personal finance transactions increasingly moving online, regulatory priorities must continue to shift from financial stability to supporting market innovation. Similarly, technologies that were unthinkable around the turn of the millennium like digital identity frameworks and distributed ledger technology have entered mainstream conversations and are likely to have profound impacts for the sector.
The report identifies a number of opportunities that lawmakers, regulators and industry may wish to take advantage of. With payments as a foundational pillar of the financial services market and wider economy, as well as a creator of jobs and investment, the report outlines how the payments sector can drive change, in-part, through self-regulation and how its future should involve collaboration between market participants and regulatory stakeholders. It goes on to discuss how UK payment firms operate internationally, the importance of international market infrastructure access, including SEPA, and the need for regulations to continue to provide international parity to support, and reduce friction in, cross-border payments.
Reviewing everything from major socioeconomic trends to recent case law, the report outlines practical next steps.
Tony Craddock, director general at The Payments Association, comments, “ It is an exciting and challenging time to be in the payments space. In a very short time, we have seen the explosive growth of the fintech industry, the arrival of distributed ledger technology like cryptocurrency and stablecoins and the UK leaving the EU while simultaneously adopting PSD2 regulations. This is a timely report that grapples with the major issues in the payments industry and produces ideas on how to create the next generation of regulations, and we are keen to see how the wider industry reacts to the proposals we make. ”
Jana Mackintosh, UK Finance, says, “ We believe that regulators and industry have an opportunity to think afresh about payments regulation and supervision. This industry report will help players in the sector to reflect on the digitalisation of payments and consolidate past learnings that can be drawn upon as the industry moves forward.
Brett Carr, senior associate fintech and payments, Latham & Watkins, adds, “ We are proud to lend our firm’ s legal expertise and deep fintech and payments experience to this report at such an important time for the sector. The UK and EU payments markets have experienced a prolonged period of regulatory change punctuated by implementation challenges, the impacts of Brexit, covid-19 and a shifting supervisory strategy of the regulators. With question marks remaining over the UK’ s priorities for the regulation and development of the fintech sector, market participants will be anticipating how the regulatory environment is set to progress. This report presents a compelling case for greater cooperation between the industry, lawmakers and regulators, and calls for an evolution in approach that both enables and supports innovation. ”
Francis is a junior journalist with a BA in Classical Civilization, he has a specialist interest in North and South America.
The Fintech Times is the world’ s first and only newspaper dedicated to fintech.
Published Bimonthly, the Fintech Times explores the explosive world of financial technology, blending first hand insight, opinion and expertise with observational journalism to provide a balanced and comprehensive perspective of this rapidly evolving industry.
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Commvault pens deal with DMP SA to become a Metallic MSP partner | Commvault, a recognised global enterprise leader in intelligent data services across on-premises, cloud and software as a service ( SaaS) environments, has appointed Data Management Professionals South Africa ( DMP SA) as a managed services provider ( MSP) for its Metallic SaaS platform in South Africa.
Gerhard Fourie, Channel Lead at Commvault Africa, says DMP SA has been a frontrunner for the MSP programme in South Africa based on its extensive understanding of Commvault’ s business model, inner workings and offering.
“ When we embarked on the Metallic MSP journey, the idea was to look at service providers that have a rich history and understanding of traditional Commvault offerings. It made sense to onboard DMP SA onto our beta programme and they provided significant input into Metallic development for the greater benefit of the customer. ”
Fourie says there is a growing interest in SaaS offerings like Metallic, as most small and large enterprise customers have come to understand the benefits of SaaS platforms during the past two years due to the impact of the COVID-19 pandemic.
Long-term relationship
DMP SA Managing Director Iniel Dreyer says the agreement was concluded off the back of the company’ s decision to expand its SaaS offerings to customers, and choosing the Metallic platform made commercial sense for the company. The deal was also underpinned by DMP SA being a long-standing Commvault reseller.
“ Since 2015, we’ ve partnered with Commvault to deliver as a service offerings to the market, constantly looking to invest into infrastructure that is capable of scaling. However, one of the biggest challenges to grow as a business has been the capital investment requirement and agility to onboard large enterprise customers, ” says Dreyer.
“ These challenges fall away with Metallic, allowing us to focus on offering data management and support to customers with ease. We are now in a position to compete head-on with any player in the data management space, with solutions that can scale to any size. ”
He adds that Metallic is a trusted product that DMP SA has been using for a while and becoming an MSP partner enables the company to deliver the same level of service to customers at a much more efficient and faster go-to-market model.
Managing complexity of enterprise data
Metallic is part of Commvault's Intelligent Data Services Platform that allows organisations to proactively simplify and manage the complexity of enterprise data. Microsoft leverages Commvault to manage and protect some of its most important data, including data in Azure, Office and other technologies.
Metallic covers the entire spectrum of data protection, with its biggest focus being the protection of Microsoft 365 environments that are hosted on the Microsoft cloud platform. It is also the ideal platform to protect hybrid cloud environments and workloads, including end-point devices, physical server environments and virtual environments.
“ Metallic is suited to any market segment, from customers who have small amounts of data and devices to enterprise-scale environments. Because this is an MSP programme, we work with Commvault in the background, but the customer gets local support, ” says Dreyer.
“ The agreement creates an entire ecosystem where vendor and MSP work together with the customer. It makes the model a lot simpler and more predictable, and the customer benefits from having their data availability and recoverability managed by DMP SA, ” Fourie concludes. | general |
Toyota launches $ 826 million stock buyback amid business disruptions | Toyota Motor Corp. said Wednesday it will initiate a 100 billion yen ( $ 826 million) stock buyback delivering on a promise to flexibly repurchase shares and pay out stable dividends to shareholders.
With Toyota shares trading more than 10 percent off recent highs, the Japanese automaker said it was taking the current stock price into account and being “ more flexible ” than ever in its implementation of buybacks, according to a statement to the Tokyo Stock Exchange.
The buyback announcement comes as the top-selling automaker’ s shares have taken a hit in recent months as it faces a windfall of disruptions.
Toyota’ s factories have been halted recently due to a cyberattack on one of its suppliers, a powerful earthquake in Japan and a Covid outbreak in the Chinese city of Changchun. Toyota’ s shares closed in Tokyo on Wednesday almost 12 percent off a record close in January.
Toyota’ s decision came at “ bargain timing ” given current stock prices, said Bloomberg Intelligence analyst Tatsuo Yoshida. While the size of the buyback may be small relative to the company’ s market capitalization, it’ s a “ positive ” for Toyota’ s shares, and a sign that the company is “ steadily doing what it says it’ ll do ” in terms of flexibly acquiring shares and paying steady dividends, Yoshida said.
Buybacks have been on investors’ minds this week in Asia, after shares in Alibaba Group Holding Ltd. surged following its announcement of an expanded $ 25 billion repurchase. Investors are betting that Tencent Holdings Ltd. could be next to jump on the bandwagon.
Toyota will repurchase the shares from Thursday through May 10, around the time the carmaker typically announces full-year earnings. | general |
Cybercrime is ramping up, Russia is primed to attack: What can CISOs and CIOs do? | Cyber and ransomware attacks on hospitals will increase and become more sophisticated, most healthcare cybersecurity experts contend. With President Biden warning just yesterday that private-sector organizations should be prepared for Russian cyberattacks as part of the country's unprovoked war with Ukraine, the situation could only get worse.
In healthcare, many other issues are making cybersecurity more challenging: chronic staffing shortages, an increase in remote work and rising complexity in maintaining the day-to-day cadence of IT operations.
Then there is the need for immutable back-ups. In cases of ransomware, too often the existing backups are infected along with the primary production environment. An immutable backup is essentially a standalone copy with separate security that is locked to prohibit edits. Hospital insurers may begin to require immutable backups, similar to the way multifactor authentication became a mandate.
On another front, healthcare has primarily invested in reactive security technologies. As the frequency of attacks becomes increasingly high, hospitals may need to consider moving away from the reactionary period in the market. Executives may need to proactively implement new technologies to help mitigate attacks.
Healthcare IT News sat down with Erik Littlejohn, CEO of CloudWave, to discuss these cybersecurity issues as well as cloud security issues.
Q. How will healthcare staffing shortages contribute to cyber and ransomware attacks on hospitals increasing this year, and potentially becoming more successful?
A. Chronic staffing shortages and remote work are increasing security challenges. Many hospitals have not heavily invested in advanced software and security tools, requiring a lot of manual processes and physical eyes on threats. Add the Great Resignation and the scarcity of local IT talent, and you have a recipe for disaster.
Healthcare staffing shortages have resulted in a growing number of hospitals using outside agencies to bring in temporary staff, which opens IT systems up to human vulnerabilities. Additionally, most workflows have transitioned to self-service online tools with remote connectivity.
Increased turnover also means having to onboard and off-board more frequently, requiring heightened diligence for security practices. Each individual needs to be aware of their impact. Many hospitals have IT resources that are single-threaded and hard to replace. There may not be skill sets available in the geographic location where they are needed. The reality is that healthcare is competing with other industries and companies that allow for remote work.
These factors and many more are contributing to increasing cyber and ransomware attacks on hospitals in 2022.
Q. What is an immutable back-up and how can it help with cyberattacks?
A. An immutable backup is an extra standalone copy with its own distinct security protocols, locked to prevent encryption, edits and deletes. It adds `` air gapping, '' meaning the protected extra copy is separated from the rest of the data storage and IT environment, and particularly from the domain structure, for an extra layer of insurance.
Health IT administrators were previously concerned with hardening copy one and it was acceptable if copy two was just `` OK. '' In today's environment, where data is both growing exponentially in volume and more critical than ever to powering healthcare, a solid third option is needed that is restorable and clean.
In addition, we're seeing malicious actors specifically targeting backup infrastructure in their attacks, because they know a valid backup is the best way to foil their plans to disrupt operations and extort ransom. Immutable backups provide a solution to these challenges.
Therefore, if a catastrophic event occurs, where a healthcare organization's primary and secondary data centers are corrupted, this third copy – the immutable backup – can be restored much more quickly than working around corrupted primary and secondary copies.
This becomes a critical element in recovering from a ransomware attack as the restoration of the immutable backup is done without needing to pay the ransom. Therefore, we are seeing more and more hospitals and their insurers require immutable backups.
Q. You suggest that healthcare provider organizations must move from reactive to proactive technology investments. Please explain.
A. As the frequency of attacks is becoming so high, many hospitals are moving away from the reactionary period. Executives now need to proactively implement new technologies to help mitigate attacks and keep up with evolving threats.
For example, new solutions use AI to be more predictive and are faster to respond to emerging threats. Modern security technologies can also help offset staffing shortages, and flag what is important to focus on as the current frequency of incidents and alerts can create a lot of `` noise. ''
With a highly remote workforce, the problem is significantly more complex, as there are hundreds of locations and personal networks involved, rather than just the `` four walls '' of a hospital environment.
Older investments are simply no longer cutting it. For example, shutting off access after multiple password attempts is not effective, because bad actors are not trying to figure out what the password is. They already have it. It's like buying a new lock when the cybercriminals have the key.
Another trend that is driving hospitals to be more proactive in technology investments, particularly related to security, is that insurance companies are taking a deeper look at process and procedure.
Q. Many hospital CIOs are determining the post-pandemic operating model and looking at how cloud technology can help manage that. What does this mean for cybersecurity and cyberattacks?
A. The cloud brings cybersecurity advancements that individual hospitals may not be able to invest in independently. This scalability of the cloud is an important benefit.
The pandemic broadly taught us that the just-in-time world was too fine-tuned. Today and in the future, many industries will need `` burst '' capacity, regardless of supply chain. If something on the scale of the COVID-19 pandemic were to happen again – where increased capacity of remote connectivity becomes critical – successful organizations will be expected to adapt on the fly.
Most of us didn't value and think about IT flexibility that much in the past. However, organizations simply need more flexibility to deal with the nature of the world today.
They must prepare for future resiliency, and plan ahead for network capacity, bandwidth, hardening assets and critical resources, because everyone is going to be chasing the same things. The cloud helps provide scalability and flexibility.
Resiliency used to mean hardening, but now it means more flexibility. Prolonged workflows on backup – like paper and pen – are not going to work. Healthcare IT leaders need to focus on speed and agility to recover and restore normal operations, and the cloud is a huge asset for enabling that.
Another area to focus on in the future is the IT supply chain. It's important to evaluate potential vendors and products for vulnerabilities. An example of this is the recent SolarWinds event. Supply chain risks and third-party risk-management are big topics to address across the board in the coming years.
Twitter: @ SiwickiHealthIT Email the writer: bsiwicki @ himss.org Healthcare IT News is a HIMSS Media publication. | tech |
With sumo flag sponsorship deal, COVID vaccine-maker Moderna reveals Japan ambition | Moderna Inc. is sponsoring sumo flags in its first such promotion in Japan, as the U.S. firm seeks to build on its newfound renown in COVID-19 vaccines and wrestle market share from compatriot Pfizer Inc.
The U.S. firm's introduction to the broader Japanese public was set back after some of its doses last year were found to be contaminated, although it has clawed back market share since with the help of a government-endorsed program.
Now, as the government plans a fourth-dose vaccination program, Moderna is looking to sumo to boost its public appeal as it seeks to expand beyond COVID-19 shots.
The flags, known as kenshō hata, are held by banner bearers circling the sumo ring and have traditionally served as ads for everyday goods such as vitamins, teas, juices and rice.
Moderna debuted its banner — a simple white design with the company name in chunky, red script — on March 13 at the start of the national sport's two-week spring tournament.
The promotion signals the company's growth aspirations in Japan, which has come to know Moderna through some 50 million doses of its mRNA-based COVID-19 vaccine imported last year by local partner Takeda Pharmaceutical Co.
Those doses made up less than 20% of shots in Japan's initial double-shot inoculation push, with the bulk made up of the vaccine Pfizer developed with Germany's BioNTech SE.
During that time, 1.63 million Moderna doses were recalled in Japan after metal fragments were found in some vials — a problem traced to a partner factory in Spain.
When booster shots became available, residents rushed to book appointments for Pfizer supplies, leaving many Moderna slots vacant. That prompted the government to actively promote a vaccine mix-and-match strategy, emphasizing speed over brand.
That helped the numbers even out, with Moderna accounting for about 42% of booster shots.
Last week, the government said vaccines for fourth doses will be split almost evenly between the two suppliers. It plans to secure 75 million doses from Pfizer and 70 million from Moderna.
For the fourth shot, which is under development and will be a combination of vaccines designed for the delta and omicron variants of the novel coronavirus, Moderna directly holds the rights in Japan, Rami Suzuki, Moderna's recently appointed representative director in Japan, said.
Takeda said it is in discussion with Moderna about distribution.
Founded in 2010 and based in Cambridge in the U.S. state of Massachusetts, Moderna did not have an office in Japan until October, and Suzuki, who previously held roles at pharmaceutical firms Janssen and Eisai Co., joined in November.
Going forward, the company plans to combine COVID-19 and influenza vaccines in one shot, with possible market introduction in 2023, Suzuki said. Later, the combined shot could include a third vaccine for respiratory syncytial virus ( RSV), she said.
The Japan push comes as Moderna increases its Asia presence with a plan to produce mRNA vaccines in Australia and create four subsidiaries in Malaysia, Taiwan, Singapore and Hong Kong.
It also has a vaccine production deal with South Korean drugmaker Samsung BioLogics Co.
Based on trials showing Moderna's shot has the strongest antibody effect when combined with other vaccines, the firm `` still has opportunity to seize market share from Pfizer in terms of boosters, '' said healthcare analyst Xinyao Wang, who publishes on the SmartKarma platform. | tech |
UK to end 25% retaliatory tariff on US milled and broken rice from June 1 | Ira Joseph, directora de gas y electricidad de Platts Analytics, y Ryan Ouwerkerk, director de...
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The UK government has agreed to lift the 25% retaliatory tariff on US milled and broken rice imports from June 1, it said late March 22.
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The tariff is currently placed on the total delivered cost of the goods, making concluding competitive trade into the country incredibly difficult given the rapid rise in freight rates since the onset of the COVID-19 pandemic.
The EU imposed the retaliatory tariffs in June 2018 -- when the UK was a part of the EU's customs union -- following the US government's announcement of the Section 232 tariff on steel and aluminum imports from various countries, including the UK and the EU.
While the EU agreed with the US government to drop retaliatory tariffs Jan. 1, this had to be separately negotiated with the UK government due to the UK since leaving the EU customs union.
The news has been welcomed by the US rice industry, with Betsy Ward, President and CEO of USA Rice, saying March 22 that `` rice exports have been unnecessarily caught in the crossfire of the steel and aluminum trade wars for nearly four years, impacting decades of business relations with our customers in Europe... We believe this will help pave the road for US-UK Free Trade Agreement negotiations to restart and further deepen our trans-Atlantic relationship. ''
Outside of a limited duty-free quota, US rice will only be subject to a GBP121/mt ( $ 160/mt) tariff on white rice and a GBP25/mt ( $ 33/mt) tariff on brown rice from June 1.
As of March 10, US rice exports to the UK in the marketing year 2021-22 ( August-July) totaled 12,219 mt, according to the US Department of Agriculture, with 10,500 mt of outstanding sales yet to be shipped.
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Sweden Jumps the Gun on Covid Strategist’ s New WHO Job | The information you requested is not available at this time, please check back again soon.
( Bloomberg) -- Sweden’ s announcement that Anders Tegnell, the mastermind behind the Scandinavian country’ s controversial Covid-19 strategy, had been hired by the World Health Organization has turned out to be premature.
The March 9 report by Sweden’ s Public Health Agency FHM said that Tegnell had resigned as state epidemiologist to become a senior expert in a group that will coordinate the work between the WHO, the UN Children’ s Fund UNICEF and vaccine organization Gavi. Svenska Dagbladet first reported that the announcement was met with “ surprise and confusion ” within the WHO.
“ We thought that the process was done, but have now realized that it was a mistake on our part, ” FHM spokesman Christer Janson said by phone on Wednesday. “ The WHO asked Sweden for technical support to this newly founded partnership, and since we appointed Tegnell in coordination with the Swedish government we thought that everything was settled. ”
The FHM is now in contact with the WHO “ to make things right, ” Janson said.
While Tegnell remains employed by the FHM, he is no longer state epidemiologist, according to the spokesman. | general |
Adapting Robotic Production Lines for a Titanium-Focused Economy | With the post-pandemic recovery well on its way, the new jobs market has placed a clear focus on hygiene.
According to CNBC, 66 percent of workers want cleaner, even sterile, working conditions, and that’ s independent of their industry. Creating the tools and surfaces required to meet this demand will fall on factories and robotic, or automated, machining.
In turn, this will require innovation to work with materials that are conducive to that sterile environment – which poses a challenge to manufacturers and their robotic factory lines.
The good news is that many of the materials that will lend themselves to a sterile workplace are ones already familiar with the industrial scene.
The need for clean surfaces has seen a resurgence in the demand for titanium, both solid and in oxide forms.
Studies have shown that the use of titanium particles can lend an antimicrobial property to surfaces, including one 2021 study published in the journal of Materials Science and Engineering.
The inclusion of titanium block in metal surfaces will enable workplaces to be cleaner – including on the factory floor where it was cut. Titanium is, of course, incredibly strong; stronger than steel yet lighter, and twice as strong as aluminium.
Today, 1 in 4 Americans live with disability, and this number is only increasing according to the CDC.
Largely due to the pandemic, and the fact that long-term Covid is not fully understood, Americans are likely to be dealing with the challenge of disability-causing conditions for years to come.
Again, this includes the importance of robot machining. The speed, or alacrity, with which robot-controlled automated lines can produce medical devices, is crucial.
In tandem with titanium, which has sterile and antimicrobial properties that make it absolutely perfect for the purpose of the likes of prosthetics, this will create a factory line for new medical devices to help support a population facing new medical challenges.
One of the most heavily impacted areas of the economy has been travel. Flight is an almost uniquely contaminant-ridden form of travel, as well as contributing negatively to climate change.
As Boeing highlights, there has been a long search for better titanium alloys for use in flight, both for environmental reasons and for hygiene; the use of titanium plates inside the aircraft will help to produce antimicrobial results for passengers.
In the factories and manufacturing plants of the world, more demand will once again arise for the need for finely tooled products. With the rush towards more environmentally friendly travel, the need for expediency in production will only become more pressing.
To that end, robot-powered factories and production lines will have a big part to play in the new economy. Titanium is a fantastic resource, and it will see more and more use across the world. | tech |
Hope and fear as Afghan girls prepare for return to school | Hi, what are you looking for?
The reopening of secondary schools for girls across Afghanistan prompted joy and apprehension among the tens of thousands of students.
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The reopening of secondary schools for girls across Afghanistan on Wednesday prompted joy and apprehension among the tens of thousands of students deprived of an education since the Taliban’ s return to power.
All schools were closed because of the Covid-19 pandemic when the Taliban took over in August last year — but only boys and some younger girls were allowed to resume classes two months later.
Here are the views of five teens on going back to school for the first time this year:
– The would-be doctor –
In Dasht-e-Barchi, a Kabul district mainly home to minority Shiite Hazaras, 14-year-old Alina Nazari is happy to be going back to class after months away.
The ninth-grade student, whose father is a taxi driver, dreams of becoming a doctor and wants to help rebuild the country.
“ I am so happy that schools are reopening, ” she told AFP from her family home.
“ Education is very important and our country needs doctors and engineers. ”
Nazari, the eldest of five siblings, does not expect going back to school will be as simple as turning the clock back to before August 15, when the Taliban took over.
“ My father is a taxi driver and his earnings are not enough, which is why even I have not purchased a new uniform or books, ” she said.
“ Many girls might be unable to attend school. ”
– Like mother, not like daughter –
In the southern province of Kandahar, the birthplace of the Taliban movement, Marwa Ayubi worries her life will turn out like her mother’ s if she is denied an education.
“ My mother does not have good memories from the Taliban’ s first regime, ” said Ayubi, 18, noting that girls were barred from formal education during the group’ s first reign from 1996 to 2001.
“ But thank God… We are able to go out of our house and now to school, ” she told AFP.
Still, she worries her education might go to waste if she is prevented from working when she graduates.
Women are largely barred from government employment under the Taliban — apart from specialised areas such as health and teaching.
“ Once we finish our higher education we should be given work, ” said Ayubi.
– The judge –
Qahera Mohammadi, who hails from the remote Panjshir Valley, believes educated women are “ the backbone ” of society.
“ At an individual level, good education builds a better personality, ” the 18-year-old told AFP — though she admits that after months of idleness her mind is not geared up for study.
“ It is all new for us, ” she says, adding she wants to become a judge — an unlikely aspiration given the Taliban’ s legal system has little place for women.
– No hurdles to medical school –
Raihana Azizi is a teenager in a hurry to resume her studies — even if it means covering up to go to school.
“ We are behind in our studies already, ” said the 17-year-old in the northern city of Kunduz, as she prepared to attend classes dressed in a black abaya, headscarf and veil.
“ Now that the schools are reopening… we expect they stay open in the future and that there are no obstacles, ” said Raihana, who also hopes to study medicine.
– The stay-at-home student –
Tamana Rahimi fears the Taliban too much to consider returning to school, and so the 19-year-old is abandoning her studies to help her mother at home in an impoverished district of Kabul.
“ I’ m afraid that I will be killed, mistreated or beaten, ” she told AFP.
Still, she says she will find contentment in what she does.
“ Being with my family and sharing responsibilities with my mother is good enough for me, ” Rahimi said.
With 2,400 staff representing 100 different nationalities, AFP covers the world as a leading global news agency. AFP provides fast, comprehensive and verified coverage of the issues affecting our daily lives.
The big issue facing Russia’ s military is the future. If the present is godawful, the future could be truly, fatally, disastrous.
One billboard depicts Russian President Vladimir Putin's face in the dirt under a boot emblazoned with the Ukrainian trident - Copyright AFP DALE DE...
Hong Kong used strict travel curbs to keep the virus at bay for two years but these left Asia's world city increasingly isolated.
Mykolaiv residents are determined to stay and defend the city despite incessant bombardment - Copyright AFP TED ALJIBESelim SAHEB ETTABAUkraine’ s strategic city of Mykolaiv...
COPYRIGHT © 1998 - 2022 DIGITAL JOURNAL INC. Digital Journal is not responsible for the content of external sites. Read more about our external linking. | general |
Miley Cyrus ' Plane Struck by Lightning, Makes Emergency Landing | We may earn commission from links on this page, but we only recommend products we love. Promise.
Miley is safe after an emergency landing.
Miley Cyrus is safe after a truly terrifying travel experience. On route to Asunción, the plane carrying Miley's crew, band, friends, and family was caught in a major storm system and struck by lightning, causing it to make an emergency landing. Miley uploaded a video of the storm outside her plane window ( plus a photo of where the plane was struck by lightning), which she captioned with a brief explanation of what happened. She also reassured her fans that she and her loved ones are safe.
`` To my fans and everyone worried after hearing about my flight to Asunción, '' Miley said. `` Our plane was caught in a major unexpected storm and struck by lighting. My crew, band, friends and family who were all traveling with me are safe after an emergency landing. We were unfortunately unable to fly into Paraguay. 💔 I LOVE YOU. ''
Miley was visiting Paraguay to headline the Asunciónico festival, which has not been held since 2019 due to the ongoing COVID-19 pandemic. According to Rolling Stone, Asunción experienced `` massive flooding and rainfall '' on Tuesday, and the opening day of the Asunciónico festival—featuring performances from the Foo Fighters, Doja Cat, and Machine Gun Kelly—was canceled. Though Machine Gun Kelly decided to hold his own mini show directly outside of his hotel in the rain after hearing the news. | general |
Op-Ed: Deltacron — A wave of hybrid COVID as new virus accused of ‘ plagiarism’ | Hi, what are you looking for?
The timing of the new variant is interesting in a black humor sort of way.
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Well, if you’ ve been wondering when the inevitable new wave of COVID was coming along, bingo… maybe. Deltacron is currently being called a mix of Delta and Omicron, with some added spike protein. That’ s according to the Pasteur Institute.
The timing of the new variant is interesting in a black humor sort of way. This new strain has also emerged as our fearless global duly elected morons cave to pressure for winding down precautions. Gutless is thy name, and useless is thy game. 1.2 million Americans got infected last month. 38,000 Americans died last month. So everything’ s fine, right? Cretins.
Media to the rescue again
A new wave of COVID coverage, informed and otherwise, is also spreading. Someone’ s even complaining about the name, saying it fuels “ panic ”. After two years of the pandemic, panic is a bit late.
On an equally predictable note – In keeping with the great tradition of calling everything fake, there’ s some older coverage from January, if you please, when the variant was first mentioned. It was called a “ false variant ” a “ hoax ”, etc. Now the Pasteur Institute, an actual global authority, has pinned it down.
( The use of the word “ hoax ” should be a criminal offense by now. That word and the political skanks using it delayed the US response to the initial pandemic by a month or so, and about 30,000 Americans are dying of it per month. The Vietnam War killed about 50,000 Americans in 10 years. Some hell of a sense of priorities you got there, guys.)
Plagiarism?
Seems the Delta virus swiped these proteins from Omicron. To my knowledge, this is a very interesting point. Do viruses swap genes? Yes, they do. When it comes to two very highly infectious directly related viruses with huge populations, it may be a natural hybridization process.
One theory is that the Delta virus is hanging in competing with Omicron by acquiring the protein spikes. Interesting, because the previous viruses didn’ t respond to Delta that way.
Viral gene mixing
I’ m sure future virology will see this as an all-time no-brainer, but this is a working case to explore. It’ s well worthy of study and, god help us, a bit of actual thinking:
How infectious is Deltacron? The usual raffle of information
From the various headlines, Deltacron is showing up in the UK, Thailand, and, of course, the US, that Happy Valley for Total Political Irresponsibility. The new virus may or may not be as contagious as measles, as some are claiming prematurely.
Can we straighten something out here:
Whatever the story with Deltacron, what’ s needed is hard information and more specifics about the actual scope of infection for the variant.
And now, a moment’ s silence, if you please, for the opportunity for the experts to do their jobs. It’ d be a nice change.
DisclaimerThe opinions expressed in this Op-Ed are those of the author. They do not purport to reflect the opinions or views of the Digital Journal or its members.
Editor-at-Large based in Sydney, Australia.
The big issue facing Russia’ s military is the future. If the present is godawful, the future could be truly, fatally, disastrous.
One billboard depicts Russian President Vladimir Putin's face in the dirt under a boot emblazoned with the Ukrainian trident - Copyright AFP DALE DE...
Hong Kong used strict travel curbs to keep the virus at bay for two years but these left Asia's world city increasingly isolated.
Mykolaiv residents are determined to stay and defend the city despite incessant bombardment - Copyright AFP TED ALJIBESelim SAHEB ETTABAUkraine’ s strategic city of Mykolaiv...
COPYRIGHT © 1998 - 2022 DIGITAL JOURNAL INC. Digital Journal is not responsible for the content of external sites. Read more about our external linking. | general |
Shanghai warns against 'panic ' as Covid cases mount | Hi, what are you looking for?
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Shanghai authorities on Wednesday called for calm as worried citizens swamped online grocery platforms to stock up on food over fears of impending lockdowns in a city struggling to halt a Covid spike.
China is experiencing its worst Covid-19 outbreak since the start of the pandemic more than two years ago, with Shanghai posting record-high case counts as the highly transmissible Omicron variant frustrates authorities.
China’ s biggest city on Wednesday reported 981 cases — all but four of them asymptomatic — a number that dwarfs any previous daily tally in the city and which is nearly one-fifth of the day’ s national total.
Shanghai has responded to the outbreak with targeted residential lockdowns in areas with confirmed cases or close contacts.
There are growing public fears of more local lockdowns or stay-at-home orders for the entire city of roughly 25 million people.
Public concern has spiralled in the city in recent days and residents have taken to social media to air their frustrations.
They have complained about unclear government messaging, alarmist posts about expanding test sites and impending lockdowns, and the announcement that at least two indoor arenas in the city had been converted into mass-quarantine sites.
“ We hope that everyone will not believe or spread rumours, and especially do not maliciously spread rumours that cause panic in society, ” Wu Jinglei, head of Shanghai’ s health commission said at a daily briefing.
Stores have seen bustling business as consumers stock up, and social media images circulated late Tuesday showing crowds of shoppers converging on outdoor vegetable markets. The images could not be independently verified.
Online shoppers on Wednesday posted complaints that platforms were crashing under the strain or that some goods were unavailable.
Spokeswoman for online grocery platform Dingdong Maicai, Chen Ying, acknowledged the company was under pressure as online demand had “ surged ”.
The coronavirus first emerged in the city of Wuhan in late 2019 but China has largely kept it under control through its tough zero-Covid strategy.
Authorities had recently suggested a lighter approach to minimise public and economic disruptions.
But Omicron is straining those plans, particularly as Beijing nervously watches a deadly Hong Kong Omicron surge that sparked panic buying and has claimed a high toll in the unvaccinated elderly.
Mainland health officials last week revealed that only around half of Chinese aged over 80 have been double-vaccinated.
Shanghai shut schools for nearly two weeks but has avoided the sort of citywide lockdown implemented in some northeastern cities hit by the current outbreak.
But the spectre of suddenly being confined at home for anything from two to 14 days has sowed public anxiety among Shanghai’ s population.
Chinese media reported that some financial traders in Shanghai and Shenzhen had been staying overnight in their offices to avoid being sequestered at home.
With 2,400 staff representing 100 different nationalities, AFP covers the world as a leading global news agency. AFP provides fast, comprehensive and verified coverage of the issues affecting our daily lives.
The big issue facing Russia’ s military is the future. If the present is godawful, the future could be truly, fatally, disastrous.
One billboard depicts Russian President Vladimir Putin's face in the dirt under a boot emblazoned with the Ukrainian trident - Copyright AFP DALE DE...
Hong Kong used strict travel curbs to keep the virus at bay for two years but these left Asia's world city increasingly isolated.
Mykolaiv residents are determined to stay and defend the city despite incessant bombardment - Copyright AFP TED ALJIBESelim SAHEB ETTABAUkraine’ s strategic city of Mykolaiv...
COPYRIGHT © 1998 - 2022 DIGITAL JOURNAL INC. Digital Journal is not responsible for the content of external sites. Read more about our external linking. | general |
Stephen Wilhite, creator of the GIF, has died | Stephen Wilhite, one of the lead inventors of the GIF, died last week from COVID at the age of 74, according to his wife, Kathaleen, who spoke to The Verge. He was surrounded by family when he passed. His obituary page notes that “ even with all his accomplishments, he remained a very humble, kind, and good man. ”
Stephen Wilhite worked on GIF, or Graphics Interchange Format, which is now used for reactions, messages, and jokes, while employed at CompuServe in the 1980s. He retired around the early 2000s and spent his time traveling, camping, and building model trains in his basement.
Although GIFs are synonymous with animated internet memes these days, that wasn’ t the reason Wilhite created the format. CompuServe introduced them in the late 1980s as a way to distribute “ high-quality, high-resolution graphics ” in color at a time when internet speeds were glacial compared to what they are today. “ He invented GIF all by himself — he actually did that at home and brought it into work after he perfected it, ” Kathaleen said. “ He would figure out everything privately in his head and then go to town programming it on the computer. ”
If you want to go more in-depth into the history of the GIF, the Daily Dot has a good explainer of how the format became an internet phenomenon.
While there have been long-standing debates about the correct pronunciation of the image format, Wilhite was very clear on how he intended for it to be said. In 2013, he told The New York Times, “ The Oxford English Dictionary accepts both pronunciations. They are wrong. It is a soft ‘ G,’ pronounced ‘ jif.’ End of story. ”
He reiterated that stance while accepting a Webby Lifetime Achievement Award for the invention of the GIF later that month, using an animation to give his acceptance speech. ( You can watch the whole clip of him receiving the award here.) “ After 25 years, they finally honored that achievement that he did, ” Kathaleen said, adding that creating the GIF was the thing he was most proud of.
Several messages from former colleagues on his obituary page said that Stephen also made other important contributions during his time at CompuServe, describing a hard worker who had a major influence on the company’ s success.
After Stephen retired, the couple traveled together. Kathaleen said that one of the most memorable trips was their honeymoon when they visited the Grand Canyon. “ I had never seen it before, and he wanted to show it to me, ” she said fondly. The couple also went camping “ all the time, ” she said.
While at home, he liked to work on his model train set. “ When we had the house built, we actually had a whole section in the basement for his train room. He always did the designs and electric work for the layout, ” said Kathaleen.
In the Times interview, Wilhite said that one of his favorite GIFs is the dancing baby meme, which went viral before “ memes ” and “ going viral ” were widely used terms. So here’ s to you, Mr. Wilhite. Thanks for creating the image format that made downloading color images over dial-up bearable before it turned into one of the internet’ s own languages. | tech |
Community Asked to Test their Internet Access and Speed - The Santa Barbara Independent |
Press releases are posted on Independent.com as a free community service.
Santa Barbara, Calif. – The Broadband Alliance of Santa Barbara County ( Alliance) launched a countywide internet needs assessment survey and speed test campaign today for the public to self-report their internet experience and speed at home, work, or wherever they connect. The campaign is part of Santa Barbara County Association of Governments ( SBCAG) effort with the Alliance to develop a countywide Broadband Strategic Plan aimed to better understand internet availability countywide and direct funding to projects that will increase affordable access to high-speed internet.
Data from the survey and speed test campaign will be mapped by GEO Software which is developed and licensed by Breaking Point Solutions, LLC and marketed by GEO Partners, LLC. The data will be used to identify areas in the county of low or no access to high-speed internet.
“ The COVID-19 pandemic brought to light what many residents were already unnecessarily enduring, the lack of reliable and affordable access to internet, ” said SBCAG Board of Directors Vice-Chair Jenelle Osborne, mayor of the City of Lompoc. “ The broadband survey and speed test is vital to our efforts to advocate for fast, flexible, affordable, and reliable internet service for all residents and businesses in our county. ”
The public is encouraged to go to www.sbcag.org/broadband to self-report their internet needs and take a speed test on a personal computer or laptop at home, work, or wherever they connect by May 31. Individuals can also identify areas with low or no service, or where access to the internet is unaffordable within this test. Those without internet access can call SBCAG at 1-805-961-8902 to report why they do not have internet access. The Broadband survey and speed test is available in English and Spanish. Privacy controls protect responses and anonymous participation is an option. Data collected will include the location, internet speed, and monthly internet cost.
“ Each of us can do one very important thing to improve internet access and affordability. If your internet is too slow or unreliable or expensive, take the one-minute broadband internet survey and speed test before May 31, ” said SBCAG Director Joan Hartmann, county supervisor. “ This will allow us to validate where we have poor coverage. Help us take charge to improve affordable access to high-speed internet in our homes, schools, businesses, and libraries.
In December 2020, Governor Gavin Newsom signed historic legislation, Broadband for All, to advance the State’ s commitment to bring affordable access to high-speed internet service across California. In Santa Barbara County an Alliance formed as a partnership between Santa Barbara County Association of Governments, Broadband Consortium of the Pacific Coast ( BCPC), County of Santa Barbara and all eight cities, the Santa Ynez Band of Chumash Indians and regional economic development organizations to collect data and information over five months related to the use, availability, and affordability of broadband internet throughout the region.
The information collected will be used to seek funding to improve affordable access to high-performing internet countywide with a goal to work toward digital inclusion.
ABOUT THE BROADBAND ALLIANCE OF SANTA BARBARA COUNTY
The Broadband Alliance of Santa Barbara County ( Alliance) formed in October 2021 as a partnership between the Santa Barbara County Association of Governments, County of Santa Barbara, and the cities of Buellton, Carpinteria, Goleta, Guadalupe, Lompoc, Santa Barbara, Santa Maria, and Solvang, the Santa Ynez Band of Chumash Indians, Broadband Consortium of the Pacific Coast ( BCPC), and regional economic development organizations. The Regional Broadband Strategic Plan aims to identify broadband internet infrastructure and affordability needs in Santa Barbara County. Once the Plan is complete, the Alliance will seek funding opportunities for projects to improve affordable access in homes, schools, businesses, healthcare, and facilities to high-speed internet countywide.
ABOUT SANTA BARBARA COUNTY ASSOCIATION OF GOVERNMENTS
The Santa Barbara County Association of Governments ( SBCAG) is a regional planning agency comprised of Santa Barbara County and all eight incorporated cities within the county. SBCAG distributes local, state, and federal transportation funds and acts as a forum for addressing regional and multi-jurisdictional issues.
ABOUT BROADBAND CONSORTIUM OF THE PACIFIC COAST
The Broadband Consortium of the Pacific Coast ( BCPC) is one of several strategic initiatives conducted by the Economic Development Collaborative in Ventura County. Formed in 2014, the consortium has served as an advocate for broadband deployment and adoption across Ventura, Santa Barbara, and San Luis Obispo counties. | general |
Priorities for NICE in health and social care - The Lancet Respiratory Medicine | Over the past 2 years there has been an unprecedented increase in medical research, the NHS has been under enormous pressure, and the UK public has become progressively more aware of science and research in response to COVID-19. Research data and information have been generated and published faster than ever before, creating new challenges for the National Institute for Health and Care Excellence ( NICE), which has been at the forefront of providing medical guidance for over 20 years. Moving beyond the COVID-19 era, NICE is reassessing and reprioritising its focus to ensure that it provides the best guidance in the areas that will provide the greatest benefit to patients.
At the time of writing, there are 2142 pieces of guidance on the NICE dashboard. This overabundance of information is difficult for clinicians and stakeholders to use, particularly when new evidence is being produced. Guidelines often compete with each other, are too confusing, and become rapidly out of date.
Patients play a huge part in the generation of life-saving research and need to be involved from the very beginning. Understanding people's attitudes to health and medicine is important, as seen with the anti-vaccine movement, so perhaps qualitative research should be valued as much as quantitative research. Understanding why people refuse vaccines and where those fears come from is important, as is education for people about science and research. Without public willingness to engage with treatments, therapies, and prevention methods, successful improvement in public health will be hindered. Patients must be seen as people with lived human experiences.
NICE has launched a project called NICE Listens, which aims to ensure that their policies reflect public opinion, particularly when thinking about potential trade-offs. The first focus of the project was health inequalities, spread across four online workshops involving 25 people sampled across age, gender, ethnicity, location, household income, and various other factors. The group debated the social, ethical, and moral issues surrounding health inequalities to understand how people feel about these issues. This first report from the NICE Listens initiative is due to be published within the next few months.
The scientific landscape is everchanging and the need for flexible and up-to-date guidance is crucial. NICE is moving towards a living guideline model that responds to emerging research and is useful, usable, and used. There are four key aims, the first being to implement a focused guideline portfolio. With so many guidelines, NICE aims to focus on high-priority areas and create connected suites of guidelines. The hope is that this will make it easier for clinicians and key stakeholders to find the answers they're looking for. These will be implemented by rolling topic committees, able to update guidance flexibly and quickly. The second aim is to create a digital guidelines platform, which makes using the recommendations easy. Guidance needs to be more structured ( ie, easy for machines to read), which requires clear coding and structures and a digital-first approach. Once guidelines are in place, NICE can work with its partners to integrate guidance into decision support tools that are embedded in the workflows of clinicians.
The third aim is to implement new mechanisms to provide feedback. NICE wants to introduce a model whereby its guidelines are embedded into a decision support system that is linked to electronic medical records. Consequently, the impact of guideline uptake can be monitored leading to more informed future strategies. The fourth aim is to have an updated manual that reflects data use and the inclusion of technologies in guideline development. Machine learning is scanning between 2000 and 3000 new records each week. Yet NICE is still keeping to its standards of robust, rigorous, and independent guidance.
Guideline implementation is another crucial step. The UK has a poor track record of getting new innovations to patients and inadequate implementation often contributes to health inequalities. Matching the speed of developing innovations with the speed of implementation is challenging, particularly with large target populations.
Potential challenges to implementation should be considered when guidelines are being developed. Patients are often asked for their approval at the end of the process, when it is too late, so allowing people to connect with the outcome from the very beginning is what's going to prevent innovations from being discarded at the last minute. The integration of new innovations into current services needs to be thought out, as do the implications for the system as a whole. New policies could disrupt policies in other areas and when patients are waiting in excess of a year for treatment, they can not afford to wait longer.
Moving forward, there must first be a need for guidance. Attention should focus on what doesn't work and where research can provide an answer. The number of guidelines needs to be reduced and converted into actionable decisions. The cost effect of new innovations should also be considered, which is currently missing in guidance, as this frequently prevents uptake. Often, investments in technology or interventions have had no meaningful clinical impact and, in some cases, have caused harm. Guidelines must be able to respond to new information and be usable, considering stakeholder preferences. Building a trusting relationship between medicine and the public is crucial, with patients and the public in the driving seat.
Priorities for NICE in Health and Social Care Conference. Feb 28, 2022. Online. Westminster Health Forum.
Priorities for NICE in Health and Social Care Conference. Feb 28, 2022. Online. Westminster Health Forum. | tech |
Moderna Will Seek FDA Approval For Low-Dose Vax For Kids | Moderna said on Wednesday that it will seek emergency authorization that would allow its COVID-19 vaccine to be used for children under six years old, saying preliminary clinical trial results with a lower dose of the vaccine for that age group show a similar immune response to adults.With this data, the American pharmaceutical company said it is `` moving forward with global regulatory submissions '' in the U.S., Europe and elsewhere that would allow for children under six, toddlers and babies over six months to be vaccinated.The study involved approximately 6,700 participants, according to Wednesday's announcement.Moderna's CEO Stéphane Bancel said... | general |
Talent Crisis: Bridging the Widening IT Skills Gap | Today’ s businesses are no stranger to innovation. From enhancing products and services with cutting-edge technologies to honing productivity with cloud-based applications and new ways of networking, innovation has become a key differentiator across virtually every industry. In the vast majority of cases, that innovation is almost wholly dependent on a company’ s IT capabilities. More IT capability means faster innovation and greater resilience, as evidenced by businesses that rapidly adapted to remote working during the pandemic. But while businesses have been dealing with a disrupted global supply chain and computer chip shortages, another potentially devastating problem now threatens every company’ s digital journey—an IT skills gap crisis.
According to Skillsoft’ s Global Knowledge 2021 IT Skills and Salary Report, more than three-quarters ( 76%) of IT decision-makers are currently experiencing skills gaps within their departments. That’ s an increase of almost 150% over the previous year, which points to the development of a very alarming trend. Any hopes that this emerging talent gap might be a one-off pandemic blip that will self-correct were dashed when The Learning and Work Insitute reported that the number of young people in the UK taking IT subjects at GCSE level had dropped by 40% since 2015. Throw the so-called ‘ Great Resignation’ into the mix, with 41% of the world’ s workforce strongly considering a change in their career and more businesses will soon be on the hunt for a diminishing and increasingly valuable resource—IT professionals.
A few years ago you’ d have been forgiven for thinking that an IT skills gap was unlikely, yet here we are. What’ s more alarming is that cybersecurity, which is now more important than ever, is at the top of the skills gap list with cloud computing closely behind it. It’ s very difficult to think of a single industry in 2022 in which cybersecurity and cloud computing aren’ t critical business components, so the term ‘ crisis’ certainly isn’ t a misnomer. If anything, it’ s an understatement. According to this year’ s Allianz Risk Barometer, cyberthreats outrank COVID-19 and broken supply chains as the number-one business risk. Check Point Software revealed a 50% increase in average weekly attacks on corporate networks between 2020 and 2021.
Businesses that are already ahead of the curve will no doubt be making provisions to increase employee retention and engagement—perhaps offering more attractive packages to secure the best talent—but even that might not be enough to remedy the emerging skills gap. So what should businesses do?
Prevention always beats cure, and that’ s as true for cybersecurity as it is for any other IT problem. Getting the IT skills and capabilities in play to spot potential issues before they become problems is the number-one way to raise cyberresilience. And getting better cyberresilience will not only help to future-proof a business but allow them to focus less on damage control and last-minute remedial action and more on proactive problem-solving and business development.
We’ re now living in an age of real-time business. Just as point-in-time audits have become somewhat meaningless when it comes to risk reporting, step-based innovation is also starting to feel obsolete. Today’ s businesses need to be in a mindset of constant innovation and continuous optimization if they are to take full advantage of the opportunities open to them. From planning to execution, businesses need to start thinking about working with what they’ ve got, as well as planning for the future if they want to earn that sought-after title of being future-proof.
Outsourcing. By 2025, the global IT outsourcing market will be worth a staggering £294 billion, with 83% of IT leaders already making plans to outsource elements of their IT security to a managed service provider in 2022. Far from being seen as an added expense, enlisting the help of a third-party IT partner is typically done to reduce costs and it can certainly take the strain off internal IT staff who, more than ever, are going to be feeling the pressure. It also takes a lot of the pressure away from HR teams who, instead of managing hires and high staff turnover in the IT department, can get on with helping to run the business.
As businesses continue to navigate the global IT talent shortage, outsourcing is set to become a core part of the so-called new normal, not necessarily to replace in-house teams but to support them and complement their efforts.
Jon, along with his business partner Jake Madders, founded Hyve Managed Hosting in the early 00s. Since then, in his role as Director, Jon has facilitated the growth of Hyve from a small start-up to a hugely successful company that has won accolades such as Cloud Company of the Year at the 2018 SVC Awards. With a background in software development, Jon has spent time at Crédit Agricole, Goldman Sachs, JPMorgan Chase and M & C Saatchi throughout his career.
jon-lucas has 3 posts and counting.See all posts by jon-lucas | general |
The crucial need for tuberculosis translational research in the time of COVID-19 - The Lancet Respiratory Medicine | The world is still grappling with the devastating effects of COVID-19 more than 2 years into the pandemic. Countries with high COVID-19 vaccination rates are transitioning to the new normal of living with SARS-CoV-2, but low-income and middle-income countries ( LMICs) are struggling to vaccinate their populations while concurrently fighting other communicable diseases, key among them tuberculosis. The burden of tuberculosis, the leading cause of death from an infectious disease before COVID-19 emerged, has been deeply affected by the pandemic.1WHOGlobal tuberculosis report 2021. World Health Organization, Geneva2021Google Scholar, 2Migliori GB Thong PM Alffenaar JW et al.Gauging the impact of the COVID-19 pandemic on tuberculosis services: a global study.Eur Respir J. 2021; 582101786Google Scholar In the first of a Series of three papers published in The Lancet Respiratory Medicine and eBioMedicine, Keertan Dheda and colleagues3Dheda K Perumal T Moultrie H et al.The intersecting pandemics of tuberculosis and COVID-19: population-level and patient-level impact, clinical presentation, and corrective interventions.Lancet Respir Med. 2022; ( published online March 23.) https: //doi.org/10.1016/S2213-2600 ( 22) 00092-3Google Scholar discuss the effects of COVID-19 on efforts to end tuberculosis and the need for wide-ranging interventions to restore tuberculosis control, including the need to implement and enhance tuberculosis diagnostic tests to reduce under-diagnosis. In the second paper, Ruvandhi Nathavitharana and colleagues4Nathavitharana RR Garcia-Basteiro AL Ruhwald M Cobelens F Theron G Reimagining the status quo: how close are we to rapid sputum-free tuberculosis diagnostics for all?.EBioMedicine. 2022; ( published online March 23.) https: //doi.org/10.1016/j.ebiom.2022.103939Google Scholar highlight progress in the development of non-sputum-based diagnostic tests with potential for decentralised deployment. Finally, Hanif Esmail and colleagues5Esmail H Macpherson L Coussens AK Houben RMGJ Mind the gap – managing tuberculosis across the disease spectrum.EBioMedicine. 2022; ( published online March 23.) https: //doi.org/10.1016/j.ebiom.2022.103928Google Scholar discuss optimal treatment regimens across the full spectrum of tuberculosis infection and tuberculosis disease, previously known as latent tuberculosis and active tuberculosis, respectively.1WHOGlobal tuberculosis report 2021. World Health Organization, Geneva2021Google Scholar Although these articles apply mainly to pulmonary tuberculosis, advances in the diagnosis and treatment of extrapulmonary tuberculosis will have to be made concurrently in addressing the substantial burden of disease. Importantly, the various sequelae after tuberculosis need to be understood and optimally managed.6Migliori GB Marx FM Ambrosino N et al.Clinical standards for the assessment, management and rehabilitation of post-TB lung disease.Int J Tuberc Lung Dis. 2021; 25: 797-813Google Scholar Finally, options for the prevention of tuberculosis in the form of robust vaccines need to be developed.7Cobelens F Suri RK Helinski M et al.Accelerating research and development of new vaccines against tuberculosis: a global roadmap.Lancet Infect Dis. 2022; ( published online Feb 28.) https: //doi.org/10.1016/S1473-3099 ( 21) 00810-0Google Scholar Translational research will underpin progress in preventing and managing the entire spectrum of tuberculosis, and a pressing need exists for investment and support to strengthen research capacity.
To improve the diagnosis of tuberculosis, new diagnostic tools, especially non-sputum-based tests, and enhancement of existing tuberculosis diagnostic tests will be crucial. Nathavitharana and colleagues4Nathavitharana RR Garcia-Basteiro AL Ruhwald M Cobelens F Theron G Reimagining the status quo: how close are we to rapid sputum-free tuberculosis diagnostics for all?.EBioMedicine. 2022; ( published online March 23.) https: //doi.org/10.1016/j.ebiom.2022.103939Google Scholar highlight the need to develop a sensitive and specific, rapid, non-sputum-based tuberculosis test by harnessing existing resources invested in COVID-19 detection. By use of easily accessible clinical samples, such as urine or oral swabs for diagnosis and implementing point-of-care tests, tuberculosis diagnosis could be enhanced in LMICs, where the majority of the world's tuberculosis burden is found.1WHOGlobal tuberculosis report 2021. World Health Organization, Geneva2021Google Scholar Such diagnostic tests need to be broadly applicable to all population types, including immunocompromised individuals, who tend to have atypical presentations and are often sputum-smear negative, which compromises the yield of the more rapid nucleic-acid tests.8Teng VYM Chua YT Lai EEN et al.Lack of latent tuberculosis ( TB) screening and delay in anti-retroviral therapy initiation in HIV-TB co-infection: an 11-year study in an intermediate TB-burden country.Int J Infect Dis. 2021; 113: 178-183Google Scholar Additionally, the performance of existing tuberculosis nucleic-acid tests is variable across specimen types, which is less than ideal and underscores the need for better diagnostic tests. The gold-standard tuberculosis cultures and drug-susceptibility tests remain unavailable in most LMICs, but the advent of whole-genome sequencing shortens the time to determine anti-tuberculosis drug susceptibility for more effective tuberculosis treatment.9The CRyPTIC Consortium and the 100,000 Genomes ProjectPrediction of susceptibility to first-line tuberculosis drugs by DNA Sequencing.N Engl J Med. 2018; 379: 1403-1415Google Scholar Such technology, if made available across resource settings, would help to stem transmission of both drug-susceptible and drug-resistant Mycobacterium tuberculosis because it allows prompt initiation of effective anti-tubercular treatment.
To optimally manage tuberculosis infection and disease, new approaches to diagnosis will need to go hand in hand with improved tuberculosis prevention and treatment, for which drug discovery together with repurposing of existing drugs needs to be undertaken. Esmail and colleagues5Esmail H Macpherson L Coussens AK Houben RMGJ Mind the gap – managing tuberculosis across the disease spectrum.EBioMedicine. 2022; ( published online March 23.) https: //doi.org/10.1016/j.ebiom.2022.103928Google Scholar propose an approach in which tuberculosis treatment and management are tailored across the tuberculosis spectrum, instead of being provided within the binary framework of tuberculosis infection and tuberculosis disease. However, extensive work is needed before this concept can be realised in clinical practice. For example, the implementation of this concept requires the development of a host-based or mycobacteria-based biomarker that indicates eradication of the pathogen, applicable to both tuberculosis infection and disease states of pulmonary and extrapulmonary tuberculosis, regardless of the level of immunity. Once validated in several independent cohorts, this biomarker would be useful in guiding the duration of treatment for infection or disease. Drug discovery and repurposing of drugs takes an excruciatingly long time in the tuberculosis field, but scientific and political will can remove barriers and expedite the process, similar to progress observed in COVID-19, with the necessary funding.10Chaisson RE Frick M Nahid P The scientific response to TB — the other deadly global health emergency.Int J Tuberc Lung Dis. 2022; 26: 186-189Google Scholar
Research on extrapulmonary tuberculosis has been modest compared with that for pulmonary tuberculosis, but remains just as important, and research efforts are needed to better understand and manage extrapulmonary tuberculosis. Patients with Pott's disease ( spinal tuberculosis) and central nervous system tuberculosis often have poor neurological and mortality outcomes despite effective tuberculosis treatment. The optimal treatment duration of each condition remains unclear for drug-susceptible tuberculosis, even less so for drug-resistant tuberculosis. Animal models that recapitulate features of human extrapulmonary disease states might hold promise for understanding mechanisms and allow testing of new therapeutics to improve both mortality and morbidity outcomes,11Poh XY Hong JM Bai C et al.Nos2−/− mice infected with M. tuberculosis develop neurobehavioral changes and immunopathology mimicking human central nervous system tuberculosis.J Neuroinflammation. 2022; 19: 21Google Scholar before studies in humans in phase 2 and 3 clinical trials.
The long-term sequelae of tuberculosis should not be forgotten. It is well recognised that lung function and quality-of-life decrease after pulmonary tuberculosis disease,12Long R Maycher B Dhar A Manfreda J Hershfield E Anthonisen N Pulmonary tuberculosis treated with directly observed therapy: serial changes in lung structure and function.Chest. 1998; 113: 933-943Google Scholar but the extent of the global burden of lung disease after tuberculosis infection is poorly defined and likely to be under-reported. Mechanisms that underlie tuberculosis tissue destruction and fibrosis are being established. Phase 2 clinical trials repurposing existing drugs, such as doxycycline and everolimus, to decrease tissue destruction hold promise in improving lung function and ameliorating sequelae from post-tuberculosis lung disease,13Miow QH Vallejo AF Wang Y et al.Doxycycline host-directed therapy in human pulmonary tuberculosis.J Clin Invest. 2021; 131e141895Google Scholar, 14Wallis RS Ginindza S Beattie T et al.Adjunctive host-directed therapies for pulmonary tuberculosis: a prospective, open-label, phase 2, randomised controlled trial.Lancet Respir Med. 2021; 9: 897-908Google Scholar but their efficacy would need to be demonstrated in larger cohorts before being implemented in practice. These measures, together with measures such as pulmonary rehabilitation, need to be adopted according to an agreed clinical standard to reduce the global burden of tuberculosis sequelae.6Migliori GB Marx FM Ambrosino N et al.Clinical standards for the assessment, management and rehabilitation of post-TB lung disease.Int J Tuberc Lung Dis. 2021; 25: 797-813Google Scholar
Altogether, tuberculosis translational research remains key to advancing prevention and management across the entire spectrum of tuberculosis, which is still a leading killer globally. Despite the catastrophic setbacks from COVID-19, researchers need to continue to push ahead to reach the ultimate goal of ending tuberculosis. As has been seen for COVID-19, a whole-of-government approach for tuberculosis is needed for the development of effective diagnostic and treatment approaches to stem transmission and save lives.
For the Tuberculosis in the time of COVID-19 Series see www.thelancet.com/series/tuberculosis-2022
For the Tuberculosis in the time of COVID-19 Series see www.thelancet.com/series/tuberculosis-2022
CWMO has received speaking fees from Qiagen, outside this work. The other authors declare no competing interests.
The intersecting pandemics of tuberculosis and COVID-19: population-level and patient-level impact, clinical presentation, and corrective interventionsThe global tuberculosis burden remains substantial, with more than 10 million people newly ill per year. Nevertheless, tuberculosis incidence has slowly declined over the past decade, and mortality has decreased by almost a third in tandem. This positive trend was abruptly reversed by the COVID-19 pandemic, which in many parts of the world has resulted in a substantial reduction in tuberculosis testing and case notifications, with an associated increase in mortality, taking global tuberculosis control back by roughly 10 years. Full-Text PDF | tech |
Supporting families with tuberculosis during COVID-19 in Khayelithsa, South Africa - The Lancet Respiratory Medicine | “ When the lockdowns first started, we thought it was the worst thing that could happen to our family ”, recalls Esihle ( not her real name), her eyes shining with tears. “ We could not work, you see, and without any money coming in, we all had to move back home to my mother's place. My brothers did too, all of us, with all of our children. There were nine of us living in that one small shack! But then my brother started to cough and I did too, and things got much, much more difficult for us all. ”
Esihle's story is one that is all-too common, reflecting the lived experiences of families all over the world, whose tenuous socioeconomic circumstances were frayed by the public health measures put into place to stop the spread of SARS-CoV-2. But while the world's attention was diverted elsewhere, another respiratory infection—tuberculosis—was thriving, perversely enabled by the steps taken to stop COVID-19. It is well documented that tuberculosis transmission occurs within households and is exacerbated by poverty, malnutrition, and overcrowding, conditions that all ballooned in magnitude as public health measures aimed at mitigating COVID-19 were enacted. Add to that the fact that health-care systems were challenged in dealing with COVID-19—forced at times to limit numbers, close entirely ( leaving sick people with nowhere to turn), or reassign staff to COVID-19 activities ( leaving other vital programs unstaffed), and the perfect storm for worsening the TB pandemic occurred. As the number of people diagnosed with and started on treatment for tuberculosis plummeted, tuberculosis transmission likely increased, since the best infection control measure for stopping the disease is the rapid identification and initiation of therapy for those who are sick. Nobody who was paying attention could, therefore, claim to be surprised when the WHO announced that, for the first time in more than a decade, deaths due to tuberculosis rose in 2020.
In the South African city of Cape Town, the same problematic pattern was being witnessed, with a disturbing drop-off in tuberculosis diagnoses and treatment initiations. This was a particularly concerning trend for severe and drug-resistant forms of tuberculosis ( DR-TB), which are common in many of the townships surrounding the city, including Khayelitsha, where Esihle and her family live. Khayelitsha is home to a population of an estimated half a million people, and with almost 200 people being diagnosed with DR-TB annually, it is considered one of the world's DR-TB hot spots. The health authorities ( City of Cape Town and the Provincial Department of Health of the Western Cape) have been responding to the DR-TB pandemic in a number of ways over the years, including through a long-standing partnership with the medical humanitarian organisation, Médecins Sans Frontières ( MSF). Actors from these public–private collaborative groups quickly sprang into action to try to address the negative impact of COVID-19 on DR-TB.
Early efforts were aimed at improving infection control practices in the clinics as well as providing health promotion and education about signs and symptoms of COVID-19 and tuberculosis. Providing integrated tuberculosis and COVID-19 screening and testing was also a key pillar of the early phases of Cape Town's TB recovery plan enacted in Khayelitsha, as were activities aimed at supporting clinic staff to be able to stay engaged with tuberculosis-related work, even as they continued to respond to COVID-19. But when it became clear that even with these interventions, both tuberculosis and DR-TB were still not being diagnosed at pre-COVID-19 levels, the partners utilised their existing community-based networks to shore up DR-TB outreach activities focused on households.
The joint programme aimed to provide diagnostic, treatment and preventive services for DR-TB within the households of persons newly diagnosed with the disease. As part of this package of services, people newly diagnosed with DR-TB were offered clinic- or phone-based counselling and support to disclose their DR-TB status to members of their household. Permission was sought from the newly diagnosed individual to arrange for a visit in the household so that screening and diagnostic activities for people living together could take place. Most people newly diagnosed with DR-TB agreed, and the health teams—usually, at first, a single nurse who could then also request additional support from lay counsellors, community health workers, and a physician, if needed—then arranged to visit homes at a date and time convenient for the family. Doing household visits reduced clinic travel costs for families, allowed for assessment of psychosocial and economic vulnerability, and contributed to building trust between the health-care team and the households.
Activities conducted during the household visit focused on children, adolescents, and vulnerable adults and included: 1) documenting all persons aged 18 years and younger residing in the household both at the time of the visit and in the month preceding the diagnosis; 2) counselling aimed at stigma reduction, tuberculosis education, and support through the diagnosis and treatment processes; 3) weighing all family members to assess for possible weight loss ( adolescents and adults) or changes in growth trajectories ( children); 4) performing a basic physical examination; 5) offering HIV counselling and testing for willing family members; 6) screening for tuberculosis symptoms ( including cough, fever, weight loss, night sweats, lethargy, or reduced playfulness in children); 7) facilitating planned referral for persons with possible tuberculosis to clinics as needed for a full medical assessment and chest radiography; 8) collecting sputum or stool samples for tuberculosis testing among those with symptoms; 9) coordinating follow up and providing results; and 10) initiating preventive therapy for DR-TB among those who qualify for such treatment and in whom active DR-TB had been ruled out.
Although formal analyses are ongoing, the programme has been perceived as a success overall. Almost 300 individuals have been reached through these family-focused activities since the community household programme became fully operational in September, 2020. Those who have benefited the most in terms of improved diagnosis appear to have been children. In the years before the COVID-19 pandemic, paediatric DR-TB represented less than 5% of the overall DR-TB burden in Khayelitsha, with fewer than 10 children diagnosed each year. Since full implementation of the community-based, family-focused programme, however, 33 children have been diagnosed and started on treatment, representing almost 15% of those treated for DR-TB in Khayelitsha. This is a notable achievement at a time when in almost all other settings and populations, DR-TB diagnoses and treatment initiations have gone down. Almost all of these paediatric patients had non-severe disease and a majority have been able to be fully treated in the community ( through a combination of home and primary care clinic visits) with child-friendly approaches, including paediatric formulations of medications.
Improvement of paediatric DR-TB diagnosis has been a significant achievement for the family-centred programme in Khayelitsha; an equally important aspect of the work has been the ability to care for children with DR-TB in their homes and communities. Although South Africa has been a global leader in the decentralisation of many types of care for DR-TB, the treatment of children has been stubbornly entrenched in a only few tertiary facilities around the country. Such highly centralised care for children often means they are kept away from their families, schools, and support systems for prolonged periods of time, which can have major negative psychological and social consequences. In Khayelitsha, the care of children with DR-TB was done largely by primary care physicians and nurses, who could be supported remotely by experts when needed. A multidisciplinary team led by an MSF social worker also helped address the other health and social needs the children and their families faced during these trying times.
Although the absolute numbers of children diagnosed and treated is small and the programme has encountered barriers—including the availability of vehicles and fuel to transport staff as well as adapting best practices to protect staff and families from COVID-19 transmission while out in the community—it is one model of how partnerships between government services and a non-governmental organisation can be utilised to enhance tuberculosis recovery efforts, especially for populations at high risk. It also illustrates the value of moving tuberculosis diagnosis, prevention, treatment, and support efforts away from facilities and into the community. The experience also revealed ways in which the health-care system needs to be fortified—through investment in continuing education and support for staff at all levels, enhanced planning for service provision, and adequate supply chain and logistic mechanisms to protect health-care workers—to continue providing those services that must still be delivered in health-care facilities.
Although there were some initial concerns that people living with DR-TB would be reluctant to be visited in their homes, most of the people living with DR-TB who participated in this project were enthusiastic about these efforts. As Esihle reported, “ When I started to cough too, we were all so scared. We thought it was COVID, but when I finally went to see the doctor a few months later, we found out that I actually had DR-TB. The counsellors asked if they could come to our home and talk to my family, and I said they could, even though I was ashamed for them to see the way we were living. But the nurses and counsellors who came to our home—we owe them our lives. They found out that three of the children also had DR-TB and were able to start them on treatment too. And they helped get my brother to the hospital. I don't know what would have happened if they had not come. ”
JF has received grant funding from the Stop TB Partnership's Global Drug Facility to support the roll-out of paediatric formulations of second-line medications for the treatment of DR-TB. All other authors declare no competing interests.
The ongoing battle to address respiratory health in people experiencing homelessnessSpurred into action by the COVID-19 pandemic, the British government tried something completely new. It made a serious effort to tackle homelessness. Local authorities in England were instructed to get people experiencing homelessness off the streets, out of communal shelters and into safe, single-room accommodation. Hotel rooms, bed and breakfasts, and student halls were booked en masse. Landlords were prevented from evicting tenants and welfare payments were increased. Full-Text PDF Why has the incidence of tuberculosis not reduced in London during the COVID-19 pandemic? The rate of tuberculosis in London, UK, has not reduced during the COVID-19 pandemic. This might be surprising given that tuberculosis is airborne, and suggests important lessons about the transmission and treatment of the disease. Full-Text PDF | tech |
Reimagining the status quo: How close are we to rapid sputum-free tuberculosis diagnostics for all? | Rapid, accurate, sputum-free tests for tuberculosis ( TB) triage and confirmation are urgently needed to close the widening diagnostic gap. We summarise key technologies and review programmatic, systems, and resource issues that could affect the impact of diagnostics. Mid-to-early-stage technologies like artificial intelligence-based automated digital chest X-radiography and capillary blood point-of-care assays are particularly promising. Pitfalls in the diagnostic pipeline, included a lack of community-based tools. We outline how these technologies may complement one another within the context of the TB care cascade, help overturn current paradigms ( eg, reducing syndromic triage reliance, permitting subclinical TB to be diagnosed), and expand options for extra-pulmonary TB. We review challenges such as the difficulty of detecting paucibacillary TB and the limitations of current reference standards, and discuss how researchers and developers can better design and evaluate assays to optimise programmatic uptake. Finally, we outline how leveraging the urgency and innovation applied to COVID-19 is critical to improving TB patients’ diagnostic quality-of-care.
Rapid, accurate, sputum-free tests for tuberculosis ( TB) triage and confirmation are urgently needed to close the widening diagnostic gap. We summarise key technologies and review programmatic, systems, and resource issues that could affect the impact of diagnostics. Mid-to-early-stage technologies like artificial intelligence-based automated digital chest X-radiography and capillary blood point-of-care assays are particularly promising. Pitfalls in the diagnostic pipeline, included a lack of community-based tools. We outline how these technologies may complement one another within the context of the TB care cascade, help overturn current paradigms ( eg, reducing syndromic triage reliance, permitting subclinical TB to be diagnosed), and expand options for extra-pulmonary TB. We review challenges such as the difficulty of detecting paucibacillary TB and the limitations of current reference standards, and discuss how researchers and developers can better design and evaluate assays to optimise programmatic uptake. Finally, we outline how leveraging the urgency and innovation applied to COVID-19 is critical to improving TB patients’ diagnostic quality-of-care.
Tuberculosis ( TB) remains a leading cause of death worldwide.1World Health Organization. Global Tuberculosis Report 2021. Geneva, Switzerland.Google Scholar TB care, which already existed in fragile and overextended healthcare systems, has been negatively impacted by the diversion of human resources and laboratory capacity for COVID-19, resulting in the number of specimens submitted for TB diagnosis plummeting from 7.1 million in 2019 to 5.8 million in 2020.2World Health Organization. Tuberculosis deaths rise for the first time in more than a decade due to the COVID-19 pandemic. https: //www.who.int/news/item/14-10-2021-tuberculosis-deaths-rise-for-the-first-time-in-more-than-a-decade-due-to-the-covid-19-pandemic. 20212021).Google Scholar 41% of the 10 million people estimated to develop TB globally each year remain undiagnosed, and TB deaths have risen for the first time in a decade.1World Health Organization. Global Tuberculosis Report 2021. Geneva, Switzerland.Google Scholar Yet COVID-19 has also demonstrated that large-scale investments ( orders of magnitude higher than that seen for TB) could facilitate rapid diagnostic technology development, including the use of novel specimen types at point-of-care ( POC). A similar approach for TB could yield major innovative advances.3Ruhwald M Carmona S Pai M. Learning from COVID-19 to reimagine tuberculosis diagnosis.Lancet Microbe. 2021; 2: e169-e270Google Scholar
Even before COVID-19, patients evaluated for TB often experienced long delays exacerbated by circuitous pathways to care with many missed opportunities for diagnosis. The quality of TB symptom screening is often poor and primary care facilities do not often have access to tests, requiring patients to travel elsewhere.4Hanson C Osberg M Brown J Durham G Chin DP. Finding the Missing Patients With Tuberculosis: Lessons Learned From Patient-Pathway Analyses in 5 Countries.J Infect Dis. 2017; 216: S686-SS95Google Scholar These individuals, often already attending decentralized health facilities, collectively represent an obvious first step in closing the diagnostic gap. Importantly, however, many people with TB never enter health facilities and will require identification in communities; which is often diagnostically challenging due to early-stage disease and lower pre-test probabilities, which mean tests require very high sensitivities, and specificities are a major determinant of cost efficacy. Technologies first need to demonstrate good performance and feasibility in local health facilities before they can be considered for community-based active case finding ( conditions are less challenging in facilities than in communities and people with TB presenting to facilities are easier to diagnose due to increased pre-test probability). Having good performance near POC in facilities is a key criterion prior to exploring community suitability.
Closing the diagnostic gap is not just a technological challenge: it also requires ensuring that high-quality and modern tests are available, in a manner that enables patients to be promptly linked to care. New technologies should be implementable at point-of-care by health care workers with minimal training, with results available in a single patient encounter.5Garcia-Basteiro AL DiNardo A Saavedra B et al.Point of care diagnostics for tuberculosis.Pulmonology. 2018; 24: 73-85Google Scholar Yet, despite the advent of World Health Organization ( WHO) -recommended rapid molecular tests ( mWRDs) such as Xpert MTB/RIF Ultra ( Ultra) ( Cepheid, Sunnyvale, USA) and Truenat MTB/RIF ( Molbio Diagnostics, Verna, India), much of the world still relies on sputum smear microscopy ( developed in the 1880s) as the initial and often only diagnostic test6Cazabon D Pande T Kik S et al.Market penetration of Xpert MTB/RIF in high tuberculosis burden countries: A trend analysis from 2014 - 2016.Gates Open Res. 2018; 2: 35Google Scholar despite poor sensitivity. The cost and infrastructure requirements of mWRDs remain prohibitive to scale-up and even when mWRDs are available, capacity is often not efficiently utilised or is misaligned.7Brown S Leavy JE Jancey J. Implementation of GeneXpert for TB testing in low-and middle-income countries: A systematic review.Global Health: Science and Practice. 2021; 9: 698-710Google Scholar,8Nalugwa T Shete PB Nantale M et al.Challenges with scale-up of GeneXpert MTB/RIF® in Uganda: a health systems perspective.BMC health services research. 2020; 20: 1-7Google Scholar Furthermore, the use of mWRDs is typically limited to sputum-based testing. Cascade of care studies, although setting-specific, indicate that approximately 15% of patients diagnosed with TB are lost-to-follow-up and do not initiate treatment.4Hanson C Osberg M Brown J Durham G Chin DP. Finding the Missing Patients With Tuberculosis: Lessons Learned From Patient-Pathway Analyses in 5 Countries.J Infect Dis. 2017; 216: S686-SS95Google Scholar,9Subbaraman R NR Satyanarayana S Pai M Thomas BE Chadha VK Rade K Swaminathan S Mayer KH The Tuberculosis Cascade of Care in India's Public Sector: A Systematic Review and Meta-Analysis.PLoS Med. 2016; 13 ( PMID: 27780217) e1002149Google Scholar,10Naidoo P Theron G Rangaka MX et al.The South African Tuberculosis Care Cascade: Estimated Losses and Methodological Challenges.J Infect Dis. 2017; 216: S702-S713Google Scholar Together, this picture shows the urgent need for decentralised testing for TB, so that the majority of patients can be tested and start treatment in one visit ( ideally irrespective of their reason for initial presentation to a facility). Such tests should be sputum-free, as high-risk groups, such as people living with HIV ( PLHIV) 11Peter JG Theron G Singh N Singh A Dheda K. Sputum induction to aid the diagnosis of smear-negative or sputum-scarce TB in adults from a HIV-endemic setting.European Respiratory Journal. 2013; Google Scholar and children12Drain PK Gardiner J Hannah H et al.Guidance for Studies Evaluating the Accuracy of Biomarker-Based Nonsputum Tests to Diagnose Tuberculosis.J Infect Dis. 2019; 220: S108-S115Google Scholar can often not naturally expectorate sputum and are at higher risk of extra-pulmonary TB.
Critically, there is growing recognition of the high proportion of cases identified in prevalence surveys who are a- or pre-symptomatic ( presumed subclinical TB) 13Frascella B Richards AS Sossen B et al.Subclinical tuberculosis disease - a review and analysis of prevalence surveys to inform definitions, burden, associations and screening methodology.Clin Infect Dis. 2020; Google Scholar, underscoring how large numbers will be missed by current symptom screening approaches.14Richards AS SB Emery JC Horton KC Heinsohn T Frascella B Balzarini F Oradini-Alacreu A Hacker B Odone A McCreesh N Grant AD Kranzer K Cobelens F Esmail H Houben RMJH The natural history of TB disease-a synthesis of data to quantify progression and regression across the spectrum.medRxiv. 2021; https: //doiorg/101101/2021091321263499Google Scholar,15Stuck L van Haaster AC Kapata-Chanda P Klinkenberg E Kapata N Cobelens F. How'subclinical ' is subclinical tuberculosis? An analysis of national prevalence survey data from Zambia.Clin Infect Dis. 2022; Google Scholar Furthermore, since patients who screen positive but have early disease may not expectorate sputum, sputum confirmatory testing may not be possible. Earlier diagnosis in such people with minimal symptoms can, on an individual-level, prevent disease progression, subsequent morbidity and mortality and, on a population-level, reduce as much as 50% of transmission ( importantly, community testing can enable earlier diagnoses than facility testing, resulting in even greater benefits).16Emery JC, et al. Estimating the contribution of sub-clinical TB disease to transmission. Union Conference on Lung Health, October 2021 ( virtual).Google Scholar Moreover, as for COVID-19, such tests can also play a critical public health role if they have the capacity to identify which patients are infectious ( eg, via Mycobacterium tuberculosis ( Mtb) measurement in aerosol) and for how long infectiousness lasts. This reinforces the urgent need for rapid, accurate, non-invasive, and sputum-free tests for triage and confirmatory diagnosis, which have been identified by the WHO as priorities for new TB diagnostics, with the Target Product Profiles ( TPP) developed in 2014.17Kik SV Denkinger CM Casenghi M Vadnais C Pai M. Tuberculosis diagnostics: which target product profiles should be prioritised?.The European respiratory journal. 2014; 44: 537-540Google Scholar
Tests and technologies that have undergone ( or are undergoing) external validation, commercial development, assessment in large-scale multi-centre field evaluations, or which are judged to show high potential for TB triage, diagnosis, or the assessment of infectiousness, are prioritised for inclusion in the review. Our review is not exhaustive nor a review of biomarkers, in-house assays, centralised platforms for reference laboratories, tests to diagnose infection or drug-resistance, or the optimal way to do important community active case finding ( high-quality reviews on these topics exist).18MacLean E Broger T Yerlikaya S Fernandez-Carballo BL Pai M Denkinger CMJNm A systematic review of biomarkers to detect active tuberculosis. 2019; 4: 748-758Google Scholar, 19Nguyen TNA Berre A-L Bañuls A-L Nguyen TVA. Molecular diagnosis of drug-resistant tuberculosis; a literature review.Frontiers in microbiology. 2019; 10: 794Google Scholar, 20Wei Z Zhang X Wei C et al.Diagnostic accuracy of in-house real-time PCR assay for Mycobacterium tuberculosis: a systematic review and meta-analysis.BMC infectious diseases. 2019; 19: 1-11Google Scholar, 21Hamada Y Cirillo DM Matteelli A Penn-Nicholson A Rangaka MX Ruhwald M. Tests for tuberculosis infection: landscape analysis.European Respiratory Journal. 2021; Google Scholar, 22Kohli M MacLean E Pai M Schumacher SG Denkinger CM. Diagnostic accuracy of centralised assays for TB detection and detection of resistance to rifampicin and isoniazid: a systematic review and meta-analysis.European Respiratory Journal. 2021; 57Google Scholar, 23Burke RM Nliwasa M Feasey HRA et al.Community-based active case-finding interventions for tuberculosis: a systematic review.Lancet Public Health. 2021; 6: e283-e299Google Scholar Rather, we focus on sputum-free diagnostic technologies and tests with demonstrated potential for decentralised deployment, ideally at the point-of-care at the peripheral health system level ( including rural settings) to facilitate prompt clinical decision making for all forms of active TB.
Figure 1 illustrates the role of triage ( which includes patients with symptoms or risk factors as well as screening of unselected populations) and confirmatory tests in a typical population of people who may have TB and move from community to clinic and hospital settings for diagnosis, the types of non-sputum specimens tested by some novel technologies under development, and a selection of these technologies, their developmental stage, likely positioning within the health system, and where gaps in the pipeline exist. Briefly, several non-invasive and easily accessible specimens hold promise as triage and confirmatory tests, however, artificial intelligence ( AI) -based digital chest X-ray ( dCXR) is the only design-locked triage test suitable for primary care ( design-locked refers to tests where manufacturers have fixed the individual subcomponents of the assay and the core of the technology should not change).24Engel N Wolffs PFG. Aligning diagnostics to the point-of-care: lessons for innovators, evaluators and decision-makers from tuberculosis and HIV.BMJ Glob Health. 2020; 5Google Scholar Table 1 lists various current and upcoming technologies, including their underlying mechanisms and principles, alignment with TPP criteria, commercial or in-development examples, diagnostic accuracy, pros and cons, and open questions. This table is summarized below, organised from, potentially, the least to most invasive specimens.Figure 1Approaches to diagnosing TB. ( a) An overview of a typical facility-based TB diagnostic algorithm. People in a community ( without risk factors for TB, white; with symptoms or risk factors for TB, grey; with TB, red) attend a health facility. After screening, all at-risk individuals are ideally identified and receive a triage test ( note in some very high burden settings, all clinical attendees may be considered at risk; the definition of at-risk is setting-specific), which is done to exclude unnecessary confirmatory testing. Patients who triage positive then receive typically expensive ( yet critical) confirmatory testing, which is used to inform treatment. Importantly, screening ( and potentially testing) could occur in the community, however, this is not shown as most new technologies need to first demonstrate potential in facilities. ( b) Some of the novel materials under investigation for triage or confirmation are shown ( some applicable to both use cases), and ( c) a selection of products and technologies that use these materials, their developmental stage ( if known to be under commercialisation), and potential health system-level of deployment. Notably, there are insufficient late-stage and design-locked triage tests, as well as early and design-locked confirmatory tests useful for facility-based point-of-care testing ( this deficit is even more serious for community-based testing, which is diagnostically and operationally more challenging). Abbreviations: AI: artificial intelligence, dCXR: digital chest X-ray.View Large Image Figure ViewerDownload Hi-res image Download ( PPT)
Tables 1a and 1bTable 1aCurrent and upcoming non-invasive specimen-based technologies for the rapid non-sputum-based diagnosis of TB. Technologies are listed by specimen and biomarker type ( least to most invasive). Examples with best available sensitivity and specificity estimates ( as well as the likely WHO target product profiles tests use case) are listed, together with known limitations. Strengths and challenges for POC deployment in high burden settings as well as open questions and considerations for researchers and implementers are discussed. Rankings of the technological level of maturity and level of confidence of available performance estimates are given.SpecimenBiomarkerPrinciple and mechanismLikely TPP for active TBSelect studies and assays≥5 years away from potential implementation, 2-5 years, ≤2 years, unclearLevel of confidence, and accuracy estimatesLow, medium, high, unclearStrengths and challenges of technology classOpen questions and key considerationsBreath and aerosolBacterial or human metabolites or antigensCompounds like volatile organics or Mtb antigens are expelled in patient aerosol and may indicate TB-associated lung inflammation and disease. Such compounds are detectable using electronic noses.TriageAeonose ( eNose) 32Nakhleh MK Jeries R Binder A et al.Detecting active pulmonary tuberculosis with a breath test using nanomaterial-based sensors.European Respiratory Journal. 2014; 43: 1522-1525Google Scholar- Sufficient data exists to generate pooled sensitivity ( 92%) and specificity ( 93%) estimates33Saktiawati AM Putera DD Setyawan A Mahendradhata Y van der Werf TS. Diagnosis of tuberculosis through breath test: a systematic review.EBioMedicine. 2019; 46: 202-214Google Scholar for this technology class but individual products are not extensively evaluated.- Aeonose, a volatile organic compound test, has shown the most promise: in a large South African cohort of presumptive TB patients it had 90% sensitivity and 59% specificity at a rule-out threshold98Esmail A, Dheda, K, Dhansay, M. TBScience conference. An exhaled-breath screening test for the detection of active pulmonary tuberculosis in patients presenting to primary health care clinics in Cape Town, South Africa. https: //www.enose.nl/clinical-results/tuberculosis/. 2021).Google Scholar- Potentially implementable at scale by non-technical personnel- Biological ( e.g., smoking) and environmental ( e.g., pollution) factors can confound readouts33Saktiawati AM Putera DD Setyawan A Mahendradhata Y van der Werf TS. Diagnosis of tuberculosis through breath test: a systematic review.EBioMedicine. 2019; 46: 202-214Google Scholar- Hardware is expensive and not yet capable of providing real-time results- Lack of independent validation data, which would be facilitated by large public data sets for discovery and training of electronic nose algorithms- Detection of some products ( metabolites) must be closely timed with collection due to degradation34Mochalski P King J Unterkofler K Amann A. Stability of selected volatile breath constituents in Tedlar, Kynar and Flexfilm sampling bags.Analyst. 2013; 138: 1405-1418Google Scholar- These technologies have diagnostic promise in people who can not expectorate sputum, but little data exists- Could directly diagnose infectiousness, creating a new use test case37Williams CM Abdulwhhab M Birring SS et al.Exhaled Mycobacterium tuberculosis output and detection of subclinical disease by face-mask sampling: prospective observational studies.The Lancet Infectious Diseases. 2020; 20: 607-617Google Scholar,99Bunyasi EW Middelkoop K Koch A et al.Molecular Detection of Airborne Mycobacterium tuberculosis in South African High Schools.American Journal of Respiratory and Critical Care Medicine. 2021; Google Scholar ( distinct from diagnosis) to identify potential transmission hotspots or “ super-spreading ” individuals for targeted case finding ( pooled aerosol from a congregate setting could also be tested) TB Breathalyser ( Rapid Biosensor Systems) 100Rapid Biosensor Systems. TB Breathalyser - TB Breath Test. http: //www.rapidbiosensor.com/tbbreathalyser. 2021).Google ScholarMtb DNATransmission occurs when Mtb is exhaled in aerosols, and detection could diagnose infectious TB.ConfirmatoryFace masks with filters or absorbent materials capture bacteria. This is a collection method and different assays could be applied.Blow tubes with filters are an alternate capture method.- Promising but too early to tell- One study found a sensitivity of 87% when Ultra was applied to face masks worn by pulmonary TB cases37Williams CM Abdulwhhab M Birring SS et al.Exhaled Mycobacterium tuberculosis output and detection of subclinical disease by face-mask sampling: prospective observational studies.The Lancet Infectious Diseases. 2020; 20: 607-617Google Scholar- Sampling over long periods possible to improve yield- Specimen processing likely simpler than for sputum- Potential to detect early disease37Williams CM Abdulwhhab M Birring SS et al.Exhaled Mycobacterium tuberculosis output and detection of subclinical disease by face-mask sampling: prospective observational studies.The Lancet Infectious Diseases. 2020; 20: 607-617Google Scholar- Collection matrices require optimisation and standardisation- No performance data for assays other than Ultra like Truenat ( Molbio) Tongue swabsMtb DNATongue papillae filter and concentrate biomass from respiratory secretions, permitting formation of Mtb-containing biofilms.TriageCollection method and not a test itself- Studies are few and heterogenous, no pooled performance estimates exist- Ultra applied to a single swab had a sensitivity of 88% in outpatients41Wood RC Andama A Hermansky G et al.Characterization of oral swab samples for diagnosis of pulmonary tuberculosis.PloS one. 2021; 16e0251422Google Scholar but only 43% sensitivity when used for active case finding in a prison40Lima F Santos AS Oliveira RD et al.Oral swab testing by Xpert® MTB/RIF Ultra for mass tuberculosis screening in prisons.Journal of clinical tuberculosis and other mycobacterial diseases. 2020; 19100148Google Scholar- TB-LAMP42Song Y Ma Y Liu R et al.Diagnostic Yield of Oral Swab Testing by TB-LAMP for Diagnosis of Pulmonary Tuberculosis.Infection and Drug Resistance. 2021; 14: 89Google Scholar applied to oral swabs had sensitivities ranging from 33-50% - FLOQSwabs ( Copan Italia) preferred41Wood RC Andama A Hermansky G et al.Characterization of oral swab samples for diagnosis of pulmonary tuberculosis.PloS one. 2021; 16e0251422Google Scholar- Self-swabbing, comparable to health worker-administered swabs for other pathogens44Tu Y-P Jennings R Hart B et al.Swabs collected by patients or health care workers for SARS-CoV-2 testing.New England Journal of Medicine. 2020; 383: 494-496Google Scholar, appears feasible- Potential for paediatric TB43Nicol MP Wood RC Workman L et al.Microbiological diagnosis of pulmonary tuberculosis in children by oral swab polymerase chain reaction.Scientific reports. 2019; 9: 1-5Google Scholar- Insufficient Mtb may be recovered from swabs in patients with low sputum bacillary load40Lima F Santos AS Oliveira RD et al.Oral swab testing by Xpert® MTB/RIF Ultra for mass tuberculosis screening in prisons.Journal of clinical tuberculosis and other mycobacterial diseases. 2020; 19100148Google Scholar- Performance of novel assays ( e.g., next-generation LAM and NAATs unknown) may overcome sensitivity limitations associated- Optimal number of swabs, swab design, and the processing method are under evaluation and may improve the release of material from swabs-No tests purpose-built for tongue swabs yet existBloodHost transcriptomemRNA blood signatures associated with the immune system's response to Mtb have shown promise for diagnosis.68Gupta RK, Turner CT, Venturini C, et al. Concise whole blood transcriptional signatures for incipient tuberculosis: a systematic review and patient-level pooled meta-analysis. 2020.Google ScholarTriageXpert Host Response ( Cepheid) - A multicentre study showed 90% sensitivity and 86% specificity64Sutherland JS van der Spuy G Gindeh A et al.Diagnostic accuracy of the Cepheid 3-gene host response fingerstick blood test in a prospective, multi-site study: interim results.Clinical Infectious Diseases. 2021; Google Scholar-Other studies have shown lower specificities ( 26% 101Södersten E Ongarello S Mantsoki A et al.Diagnostic Accuracy Study of a Novel Blood-Based Assay for Identification of Tuberculosis in People Living with HIV.Journal of clinical microbiology. 2021; 59 ( e01643-20) Google Scholar, 53% 102Moreira FMF Verma R Dos Santos PCP et al.Blood-based host biomarker diagnostics in active case finding for pulmonary tuberculosis: A diagnostic case-control study.EClinicalMedicine. 2021; 33100776Google Scholar) at > 90% sensitivity- Limited data with small numbers of cases, however, multicentre studies are emerging- Xpert HR has the most data available- RNA is labile and, for Xpert HR, time from blood collection to testing must be < 30 min and stabilisation agents may be required- Cost unclear, but likely high- Potential utility treatment response monitoring, management of diseases other than TB ( signature-positive patients without TB could have other infections95Mulenga H Musvosvi M Mendelsohn SC et al.Longitudinal Dynamics of a Blood Transcriptomic Signature of Tuberculosis.American Journal of Respiratory and Critical Care Medicine. 2021; ( ja) Google Scholar), and false-positive TB PCR results65Turner CT, Gupta RK, Tsaliki E, et al. Blood transcriptional biomarkers for active pulmonary tuberculosis in a high-burden setting: a prospective, observational, diagnostic accuracy study. 2020.Google Scholar, which are frequent in people with previous TB68Gupta RK, Turner CT, Venturini C, et al. Concise whole blood transcriptional signatures for incipient tuberculosis: a systematic review and patient-level pooled meta-analysis. 2020.Google Scholar,84Mishra H Reeve BWP Palmer Z et al.Xpert MTB/RIF Ultra and Xpert MTB/RIF for diagnosis of tuberculosis in an HIV-endemic setting with a high burden of previous tuberculosis: a two-cohort diagnostic accuracy study.Lancet Respir Med. 2020; 8: 368-382Google Scholar,103Theron G Venter R Smith L et al.False positive Xpert MTB/RIF results in re-tested patients with previous tuberculosis: frequency, profile, and prospective clinical outcomes.Journal of clinical microbiology. 2018; ( JCM. 01696-17) Google Scholar- Signatures ( including Sweeney3 in Xpert HR) measured using ultra-sensitive methods ( sequencing, Nanostring) 68Gupta RK, Turner CT, Venturini C, et al. Concise whole blood transcriptional signatures for incipient tuberculosis: a systematic review and patient-level pooled meta-analysis. 2020.Google Scholar struggle to meet WHO TPPs65Turner CT, Gupta RK, Tsaliki E, et al. Blood transcriptional biomarkers for active pulmonary tuberculosis in a high-burden setting: a prospective, observational, diagnostic accuracy study. 2020.Google Scholar,66Hoang LT Jain P Pillay TD et al.Transcriptomic signatures for diagnosing tuberculosis in clinical practice: a prospective, multicentre cohort study.The Lancet Infectious Diseases. 2021; 21: 366-375Google Scholar, suggesting a performance ceiling for tests based on these signatures- Signatures insufficiently tested in PLHIV, EPTB, children, contacts, and for subclinical disease, nor head-to-head with cheap markers like CRP- Optimal placement in algorithms remains unclearRISK6 signature ( QuantumDx) - No product-specific data, but signature performance measured by real-time PCR is 91% sensitivity and 56% specificity ( increasing to 75% in patients without previous TB) 67Penn-Nicholson A Mbandi SK Thompson E et al.RISK6, a 6-gene transcriptomic signature of TB disease risk, diagnosis and treatment response. 2020; 10: 1-21Google ScholarcfDNAExtracellular Mtb DNA fragments can be detected in accessible body fluids like bloodConfirmatoryNo prototypes with public data- A systematic review and meta-analysis of different cfDNA in-house assays found a sensitivity and specificity of 78% and 97% respectively but large heterogeneity noted62Yu G Shen Y Ye B Shi Y. Diagnostic accuracy of Mycobacterium tuberculosis cell-free DNA for tuberculosis: A systematic review and meta-analysis.PLOS ONE. 2021; 16e0253658Google Scholar- Technical collection parameters influence performance81Murugesan K Hogan CA Palmer Z et al.Investigation of preanalytical variables impacting pathogen cell-free DNA in blood and urine.Journal of clinical microbiology. 2019; 57 ( e00782-19) Google Scholar- Tests on plasma appear to perform better than on other fluids61Oreskovic A Panpradist N Marangu D et al.Diagnosing pulmonary tuberculosis using sequence-specific purification of urine cell-free DNA.Journal of Clinical Microbiology. 2021; ( JCM. 00074-21) Google Scholar,81Murugesan K Hogan CA Palmer Z et al.Investigation of preanalytical variables impacting pathogen cell-free DNA in blood and urine.Journal of clinical microbiology. 2019; 57 ( e00782-19) Google Scholar- Still at proof-of-concept stage- Collection and detection approaches unstandardised- Product pipeline uncertainHost markersMarkers of inflammation made in response to disease may assist in screening and triage.TriageCRP ( near-POC instruments like the iChroma platform ( Boditech)) and other instrument-free rapid diagnostic tests are commercially-available) - Robust meta-analysis data show sensitivity and specificity of 77% and 74% in PLHIV104Dhana A Hamada Y Kengne AP et al.Tuberculosis screening among ambulatory people living with HIV: a systematic review and individual participant data meta-analysis.Lancet Infect Dis. 2021; Google Scholar.-At > 90% sensitivity ( 10 mg/L threshold), specificities of 62% and 43% have been reported in HIV-negative and -positive patients, respectively75Calderwood CJ Reeve BW Mann T et al.C-reactive protein as a triage tool for adults with presumptive pulmonary tuberculosis in South Africa: a prospective cohort study.medRxiv. 2021; Google Scholar- CRP outperforms WHO 4-symptom based screening in PLHIV104Dhana A Hamada Y Kengne AP et al.Tuberculosis screening among ambulatory people living with HIV: a systematic review and individual participant data meta-analysis.Lancet Infect Dis. 2021; Google Scholar- Instrument free CRP tests do not yet exist- More CRP data needed in HIV-negatives and PLHIV ( some studies report large specificity differences by HIV status76Samuels TH Wyss R Ongarello S Moore DA Schumacher SG Denkinger CM. Evaluation of the diagnostic performance of laboratory-based c-reactive protein as a triage test for active pulmonary tuberculosis.PloS one. 2021; 16e0254002Google Scholar) and EPTB- Programmes lack guidance on how to implement CRP-based screening, given recent policy updates48Organization WH. Rapid communication on systematic screening for tuberculosis. 2020.Google Scholar- CRP should be included as a comparator for all biomarker studiesAntigens, cytokines, and antibodiesAltered molecular signatures are detectable in bloodTriageMBT assay- A LFA five marker prototype had 94% sensitivity and 96% specificity72Corstjens P Hooij AV Tjon Kon Fat E et al.OC 8435 Multi-biomarker test strip for point-of-care screening for active tuberculosis: a five-country multi-centre test evaluation.BMJ Global Health. 2019; 4 ( A6-A) Google Scholar- High POC potential-Regional differences in performance may make it difficult to derive standardised panels for global use- Potential utility on saliva105Jacobs R Tshehla E Malherbe S et al.Host biomarkers detected in saliva show promise as markers for the diagnosis of pulmonary tuberculosis disease and monitoring of the response to tuberculosis treatment.Cytokine. 2016; 81: 50-56Google Scholar, for progression to incident TB106Penn-Nicholson A Hraha T Thompson EG et al.Discovery and validation of a prognostic proteomic signature for tuberculosis progression: a prospective cohort study.PLoS medicine. 2019; 16e1002781Google Scholar and treatment monitoring107Sigal G Segal M Mathew A et al.Biomarkers of tuberculosis severity and treatment effect: a directed screen of 70 host markers in a randomized clinical trial.EBioMedicine. 2017; 25: 112-121Google Scholar- Signatures should be concise ( max. three targets) to improve POC feasibility- Other than CRP, all tests are prototypes- Most assays have sensitivity limitations and require independent validation, especially in high burden, HIV-endemic settings ( trials underway108Rapid Research in Diagnostics Development for TB Network ( R2D2TB Network). https: //clinicaltrials.gov/ct2/show/NCT04923958.Google Scholar, 109Evaluation of a Rapid Point-of-Care Serological Triage Test for Active TB ( SeroSelectTB). https: //clinicaltrials.gov/ct2/show/NCT04752592.Google Scholar, 110Evaluation of Host Biomarker-based Point-of-care Tests for Targeted Screening for Active TB ( ScreenTB). https: //clinicaltrials.gov/ct2/show/NCT03350048? term=walzl & cond=tuberculosis & draw=2 & rank=1.Google Scholar, 111Point-of-care Triage Test for Active Tuberculosis ( TriageTB). https: //clinicaltrials.gov/ct2/show/NCT04232618? term=walzl & cond=tuberculosis & draw=2 & rank=2.Google Scholar) - Stakeholders should plan how a TPP-compliant test could be implementedSeroSelectTB- A LFA protype had 84% sensitivity and 97% specificity73Borain N Petersen L Du Plessis J Theron G Holm-Hansen C. A rapid serological triage test for detecting active tuberculosis.BMJ Global Health. 2017; 2Google ScholarSimoa array panel- 86% sensitivity and 69% specificity in a multinational global validation cohort74Ahmad R Xie L Pyle M et al.A rapid triage test for active pulmonary tuberculosis in adult patients with persistent cough.Science translational medicine. 2019; 11Google ScholarMtb peptidesTriage, confirmatoryNanoDisk-MS ( Nanopin) - 88% sensitivity and 96% specificity in a large Chinese cohort79Liu C Lyon CJ Bu Y et al.Clinical evaluation of a blood assay to diagnose paucibacillary tuberculosis via bacterial antigens.Clinical chemistry. 2018; 64: 791-800Google ScholarImmune cell profilingT-cell activation markers can discriminate active disease from other formsConfirmatoryTAM-TB ( Beckman Coulter) - A prospective study with non-TB infected controls showed 82% sensitivity and 93% specificity, which were unaffected by HIV70Hiza H Hella J Arbués A et al.Case–control diagnostic accuracy study of a non-sputum CD38-based TAM-TB test from a single milliliter of blood.Scientific Reports. 2021; 11: 1-9Google Scholar- Demonstrated potential in children69Portevin D Moukambi F Clowes P et al.Assessment of the novel T-cell activation marker–tuberculosis assay for diagnosis of active tuberculosis in children: a prospective proof-of-concept study.The Lancet infectious diseases. 2014; 14: 931-938Google Scholar and treatment response 71Ahmed MI Ntinginya NE Kibiki G et al.Phenotypic changes on Mycobacterium tuberculosis-specific CD4 T cells as surrogate markers for tuberculosis treatment efficacy.Frontiers in immunology. 2018; 9: 2247Google Scholar- Hardware ( and expertise) not POC amenable and may need laboratories- Validations required- Hardware requires simplification- Related methods that detect Mtb in immune cells require investigation80Belay M Tulu B Younis S et al.Detection of Mycobacterium tuberculosis complex DNA in CD34-positive peripheral blood mononuclear cells of asymptomatic tuberculosis contacts: an observational study.The Lancet Microbe. 2021; 2: e267-e275Google ScholarStoolMtb DNASwallowed or disseminated Mtb may be detectable in stoolConfirmatoryUltra- A Tanzanian study in presumptive TB patients found sensitivity to range from 63-84% and specificity from 76-93% depending of the type of laboratory45Ngadaya E Kimaro G Sandi E et al.Evaluation of stool GeneXpert MTB/RIF for the diagnosis of pulmonary tuberculosis among presumptive patients in Tanzania.Journal of Clinical Tuberculosis and Other Mycobacterial Diseases. 2020; 21100195Google Scholar- A systematic review and meta-analysis of Xpert for paediatric TB found similar performance46MacLean E Sulis G Denkinger CM Johnston JC Pai M Ahmad Khan F Diagnostic accuracy of stool Xpert MTB/RIF for detection of pulmonary tuberculosis in children: a systematic review and meta-analysis.Journal of clinical microbiology. 2019; 57 ( e02057-18) Google Scholar- Evidence to support use in children46MacLean E Sulis G Denkinger CM Johnston JC Pai M Ahmad Khan F Diagnostic accuracy of stool Xpert MTB/RIF for detection of pulmonary tuberculosis in children: a systematic review and meta-analysis.Journal of clinical microbiology. 2019; 57 ( e02057-18) Google Scholar and sputum-scarce TB- Added complexity due to specimen processing requirements- Data in adults ( including PLHIV) scarce- Specimen provision challenging in outpatients, but rectal swabs may have utilityUrineLAMUrine is easy to collect and will have high diagnostic yield. Mtb cellular components ( nucleic acids, complex molecules, or even intact cells) can filter through the kidney barrier. The Mtb cell wall and virulence factor LAM are the most promising urine markers.ConfirmatoryFujiLAM ( FujiFILM) - In a large multicentre head-to-head evaluation in HIV-negative outpatients, sensitivity was 53% and specificity 99% and highly variable between settings57Broger T Nicol MP Sigal GB et al.Diagnostic accuracy of 3 urine lipoarabinomannan tuberculosis assays in HIV-negative outpatients.The Journal of clinical investigation. 2020; 130Google Scholar- Another study in HIV-positive inpatients, sensitivity was 70% and specificity 91% 56Broger T Sossen B du Toit E et al.Novel lipoarabinomannan point-of-care tuberculosis test for people with HIV: a diagnostic accuracy study.The Lancet Infectious Diseases. 2019; 19: 852-861Google Scholar- Utility for EPTB58Kerkhoff AD Sossen B Schutz C et al.Diagnostic sensitivity of SILVAMP TB-LAM ( FujiLAM) point-of-care urine assay for extra-pulmonary tuberculosis in people living with HIV.European Respiratory Journal. 2020; 55Google Scholar- Significant technological development still needed for some assays ( e.g., FLOW-TB, Mologic) compared to Determine TB-LAM ( Alere) and FujiLAM- Sensitivity inversely proportion to the degree of immunosuppression ( e.g., CD4 count), and this should be used to guide roll-out- For cfDNA,61Oreskovic A Panpradist N Marangu D et al.Diagnosing pulmonary tuberculosis using sequence-specific purification of urine cell-free DNA.Journal of Clinical Microbiology. 2021; ( JCM. 00074-21) Google Scholar specialised specimen processing methods may overcome sensitivity limitations to meet TPP criteria but will detract from POC potential- Data in important patient groups like HIV-negatives are lacking- Comparative performance data of different LAM assays is needed ( in one study in HIV-negatives EclLAM, which is laboratory-based, outperformed other LAM tests that were more suitable to POC) 57Broger T Nicol MP Sigal GB et al.Diagnostic accuracy of 3 urine lipoarabinomannan tuberculosis assays in HIV-negative outpatients.The Journal of clinical investigation. 2020; 130Google Scholar- For urine cfDNA, many of the same considerations as for blood apply- Enrichment prior to testing may improve diagnostic yieldFLOW-TB ( Salus Discovery) A second-generation version of the assay had a sensitivity of 86% and specificity 89% in inpatients59Shapiro AE NM Magcaba ZP Boyle D Cantera J Lillis L Mullins B Wittwer T Hannah H Warrick J Berry S Beebe DJ Wilson DPK Drain PK Validation of a laboratory-based reference test for TB-LAM and FLOW-TB, a novel point-of-care TB diagnostic assay, in a high-HIV-prevalence clinical cohort from KwaZulu-Natal, South Africa.in: International AIDS Conference. July 2020Google ScholarTB-LAM ( Biopromic) Unclear ( in development) 60Wood A Barizuddin S Darr CM et al.Ultrasensitive detection of lipoarabinomannan with plasmonic grating biosensors in clinical samples of HIV negative patients with tuberculosis.PloS one. 2019; 14e0214161Google ScholarTB-LAM ( Mologic) Unclear ( in development) 112Bill and Melinda Gates Foundation. Mologic Limited LAM RDT Award. https: //www.gatesfoundation.org/about/committed-grants/2019/03/opp1193635. 2021).Google ScholarcfDNANo prototypes with public dataA proof-of-concept study with an enrichment step had a sensitivity of 84% and specificity 100% 61Oreskovic A Panpradist N Marangu D et al.Diagnosing pulmonary tuberculosis using sequence-specific purification of urine cell-free DNA.Journal of Clinical Microbiology. 2021; ( JCM. 00074-21) Google ScholarAbbreviations: LFA: lateral flow antigen, POC: point of care Open table in a new tab Table 1bCurrent and upcoming non-invasive non-specimen-based digital and/or AI-based technologies for the rapid non-sputum-based diagnosis of TB. Technologies are listed by specimen and biomarker type ( least to most invasive). Examples with best available sensitivity and specificity estimates ( as well as the likely WHO target product profiles tests use case) are listed, together with known limitations. Strengths and challenges for POC deployment in high burden settings as well open questions and considerations for researchers and implementers are discussed. Rankings of the technological level of maturity and level of confidence of available performance estimates are given.SpecimenBiomarkerPrinciple and mechanismLikely TPP for active TBSelect studies and assays≥5 years away from potential implementation, 2-5 years, ≤2 years, unclearLevel of confidence, and accuracy estimatesLow, medium, high, unclearStrengths and challenges of technology classOpen questions and key considerationsAudioCough soundsTB disease distorts lung architecture, affecting chest sounds in a way detectable by portable digital signal processing.25Botha G Theron G Warren R et al.Detection of tuberculosis by automatic cough sound analysis.Physiological measurement. 2018; 39045005Google Scholar,26Becker K Scheffer C Blanckenberg M Diacon A. Analysis of adventitious lung sounds originating from pulmonary tuberculosis.Annu Int Conf IEEE Eng Med Biol Soc. 2013; 2013: 4334-4337Google Scholar Classification technologies are distinct from cough counting, which may have treatment monitoring utility.113Lee GO Comina G Hernandez-Cordova G et al.Cough dynamics in adults receiving tuberculosis treatment.PloS one. 2020; 15e0231167Google ScholarTriage- Only proof-of-concept studies exist25Botha G Theron G Warren R et al.Detection of tuberculosis by automatic cough sound analysis.Physiological measurement. 2018; 39045005Google Scholar- Smartphone applications are undergoing evaluation ( TimBre,114Pathri R. TimBre: acoustic-based non-invasive point of care screening of tuberculosis. SOA-01-1005-31 Union World Congress on Lung Health, 2019Google Scholar Hyfe) 27Hyfe. AI-powered cough counting: an objective and scalable endpoint. https: //uploads-ssl.webflow.com/601331581ba868154325 e525/608957a21c175c2e8f10d7fe WP3-Clinical-EndPoints.pdf.Google Scholar,108Rapid Research in Diagnostics Development for TB Network ( R2D2TB Network). https: //clinicaltrials.gov/ct2/show/NCT04923958.Google Scholar- Promising but too early to tell.- One study with non-TB infected controls obtained a sensitivity of 93% and specificity of 95%.29Pahar M Klopper M Reeve B Warren R Theron G Niesler TR. Automatic cough classification for tuberculosis screening in a real-world environment.Physiological Measurement. 2021; Google Scholar- Able to rapidly screen all facility entrants- Specimen free- Rapidly scalable on mobile phones- Abnormal sounds in the absence of TB could be used to diagnose other respiratory diseases- No external validation data- Early-stage technology- Standardised large-scale data collection and curation required for algorithm development and testing- Performance likely highly setting-specific, especially when other lung diseases are frequent- Potential utility for evaluating post TB lung damageStethoscopes- Stethee28Stethee Pro. https: //www.m3dicine.com/ # fresh air.Google Scholar,108Rapid Research in Diagnostics Development for TB Network ( R2D2TB Network). https: //clinicaltrials.gov/ct2/show/NCT04923958.Google Scholar and others undergoing evaluation- No published studies- UnknownImagingPortable dCXRCXR highly sensitive and increasingly feasible to be near POC due to advances in low-dose portable instruments and automated image reading.TriageSoftware products include: qXR ( QURE.ai Technologies), CAD4TB ( Delft Imaging Systems), and Lunit ( FujiFILM), CAD4Good ( EPCON) ( see AI4HLTH for a complete overview) 30AI4Health Initiative. https: //www.ai4hlth.org/. Accessed Oct 7, 2021.Google Scholar- In a very large evaluation in Bangladesh, qXR and CAD4-TB have the highest specificities ( both 73%) at > 90% sensitivity50Qin ZZ Ahmed S Sarker MS et al.Tuberculosis detection from chest x-rays for triaging in a high tuberculosis-burden setting: an evaluation of five artificial intelligence algorithms.The Lancet Digital Health. 2021; 3: e543-e554Google Scholar- Automated reading systems can overcome radiologist shortages and are WHO-endorsed48Organization WH. Rapid communication on systematic screening for tuberculosis. 2020.Google Scholar- Expensive equipment and infrastructure ( including high-speed internet) required52Digital Chest Radiography and Computer-AidedDetection ( CAD) Solutions for Tuberculosis Diagnostics - Technology Landscape Analysis.FIND. 2021; Google Scholar, however, existing equipment may be retrofitted such that analogue images can be converted to digital ones- Market rapidly evolving and selection of the right solutions challenging- Challenges in identifying which settings for prioritisation, including case finding scenarios where pre-symptomatic TB can be detected115Fehr J Konigorski S Olivier S et al.Computer-aided interpretation of chest radiography reveals the spectrum of tuberculosis in rural South Africa.npj Digital Medicine. 2021; 4: 1-10Google Scholar- Achieving adequate throughput to maximise utility is challenging- Unclear how these technologies will benefit diagnosis of other diseases- Open source social impact programs such as CAD4Good may reduce costs30AI4Health Initiative. https: //www.ai4hlth.org/. Accessed Oct 7, 2021.Google ScholarPOCUSImproving affordability and portability of ultrasound devices has led to interest in the use of POCUS.TriageMany ( most standard point-of-care ultrasound machines can be used) - Systematic review reported sensitivities ranging from 73-100% for subpleural nodules detected and 47-80% for lung consolidation54Bigio J Kohli M Klinton JS et al.Diagnostic accuracy of point-of-care ultrasound for pulmonary tuberculosis: A systematic review.PLoS One. 2021; 16e0251236Google ScholarPotential to expand diagnosis of extrapulmonary TB and increase diagnostic yield in populations such as children or PLHIV- Limited data, currently majority of studies in adults and for pulmonary TB- Effects of operator and machine variability unclear- Optimal imaging protocols unclear Open table in a new tab
The growing interest in AI has opened the possibility of non-invasively detecting cough changes or lung sounds that differentiate people with and without TB, with potential for use as a triage test.25Botha G Theron G Warren R et al.Detection of tuberculosis by automatic cough sound analysis.Physiological measurement. 2018; 39045005Google Scholar,26Becker K Scheffer C Blanckenberg M Diacon A. Analysis of adventitious lung sounds originating from pulmonary tuberculosis.Annu Int Conf IEEE Eng Med Biol Soc. 2013; 2013: 4334-4337Google Scholar This could be done using portable digital recording and signal processing mobile phone enabled applications27Hyfe. AI-powered cough counting: an objective and scalable endpoint. https: //uploads-ssl.webflow.com/601331581ba868154325 e525/608957a21c175c2e8f10d7fe WP3-Clinical-EndPoints.pdf.Google Scholar or digital stethoscopes.28Stethee Pro. https: //www.m3dicine.com/ # fresh air.Google Scholar Such specimen free technologies, could provide a more objective measure of symptoms such as cough, in contrast to subjective and challenging syndromic screening, and are potentially scalable given a theoretical ease-of-use and rapidity of turnaround ( seconds). Nonetheless, these technologies are early stage, with signatures yet to be externally validated and limited clinical data to support use ( one study reported a sensitivity of 93% and specificity of 95% of AI-based cough classification when comparing the coughs of people with and without TB).25Botha G Theron G Warren R et al.Detection of tuberculosis by automatic cough sound analysis.Physiological measurement. 2018; 39045005Google Scholar,29Pahar M Klopper M Reeve B Warren R Theron G Niesler TR. Automatic cough classification for tuberculosis screening in a real-world environment.Physiological Measurement. 2021; Google Scholar Initiatives to assemble large collections of cough audio recordings that can be used to train and test algorithms are needed, similar to what was successfully done for dCXR, where a global image archive from diverse settings and populations was made available to developers.30AI4Health Initiative. https: //www.ai4hlth.org/. Accessed Oct 7, 2021.Google Scholar Performance of audio analyses is likely to be setting-specific and impacted by the prevalence of other lung diseases in the population but, as a new field, acoustic epidemiology31The Hyfe Team. A coustic AI as a scalable tool for diagnostics & monitoring: Hyfe's impact vision. https: //global-uploads.webflow.com/601331581ba868154325e525/604284b73f6cc81c541b7fe6 Hyfe-Vision-Paper-v2.2.pdf. 2021).Google Scholar holds tremendous promise for identifying patients for confirmatory testing, monitoring treatment response, and assessing population-level lung health.
Differences in signatures of volatile organic compounds expelled in breath can be analysed to facilitate detection of pulmonary diseases like TB, most likely as a triage test. Such compounds can be detected using electronic nose devices or captured and concentrated using a collection bag and detected by methods like gas chromatography.32Nakhleh MK Jeries R Binder A et al.Detecting active pulmonary tuberculosis with a breath test using nanomaterial-based sensors.European Respiratory Journal. 2014; 43: 1522-1525Google Scholar Although a recent systematic review suggested that electronic nose diagnostic tests may have high accuracy ( pooled sensitivity and specificity both 93%),33Saktiawati AM Putera DD Setyawan A Mahendradhata Y van der Werf TS. Diagnosis of tuberculosis through breath test: a systematic review.EBioMedicine. 2019; 46: 202-214Google Scholar these tests were often evaluated in case-controlled studies comparing people with TB to healthy controls and not in the intended setting of use ( potential spectrum bias leading to accuracy overestimation). Other tests in this review had sensitivities from 62-100% and specificities from 11-84%.33Saktiawati AM Putera DD Setyawan A Mahendradhata Y van der Werf TS. Diagnosis of tuberculosis through breath test: a systematic review.EBioMedicine. 2019; 46: 202-214Google Scholar Notably, however, data were insufficient to obtain pooled estimates for a single type of test. While the non-invasive nature of such tests is appealing, large public datasets are, like for audio, needed for algorithm generation and training. However, methods of collection ( which can lead to the combination of volatile organic compounds with sample bag material), analytical approaches, or confounders ( like pulmonary comorbidities or smoking), can all introduce variation. Important operational challenges, including the need for prompt ( ideally real-time) volatile organic compound detection post-collection ( samples undergo degradation after collection) and hardware complexity remain.34Mochalski P King J Unterkofler K Amann A. Stability of selected volatile breath constituents in Tedlar, Kynar and Flexfilm sampling bags.Analyst. 2013; 138: 1405-1418Google Scholar Tests that require specimen shipment off to a central laboratory hold less appeal.
Tests to diagnose subclinical ( asymptomatic) TB are lacking. This state ( bacteriologically-positive TB in those reporting no symptoms and typically not seeking healthcare) is more prevalent than previously estimated, with highly variable duration ( six months to beyond five years) 35Ku C-C MacPherson P Khundi M et al.Durations of asymptomatic, symptomatic, and care-seeking phases of tuberculosis disease with a Bayesian analysis of prevalence survey and notification data.BMC medicine. 2021; 19: 1-13Google Scholar,36Richards AS Sossen B Emery JC et al.The natural history of TB disease-a synthesis of data to quantify progression and regression across the spectrum.medRxiv. 2021; ( 2021.09.13.21263499) Google Scholar and may be responsible for more than half of TB transmission.16Emery JC, et al. Estimating the contribution of sub-clinical TB disease to transmission. Union Conference on Lung Health, October 2021 ( virtual).Google Scholar The detection of Mtb bacilli or DNA in aerosols has been facilitated by the development of face masks, with capture filters or absorbent materials, or blow tubes with a capture filter.37Williams CM Abdulwhhab M Birring SS et al.Exhaled Mycobacterium tuberculosis output and detection of subclinical disease by face-mask sampling: prospective observational studies.The Lancet Infectious Diseases. 2020; 20: 607-617Google Scholar, 38Williams CM Cheah ES Malkin J et al.Face mask sampling for the detection of Mycobacterium tuberculosis in expelled aerosols.PloS one. 2014; 9e104921Google Scholar, 39Patterson B Bryden W Call C et al.Cough-independent production of viable Mycobacterium tuberculosis in bioaerosol.Tuberculosis. 2021; 126102038Google Scholar Although capture methods are still under development, early results have been promising, suggesting high diagnostic yield ( one study demonstrated 87% sensitivity when Ultra was used to analyse samples collected from face masks), and may identify patients with subclinical disease earlier than sputum-based sampling.37Williams CM Abdulwhhab M Birring SS et al.Exhaled Mycobacterium tuberculosis output and detection of subclinical disease by face-mask sampling: prospective observational studies.The Lancet Infectious Diseases. 2020; 20: 607-617Google Scholar Furthermore, these methods can be applied to people before they cough: sampling aerosol from tidal breathing has yielded culturable Mtb bacilli, suggesting cough is not a transmission prerequisite.39Patterson B Bryden W Call C et al.Cough-independent production of viable Mycobacterium tuberculosis in bioaerosol.Tuberculosis. 2021; 126102038Google Scholar Detection of Mtb in expelled aerosols may thus play a role in identifying early disease, thought to be important for transmission,41Wood RC Andama A Hermansky G et al.Characterization of oral swab samples for diagnosis of pulmonary tuberculosis.PloS one. 2021; 16e0251422Google Scholar and assessment of treatment response ( important for infection control); however, this technology remains early stage.
Mtb in tongue papillae biofilms may be detected using existing molecular technologies such as Ultra40Lima F Santos AS Oliveira RD et al.Oral swab testing by Xpert® MTB/RIF Ultra for mass tuberculosis screening in prisons.Journal of clinical tuberculosis and other mycobacterial diseases. 2020; 19100148Google Scholar with high sensitivity: 88% relative to sputum Ultra41Wood RC Andama A Hermansky G et al.Characterization of oral swab samples for diagnosis of pulmonary tuberculosis.PloS one. 2021; 16e0251422Google Scholar based on single flocked swab sampling in symptomatic outpatients; however, sensitivity may be heavily setting dependent ( a prison-based active case finding study reported a sensitivity of Ultra on a single swab of 43%).40Lima F Santos AS Oliveira RD et al.Oral swab testing by Xpert® MTB/RIF Ultra for mass tuberculosis screening in prisons.Journal of clinical tuberculosis and other mycobacterial diseases. 2020; 19100148Google Scholar Tongue swab-based diagnoses are also possible using TB-LAMP.42Song Y Ma Y Liu R et al.Diagnostic Yield of Oral Swab Testing by TB-LAMP for Diagnosis of Pulmonary Tuberculosis.Infection and Drug Resistance. 2021; 14: 89Google Scholar In general, however, the optimal number of swabs and approach needed to maximize DNA recovery during processing remains the subject of active investigation. Next-generation ultra-sensitive tests may further increase the feasibility of tongue swab-based methods as current generation tests still have sensitivity limitations and automated extraction and wash steps were designed for sputum not tongue swabs. If increased sensitivity could be achieved, tongue swab-based approaches could be particularly useful as a diagnostic test in children, where feasibility with Ultra from tongue swab has been demonstrated43Nicol MP Wood RC Workman L et al.Microbiological diagnosis of pulmonary tuberculosis in children by oral swab polymerase chain reaction.Scientific reports. 2019; 9: 1-5Google Scholar, as well as other sputum-scarce populations. Lastly, tongue swab ( self) -collection has been done reliably by patients for SARS-CoV-2 testing44Tu Y-P Jennings R Hart B et al.Swabs collected by patients or health care workers for SARS-CoV-2 testing.New England Journal of Medicine. 2020; 383: 494-496Google Scholar, which is an important consideration for scale-up and potential community- or home-based TB testing in under-resourced settings.
Tests on stool currently have the most utility in diagnosing childhood TB, given the challenges in obtaining sputum; although their suboptimal sensitivity ( pooled sensitivity from nine studies was 67%) 45Ngadaya E Kimaro G Sandi E et al.Evaluation of stool GeneXpert MTB/RIF for the diagnosis of pulmonary tuberculosis among presumptive patients in Tanzania.Journal of Clinical Tuberculosis and Other Mycobacterial Diseases. 2020; 21100195Google Scholar,46MacLean E Sulis G Denkinger CM Johnston JC Pai M Ahmad Khan F Diagnostic accuracy of stool Xpert MTB/RIF for detection of pulmonary tuberculosis in children: a systematic review and meta-analysis.Journal of clinical microbiology. 2019; 57 ( e02057-18) Google Scholar remains a barrier. In adults, stool-based tests may play a role in the diagnosis of extrapulmonary TB, particularly in groups such as PLHIV who are more likely to have disseminated disease. Rectal swabs may facilitate specimen collection and processing, making the approach more amenable to POC during a single encounter, although accuracy data are limited ( one study demonstrated the sensitivity of stool Xpert testing using FLOQswabs was 47%).47Nicol MP Spiers K Workman L et al.Xpert MTB/RIF testing of stool samples for the diagnosis of pulmonary tuberculosis in children.Clin Infect Dis. 2013; 57: e18-e21Google Scholar Generally, stool-based approaches are hampered by the need for non-POC specimen processing.
Several AI computer-aided detection ( CAD) software platforms for TB triage30AI4Health Initiative. https: //www.ai4hlth.org/. Accessed Oct 7, 2021.Google Scholar are recommended by WHO as an alternative to human reading, given their potential to overcome the lack of qualified readers and the overwhelming need for improved triage methods given limited resources for confirmatory testing.48Organization WH. Rapid communication on systematic screening for tuberculosis. 2020.Google Scholar An evaluation of 1032 images demonstrated that six out of 12 CAD platforms ( Qure.ai, DeepTek, Delft Imaging, JF Healthcare, OXIPIT, Lunit) performed similarly to an expert reader, only three of which ( Qure.ai, Delft Imaging and Lunit) performed significantly better than an intermediate reader.49Codlin AJ Dao TP Vo LNQ et al.Independent evaluation of 12 artificial intelligence solutions for the detection of tuberculosis.Sci Rep. 2021; 11: 23895Google Scholar A large evaluation of almost 24 000 outpatients, the majority of whom had symptoms, demonstrated that all five of the algorithms evaluated reduced the number of molecular tests required by 50% while maintaining an overall sensitivity of 90%. Two products: qXR ( qure.ai, India) and CAD4TB ( Delft Imaging Systems, Netherlands) met the triage TPP criteria.50Qin ZZ Ahmed S Sarker MS et al.Tuberculosis detection from chest x-rays for triaging in a high tuberculosis-burden setting: an evaluation of five artificial intelligence algorithms.The Lancet Digital Health. 2021; 3: e543-e554Google Scholar Ongoing challenges include the need to adapt score thresholds to local epidemiology and use case scenarios ( e.g., triage versus mass population screening, different clinical settings, pre-symptomatic patients), as software performance, particularly with respect to specificity, can be variable and precludes it from serving as a diagnostic test.51Tavaziva G Harris M Abidi SK et al.Chest X-ray analysis with deep learning-based software as a triage test for pulmonary tuberculosis: an individual patient data meta-analysis of diagnostic accuracy.Clinical Infectious Diseases: an Official Publication of the Infectious Diseases Society of America. 2021; Google Scholar While the equipment cost remains prohibitive52Digital Chest Radiography and Computer-AidedDetection ( CAD) Solutions for Tuberculosis Diagnostics - Technology Landscape Analysis.FIND. 2021; Google Scholar, there are advances in the use of POC imaging devices ( including smartphones) that may bridge this barrier as the market rapidly evolves, particularly given the potential of this technology class to be used as part of integrated management of other diseases such as COVID-19, which may ensure adequate throughput to justify costs.53Nathavitharana RR Lederer P Chaplin M Bjerrum S Steingart KR Shah M. Impact of diagnostic strategies for tuberculosis using lateral flow urine lipoarabinomannan assay in people living with HIV.Cochrane Database Syst Rev. 2021; 8CD014641Google Scholar Other imaging technologies of interest include point-of-care ultrasound ( POCUS), for which a systematic review revealed sensitivities from 73-100% for subpleural nodules and 47-80% for lung consolidation; however, data are limited with high risk of bias.54Bigio J Kohli M Klinton JS et al.Diagnostic accuracy of point-of-care ultrasound for pulmonary tuberculosis: A systematic review.PLoS One. 2021; 16e0251236Google Scholar
Urine is appealing given ease-of-collection, limited infection control requirements, and potential for extrapulmonary and pulmonary TB. Mtb cellular components ( nucleic acids, molecules, cells) can filter through the kidney barrier into urine. Urine lipoarabinomannan ( LAM) is the only WHO-recommended biomarker for TB diagnosis ( specifically the AlereLAM test).55World Health OrganizationThe use of lateral flow urine lipoarabinomannan assay ( LF-LAM) for the diagnosis and screening of active tuberculosis in people living with HIV TB.2015Google Scholar Other next-generation LAM assays from FujiFilm, SD Biosensor, Biopromic, Salus, and others are at different developmental stages. Studies comparing SILVAMP TB LAM ( FujiFilm) to AlereLAM demonstrate a higher sensitivity ( 70% vs. 42% in PLHIV, 67% vs. 53% in people without HIV).56Broger T Sossen B du Toit E et al.Novel lipoarabinomannan point-of-care tuberculosis test for people with HIV: a diagnostic accuracy study.The Lancet Infectious Diseases. 2019; 19: 852-861Google Scholar, 57Broger T Nicol MP Sigal GB et al.Diagnostic accuracy of 3 urine lipoarabinomannan tuberculosis assays in HIV-negative outpatients.The Journal of clinical investigation. 2020; 130Google Scholar, 58Kerkhoff AD Sossen B Schutz C et al.Diagnostic sensitivity of SILVAMP TB-LAM ( FujiLAM) point-of-care urine assay for extra-pulmonary tuberculosis in people living with HIV.European Respiratory Journal. 2020; 55Google Scholar Several ultra-sensitive 3rd generation LAM assays59Shapiro AE NM Magcaba ZP Boyle D Cantera J Lillis L Mullins B Wittwer T Hannah H Warrick J Berry S Beebe DJ Wilson DPK Drain PK Validation of a laboratory-based reference test for TB-LAM and FLOW-TB, a novel point-of-care TB diagnostic assay, in a high-HIV-prevalence clinical cohort from KwaZulu-Natal, South Africa.in: International AIDS Conference. July 2020Google Scholar,60Wood A Barizuddin S Darr CM et al.Ultrasensitive detection of lipoarabinomannan with plasmonic grating biosensors in clinical samples of HIV negative patients with tuberculosis.PloS one. 2019; 14e0214161Google Scholar to be used irrespective of HIV status will enter trials in 2023. Lastly, emerging data points to a potential role for urine cell-free DNA for TB diagnosis; 61Oreskovic A Panpradist N Marangu D et al.Diagnosing pulmonary tuberculosis using sequence-specific purification of urine cell-free DNA.Journal of Clinical Microbiology. 2021; ( JCM. 00074-21) Google Scholar however, the need for specialised processing methods must be overcome for wide use.
While there are no validated blood tests for active TB, there is increasing optimism regarding the detection of antigens, immune cell profiling, host transcriptomics, or cell-free Mtb DNA.62Yu G Shen Y Ye B Shi Y. Diagnostic accuracy of Mycobacterium tuberculosis cell-free DNA for tuberculosis: A systematic review and meta-analysis.PLOS ONE. 2021; 16e0253658Google Scholar Several studies have demonstrated associations between host mRNA signatures and TB risk, although preventive therapy guided by one such mRNA biosignature failed to reduce TB incidence in a large randomised controlled trial.63Scriba TJ Fiore-Gartland A Penn-Nicholson A et al.Biomarker-guided tuberculosis preventive therapy ( CORTIS): a randomised controlled trial.The Lancet Infectious Diseases. 2021; 21: 354-365Google Scholar Despite commercial progress to develop mRNA biosignature assays, foremost of which is the Xpert Host Response ( Xpert HR) cartridge that detects a 3-gene signature in capillary blood directly using the widely-deployed GeneXpert platform,64Sutherland JS van der Spuy G Gindeh A et al.Diagnostic accuracy of the Cepheid 3-gene host response fingerstick blood test in a prospective, multi-site study: interim results.Clinical Infectious Diseases. 2021; Google Scholar independent validations65Turner CT, Gupta RK, Tsaliki E, et al. Blood transcriptional biomarkers for active pulmonary tuberculosis in a high-burden setting: a prospective, observational, diagnostic accuracy study. 2020.Google Scholar,66Hoang LT Jain P Pillay TD et al.Transcriptomic signatures for diagnosing tuberculosis in clinical practice: a prospective, multicentre cohort study.The Lancet Infectious Diseases. 2021; 21: 366-375Google Scholar demonstrate most transcriptomic biomarkers will not meet the WHO diagnostic accuracy criteria for triage or confirmation.65Turner CT, Gupta RK, Tsaliki E, et al. Blood transcriptional biomarkers for active pulmonary tuberculosis in a high-burden setting: a prospective, observational, diagnostic accuracy study. 2020.Google Scholar, 66Hoang LT Jain P Pillay TD et al.Transcriptomic signatures for diagnosing tuberculosis in clinical practice: a prospective, multicentre cohort study.The Lancet Infectious Diseases. 2021; 21: 366-375Google Scholar, 67Penn-Nicholson A Mbandi SK Thompson E et al.RISK6, a 6-gene transcriptomic signature of TB disease risk, diagnosis and treatment response. 2020; 10: 1-21Google Scholar Furthermore, tests will still likely require costly processing methods that preclude scale-up.68Gupta RK, Turner CT, Venturini C, et al. Concise whole blood transcriptional signatures for incipient tuberculosis: a systematic review and patient-level pooled meta-analysis. 2020.Google Scholar Tests that measure T-cell activation such as TAM-TB have demonstrated potential for active TB in children ( 83% sensitivity vs. culture) 69Portevin D Moukambi F Clowes P et al.Assessment of the novel T-cell activation marker–tuberculosis assay for diagnosis of active tuberculosis in children: a prospective proof-of-concept study.The Lancet infectious diseases. 2014; 14: 931-938Google Scholar,70Hiza H Hella J Arbués A et al.Case–control diagnostic accuracy study of a non-sputum CD38-based TAM-TB test from a single milliliter of blood.Scientific Reports. 2021; 11: 1-9Google Scholar and may have a role in treatment response monitoring,71Ahmed MI Ntinginya NE Kibiki G et al.Phenotypic changes on Mycobacterium tuberculosis-specific CD4 T cells as surrogate markers for tuberculosis treatment efficacy.Frontiers in immunology. 2018; 9: 2247Google Scholar however, TAM-TB's reliance on flow cytometry may restrict deployment to clinical laboratories. Detection of TB antigens72Corstjens P Hooij AV Tjon Kon Fat E et al.OC 8435 Multi-biomarker test strip for point-of-care screening for active tuberculosis: a five-country multi-centre test evaluation.BMJ Global Health. 2019; 4 ( A6-A) Google Scholar, 73Borain N Petersen L Du Plessis J Theron G Holm-Hansen C. A rapid serological triage test for detecting active tuberculosis.BMJ Global Health. 2017; 2Google Scholar, 74Ahmad R Xie L Pyle M et al.A rapid triage test for active pulmonary tuberculosis in adult patients with persistent cough.Science translational medicine. 2019; 11Google Scholar and other molecular biomarkers also holds great potential for scale-up in POC tests. For example, despite being a non-specific biomarker of inflammation, C-reactive protein ( CRP) is recommended by the WHO as a screening test in PLHIV given its superior accuracy for TB compared to symptom screening75Calderwood CJ Reeve BW Mann T et al.C-reactive protein as a triage tool for adults with presumptive pulmonary tuberculosis in South Africa: a prospective cohort study.medRxiv. 2021; Google Scholar,76Samuels TH Wyss R Ongarello S Moore DA Schumacher SG Denkinger CM. Evaluation of the diagnostic performance of laboratory-based c-reactive protein as a triage test for active pulmonary tuberculosis.PloS one. 2021; 16e0254002Google Scholar; however improved implementation guidance is needed.77WHO consolidated guidelines on tuberculosisModule 2: Screening – systematic screening for tuberculosis disease. World Health Organization, Geneva2021Google Scholar Other assays to detect inflammatory biomarkers78Santos VS Goletti D Kontogianni K et al.Acute phase proteins and IP-10 as triage tests for the diagnosis of tuberculosis: systematic review and meta-analysis.Clin Microbiol Infect. 2019; 25: 169-177Google Scholar or TB peptides79Liu C Lyon CJ Bu Y et al.Clinical evaluation of a blood assay to diagnose paucibacillary tuberculosis via bacterial antigens.Clinical chemistry. 2018; 64: 791-800Google Scholar remain in the prototype phase but have POC deployment potential. Proof-of-concept data has been generated for Mtb DNA detection in peripheral blood mononuclear cells80Belay M Tulu B Younis S et al.Detection of Mycobacterium tuberculosis complex DNA in CD34-positive peripheral blood mononuclear cells of asymptomatic tuberculosis contacts: an observational study.The Lancet Microbe. 2021; 2: e267-e275Google Scholar and cell-free DNA but no prototypes with public data are available.62Yu G Shen Y Ye B Shi Y. Diagnostic accuracy of Mycobacterium tuberculosis cell-free DNA for tuberculosis: A systematic review and meta-analysis.PLOS ONE. 2021; 16e0253658Google Scholar,81Murugesan K Hogan CA Palmer Z et al.Investigation of preanalytical variables impacting pathogen cell-free DNA in blood and urine.Journal of clinical microbiology. 2019; 57 ( e00782-19) Google Scholar
Select considerations for developers and evaluators are in Table 2, together with issues for implementers and policymakers, which are interlinked and fall across multiple themes, are discussed in the following sections.Table 2Key challenges that need to be overcome for new diagnostic technologies to have a transformative impact on the TB epidemic. These issues are complex, multifactorial, and interdisciplinary, however, together they create a significant barrier to the adoption of promising new non-invasive TB tests at the point-of-care. When developing and planning to implement a new test, all factors require consideration, otherwise potential impact is undermined.Colour theme key: Red- technical; orange- programmatic; purple- policy.Abbreviations: POC: point of care, DST: drug susceptibility testing. Open table in a new tab
Colour theme key: Red- technical; orange- programmatic; purple- policy.
Abbreviations: POC: point of care, DST: drug susceptibility testing.
From a technical perspective, developing POC tests is challenging due to disease complexity and the slow growth of Mtb. While ultra-sensitive tests are still needed to detect early disease ( especially in the context of active case finding),36Richards AS Sossen B Emery JC et al.The natural history of TB disease-a synthesis of data to quantify progression and regression across the spectrum.medRxiv. 2021; ( 2021.09.13.21263499) Google Scholar,82Kendall EA Kitonsa PJ Nalutaaya A et al.The spectrum of tuberculosis disease in an urban Ugandan community and its health facilities.Clinical infectious diseases: an official publication of the Infectious Diseases Society of America. 2020; Google Scholar as tests slowly increase in sensitivity, diagnostic accuracy assessments may be compromised by reference standard limitations, especially as bacteriological tests like liquid culture are often only applied to sputum.83Saavedra B Mambuque E Nguenha D et al.Performance of Xpert MTB/RIF Ultra for tuberculosis diagnosis in the context of passive and active case finding.The European respiratory journal. 2021; Google Scholar Thus, positive results from highly sensitive tests could be classified as false positives, representing potentially missed treatment opportunities. This false-positivity issue may be of less concern for tests that use antigens or DNA rather than host biosignatures such as mRNA, however, challenges remain: for example, sputum Ultra trace semi-quantitation results are often culture-negative, especially in settings where patients have high rates of previous TB or a where there is a high background intensity of TB transmissiont.84Mishra H Reeve BWP Palmer Z et al.Xpert MTB/RIF Ultra and Xpert MTB/RIF for diagnosis of tuberculosis in an HIV-endemic setting with a high burden of previous tuberculosis: a two-cohort diagnostic accuracy study.Lancet Respir Med. 2020; 8: 368-382Google Scholar Biomarkers like host RNA and CRP have potential for resolving Ultra false-positive results ( if biomarker levels are low),65Turner CT, Gupta RK, Tsaliki E, et al. Blood transcriptional biomarkers for active pulmonary tuberculosis in a high-burden setting: a prospective, observational, diagnostic accuracy study. 2020.Google Scholar,75Calderwood CJ Reeve BW Mann T et al.C-reactive protein as a triage tool for adults with presumptive pulmonary tuberculosis in South Africa: a prospective cohort study.medRxiv. 2021; Google Scholar thus Ultra traces could, for example, be reflexed to a test like Xpert HR. Aside from limit of detection differences, other reasons for discrepant results include variations in specimen quality and processing, extra-pulmonary TB, and non-culturable Mtb ( the clinical relevance of which is not well understood). Composite reference standards that incorporate additional information ( e.g., imaging and treatment response) may be useful, however, these substantially increase expense. Extra-pulmonary TB, which accounts for around 16% of all global TB cases,1World Health Organization. Global Tuberculosis Report 2021. Geneva, Switzerland.Google Scholar presents additional diagnostic challenges due to invasive sampling to obtain site-specific tissue or fluid, on which the sensitivity of existing tests is generally lower than on pulmonary specimens.85Kohli M Schiller I Dendukuri N et al.Xpert ( ( R)) MTB/RIF assay for extrapulmonary tuberculosis and rifampicin resistance.Cochrane Database Syst Rev. 2018; 8CD012768Google Scholar In addition, for several tests there are data or potential for extra-pulmonary TB, indicating that invasive sampling could be obviated ( see Table 1).
Although rapid POC biosignature tests may contribute substantially to reducing those patients lost to follow up between diagnosis and treatment, one limitation ( especially for host biomarker tests) is that they are unlikely to provide drug susceptibility information to guide appropriate treatment, in contrast to tests that directly detect Mtb. The latter should be given higher priority by developers and implementers in high DR-TB burden settings.
Consideration of the feasibility of obtaining alternative specimen types ( such as urine or stool) in routine settings, although non-invasive, is important to avoid undermining potential benefits. Blood volumes for biomarker tests could also be a concern and these should ideally require only a finger prick. During development, any platform-based assay should consider potential maintenance and quality assurance needs for field use and address these during validation or early field evaluation studies, rather than leaving this for post-market evaluation. Furthermore, local communities’ perceptions about specific specimen types ( e.g., stool) or tests ( e.g., audio) should be carefully studied. TB diagnostics research should utilise interdisciplinary quantitative and qualitative approaches to maximise the high quality uptake of testing algorithms by patients and health care providers.
Systematic reviews evaluating the effect of Xpert MTB/RIF and LAM on patient-important outcomes like mortality demonstrate the challenges of moving from diagnostic test accuracy assessment to proving impact.53Nathavitharana RR Lederer P Chaplin M Bjerrum S Steingart KR Shah M. Impact of diagnostic strategies for tuberculosis using lateral flow urine lipoarabinomannan assay in people living with HIV.Cochrane Database Syst Rev. 2021; 8CD014641Google Scholar,86Haraka F Kakolwa M Schumacher SG et al.Impact of the diagnostic test Xpert MTB/RIF on patient outcomes for tuberculosis.Cochrane Database Syst Rev. 2021; 5CD012972Google Scholar Careful evaluation of intended and actual test placement and use within the wider TB care cascade is needed to understand potential implementation barriers,87Subbaraman R Jhaveri T Nathavitharana RR. Closing gaps in the tuberculosis care cascade: an action-oriented research agenda.J Clin Tuberc Other Mycobact Dis. 2020; 19100144Google Scholar,88Pai M Schumacher SG Abimbola S. Surrogate endpoints in global health research: still searching for killer apps and silver bullets?.BMJ Glob Health. 2018; 3e000755Google Scholar such as gaps in linkage and engagement with care. The global roll-out of Xpert MTB/RIF has provided key lessons for policy makers and program implementers,89Albert H Nathavitharana RR Isaacs C Pai M Denkinger CM Boehme CC. Development, roll-out and impact of Xpert MTB/RIF for tuberculosis: what lessons have we learnt and how can we do better?.The European respiratory journal. 2016; 48: 516-525Google Scholar which include recognising that high costs and unfulfilled quality assurance and maintenance needs in chronically underfunded programmes will continue to result in underutilisation.90Nalugwa T Shete PB Nantale M et al.Challenges with scale-up of GeneXpert MTB/RIF ( R) in Uganda: a health systems perspective.BMC Health Serv Res. 2020; 20: 162Google Scholar Technologies can mitigate these barriers if a POC test can be electricity-free, deployable at wide temperature ranges, have long shelf life, and the potential for online and offline use. National TB programmes must facilitate less restrictive use of new tests to increase utilisation volumes, requiring price negotiations with test manufacturers, and comprehensive health worker training. Furthermore, continuous quality assurance programmes should ensure tests are being used, interpreted, and acted upon correctly and promptly.91Cattamanchi A Berger CA Shete PB et al.Implementation science to improve the quality of tuberculosis diagnostic services in Uganda.J Clin Tuberc Other Mycobact Dis. 2020; 18100136Google Scholar
Improving TB diagnosis, particularly given the renewed focus on active case finding, needs to be viewed within the broader context of health systems strengthening. Despite the release of the WHO's first Essential Diagnostics List in 2019,92Organization WH. The selection and use of essential in vitro diagnostics: report of the second meeting of the WHO Strategic Advisory Group of Experts on In Vitro Diagnostics ( including the second WHO model list of essential in vitro diagnostics). 2019.Google Scholar country-level investment, particularly to strengthen primary health care in high TB incidence settings, falls short of ensuring availability of essential tests and infrastructure, such as dCXR with CAD in peripheral healthcare settings.93Huddart S MacLean E Pai M. Location, location, location: tuberculosis services in highest burden countries.Lancet Glob Health. 2016; 4: e907-e908Google Scholar Syndromic rather than test-guided management remains highly prevalent.94Pai M Walia K Boehme CC. Essential medicines and essential diagnostics: a package deal.Lancet Public Health. 2019; 4: e492Google Scholar It is critical that health care providers are trained to act rapidly on test results to link patients to care, as well as to interpret negative tests to determine appropriate follow-up investigations and avoid patients being lost to care without a working diagnosis.
Even the most promising triage tests ( CRP, host transcriptome signatures) have specificity limitations, since other conditions ( viral infections, cancers) can produce readouts that may resemble TB,95Mulenga H Musvosvi M Mendelsohn SC et al.Longitudinal Dynamics of a Blood Transcriptomic Signature of Tuberculosis.American Journal of Respiratory and Critical Care Medicine. 2021; ( ja) Google Scholar which impact implementation potential given that triage test specificity is the primary cost driver.96van't Hoog AH Cobelens F Vassall A et al.Optimal triage test characteristics to improve the cost-effectiveness of the Xpert MTB/RIF assay for TB diagnosis: a decision analysis.PloS one. 2013; 8: e82786Google Scholar Hence, with the introduction of novel tests, a negative test in a triage-positive person should inform further non-TB diagnostic decision making to justify these tools ' cost. Most modelling exercises do not factor in potential benefits of non-TB diagnoses, which may underestimate overall impact. These diagnostic algorithms, including alternative diagnoses to be considered in patients without TB would need to be setting- and population-specific.
The COVID-19 pandemic has prompted the international scientific community to develop highly accurate SARS-CoV-2 diagnostic tests in record time, with advances in sample collection, including specimens such as saliva, oral swabs and absorbent strips in facemasks, and decentralised testing, including the use of home-based testing kits.14Richards AS SB Emery JC Horton KC Heinsohn T Frascella B Balzarini F Oradini-Alacreu A Hacker B Odone A McCreesh N Grant AD Kranzer K Cobelens F Esmail H Houben RMJH The natural history of TB disease-a synthesis of data to quantify progression and regression across the spectrum.medRxiv. 2021; https: //doiorg/101101/2021091321263499Google Scholar The TB diagnostic community needs to follow similar development pathways, including integrated testing for respiratory diseases such as TB and COVID-19, utilizing multi-disease molecular diagnostic platforms ( for example, GeneXpert and Truenat), which leverages the setting-specific feasibility of automatically testing a specimen for multiple diseases. Digital connectivity tools can facilitate community-based testing, referrals, contact tracing, linkage to care and/or indicate the need for alternative clinical evaluation.3Ruhwald M Carmona S Pai M. Learning from COVID-19 to reimagine tuberculosis diagnosis.Lancet Microbe. 2021; 2: e169-e270Google Scholar,97Bigio J Sassi A Temesgen Z Pai M. Improving the quality of tuberculosis care in the post-pandemic world.J Clin Tuberc Other Mycobact Dis. 2021; 23100212Google Scholar
Most upcoming technologies for sputum-free TB tests are at an early developmental phase. Furthermore, many methods that use novel specimens are still reliant on existing molecular tests not originally designed for that purpose ( e.g., Ultra on tongue swabs) or require infrastructure unavailable at primary care. Despite serious gaps in the diagnostic pipeline, exploring the potential for several prototype tests that show promise for POC deployment across different use case scenarios ( TPPs) is critical. Nonetheless, given growing recognition of the high proportion of people with subclinical TB and the nuances of use case scenarios for screening versus triage, revised TPPs are needed. Key needs to accelarate test development include publicly available standardised datasets and large-scale validation cohorts that facilitate test design and evaluation from the outset in populations and settings that reflect their final intended field of use. To overcome these barriers, it is critical to leverage the resources and diagnostic innovation and momentum behind the COVID-19 response, including scale-up of SARS-CoV-2 test capacity and connectivity tools. Only then can the promise of novel sputum-free TB tests be realised.
Data for this Review were identified by searches of the PubMed database, and references from relevant articles, using the search terms ( Tuberculosis or TB) AND ( diagnosis) without restrictions based on language, date, study type, or setting. Given the focus on novel technology, additional references were obtained from abstracts, meeting reports, and clinical trial registration websites, where relevant.
RRN, ALGB, and GT drafted the initial manuscript with critical input from MR and FC. All authors read and approved the final version of the manuscript.
M. Ruhwald reports working for FIND. FIND conducts multiple clinical research projects to evaluate new diagnostic tests against published target product profiles that have been defined through consensus processes. These include studies of diagnostic products developed by private sector companies who provide access to know-how, equipment/reagents, and may contribute through unrestricted donations according to FIND policies and in line with guidance from the organisation's external scientific advisory council. FIND does not attribute any financial value to such access. The other authors have no competing interests to declare.
RRN is supported by National Institutes of Health Career Development Award ( NIAID K23 AI132648-04) and an American Society of Tropical Medicine and Hygiene Burroughs Wellcome Fellowship. GT acknowledges funding from the EDCTP2 programme supported by the European Union ( grant SF1401, OPTIMAL DIAGNOSIS; grant RIA2020I-3305, CAGE-TB) and the National Institute of Allergy and Infection Diseases of the National Institutes of Health ( U01AI152087). GT’ s research group has received funding and/or in-kind donations in the last five years via his employer from Bruker Hain Lifesciences, Cepheid, LumiraDx, FIND, Biopromic, Newmark Diagnostics, Hemocue, Boditech, and Copan.
None of the funders had any role in paper design, data collection, data analysis, interpretation, writing of the paper. | tech |
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The intersecting pandemics of tuberculosis and COVID-19: population-level and patient-level impact, clinical presentation, and corrective interventions - The Lancet Respiratory Medicine | The global tuberculosis burden remains substantial, with more than 10 million people newly ill per year. Nevertheless, tuberculosis incidence has slowly declined over the past decade, and mortality has decreased by almost a third in tandem. This positive trend was abruptly reversed by the COVID-19 pandemic, which in many parts of the world has resulted in a substantial reduction in tuberculosis testing and case notifications, with an associated increase in mortality, taking global tuberculosis control back by roughly 10 years. Here, we consider points of intersection between the tuberculosis and COVID-19 pandemics, identifying wide-ranging approaches that could be taken to reverse the devastating effects of COVID-19 on tuberculosis control. We review the impact of COVID-19 at the population level on tuberculosis case detection, morbidity and mortality, and the patient-level impact, including susceptibility to disease, clinical presentation, diagnosis, management, and prognosis. We propose strategies to reverse or mitigate the deleterious effects of COVID-19 and restore tuberculosis services. Finally, we highlight research priorities and major challenges and controversies that need to be addressed to restore and advance the global response to tuberculosis.
The global tuberculosis burden remains substantial, with more than 10 million people newly ill per year. Nevertheless, tuberculosis incidence has slowly declined over the past decade, and mortality has decreased by almost a third in tandem. This positive trend was abruptly reversed by the COVID-19 pandemic, which in many parts of the world has resulted in a substantial reduction in tuberculosis testing and case notifications, with an associated increase in mortality, taking global tuberculosis control back by roughly 10 years. Here, we consider points of intersection between the tuberculosis and COVID-19 pandemics, identifying wide-ranging approaches that could be taken to reverse the devastating effects of COVID-19 on tuberculosis control. We review the impact of COVID-19 at the population level on tuberculosis case detection, morbidity and mortality, and the patient-level impact, including susceptibility to disease, clinical presentation, diagnosis, management, and prognosis. We propose strategies to reverse or mitigate the deleterious effects of COVID-19 and restore tuberculosis services. Finally, we highlight research priorities and major challenges and controversies that need to be addressed to restore and advance the global response to tuberculosis.
Historically, tuberculosis has arguably been the biggest killer of humans and it remains one of the foremost global infectious causes of death.1WHOGlobal tuberculosis report 2020. World Health Organization, Geneva2020Google Scholar The incidence of tuberculosis has been slowly declining over the past decade, and mortality had decreased by almost a third, although the global burden remains substantial at more than 10 million people per year newly ill with the disease.1WHOGlobal tuberculosis report 2020. World Health Organization, Geneva2020Google Scholar Although the declining trajectory would have fallen far short of milestones outlined in the UN Sustainable Development Goals and the WHO End TB Strategy targets, there was encouraging movement in the right direction. This positive trend has been abruptly and dramatically reversed by the COVID-19 pandemic, which in many parts of the world has resulted in a substantial reduction in tuberculosis testing and access to tuberculosis health services. Data from the latest global tuberculosis report by WHO shows an 18% reduction in the number of tuberculosis cases notified in 2020 compared with 2019.2WHOGlobal tuberculosis report 2021. World Health Organization, Geneva2021Google Scholar These losses have overshadowed the potential reductions in Mycobacterium tuberculosis transmission because of mask use and physical distancing, and have increased the global tuberculosis burden and associated mortality, taking tuberculosis control efforts backwards by approximately a decade.2WHOGlobal tuberculosis report 2021. World Health Organization, Geneva2021Google Scholar, 3Glaziou P Predicted impact of the COVID-19 pandemic on global tuberculosis deaths in 2020.medRxiv. 2020; ( published online May 4.) ( preprint).https: //doi.org/10.1101/2020.04.28.20079582Google Scholar, 4The Stop TB Partnership12 months of COVID-19 eliminated 12 years of progress in the global fight against tuberculosis.http: //www.stoptb.org/news/stories/2021/ns21 011.htmlDate: 2021Date accessed: September 3, 2021Google Scholar With the current delta and omicron variant-driven surges in many low-income and middle-income countries ( LMICs), and with the challenges of SARS-CoV-2 vaccine access for most LMICs, it is likely that the negative impact of the COVID-19 pandemic on efforts to control tuberculosis ( as well as other major infectious diseases, such as HIV and malaria) 5Roberts L How COVID is derailing the fight against HIV, TB and malaria.https: //www.nature.com/articles/d41586-021-02469-8Date: Sept 10, 2021Date accessed: September 10, 2021Google Scholar, 6Roberts L How COVID hurt the fight against other dangerous diseases.Nature. 2021; 592: 502-504Google Scholar will continue well into 2022, especially with 3 billion people still waiting to receive their first dose of SARS-CoV-2 vaccine.
The aim of this Series paper is to review the interactions between COVID-19 and tuberculosis, including the population-level impact of COVID-19 on tuberculosis outcomes, the clinical presentation and diagnosis of tuberculosis–COVID-19 co-infection, the patient-level impact of COVID-19 on the management and prognosis of tuberculosis, and interventional strategies that could be used to mitigate the devastating effects of COVID-19 on the global burden of tuberculosis, including lessons learned from responses to the COVID-19 pandemic. We emphasise the ways in which tuberculosis care and management have been neglected compared with COVID-19, and how low SARS-CoV-2 vaccine coverage in tuberculosis-endemic countries, despite the high rates of infection and emergence of new variants, will continue to fuel the global tuberculosis pandemic. Priorities for the rapid restoration of tuberculosis care and prevention—and progress towards End TB Strategy targets—in the era of COVID-19 are presented in panel 1.Panel 1Priorities for rapid restoration of tuberculosis care and prevention in the era of COVID-19Priorities for resource allocation, case finding and prevention, and treatment for tuberculosis in the time of COVID-19 are listed below. Communication with the public, training of health-care workers, ongoing monitoring and evaluation, and tuberculosis advocacy are cross-cutting themes across these domains.Resource allocation•Increase budget and human resources for existing tuberculosis and other health infrastructures and for operational research, with a view to reducing the fragility of health systems, including through public–private partnerships•Mobilise community-based organisations and partners to advocate for more resources for care and prevention ( eg, personnel, equipment, consumables) •Develop digital platforms for training and health education•Develop public-facing dashboards for tuberculosis surveillance data•Ensure availability and supply of high-quality personal protective equipment for health-care workers and other highly exposed individuals, including N95 ( or equivalent) respirators•Improve and broaden social protection for individuals who develop tuberculosis, COVID-19, or both•Actively identify and remove sources of structural violence, systemic racism, and discrimination, especially those affecting access to essential services and equitable, high-quality health care•Integrate tuberculosis and COVID-19 responses at multiple levels, including screening and testingCase finding and prevention•Target high-risk groups for consent-based universal testing•Strengthen community-based active case finding and tuberculosis diagnostic services ( including in shelters for people who are homeless) •Enhance screening through the use of mHealth and self-screening apps•Develop telemedicine with the use of digital platforms for consultation•Strengthen availability, speed, and reliability of specimen transportation•Use rapid turnaround molecular tests with high sensitivity and specificity for dual diagnostic testing for tuberculosis and COVID-19•Strengthen contact tracing, investigation, and the provision of tuberculosis preventive therapy•Broaden use of chest radiography with or without computer-aided detection for the tuberculosis community, and improve facility-based screening•Enhance screening and case-finding activities at health facilities, including targeting high-risk groups ( eg, urine lipoarabinomannan and C-reactive protein as a screening tool in people with HIV) •Strengthen provision of Bacillus Calmette-Guérin vaccination and invest in new vaccine development•Ensure separation and prompt treatment of those with disease to reduce Mycobacterium tuberculosis and SARS-CoV-2 transmission in health-care settingsTreatment•Strengthen community-based tuberculosis treatment services•Scale up virtual care, digital health, and community-monitoring solutions to provide remote support such as video-supported therapy•Scale up SMS-based communication to improve treatment adherence and patient-centred care and support•Use bulk dispensing, open-air dispensing, or both to reduce barriers to care and minimise risk to patients and health-care workers
Priorities for resource allocation, case finding and prevention, and treatment for tuberculosis in the time of COVID-19 are listed below. Communication with the public, training of health-care workers, ongoing monitoring and evaluation, and tuberculosis advocacy are cross-cutting themes across these domains.
Compared with 2019, tuberculosis case detection in 2020 was reduced by 18% globally ( a decrease from 7·1 million to 5·8 million cases) and by up to 24% in the ten worst-affected countries with high tuberculosis burden.2WHOGlobal tuberculosis report 2021. World Health Organization, Geneva2021Google Scholar, 7WHOImpact of the COVID-19 pandemic on TB detection and mortality in 2020. World Health Organization, Geneva2021Google Scholar India, Indonesia, the Philippines, and China account for 1·3 million cases ( 93%) in the global decline in tuberculosis case detection ( figure 1). Major reductions in notified cases have been seen in the Philippines ( 37%), Indonesia ( 31%), South Africa ( 26%), and India ( 25%; table 1 and figure 1).Figure 1Impact of the COVID-19 pandemic on global, regional, and national tuberculosis detection and mortalityShow full captionThere has been a substantial decline in tuberculosis case detection globally of about 18% in newly ill people reported with tuberculosis at the global ( A), regional ( B), and national ( C) levels, across key regions. Modelling has predicted that this acute drop will probably be followed by a rebound increase in tuberculosis incidence ( C); data from three exemplar countries are shown relative to baseline trajectories before COVID-19. The decline in case detection is also estimated to have resulted in an acute increase in mortality in 2020 and is anticipated to take the next few years to reach prepandemic baselines ( D); data from three exemplar countries are shown relative to baseline trajectories before COVID-19. Images reproduced by permission of WHO.2WHOGlobal tuberculosis report 2021. World Health Organization, Geneva2021Google ScholarView Large Image Figure ViewerDownload Hi-res image Download ( PPT) Table 1Tuberculosis case detection in ten selected countries with high tuberculosis burden in 2019 and 2020Number of tuberculosis cases notified to WHOReduction ( shortfall) in tuberculosis case detection from 2019 to 202020192020Philippines409 167256 54137·3% Indonesia559 847384 02531·4% South Africa209 545154 34426·3% India2 176 6771 629 30125·1% Bangladesh291 595230 08121·1% Russia73 32858 72319·9% Pakistan328 312272 99016·9% Kenya84 34571 64615·1% Angola74 10563 14714·7% China728 265624 71514·2% All countries reporting quarterly and monthly data ( n=84) 5 058 8013 833 14824·3% Countries providing quarterly and monthly data are listed in descending order of shortfall ( for the full list of countries, see appendix p 14). Reproduced and adapted by permission of WHO.2WHOGlobal tuberculosis report 2021. World Health Organization, Geneva2021Google Scholar Open table in a new tab
There has been a substantial decline in tuberculosis case detection globally of about 18% in newly ill people reported with tuberculosis at the global ( A), regional ( B), and national ( C) levels, across key regions. Modelling has predicted that this acute drop will probably be followed by a rebound increase in tuberculosis incidence ( C); data from three exemplar countries are shown relative to baseline trajectories before COVID-19. The decline in case detection is also estimated to have resulted in an acute increase in mortality in 2020 and is anticipated to take the next few years to reach prepandemic baselines ( D); data from three exemplar countries are shown relative to baseline trajectories before COVID-19. Images reproduced by permission of WHO.2WHOGlobal tuberculosis report 2021. World Health Organization, Geneva2021Google Scholar
Countries providing quarterly and monthly data are listed in descending order of shortfall ( for the full list of countries, see appendix p 14). Reproduced and adapted by permission of WHO.2WHOGlobal tuberculosis report 2021. World Health Organization, Geneva2021Google Scholar
Previously unpublished data from South Africa's National Institute for Communicable Diseases ( NICD) show substantial reductions in tuberculosis testing and case detection nationwide, coinciding with each wave of COVID-19 and the subsequent national lockdown ( appendix p 4). In our analysis of NICD data, predictions for 2020 were based on national data from 2018 and 2019, and adjusted for seasonality; detailed methods are available in the appendix ( p 1). By May, 2020, tuberculosis testing in South Africa had decreased by more than 50% compared with the previous year: of 193 067 ( 95% CI 181 119–205 014) expected Xpert MTB/RIF nucleic acid amplification tests ( NAATs) for the detection of M tuberculosis for the month, only 99 513 were actually done. The microbiological confirmation of drug-sensitive tuberculosis also declined by 40%, and numbers of rifampicin-resistant tuberculosis cases fell by about 50% ( appendix p 5). By the end of 2020, South Africa saw an overall decrease in tuberculosis testing of 22% ( 95% CI 15–28), and rates of confirmed active tuberculosis cases fell by 15% ( 9–20%) in the public sector. In addition, there was an 18% reduction in attendance at primary health-care facilities. These trends are substantial given that the highest population-wide limitations to public activities and social interaction occurred for only 6 months of the year.8Pillay Y Pienaar S Barron P Zondi T Impact of COVID-19 on routine primary healthcare services in South Africa.SA Med J. 2021; 111: 714Google Scholar These patterns extended to other endemic countries such as India and China ( Panel 2, Panel 3; detailed versions are available in the appendix, pp 1–2).9Udwadia ZF Koul PA Richeldi L Post-COVID lung fibrosis: the tsunami that will follow the earthquake.Lung India. 2021; 38: S41-S47Google Scholar, 10Ravimohan S Kornfeld H Weissman D Bisson GP Tuberculosis and lung damage: from epidemiology to pathophysiology.Eur Respir Rev. 2018; 27170077Google Scholar, 11Raman R Rajalakshmi R Surya J et al.Impact on health and provision of healthcare services during the COVID-19 lockdown in India: a multicentre cross-sectional study.BMJ Open. 2021; 11e043590Google Scholar, 12Shrinivasan R Rane S Pai M India's syndemic of tuberculosis and COVID-19.BMJ Glob Health. 2020; 5e003979Google Scholar, 13Cilloni L Fu H Vesga JF et al.The potential impact of the COVID-19 pandemic on the tuberculosis epidemic a modelling analysis.EClinicalMedicine. 2020; 28100603Google Scholar, 14Chen H Zhang K Insight into impact of COVID-19 epidemic on tuberculosis burden in China.Eur Respir J. 2020; 562002710Google Scholar, 15Chiang C-Y Islam T Xu C et al.The impact of COVID-19 and the restoration of tuberculosis services in the Western Pacific region.Eur Respir J. 2020; 562003054Google Scholar, 16Pang Y Liu Y Du J Gao J Li L Impact of COVID-19 on tuberculosis control in China.Int J Tuberc Lung Dis. 2020; 24: 545-547Google Scholar, 17Shen X Sha W Yang C et al.Continuity of TB services during the COVID-19 pandemic in China.Int J Tuberc Lung Dis. 2021; 25: 81-83Google Scholar, 18Chen Y Wang Y Fleming J et al.Active or latent tuberculosis increases susceptibility to COVID-19 and disease severity.medRxiv. 2020; ( published online March 16.) ( preprint).https: //doi.org/10.1101/2020.03.10.20033795Google Scholar, 19Wu Z Chen J Xia Z et al.Impact of the COVID-19 pandemic on the detection of TB in Shanghai, China.Int J Tuberc Lung Dis. 2020; 24: 1122-1124Google Scholar, 20Liu Q Lu P Shen Y et al.Collateral impact of the coronavirus disease 2019 ( COVID-19) pandemic on tuberculosis control in Jiangsu Province, China.Clin Infect Dis. 2021; 73: 542-544Google Scholar, 21Wang X He W Lei J Liu G Huang F Zhao Y Impact of COVID-19 pandemic on pre-treatment delays, detection, and clinical characteristics of tuberculosis patients in Ningxia Hui autonomous region, China.Front Public Health. 2021; 9644536Google Scholar, 22Fei H Yinyin X Hui C et al.The impact of the COVID-19 epidemic on tuberculosis control in China.Lancet Reg Health West Pac. 2020; 3100032Google Scholar, 23Centre for Health Protection Department of HealthNumber of notifiable infectious diseases by month in 2019.https: //www.chp.gov.hk/en/statistics/data/10/26/43/6830.htmlDate: Feb 10, 2021Date accessed: July 5, 2021Google Scholar, 24Centre for Health Protection Department of HealthNumber of notifiable infectious diseases by month in 2020.https: //www.chp.gov.hk/en/statistics/data/10/26/43/6896.htmlDate: July 12, 2021Date accessed: July 5, 2021Google Scholar The full impact of the current omicron wave in South Africa and other tuberculosis-endemic countries is unknown, but likely to be negative for tuberculosis services. The 2021 WHO global tuberculosis report estimated about a 15% reduction in the number of people treated for drug-resistant tuberculosis, and a 21% decrease in people receiving preventive therapy for latent tuberculosis infection globally.2WHOGlobal tuberculosis report 2021. World Health Organization, Geneva2021Google ScholarPanel 2Perspective from IndiaAt least 30 million people have developed COVID-19 in India, and a devastating second wave has left many individuals with severe acute respiratory distress syndrome, a proportion of whom might develop post-COVID fibrotic sequelae.9Udwadia ZF Koul PA Richeldi L Post-COVID lung fibrosis: the tsunami that will follow the earthquake.Lung India. 2021; 38: S41-S47Google Scholar India also has the largest number of people living with chronic fibrotic lung scarring caused by tuberculosis.10Ravimohan S Kornfeld H Weissman D Bisson GP Tuberculosis and lung damage: from epidemiology to pathophysiology.Eur Respir Rev. 2018; 27170077Google Scholar Post-COVID sequelae superimposed on post-tuberculosis fibrosis is likely to result in considerable disability in many of these individuals.In March, 2020, the prime minister, Narendra Modi, announced a prolonged and stringent lockdown11Raman R Rajalakshmi R Surya J et al.Impact on health and provision of healthcare services during the COVID-19 lockdown in India: a multicentre cross-sectional study.BMJ Open. 2021; 11e043590Google Scholar that had catastrophic effects on health-care provision and severely restricted access to tuberculosis diagnosis and treatment. Staff and resources from tuberculosis programmes and health facilities were diverted to COVID-19 efforts, and drug stockouts were common.12Shrinivasan R Rane S Pai M India's syndemic of tuberculosis and COVID-19.BMJ Glob Health. 2020; 5e003979Google Scholar Bacillus Calmette-Guérin vaccination rates also plummeted; in April, 2020, 1 million fewer children were vaccinated than in the same month in 2019.6Roberts L How COVID hurt the fight against other dangerous diseases.Nature. 2021; 592: 502-504Google Scholar Tuberculosis notification rates decreased by 50% in private and public sectors.3Glaziou P Predicted impact of the COVID-19 pandemic on global tuberculosis deaths in 2020.medRxiv. 2020; ( published online May 4.) ( preprint).https: //doi.org/10.1101/2020.04.28.20079582Google Scholar Treatment completion rates also decreased, as patients delayed diagnosis and were often unable to reach clinics. For details of the potential impact of COVID-19 on tuberculosis indices in India, see appendix p 12.A modelling study in 2020 estimated that each month of lockdown would result in 40 685 additional people developing tuberculosis that year and an additional 151 120 tuberculosis deaths over the next 5 years.13Cilloni L Fu H Vesga JF et al.The potential impact of the COVID-19 pandemic on the tuberculosis epidemic a modelling analysis.EClinicalMedicine. 2020; 28100603Google Scholar In 2020, the number of tuberculosis cases from India notified to WHO was 1 629 301, a reduction of 25·1% from the 2019 number.1WHOGlobal tuberculosis report 2020. World Health Organization, Geneva2020Google Scholar Further details about the perspective from India are provided in the appendix ( p 1).Panel 3Perspective from ChinaCOVID-19 prevalence peaked in China in February, 2020 ( n=68 033 confirmed cases), but by May, 2020, numbers had fallen by 99·8% to 143 confirmed cases.14Chen H Zhang K Insight into impact of COVID-19 epidemic on tuberculosis burden in China.Eur Respir J. 2020; 562002710Google Scholar Emergency measures deployed to control the virus included cancellation of public transport, prohibition of public gatherings, closing of schools and public amenities, enhanced disinfection, social distancing, stay-at-home orders, and home quarantine for individuals from epidemic areas.14Chen H Zhang K Insight into impact of COVID-19 epidemic on tuberculosis burden in China.Eur Respir J. 2020; 562002710Google Scholar, 15Chiang C-Y Islam T Xu C et al.The impact of COVID-19 and the restoration of tuberculosis services in the Western Pacific region.Eur Respir J. 2020; 562003054Google Scholar, 16Pang Y Liu Y Du J Gao J Li L Impact of COVID-19 on tuberculosis control in China.Int J Tuberc Lung Dis. 2020; 24: 545-547Google Scholar Moreover, major tuberculosis hospitals were redesignated as COVID-19 hospitals; 16Pang Y Liu Y Du J Gao J Li L Impact of COVID-19 on tuberculosis control in China.Int J Tuberc Lung Dis. 2020; 24: 545-547Google Scholar, 17Shen X Sha W Yang C et al.Continuity of TB services during the COVID-19 pandemic in China.Int J Tuberc Lung Dis. 2021; 25: 81-83Google Scholar staff from tuberculosis programmes, laboratories, and wards were diverted to the COVID-19 response,14Chen H Zhang K Insight into impact of COVID-19 epidemic on tuberculosis burden in China.Eur Respir J. 2020; 562002710Google Scholar, 15Chiang C-Y Islam T Xu C et al.The impact of COVID-19 and the restoration of tuberculosis services in the Western Pacific region.Eur Respir J. 2020; 562003054Google Scholar, 16Pang Y Liu Y Du J Gao J Li L Impact of COVID-19 on tuberculosis control in China.Int J Tuberc Lung Dis. 2020; 24: 545-547Google Scholar, 17Shen X Sha W Yang C et al.Continuity of TB services during the COVID-19 pandemic in China.Int J Tuberc Lung Dis. 2021; 25: 81-83Google Scholar, 18Chen Y Wang Y Fleming J et al.Active or latent tuberculosis increases susceptibility to COVID-19 and disease severity.medRxiv. 2020; ( published online March 16.) ( preprint).https: //doi.org/10.1101/2020.03.10.20033795Google Scholar, 19Wu Z Chen J Xia Z et al.Impact of the COVID-19 pandemic on the detection of TB in Shanghai, China.Int J Tuberc Lung Dis. 2020; 24: 1122-1124Google Scholar and there have been substantial reductions in the number of tuberculosis hospital beds and outpatient visits.19Wu Z Chen J Xia Z et al.Impact of the COVID-19 pandemic on the detection of TB in Shanghai, China.Int J Tuberc Lung Dis. 2020; 24: 1122-1124Google ScholarAcross the country, tuberculosis notifications were substantially lower in the first 5 months of 2020, decreasing by 24%, 39%, 25%, 15%, and 13% per month, compared with the same months in 2019.14Chen H Zhang K Insight into impact of COVID-19 epidemic on tuberculosis burden in China.Eur Respir J. 2020; 562002710Google Scholar, 15Chiang C-Y Islam T Xu C et al.The impact of COVID-19 and the restoration of tuberculosis services in the Western Pacific region.Eur Respir J. 2020; 562003054Google Scholar, 16Pang Y Liu Y Du J Gao J Li L Impact of COVID-19 on tuberculosis control in China.Int J Tuberc Lung Dis. 2020; 24: 545-547Google Scholar, 17Shen X Sha W Yang C et al.Continuity of TB services during the COVID-19 pandemic in China.Int J Tuberc Lung Dis. 2021; 25: 81-83Google Scholar, 18Chen Y Wang Y Fleming J et al.Active or latent tuberculosis increases susceptibility to COVID-19 and disease severity.medRxiv. 2020; ( published online March 16.) ( preprint).https: //doi.org/10.1101/2020.03.10.20033795Google Scholar, 19Wu Z Chen J Xia Z et al.Impact of the COVID-19 pandemic on the detection of TB in Shanghai, China.Int J Tuberc Lung Dis. 2020; 24: 1122-1124Google Scholar Several studies found reductions in tuberculosis notifications at provincial levels,17Shen X Sha W Yang C et al.Continuity of TB services during the COVID-19 pandemic in China.Int J Tuberc Lung Dis. 2021; 25: 81-83Google Scholar, 19Wu Z Chen J Xia Z et al.Impact of the COVID-19 pandemic on the detection of TB in Shanghai, China.Int J Tuberc Lung Dis. 2020; 24: 1122-1124Google Scholar, 20Liu Q Lu P Shen Y et al.Collateral impact of the coronavirus disease 2019 ( COVID-19) pandemic on tuberculosis control in Jiangsu Province, China.Clin Infect Dis. 2021; 73: 542-544Google Scholar, 21Wang X He W Lei J Liu G Huang F Zhao Y Impact of COVID-19 pandemic on pre-treatment delays, detection, and clinical characteristics of tuberculosis patients in Ningxia Hui autonomous region, China.Front Public Health. 2021; 9644536Google Scholar, 22Fei H Yinyin X Hui C et al.The impact of the COVID-19 epidemic on tuberculosis control in China.Lancet Reg Health West Pac. 2020; 3100032Google Scholar with missed or delayed sputum and follow-up examinations; 22Fei H Yinyin X Hui C et al.The impact of the COVID-19 epidemic on tuberculosis control in China.Lancet Reg Health West Pac. 2020; 3100032Google Scholar increased patient delays,21Wang X He W Lei J Liu G Huang F Zhao Y Impact of COVID-19 pandemic on pre-treatment delays, detection, and clinical characteristics of tuberculosis patients in Ningxia Hui autonomous region, China.Front Public Health. 2021; 9644536Google Scholar increased incidence of positive sputum smears and cavities in baseline chest radiographs,21Wang X He W Lei J Liu G Huang F Zhao Y Impact of COVID-19 pandemic on pre-treatment delays, detection, and clinical characteristics of tuberculosis patients in Ningxia Hui autonomous region, China.Front Public Health. 2021; 9644536Google Scholar and reduced treatment success and multidrug-resistant tuberculosis screening were also reported.20Liu Q Lu P Shen Y et al.Collateral impact of the coronavirus disease 2019 ( COVID-19) pandemic on tuberculosis control in Jiangsu Province, China.Clin Infect Dis. 2021; 73: 542-544Google ScholarSince the national lockdown was lifted, tuberculosis notifications have gradually approached pre-lockdown levels.19Wu Z Chen J Xia Z et al.Impact of the COVID-19 pandemic on the detection of TB in Shanghai, China.Int J Tuberc Lung Dis. 2020; 24: 1122-1124Google Scholar, 21Wang X He W Lei J Liu G Huang F Zhao Y Impact of COVID-19 pandemic on pre-treatment delays, detection, and clinical characteristics of tuberculosis patients in Ningxia Hui autonomous region, China.Front Public Health. 2021; 9644536Google Scholar, 22Fei H Yinyin X Hui C et al.The impact of the COVID-19 epidemic on tuberculosis control in China.Lancet Reg Health West Pac. 2020; 3100032Google Scholar, 23Centre for Health Protection Department of HealthNumber of notifiable infectious diseases by month in 2019.https: //www.chp.gov.hk/en/statistics/data/10/26/43/6830.htmlDate: Feb 10, 2021Date accessed: July 5, 2021Google Scholar, 24Centre for Health Protection Department of HealthNumber of notifiable infectious diseases by month in 2020.https: //www.chp.gov.hk/en/statistics/data/10/26/43/6896.htmlDate: July 12, 2021Date accessed: July 5, 2021Google Scholar The observed effect on tuberculosis control has been attributed to traffic restrictions, disrupted tuberculosis services, and the fear of catching COVID-19 among members of the population.15Chiang C-Y Islam T Xu C et al.The impact of COVID-19 and the restoration of tuberculosis services in the Western Pacific region.Eur Respir J. 2020; 562003054Google Scholar, 17Shen X Sha W Yang C et al.Continuity of TB services during the COVID-19 pandemic in China.Int J Tuberc Lung Dis. 2021; 25: 81-83Google Scholar, 19Wu Z Chen J Xia Z et al.Impact of the COVID-19 pandemic on the detection of TB in Shanghai, China.Int J Tuberc Lung Dis. 2020; 24: 1122-1124Google Scholar, 22Fei H Yinyin X Hui C et al.The impact of the COVID-19 epidemic on tuberculosis control in China.Lancet Reg Health West Pac. 2020; 3100032Google Scholar Further details about the perspective from China are provided in the appendix ( pp 1–2).
At least 30 million people have developed COVID-19 in India, and a devastating second wave has left many individuals with severe acute respiratory distress syndrome, a proportion of whom might develop post-COVID fibrotic sequelae.9Udwadia ZF Koul PA Richeldi L Post-COVID lung fibrosis: the tsunami that will follow the earthquake.Lung India. 2021; 38: S41-S47Google Scholar India also has the largest number of people living with chronic fibrotic lung scarring caused by tuberculosis.10Ravimohan S Kornfeld H Weissman D Bisson GP Tuberculosis and lung damage: from epidemiology to pathophysiology.Eur Respir Rev. 2018; 27170077Google Scholar Post-COVID sequelae superimposed on post-tuberculosis fibrosis is likely to result in considerable disability in many of these individuals.
In March, 2020, the prime minister, Narendra Modi, announced a prolonged and stringent lockdown11Raman R Rajalakshmi R Surya J et al.Impact on health and provision of healthcare services during the COVID-19 lockdown in India: a multicentre cross-sectional study.BMJ Open. 2021; 11e043590Google Scholar that had catastrophic effects on health-care provision and severely restricted access to tuberculosis diagnosis and treatment. Staff and resources from tuberculosis programmes and health facilities were diverted to COVID-19 efforts, and drug stockouts were common.12Shrinivasan R Rane S Pai M India's syndemic of tuberculosis and COVID-19.BMJ Glob Health. 2020; 5e003979Google Scholar Bacillus Calmette-Guérin vaccination rates also plummeted; in April, 2020, 1 million fewer children were vaccinated than in the same month in 2019.6Roberts L How COVID hurt the fight against other dangerous diseases.Nature. 2021; 592: 502-504Google Scholar Tuberculosis notification rates decreased by 50% in private and public sectors.3Glaziou P Predicted impact of the COVID-19 pandemic on global tuberculosis deaths in 2020.medRxiv. 2020; ( published online May 4.) ( preprint).https: //doi.org/10.1101/2020.04.28.20079582Google Scholar Treatment completion rates also decreased, as patients delayed diagnosis and were often unable to reach clinics. For details of the potential impact of COVID-19 on tuberculosis indices in India, see appendix p 12.
A modelling study in 2020 estimated that each month of lockdown would result in 40 685 additional people developing tuberculosis that year and an additional 151 120 tuberculosis deaths over the next 5 years.13Cilloni L Fu H Vesga JF et al.The potential impact of the COVID-19 pandemic on the tuberculosis epidemic a modelling analysis.EClinicalMedicine. 2020; 28100603Google Scholar In 2020, the number of tuberculosis cases from India notified to WHO was 1 629 301, a reduction of 25·1% from the 2019 number.1WHOGlobal tuberculosis report 2020. World Health Organization, Geneva2020Google Scholar Further details about the perspective from India are provided in the appendix ( p 1).
COVID-19 prevalence peaked in China in February, 2020 ( n=68 033 confirmed cases), but by May, 2020, numbers had fallen by 99·8% to 143 confirmed cases.14Chen H Zhang K Insight into impact of COVID-19 epidemic on tuberculosis burden in China.Eur Respir J. 2020; 562002710Google Scholar Emergency measures deployed to control the virus included cancellation of public transport, prohibition of public gatherings, closing of schools and public amenities, enhanced disinfection, social distancing, stay-at-home orders, and home quarantine for individuals from epidemic areas.14Chen H Zhang K Insight into impact of COVID-19 epidemic on tuberculosis burden in China.Eur Respir J. 2020; 562002710Google Scholar, 15Chiang C-Y Islam T Xu C et al.The impact of COVID-19 and the restoration of tuberculosis services in the Western Pacific region.Eur Respir J. 2020; 562003054Google Scholar, 16Pang Y Liu Y Du J Gao J Li L Impact of COVID-19 on tuberculosis control in China.Int J Tuberc Lung Dis. 2020; 24: 545-547Google Scholar Moreover, major tuberculosis hospitals were redesignated as COVID-19 hospitals; 16Pang Y Liu Y Du J Gao J Li L Impact of COVID-19 on tuberculosis control in China.Int J Tuberc Lung Dis. 2020; 24: 545-547Google Scholar, 17Shen X Sha W Yang C et al.Continuity of TB services during the COVID-19 pandemic in China.Int J Tuberc Lung Dis. 2021; 25: 81-83Google Scholar staff from tuberculosis programmes, laboratories, and wards were diverted to the COVID-19 response,14Chen H Zhang K Insight into impact of COVID-19 epidemic on tuberculosis burden in China.Eur Respir J. 2020; 562002710Google Scholar, 15Chiang C-Y Islam T Xu C et al.The impact of COVID-19 and the restoration of tuberculosis services in the Western Pacific region.Eur Respir J. 2020; 562003054Google Scholar, 16Pang Y Liu Y Du J Gao J Li L Impact of COVID-19 on tuberculosis control in China.Int J Tuberc Lung Dis. 2020; 24: 545-547Google Scholar, 17Shen X Sha W Yang C et al.Continuity of TB services during the COVID-19 pandemic in China.Int J Tuberc Lung Dis. 2021; 25: 81-83Google Scholar, 18Chen Y Wang Y Fleming J et al.Active or latent tuberculosis increases susceptibility to COVID-19 and disease severity.medRxiv. 2020; ( published online March 16.) ( preprint).https: //doi.org/10.1101/2020.03.10.20033795Google Scholar, 19Wu Z Chen J Xia Z et al.Impact of the COVID-19 pandemic on the detection of TB in Shanghai, China.Int J Tuberc Lung Dis. 2020; 24: 1122-1124Google Scholar and there have been substantial reductions in the number of tuberculosis hospital beds and outpatient visits.19Wu Z Chen J Xia Z et al.Impact of the COVID-19 pandemic on the detection of TB in Shanghai, China.Int J Tuberc Lung Dis. 2020; 24: 1122-1124Google Scholar
Across the country, tuberculosis notifications were substantially lower in the first 5 months of 2020, decreasing by 24%, 39%, 25%, 15%, and 13% per month, compared with the same months in 2019.14Chen H Zhang K Insight into impact of COVID-19 epidemic on tuberculosis burden in China.Eur Respir J. 2020; 562002710Google Scholar, 15Chiang C-Y Islam T Xu C et al.The impact of COVID-19 and the restoration of tuberculosis services in the Western Pacific region.Eur Respir J. 2020; 562003054Google Scholar, 16Pang Y Liu Y Du J Gao J Li L Impact of COVID-19 on tuberculosis control in China.Int J Tuberc Lung Dis. 2020; 24: 545-547Google Scholar, 17Shen X Sha W Yang C et al.Continuity of TB services during the COVID-19 pandemic in China.Int J Tuberc Lung Dis. 2021; 25: 81-83Google Scholar, 18Chen Y Wang Y Fleming J et al.Active or latent tuberculosis increases susceptibility to COVID-19 and disease severity.medRxiv. 2020; ( published online March 16.) ( preprint).https: //doi.org/10.1101/2020.03.10.20033795Google Scholar, 19Wu Z Chen J Xia Z et al.Impact of the COVID-19 pandemic on the detection of TB in Shanghai, China.Int J Tuberc Lung Dis. 2020; 24: 1122-1124Google Scholar Several studies found reductions in tuberculosis notifications at provincial levels,17Shen X Sha W Yang C et al.Continuity of TB services during the COVID-19 pandemic in China.Int J Tuberc Lung Dis. 2021; 25: 81-83Google Scholar, 19Wu Z Chen J Xia Z et al.Impact of the COVID-19 pandemic on the detection of TB in Shanghai, China.Int J Tuberc Lung Dis. 2020; 24: 1122-1124Google Scholar, 20Liu Q Lu P Shen Y et al.Collateral impact of the coronavirus disease 2019 ( COVID-19) pandemic on tuberculosis control in Jiangsu Province, China.Clin Infect Dis. 2021; 73: 542-544Google Scholar, 21Wang X He W Lei J Liu G Huang F Zhao Y Impact of COVID-19 pandemic on pre-treatment delays, detection, and clinical characteristics of tuberculosis patients in Ningxia Hui autonomous region, China.Front Public Health. 2021; 9644536Google Scholar, 22Fei H Yinyin X Hui C et al.The impact of the COVID-19 epidemic on tuberculosis control in China.Lancet Reg Health West Pac. 2020; 3100032Google Scholar with missed or delayed sputum and follow-up examinations; 22Fei H Yinyin X Hui C et al.The impact of the COVID-19 epidemic on tuberculosis control in China.Lancet Reg Health West Pac. 2020; 3100032Google Scholar increased patient delays,21Wang X He W Lei J Liu G Huang F Zhao Y Impact of COVID-19 pandemic on pre-treatment delays, detection, and clinical characteristics of tuberculosis patients in Ningxia Hui autonomous region, China.Front Public Health. 2021; 9644536Google Scholar increased incidence of positive sputum smears and cavities in baseline chest radiographs,21Wang X He W Lei J Liu G Huang F Zhao Y Impact of COVID-19 pandemic on pre-treatment delays, detection, and clinical characteristics of tuberculosis patients in Ningxia Hui autonomous region, China.Front Public Health. 2021; 9644536Google Scholar and reduced treatment success and multidrug-resistant tuberculosis screening were also reported.20Liu Q Lu P Shen Y et al.Collateral impact of the coronavirus disease 2019 ( COVID-19) pandemic on tuberculosis control in Jiangsu Province, China.Clin Infect Dis. 2021; 73: 542-544Google Scholar
Since the national lockdown was lifted, tuberculosis notifications have gradually approached pre-lockdown levels.19Wu Z Chen J Xia Z et al.Impact of the COVID-19 pandemic on the detection of TB in Shanghai, China.Int J Tuberc Lung Dis. 2020; 24: 1122-1124Google Scholar, 21Wang X He W Lei J Liu G Huang F Zhao Y Impact of COVID-19 pandemic on pre-treatment delays, detection, and clinical characteristics of tuberculosis patients in Ningxia Hui autonomous region, China.Front Public Health. 2021; 9644536Google Scholar, 22Fei H Yinyin X Hui C et al.The impact of the COVID-19 epidemic on tuberculosis control in China.Lancet Reg Health West Pac. 2020; 3100032Google Scholar, 23Centre for Health Protection Department of HealthNumber of notifiable infectious diseases by month in 2019.https: //www.chp.gov.hk/en/statistics/data/10/26/43/6830.htmlDate: Feb 10, 2021Date accessed: July 5, 2021Google Scholar, 24Centre for Health Protection Department of HealthNumber of notifiable infectious diseases by month in 2020.https: //www.chp.gov.hk/en/statistics/data/10/26/43/6896.htmlDate: July 12, 2021Date accessed: July 5, 2021Google Scholar The observed effect on tuberculosis control has been attributed to traffic restrictions, disrupted tuberculosis services, and the fear of catching COVID-19 among members of the population.15Chiang C-Y Islam T Xu C et al.The impact of COVID-19 and the restoration of tuberculosis services in the Western Pacific region.Eur Respir J. 2020; 562003054Google Scholar, 17Shen X Sha W Yang C et al.Continuity of TB services during the COVID-19 pandemic in China.Int J Tuberc Lung Dis. 2021; 25: 81-83Google Scholar, 19Wu Z Chen J Xia Z et al.Impact of the COVID-19 pandemic on the detection of TB in Shanghai, China.Int J Tuberc Lung Dis. 2020; 24: 1122-1124Google Scholar, 22Fei H Yinyin X Hui C et al.The impact of the COVID-19 epidemic on tuberculosis control in China.Lancet Reg Health West Pac. 2020; 3100032Google Scholar Further details about the perspective from China are provided in the appendix ( pp 1–2).
However, it remains unclear to what extent diminished case detection can be attributed to reduced access to care versus reduction in M tuberculosis transmission from non-pharmaceutical interventions ( eg, mask wearing or lockdowns), like those seen for other respiratory infections such as influenza, respiratory syncytial virus, Streptococcus pneumoniae, and Haemophilus influenzae.25Olsen SJ Azziz-Baumgartner E Budd AP et al.Decreased influenza activity during the COVID-19 pandemic—United States, Australia, Chile, and South Africa, 2020.MMWR Morb Mortal Week Rep. 2020; 69: 1305-1309Google Scholar, 26Tempia S Walaza S Bhiman JN et al.Decline of influenza and respiratory syncytial virus detection in facility-based surveillance during the COVID-19 pandemic, South Africa, January to October 2020.Euro Surveill. 2021; 26: 1Google Scholar, 27Brueggemann AB Jansen Van Rensburg MJ Shaw D et al.Changes in the incidence of invasive disease due to Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis during the COVID-19 pandemic in 26 countries and territories in the Invasive Respiratory Infection Surveillance Initiative: a prospective analysis of surveillance data.Lancet Digit Health. 2021; 3: e360-e370Google Scholar It is widely assumed that reduced health-care access dominates and offsets any transmission reduction; this assumption is supported by the acute nature of the reductions in case detection, as the effects of decreased transmission would probably only be seen months later. Thus, the acute reduction in detection supports reduced access but does not exclude or confirm the effect of reduced transmission.
Several modelling studies suggested that COVID-19 and the pandemic response might lead to an increase in tuberculosis mortality, driven primarily by reduced access to health services. Cilloni and colleagues13Cilloni L Fu H Vesga JF et al.The potential impact of the COVID-19 pandemic on the tuberculosis epidemic a modelling analysis.EClinicalMedicine. 2020; 28100603Google Scholar forecast in 2020 that global deaths would return to those seen in 2013, undoing almost a decade of work, whereas Hogan and colleagues28Hogan AB Jewell BL Sherrard-Smith E et al.Potential impact of the COVID-19 pandemic on HIV, tuberculosis, and malaria in low-income and middle-income countries: a modelling study.Lancet Glob Health. 2020; 8: e1132-e1141Google Scholar estimated that tuberculosis mortality could increase by up to 20% between 2020 and 2025, and stressed the importance of maintaining tuberculosis service provision despite pandemic-related disruption. Analyses from WHO and the Stop TB Partnership predicted, respectively, 190 000 additional tuberculosis deaths in 2020 and about 1·4 million additional tuberculosis deaths between 2020 and 2025, worsened for every month taken to achieve restoration of services.3Glaziou P Predicted impact of the COVID-19 pandemic on global tuberculosis deaths in 2020.medRxiv. 2020; ( published online May 4.) ( preprint).https: //doi.org/10.1101/2020.04.28.20079582Google Scholar, 13Cilloni L Fu H Vesga JF et al.The potential impact of the COVID-19 pandemic on the tuberculosis epidemic a modelling analysis.EClinicalMedicine. 2020; 28100603Google Scholar, 29McQuaid CF McCreesh N Read JM et al.The potential impact of COVID-19-related disruption on tuberculosis burden.Eur Respir J. 2020; 562001718Google Scholar
The latest WHO global tuberculosis report provides data to substantiate the models. In 2020, there were roughly 1·32 million tuberculosis deaths worldwide.2WHOGlobal tuberculosis report 2021. World Health Organization, Geneva2021Google Scholar These numbers represent the first year-over-year increase in tuberculosis deaths since 2005. The impact of the pandemic on tuberculosis deaths during 2021 is unclear, but probably substantially worse following the large delta-driven surges in many tuberculosis-endemic countries and the current wave of the omicron variant globally. The issue is complicated by the methods used to estimate tuberculosis mortality, which rely heavily on indirect estimates and extrapolation,30Glaziou P Dodd P Dean A Floyd K Methods used by WHO to estimate the global burden of TB disease.https: //www.who.int/tb/publications/global report/TB20 Technical Appendix 20201014.pdfDate: 2020Date accessed: August 23, 2021Google Scholar in part because civil registration and vital statistics systems are weak in many countries with high tuberculosis burden.31Mikkelsen L Phillips DE Abouzahr C et al.A global assessment of civil registration and vital statistics systems: monitoring data quality and progress.Lancet. 2015; 386: 1395-1406Google Scholar In addition, given the frequent underdiagnosis of active tuberculosis among people who die, even outside of a pandemic,32Gupta RK Lucas SB Fielding KL Lawn SD Prevalence of tuberculosis in post-mortem studies of HIV-infected adults and children in resource-limited settings.AIDS. 2015; 29: 1987-2002Google Scholar, 33Garcia-Basteiro AL Hurtado JC Castillo P et al.Unmasking the hidden tuberculosis mortality burden in a large post mortem study in Maputo Central Hospital, Mozambique.Eur Respir J. 2019; 541900312Google Scholar the disruptions to services and reductions in tuberculosis testing are likely to result in under-reporting of tuberculosis deaths. The expected underdetection yet predicted increase in mortality represents an epidemiological and surveillance conundrum. Preliminary reports provide insight into some of these aspects. A small Italian study reported significantly higher loss to follow-up ( p=0·03) and mortality ( p=0·04) during the pandemic than in a control period the year before.34Magro P Formenti B Marchese V et al.Impact of the SARS-CoV-2 epidemic on tuberculosis treatment outcome in Northern Italy.Eur Respir J. 2020; 562002665Google Scholar Similarly, brief reports from Pakistan,35Jamal WZ Habib S Khowaja S Safdar N Zaidi SMA COVID-19: ensuring continuity of TB services in the private sector.Int J Tuberc Lung Dis. 2020; 24: 870-872Google Scholar China,20Liu Q Lu P Shen Y et al.Collateral impact of the coronavirus disease 2019 ( COVID-19) pandemic on tuberculosis control in Jiangsu Province, China.Clin Infect Dis. 2021; 73: 542-544Google Scholar and Ethiopia36Mohammed H Oljira L Roba KT Yimer G Fekadu A Manyazewal T Containment of COVID-19 in Ethiopia and implications for tuberculosis care and research.Infect Dis Povert. 2020; 9: 131Google Scholar document deteriorations in treatment outcomes and patient support.
The COVID-19 pandemic has also affected other tuberculosis outcomes and preventive strategies. COVID-19 has affected tuberculosis vaccination, including a reduction in Bacillus Calmette-Guérin ( BCG) vaccination of up to 60% in some parts of the world ( figure 2).6Roberts L How COVID hurt the fight against other dangerous diseases.Nature. 2021; 592: 502-504Google Scholar According to a modelling study,37Shaikh N Pelzer PT Thysen SM Roy P Harris RC White RG Impact of COVID-19 disruptions on global BCG coverage and paediatric TB mortality: a modelling study.Vaccines ( Basel). 2021; 91228Google Scholar the consequences of delayed and missed BCG vaccination might account for up to 33 074 additional paediatric deaths related to tuberculosis. Apart from tuberculosis mortality, other unfavourable outcomes such as treatment failure and loss to follow-up have been negatively affected and are discussed hereafter ( figure 2), as is the occurrence of persistent lung disease after active tuberculosis.Figure 2Tuberculosis cascade of care and the potential effects of the COVID-19 pandemicShow full captionA detailed look at the potential effects of the COVID-19 pandemic at each step of the typical tuberculosis care cascade: exposure and susceptibility to Mycobacterium tuberculosis; access to preventive services; testing, diagnosis, and treatment initiation; and completion. The effects of COVID-19 at each step of the tuberculosis care cascade ( blue) are detailed in the adjacent boxes, with an increase in the burden of tuberculosis denoted by red text or a decrease denoted by green text. ACF=active case finding. BCG=Bacillus Calmette-Guérin. HCW=health-care worker. IPC=infection prevention and control. PTLF=pretreatment loss to follow-up.View Large Image Figure ViewerDownload Hi-res image Download ( PPT)
A detailed look at the potential effects of the COVID-19 pandemic at each step of the typical tuberculosis care cascade: exposure and susceptibility to Mycobacterium tuberculosis; access to preventive services; testing, diagnosis, and treatment initiation; and completion. The effects of COVID-19 at each step of the tuberculosis care cascade ( blue) are detailed in the adjacent boxes, with an increase in the burden of tuberculosis denoted by red text or a decrease denoted by green text. ACF=active case finding. BCG=Bacillus Calmette-Guérin. HCW=health-care worker. IPC=infection prevention and control. PTLF=pretreatment loss to follow-up.
The COVID-19 pandemic has had staggering consequences for the global economy. Economic losses in 2020 were 4% ( about US $ 3 trillion) of the global gross domestic product ( GDP),38United NationsWorld economic situation and prospects as of mid-2021.https: //www.un.org/development/desa/dpad/publication/world-economic-situation-and-prospects-as-of-mid-2021/ #: ~: text=According% 20to% 20the% 20World% 20Economic, UN% 20forecasts% 20released% 20in% 20JanuaryDate: 2021Date accessed: August 16, 2021Google Scholar with LMICs disproportionately affected.
Several modelling estimates indicate that the tuberculosis case burden will increase by up to 15% ( > 1 million cases in total) by 2025.3Glaziou P Predicted impact of the COVID-19 pandemic on global tuberculosis deaths in 2020.medRxiv. 2020; ( published online May 4.) ( preprint).https: //doi.org/10.1101/2020.04.28.20079582Google Scholar, 13Cilloni L Fu H Vesga JF et al.The potential impact of the COVID-19 pandemic on the tuberculosis epidemic a modelling analysis.EClinicalMedicine. 2020; 28100603Google Scholar, 28Hogan AB Jewell BL Sherrard-Smith E et al.Potential impact of the COVID-19 pandemic on HIV, tuberculosis, and malaria in low-income and middle-income countries: a modelling study.Lancet Glob Health. 2020; 8: e1132-e1141Google Scholar, 29McQuaid CF McCreesh N Read JM et al.The potential impact of COVID-19-related disruption on tuberculosis burden.Eur Respir J. 2020; 562001718Google Scholar, 39Harimurti P Pradhan E Cheikh N et al.Tuberculosis in Indonesia: epidemic projections and opportunities to accelerate control: findings from an optima TB analysis. The World Bank Group, Washington, DC2020Google Scholar, 40Bhargava A Shewade HD The potential impact of the COVID-19 response related lockdown on TB incidence and mortality in India.Indian J Tuberc. 2020; 67: S139-S146Google Scholar From a societal perspective, rising unemployment and money required for transport, medication, and food are expected to increase the catastrophic costs substantially ( > 20% of household income), particularly in tuberculosis-endemic countries where these costs were already high in the prepandemic era.41Fuady A Houweling TAJ Richardus JH COVID-19 and tuberculosis-related catastrophic costs.Am J Trop Med Hyg. 2020; 104: 436-440Google Scholar
These costs have affected the global tuberculosis response at multiple levels and led to worsening poverty, and hence increased susceptibility to tuberculosis mortality, thus exacerbating the vicious cycle of susceptibility, death, and poverty ( figure 3). Notably, tuberculosis itself has historically caused economic losses, estimated at 2–3% of GDP in tuberculosis-endemic countries.42KPMGGlobal economic impact of tuberculosis.https: //mv.ecuo.org/wp-content/uploads/sites/4/2017/12/Global-Economic-Impacts-of-TB.pdfDate: 2017Date accessed: August 31, 2021Google Scholar, 43The Economist Intelligence UnitA call to action: it's time to end drug-resistant tuberculosis.https: //www.eiu.com/graphics/marketing/pdf/its-time-to-end-drug-resistant-tuberculosis-summary-report.pdfDate: 2021Date accessed: August 31, 2021Google Scholar Reduced funding of tuberculosis programmes has already been reported in several countries because of the diversion of resources to the COVID-19 response,1WHOGlobal tuberculosis report 2020. World Health Organization, Geneva2020Google Scholar, 44The Stop TB PartnershipThe impact of COVID-19 on the TB epidemic: a community perspective.http: //www.stoptb.org/assets/documents/resources/publications/acsm/Civil% 20Society% 20Report% 20on% 20TB% 20and% 20COVID.df? fbclid=IwAR3SOY4kyBs5a 35HIeUhcvwRIWspePA4vVHESqcQxio7G4irivJ90cSU8kDate: 2021Date accessed: September 5, 2021Google Scholar including fewer health-care workers ( HCWs) for tuberculosis services, reduced supply of personal protective equipment ( PPE) for tuberculosis exposure, diversion of diagnostic testing services to COVID-19, and reductions in support services for patients with tuberculosis ( eg, nutrition and mental health; figure 3). The Global Fund estimates that approximately an additional $ 30 billion will be required to bolster tuberculosis, HIV, and malaria programmes in the wake of COVID-19.45The Global FundMitigating the impact of COVID-19 on countries affected by HIV, tuberculosis, and malaria. Global Health Campus, Geneva2020Google ScholarFigure 3Catastrophic effects of the COVID-19 pandemic on global tuberculosis response and the global economyShow full captionAn overview of how the COVID-19 pandemic has affected the resources available for tuberculosis control efforts and its effect on individual households leading to a cycle of increased susceptibility, death, and poverty. Poverty is driven by tuberculosis-related and COVID-19-related deterioration in macroeconomic conditions, leading to catastrophic costs at the patient level, and is a proxy for increased mortality and burden of tuberculosis. GDP=gross domestic product. LMICs=low-income and middle-income countries. PPE=personal protective equipment.View Large Image Figure ViewerDownload Hi-res image Download ( PPT)
An overview of how the COVID-19 pandemic has affected the resources available for tuberculosis control efforts and its effect on individual households leading to a cycle of increased susceptibility, death, and poverty. Poverty is driven by tuberculosis-related and COVID-19-related deterioration in macroeconomic conditions, leading to catastrophic costs at the patient level, and is a proxy for increased mortality and burden of tuberculosis. GDP=gross domestic product. LMICs=low-income and middle-income countries. PPE=personal protective equipment.
Few of the models discussed accounted for the brutal reality of 2021, during which we witnessed devastating COVID-19 surges in many countries with a high tuberculosis burden, driven by the delta variant from April, 2021, and the omicron variant since November, 2021. Large new delta variant waves in countries such as India, Bangladesh, Nepal, Indonesia, Myanmar, Uganda, and South Africa again forced these countries into new lockdowns and further disruptions of routine tuberculosis and all other essential health services. Many South American countries with high tuberculosis burdens ( eg, Brazil and Peru) have also seen massive COVID-19 surges. Since November, 2021, South Africa has been dealing with a large omicron wave, and this new variant is now sweeping the world and keeping the pandemic alive during 2022.
Given the emergence of a highly transmissible omicron variant, and the pre-existing and growing inequity in SARS-CoV-2 vaccine access, in which less than 15% of people in low-income countries have received even one dose of the vaccine ( as of March, 2022), additional new waves are highly likely in 2022 and beyond. Simply put, we do not see any easy way out for LMICs to end this pandemic in the near future, unless we vaccinate the whole world.46Pai M Olatunbosun-Alakija A Vax the world.Science. 2021; 3741031Google Scholar This means that the impact of the COVID-19 pandemic on tuberculosis will probably be worse than any mathematical modelling prediction thus far. This scenario and combination of events perpetuate the pervading global apathy and neglect of tuberculosis. None of the End TB Strategy targets for tuberculosis are likely to be achieved by 2030.
Does tuberculosis increase susceptibility to COVID-19, and does COVID-19 increase susceptibility to tuberculosis? There are no published data around these questions yet. However, we know—based on a meta-analysis incorporating 19 studies—that active tuberculosis increases susceptibility to influenza virus47Walaza S Cohen C Tempia S et al.Influenza and tuberculosis co-infection: a systematic review.Influenza Other Respir Vir. 2020; 14: 77-91Google Scholar and is a risk factor for subsequent influenza hospitalisation48Abadom TR Smith AD Tempia S Madhi SA Cohen C Cohen AL Risk factors associated with hospitalisation for influenza-associated severe acute respiratory illness in South Africa: a case-population study.Vaccine. 2016; 34: 5649-5655Google Scholar and increased mortality.49Cohen C Moyes J Tempia S et al.Mortality amongst patients with influenza-associated severe acute respiratory illness, South Africa, 2009–2013.PLoS One. 2015; 10e0118884Google Scholar The reverse has also proved to be true: influenza is associated with increased susceptibility to pulmonary tuberculosis disease ( and disease severity). This relationship was also reported anecdotally during the 1918 influenza pandemic. It is speculated that this might be through antagonism of the interferon-γ pathway ( by type-1 interferons such as α and β), with excessive production of interleukin-10 and increased apoptosis.50Tisoncik JR Korth MJ Simmons CP Farrar J Martin TR Katze MG Into the eye of the cytokine storm.Microbiol Mol Biol Rev. 2012; 76: 16-32Google Scholar It is possible that a similar interaction ( increased disease susceptibility and severity) could be occurring between COVID-19 and active tuberculosis, although this remains to be proven. A study showed that individuals with COVID-19 had a reduced frequency of M tuberculosis-specific CD4 T cells in the peripheral blood compartment, supporting the hypothesis that COVID-19 might increase susceptibility to and progression to active tuberculosis.51Riou C Du Bruyn E Stek C et al.Relationship of SARS-CoV-2–specific CD4 response to COVID-19 severity and impact of HIV-1 and tuberculosis coinfection.J Clin Invest. 2021; 131e149125Google Scholar
The mode of transmission of SARS-CoV-2 was initially thought to be limited to large respiratory droplets ( > 5–10 μm) —as it used to be for tuberculosis—a conclusion biased by the decades-old assumption that most respiratory viruses are not transmitted by the airborne route. Much of this bias was caused by the so-called proximity pitfall, the fallacious logic that if there is evidence of transmission of respiratory pathogens at close contact ( eg, 1 m), then there is no transmission at a distance.52Fennelly KP Particle sizes of infectious aerosols: implications for infection control.Lancet Respir Med. 2020; 8: 914-924Google Scholar The 1 m rule is also now known to be false. Large droplets of up to 100 μm have been shown to be carried in turbulent gas clouds for 7–8 m.53Bourouiba L Turbulent gas clouds and respiratory pathogen emissions.JAMA. 2020; 323: 1837-1838Google Scholar We have also learned that human coughs and sneezes create plumes of both small and large particles—ie, both aerosol ( ≤5 μm) and droplets ( > 5 μm) that are highest in concentration close to the source case and dissipate with distance. This is the principle underlying the benefit of physical distancing. However, patients with either COVID-19 or active tuberculosis, or both, often need medical, nursing, and other care requiring close contact. This can result in exposure to infectious aerosols that include both larger droplets and smaller aerosol particles. In the case of tuberculosis, only the small particles are likely to transmit disease. In the case of COVID-19, it appears that both the droplets and aerosol particles transmit disease. Fortunately, all infection prevention and control ( IPC) practices that prevent transmission of aerosols also prevent transmission of droplets.
The clinical presentations of COVID-19 and active tuberculosis, either alone or as co-infection, can be similar, as discussed hereafter. We are not aware of published data on the transmission of either SARS-CoV-2 or M tuberculosis during co-infection, but both can probably be transmitted if there is evidence of both pathogens in respiratory secretions. As the transmission of these diseases shares many common elements ( table 2), methods to prevent transmission are nearly identical. A lesson learned from the outbreaks of multidrug-resistant tuberculosis in the 1980s and 1990s was that the airborne transmission of M tuberculosis was preventable by the implementation of administrative, engineering, and personal respiratory-protection control measures.54Jensen PA Lambert LA Iademarco MF Ridzon R Guidelines for preventing the transmission of Mycobacterium tuberculosis in health-care settings, 2005.MMWR Recomm Rep. 2005; 54: 1-141Google Scholar In tuberculosis-endemic settings, almost all the spread of rifampicin-resistant and fluoroquinolone-resistant tuberculosis is by primary rather than acquired transmission.55Dheda K Gumbo T Maartens G et al.The epidemiology, pathogenesis, transmission, diagnosis, and management of multidrug-resistant and incurable tuberculosis.Lancet Respir Med. 2019; 7: 820-826Google Scholar The only major difference now is that vaccination is the most important administrative control measure for COVID-19, markedly reducing the susceptibility of exposed HCWs.56Cabezas C Coma E Mora-Fernandez N et al.Associations of BNT162b2 vaccination with SARS-CoV-2 infection and hospital admission and death with covid-19 in nursing homes and healthcare workers in Catalonia: prospective cohort study.BMJ. 2021; 374n1868Google Scholar The most important administrative control measure for active tuberculosis remains rapid diagnosis and treatment, rendering the patient non-infectious. These findings, apart from their applicability to frontline HCWs caring for patients with possible active tuberculosis or COVID-19, or both, and the use of N95-equivalent respirators,57Mottay L le Roux J Perumal R et al.KN95 filtering facepiece respirators distributed in South Africa fail safety testing protocols.S Afr Med J. 2020; 111: 234-239Google Scholar have several implications for COVID-19 control, including improved ventilation in congregate settings ( eg, schools, buses, taxis, places of worship, restaurants, and shopping malls) and wider use of masking to prevent transmission and superspreader events. Improved COVID-19 control would be beneficial for tuberculosis management at the patient and HCW level.Table 2Evidence for factors related to transmission by Mycobacterium tuberculosis and SARS-CoV-2Mycobacterium tuberculosisSARS-CoV-2Transmission by small aerosol particlesStrongStrongTransmission by large aerosol particles ( droplets) RareStrongTransmission by fomites or contactNoWeakIsolation of viable pathogen in room airNoYesIdentification of pathogen by PCR in room airYesYesIsolation ( culture) of pathogen from cough aerosolsYesNoIsolation of pathogen from exhaled breathYesYesRisk to household contactsHighHighRisk to health-care providersHighHighRisk with proximity to index caseHighHighRisk of transmission from asymptomatic caseProbableHighRisk of transmission outdoorsLowLowRisk of transmission indoorsHighHighReduction of risk by patient mask useYesYesSusceptibility of pathogen to ultraviolet lightHighProbably highSuperspreading epidemiologyYesYes Open table in a new tab
Few comprehensive studies document the prevalence of tuberculosis in patients with COVID-19. Tuberculosis prevalence ( past, current, or past and current) is estimated to vary by between about 2% and 8% in hospitalised COVID-19 cohorts from tuberculosis-endemic countries; for example, an analysis of surveillance data from South Africa found that among 3217 individuals hospitalised with COVID-19, 5·5% had current tuberculosis and 4·0% had previous tuberculosis ( data from the South African NICD). In a population cohort study of about 3·5 million patients from the Western Cape province of South Africa ( 22 308 of whom were diagnosed with COVID-19), about 10% of those with COVID-19 had a diagnosis of previous tuberculosis or current active tuberculosis, with about 2% having concurrent active tuberculosis and COVID-19 in an inpatient setting.58Western Cape Department of Health in collaboration with the National Institute for Communicable DiseasesRisk factors for coronavirus disease 2019 ( COVID-19) death in a population cohort study from the Western Cape Province, South Africa.Clin Infect Dis. 2021; 73: e2005-e2015Google Scholar In another study of 219 265 individuals who were hospitalised with COVID-19, 5·0% of those aged 20–39 years had concurrent active tuberculosis ( figure 4A),59Jassat W Mudara C Ozougwu L et al.Difference in mortality among individuals admitted to hospital with COVID-19 during the first and second waves in South Africa: a cohort study.Lancet Glob Health. 2021; 9: e1216-e1225Google Scholar although this is probably an underestimate given the scarcity of comprehensive testing for tuberculosis and because of other reasons, such as lack of clinical suspicion. In a limited ( minimally invasive tissue sampling) post-mortem biopsy study undertaken in Johannesburg, South Africa ( n=150), microbiologically proven tuberculosis was detected in 3% of COVID-19-positive biopsies and 13% of COVID-19-negative biopsies.61Nunes MC Hale MJ Mahtab S et al.Clinical characteristics and histopathology of COVID-19 related deaths in South African adults.PLoS One. 2022; 17e0262179Google Scholar For comparative purposes, the prevalence of tuberculosis in the same general population, including those with subclinical or undiagnosed tuberculosis in the community, is about 0·5–1%.62South African Medical Research CouncilThe first national TB prevalence survey South Africa 2018.https: //www.knowledgehub.org.za/elibrary/first-national-tb-prevalence-survey-south-africa-2018Date: June 10, 2020Date accessed: August 12, 2021Google ScholarFigure 4Co-prevalence of COVID-19, tuberculosis, HIV, and non-communicable diseasesShow full caption ( A) Euler diagram of the estimated prevalence of HIV, current tuberculosis, and non-communicable comorbid conditions in patients admitted to hospital with SARS-CoV-2 infection by age group. ( B) Forest plot of the effect of HIV and active tuberculosis on the risk of mortality associated with COVID-19. Multivariable analysis of factors associated with COVID-19 in-hospital mortality from published South African data is shown.59Jassat W Mudara C Ozougwu L et al.Difference in mortality among individuals admitted to hospital with COVID-19 during the first and second waves in South Africa: a cohort study.Lancet Glob Health. 2021; 9: e1216-e1225Google Scholar, 60Jassat W Cohen C Tempia S et al.Risk factors for COVID-19-related in-hospital mortality in a high HIV and tuberculosis prevalence setting in South Africa: a cohort study.Lancet HIV. 2021; 8: e554-e567Google Scholar The model adjusted for age, sex, race, other comorbid conditions, health sector, province, and month of admission. Adjusted odds ratios and 95% CIs are shown for HIV only, current tuberculosis only, and HIV and tuberculosis co-infection. Values that overlap between comorbidities are noted in the appendix ( p 13).View Large Image Figure ViewerDownload Hi-res image Download ( PPT)
( A) Euler diagram of the estimated prevalence of HIV, current tuberculosis, and non-communicable comorbid conditions in patients admitted to hospital with SARS-CoV-2 infection by age group. ( B) Forest plot of the effect of HIV and active tuberculosis on the risk of mortality associated with COVID-19. Multivariable analysis of factors associated with COVID-19 in-hospital mortality from published South African data is shown.59Jassat W Mudara C Ozougwu L et al.Difference in mortality among individuals admitted to hospital with COVID-19 during the first and second waves in South Africa: a cohort study.Lancet Glob Health. 2021; 9: e1216-e1225Google Scholar, 60Jassat W Cohen C Tempia S et al.Risk factors for COVID-19-related in-hospital mortality in a high HIV and tuberculosis prevalence setting in South Africa: a cohort study.Lancet HIV. 2021; 8: e554-e567Google Scholar The model adjusted for age, sex, race, other comorbid conditions, health sector, province, and month of admission. Adjusted odds ratios and 95% CIs are shown for HIV only, current tuberculosis only, and HIV and tuberculosis co-infection. Values that overlap between comorbidities are noted in the appendix ( p 13).
Active tuberculosis is often not considered by clinicians in the setting of acute lower respiratory tract infection ( LRTI) or acute community-acquired pneumonia. However, this often reflects a misunderstanding and unfamiliarity with the concept of tuberculosis-associated community-acquired pneumonia. Active tuberculosis presenting as an acute LRTI is well documented, but a poorly appreciated and inadequately studied entity.63Dheda K Makambwa E Esmail A The Great masquerader: tuberculosis presenting as community-acquired pneumonia.Semin Respir Crit Care Med. 2020; 41: 592-604Google Scholar A systematic review across several countries in Africa and Asia ( including China, India, Malaysia, Cambodia, and Vietnam) showed that 10–15% of community-acquired pneumonia cases or LRTIs in these settings are caused by M tuberculosis.64Wei M Yongjie Z Zhuoyu Q et al.Pneumonia caused by Mycobacterium tuberculosis.Microb Infect. 2020; 22: 278-284Google Scholar Duration of symptoms is a poor guide to the likelihood of tuberculosis; a study of almost 2500 individuals with respiratory tract infection admitted to two hospitals in South Africa between 2012 and 2014 showed that when the duration of symptoms was less than 14 days, a staggering 18% of participants still had positive microbiological tests for tuberculosis.65Walaza S Tempia S Dreyer A et al.The burden and clinical presentation of pulmonary tuberculosis in adults with severe respiratory illness in a high human immunodeficiency virus prevalence setting, 2012–2014.Open Forum Infectious Diseases. 2017; 4ofx116Google Scholar The key message is that in certain high tuberculosis-burden settings, symptom duration of less than 14 days and acute presentation of LRTIs does not exclude the possibility of active tuberculosis. Collectively, these data suggest that the burden of active tuberculosis in people hospitalised with COVID-19 ( as aforementioned) is probably underestimated. A patient perspective provided by AvD and DvD is outlined in panel 4; a more detailed version is available in the appendix ( p 2).Panel 4Patient perspectiveSocial stigma kills. Like tuberculosis, COVID-19 has fuelled social stigma because it is easy for societies to associate the fear of the unknown with others; 66WHOSocial stigma associated with COVID-19, 2020. World Health Organization, Geneva2020Google Scholar we have seen people afraid of testing and disclosing test results, and not adhering to guidelines to prevent the spread of disease.Afraid of being labelled as weak, scared, or sickly, individuals might hide their disease status or struggle with the mental and social challenges of existential stigma.67Flak G STIGMA: how we treat outsiders. Prometheus Books, New York2001Google Scholar To ask those who must battle an airborne infectious disease in isolation to simultaneously fight social stigma and question their worth is unacceptable. To find meaning in the devastation of tuberculosis and COVID-19, and to mitigate the effects of future pandemics, we need a shift in the way in which society views infectious diseases and health.Like tuberculosis, COVID-19 can cause death in one person but no symptoms in another; we know that some conditions predispose individuals to infection or more severe disease, but we do not always know why some apparently healthy individuals are vulnerable and become so ill. These unknowns can drive stigma.Understanding the responses of members of society—individuals and communities—to the threats posed by an infectious disease outbreak is crucial to implementing effective strategies for infection prevention and control, and to minimising the negative health impacts of mitigation strategies.Patient groups have raised concerns about the regrettable inevitability of the destruction caused to affected communities by tuberculosis because of the supposedly insurmountable shortage of resources. Yet US $ 9 billion were invested in research and development in the first 9 months of the COVID-19 pandemic,68Policy Cures ResearchCOVID-19 R & D tracker.https: //www.policycuresresearch.org/covid-19-r-d-trackerDate: 2020Date accessed: September 1, 2021Google Scholar which claimed 1 million lives in that same time. This is the same amount invested in tuberculosis in the preceding 14 years,69Treatment Action GroupTuberculosis research funding trends, 2005–2019. The Stop TB Partnership, New York2020Google Scholar at the cost of 25 million lives.1WHOGlobal tuberculosis report 2020. World Health Organization, Geneva2020Google Scholar The COVID-19 response has been lauded for its unprecedented global solidarity. Similar shared promises have been made for tuberculosis at the highest levels, but these have repeatedly failed to result in desperately needed actions and investments. Are the lives lost to tuberculosis really worth so much less than those lost to COVID-19?
Social stigma kills. Like tuberculosis, COVID-19 has fuelled social stigma because it is easy for societies to associate the fear of the unknown with others; 66WHOSocial stigma associated with COVID-19, 2020. World Health Organization, Geneva2020Google Scholar we have seen people afraid of testing and disclosing test results, and not adhering to guidelines to prevent the spread of disease.
Afraid of being labelled as weak, scared, or sickly, individuals might hide their disease status or struggle with the mental and social challenges of existential stigma.67Flak G STIGMA: how we treat outsiders. Prometheus Books, New York2001Google Scholar To ask those who must battle an airborne infectious disease in isolation to simultaneously fight social stigma and question their worth is unacceptable. To find meaning in the devastation of tuberculosis and COVID-19, and to mitigate the effects of future pandemics, we need a shift in the way in which society views infectious diseases and health.
Like tuberculosis, COVID-19 can cause death in one person but no symptoms in another; we know that some conditions predispose individuals to infection or more severe disease, but we do not always know why some apparently healthy individuals are vulnerable and become so ill. These unknowns can drive stigma.
Understanding the responses of members of society—individuals and communities—to the threats posed by an infectious disease outbreak is crucial to implementing effective strategies for infection prevention and control, and to minimising the negative health impacts of mitigation strategies.
Patient groups have raised concerns about the regrettable inevitability of the destruction caused to affected communities by tuberculosis because of the supposedly insurmountable shortage of resources. Yet US $ 9 billion were invested in research and development in the first 9 months of the COVID-19 pandemic,68Policy Cures ResearchCOVID-19 R & D tracker.https: //www.policycuresresearch.org/covid-19-r-d-trackerDate: 2020Date accessed: September 1, 2021Google Scholar which claimed 1 million lives in that same time. This is the same amount invested in tuberculosis in the preceding 14 years,69Treatment Action GroupTuberculosis research funding trends, 2005–2019. The Stop TB Partnership, New York2020Google Scholar at the cost of 25 million lives.1WHOGlobal tuberculosis report 2020. World Health Organization, Geneva2020Google Scholar The COVID-19 response has been lauded for its unprecedented global solidarity. Similar shared promises have been made for tuberculosis at the highest levels, but these have repeatedly failed to result in desperately needed actions and investments. Are the lives lost to tuberculosis really worth so much less than those lost to COVID-19?
Although night sweats, haemoptysis, loss of weight, and isolated upper-zone pulmonary infiltrates are more suggestive of active tuberculosis, symptoms of active tuberculosis and COVID-19 often overlap.70Dheda K Jaumdally S Davids M et al.Diagnosis of COVID-19: Considerations, controversies and challenges.Afr J Thorac Crit Care Med. 2020; 26: 36Google Scholar Furthermore, although isolated upper-lobe pulmonary infiltrates might indicate active tuberculosis and lower infiltrates might be suggestive of other bacterial infection, the radiology of active tuberculosis and COVID-19 are often similar ( appendix p 7). Indeed, tuberculosis-associated community-acquired pneumonia can present as bilateral nodular-to-confluent shadowing, which is often also seen with COVID-19.70Dheda K Jaumdally S Davids M et al.Diagnosis of COVID-19: Considerations, controversies and challenges.Afr J Thorac Crit Care Med. 2020; 26: 36Google Scholar A study indicated that in almost half the cases of active tuberculosis and COVID-19 co-infection, radiological features were unhelpful diagnostically, and in 40% of cases, CT findings were consistent with COVID-19.71Motta I Centis R D'Ambrosio L et al.Tuberculosis, COVID-19 and migrants: preliminary analysis of deaths occurring in 69 patients from two cohorts.Pulmonology. 2020; 26: 233-240Google Scholar, 72Tadolini M Codecasa LR García-García J-M et al.Active tuberculosis, sequelae and COVID-19 co-infection: first cohort of 49 cases.Eur Respir J. 2020; 562001398Google Scholar Furthermore, COVID-19 might also occur during tuberculosis treatment, and SARS-CoV-2 infection might unmask a diagnosis of subclinical tuberculosis. In tuberculosis-endemic countries, such an occurrence is not unusual, given the very high incidence of tuberculosis. Indeed, in the South African 2018 national tuberculosis prevalence survey ( which estimated an annual incidence of 737 cases per 100 000 people), 58% of patients with culture-proven active tuberculosis did not report any tuberculosis-related symptoms ( and thus tuberculosis would have remained undetected were it not for COVID-19-related hospitalisation or presentation).62South African Medical Research CouncilThe first national TB prevalence survey South Africa 2018.https: //www.knowledgehub.org.za/elibrary/first-national-tb-prevalence-survey-south-africa-2018Date: June 10, 2020Date accessed: August 12, 2021Google Scholar
Biomarkers are often unhelpful in distinguishing tuberculosis from COVID-19. Both diseases can cause lymphopenia and raise inflammatory markers, including C-reactive protein ( CRP). HIV co-infection can further complicate the picture, especially in African settings, because HIV can suppress typical symptoms of active tuberculosis, modulate radiological findings, and influence biomarker profiles.
To further complicate matters, tuberculosis and COVID-19-specific NAATs have a false-negative rate of 20–30% because of the sampling error and variability in pathogen load,70Dheda K Jaumdally S Davids M et al.Diagnosis of COVID-19: Considerations, controversies and challenges.Afr J Thorac Crit Care Med. 2020; 26: 36Google Scholar patients with tuberculosis are not uncommonly sputum scarce, sputum induction is unavailable or inappropriate in a COVID-19 setting, and tuberculosis-specific NAATs might give false-positives in cases of previous tuberculosis.73Theron G Venter R Smith L et al.False-positive Xpert MTB/RIF results in retested patients with previous tuberculosis: frequency, profile, and prospective clinical outcomes.J Clin Microbiol. 2018; 56: e01696-e01717Google Scholar, 74Theron G Venter R Calligaro G et al.Xpert MTB/RIF results in patients with previous tuberculosis: can we distinguish true from false positive results?.Clin Infect Dis. 2016; 62: 995-1001Google Scholar Thus, alternative non-respiratory tract-based tests for active tuberculosis and COVID-19 are urgently required. Repeat COVID-19 testing is often required, and tuberculosis culture positivity can only be detected several weeks down the line, which can further complicate the diagnosis. In people who are HIV positive with advanced immunosuppression, testing for urine lipoarabinomannan ( LAM) 75Peter JG Theron G Dheda K Can point-of-care urine LAM strip testing for tuberculosis add value to clinical decision making in hospitalised hiv-infected persons?.PLoS One. 2013; 8e54875Google Scholar and using abdominal ultrasound to detect lymphadenopathy and liver and splenic abscesses could be useful.76Heller T Mtemang'Ombe EA Huson MAM et al.Ultrasound for patients in a high HIV/tuberculosis prevalence setting: a needs assessment and review of focused applications for Sub-Saharan Africa.Int J Infect Dis. 2017; 56: 229-236Google Scholar, 77WHOLateral flow urine lipoarabinomannan assay ( LF-LAM) for the diagnosisi of active tuberculosis in people living with HIV. World Health Organization, Geneva2019Google Scholar
In summary, reliance on typical patterns of presentation of active tuberculosis and COVID-19 ( including in tuberculosis-endemic settings) to ascertain a clinicoradiological diagnosis is unreliable, and one should test for both diseases ( separate samples are required), or at least have a low index for also testing for tuberculosis when testing for COVID-19.78Song W-M Zhao J-Y Zhang Q-Y et al.COVID-19 and tuberculosis coinfection: an overview of case reports/case series and meta-znalysis.Front Med ( Lausanne). 2021; 8: 48-50Google Scholar
The ambiguous presentation of tuberculosis in the context of COVID-19 has implications for HCWs and clinical practice. It is well recognised that HCWs are at increased risk ( compared with the general population) of both COVID-19 and tuberculosis.79Uden L Barber E Ford N Cooke GS Risk of tuberculosis infection and disease for health care workers: an updated meta-analysis.Open Forum Infect Dis. 2017; 4ofx137Google Scholar, 80Baussano I Nunn P Williams B Pivetta E Bugiani M Scano F Tuberculosis among health care workers.Emerg Infect Dis. 2011; 17: 488-494Google Scholar, 81Bandyopadhyay S Baticulon RE Kadhum M et al.Infection and mortality of healthcare workers worldwide from COVID-19: a systematic review.BMJ Glob Health. 2020; 5e003097Google Scholar In many settings, including in Africa, HCWs might have HIV, placing them at even higher risk of both diseases. Because active tuberculosis and COVID-19 might have similar presentations, present simultaneously, often have overlapping risk factors and imaging characteristics, and take time ( usually 24–72 h) to diagnose ( especially during surges), and because active tuberculosis might present as an acute LRTI,63Dheda K Makambwa E Esmail A The Great masquerader: tuberculosis presenting as community-acquired pneumonia.Semin Respir Crit Care Med. 2020; 41: 592-604Google Scholar HCWs might be exposed to infectious aerosols of SARS-CoV-2, M tuberculosis, or both for a prolonged period of time. Effectively, it is impossible to clinically tell the difference between active tuberculosis and COVID-19. Thus, airborne IPC packages must be prioritised and implemented,82WHOWHO guidelines on tuberculosis infection, prevention and control. World Health Organization, Geneva2019Google Scholar particularly in tuberculosis-endemic settings. Such packages will include administrative, environmental, and personal protection measures, including access to particulate filtering facepiece ( N95, FFP2, or equivalent) respirators to ensure HCW safety, as well as adequate ventilation. As aerosol transmission of SARS-CoV-2 has been more widely recognised, several international bodies ( including WHO, the US Centers for Disease Control and Prevention, and the European Centre for Disease Prevention and Control) have updated their guidelines to recommend the use of respirators for routine care of individuals thought or known to have COVID-19.83WHOCOVID-19: occupational health and safety for health workers: interim guidance. World Health Organization, Geneva2021Google Scholar, 84European Centre for Disease Prevention and ControlInfection prevention and control and preparedness for COVID-19 in healthcare settings. European Centre for Disease Prevention and Control, Stockholm2021Google Scholar, 85Centers for Disease Control and PreventionUsing personal protective equipment ( PPE).https: //www.cdc.gov/coronavirus/2019-ncov/hcp/using-ppe.htmlDate: Aug 19, 2020Date accessed: August 23, 2021Google Scholar It is already established best practice to protect against M tuberculosis in high tuberculosis-burden settings, but this is rarely implemented in LMICs.82WHOWHO guidelines on tuberculosis infection, prevention and control. World Health Organization, Geneva2019Google Scholar This is a complex topic with many challenges, including the global shortage of PPE, and several relevant aspects have been reviewed in detail elsewhere as part of South African guidance on protecting HCWs.86Dheda K Charalambous S Karat AS et al.A position statement and practical guide to the use of particulate filtering facepiece respirators ( N95, FFP2, or equivalent) for South African health workers exposed to respiratory pathogens including Mycobacterium tuberculosis and SARS-CoV-2.Afr J Thorac Crit Care Med. 2021; 26: 10Google Scholar
Management of COVID-19 is similar in patients with both active tuberculosis and COVID-19. The need for steroids and respiratory support is dictated by indices of oxygenation ( eg, oxygen saturation and partial pressure of oxygen) and clinical presentation. If steroids are indicated for the treatment of COVID-19 in patients with active tuberculosis, then the dose is generally doubled because of the liver enzyme-inducing effect of rifampicin. Similar considerations might apply to some antiviral therapies; for instance, rifampicin is predicted to reduce exposure to remdesivir, although the clinical importance of this exposure remains unclarified.87Yang K What do we know about remdesivir drug interactions?.Clin Translat Sci. 2020; 13: 842-844Google Scholar, 88Liverpool Drug Interactions Group University of LiverpoolCOVID-19 drug interactions.https: //www.covid19-druginteractions.org/Date: 2021Date accessed: May 4, 2021Google Scholar The pharmacokinetic effect of rifampicin on newer antivirals such as molnupiravir and paxlovid remains to be clarified. In patients who require mechanical ventilation, tuberculosis treatment might need to be given intravenously or via a nasogastric tube.89Esmail A Sabur NF Okpechi I Dheda K Management of drug-resistant tuberculosis in special sub-populations including those with HIV co-infection, pregnancy, diabetes, organ-specific dysfunction, and in the critically ill.J Thorac Dis. 2018; 10: 3102-3118Google Scholar Administration via nasogastric tube might necessitate therapeutic drug monitoring.89Esmail A Sabur NF Okpechi I Dheda K Management of drug-resistant tuberculosis in special sub-populations including those with HIV co-infection, pregnancy, diabetes, organ-specific dysfunction, and in the critically ill.J Thorac Dis. 2018; 10: 3102-3118Google Scholar The management of people with rifampicin-resistant active tuberculosis and COVID-19 co-infection is similar to that of people who do not have a co-infection. Given the growing recognition of fungal infections ( eg, mucormycoses) among people who survive COVID-19, potentially driven by diabetes and prolonged steroid use, it is important to achieve good glycaemic control and avoid steroid overuse, especially in people with concurrent active tuberculosis.
Data from South Africa59Jassat W Mudara C Ozougwu L et al.Difference in mortality among individuals admitted to hospital with COVID-19 during the first and second waves in South Africa: a cohort study.Lancet Glob Health. 2021; 9: e1216-e1225Google Scholar and elsewhere58Western Cape Department of Health in collaboration with the National Institute for Communicable DiseasesRisk factors for coronavirus disease 2019 ( COVID-19) death in a population cohort study from the Western Cape Province, South Africa.Clin Infect Dis. 2021; 73: e2005-e2015Google Scholar suggest that, similar to co-infection with influenza and active tuberculosis,47Walaza S Cohen C Tempia S et al.Influenza and tuberculosis co-infection: a systematic review.Influenza Other Respir Vir. 2020; 14: 77-91Google Scholar and bacterial co-infection with active tuberculosis,90Moore DP Klugman KP Madhi SA Role of Streptococcus pneumoniae in hospitalization for acute community-acquired pneumonia associated with culture-confirmed Mycobacterium tuberculosis in children: a pneumococcal conjugate vaccine probe study.Pediatr Infect Dis J. 2010; 29: 1099-1104Google Scholar patients with COVID-19 and concurrent or past history of tuberculosis have an approximately two-times greater risk of hospital-based mortality than do those without tuberculosis. HIV and COVID-19 co-infection alone is also associated with a similar increased risk of mortality,58Western Cape Department of Health in collaboration with the National Institute for Communicable DiseasesRisk factors for coronavirus disease 2019 ( COVID-19) death in a population cohort study from the Western Cape Province, South Africa.Clin Infect Dis. 2021; 73: e2005-e2015Google Scholar, 60Jassat W Cohen C Tempia S et al.Risk factors for COVID-19-related in-hospital mortality in a high HIV and tuberculosis prevalence setting in South Africa: a cohort study.Lancet HIV. 2021; 8: e554-e567Google Scholar and HIV, active tuberculosis, and COVID-19 co-infection increases this mortality risk even further ( figure 4B), with the highest mortality risk in those with advanced immunosuppression and not on antiretroviral therapy.
These risk factors have implications for triaging patients for more advanced respiratory support in tuberculosis-endemic settings and, given the higher mortality in patients co-infected with active tuberculosis and COVID-19, supports a role for giving patients with active tuberculosis and survivors of tuberculosis priority for earlier SARS-CoV-2 vaccination, testing for tuberculosis in all people with COVID-19, and testing for COVID-19 in all people with newly diagnosed active tuberculosis when there is still substantial community transmission of SARS-CoV-2. Moreover, people co-infected with active tuberculosis and COVID-19 should be monitored more closely with a lower threshold for referral and intervention.
In addition to affecting mortality risk in patients with tuberculosis, COVID-19 has also been shown to negatively affect other tuberculosis outcomes, including treatment failure and loss to follow-up rates through several mechanisms ( figure 2).
Persistent pulmonary impairment, disability, or both after active tuberculosis ( due to pulmonary remodelling associated with cavitation, fibrosis, and bronchiectasis) is present in about 50% of tuberculosis survivors ( a higher proportion in the severe disease group) despite successful microbiological treatment.10Ravimohan S Kornfeld H Weissman D Bisson GP Tuberculosis and lung damage: from epidemiology to pathophysiology.Eur Respir Rev. 2018; 27170077Google Scholar This impairment is one reason why tuberculosis co-infection might be associated with increased susceptibility to COVID-19 and a higher risk of mortality in people with COVID-19.58Western Cape Department of Health in collaboration with the National Institute for Communicable DiseasesRisk factors for coronavirus disease 2019 ( COVID-19) death in a population cohort study from the Western Cape Province, South Africa.Clin Infect Dis. 2021; 73: e2005-e2015Google Scholar
Patients with lung disease after tuberculosis might be at greater risk of developing COVID-19 pneumonia, and hence lung disease after COVID-19, and are at increased risk of death when hospitalised with COVID-19 pneumonia, as discussed in the previous subsection. On the basis of animal studies and data obtained from patients with active tuberculosis, dysregulated immunity in patients with lung disease after tuberculosis is probably characterised by the unchecked activity of matrix metalloproteinases, a proinflammatory and fibrogenic cytokine profile, an abundance of neutrophil extracellular traps, and uncontrolled CD4 T-cell activation; these factors might contribute to a heightened risk of developing lung disease after COVID-19 in these patients.10Ravimohan S Kornfeld H Weissman D Bisson GP Tuberculosis and lung damage: from epidemiology to pathophysiology.Eur Respir Rev. 2018; 27170077Google Scholar, 91Dheda K Booth H Jim Margaret Zumla A Graham Lung remodeling in pulmonary tuberculosis.J Infect Dis. 2005; 192: 1201-1209Google Scholar Genetic polymorphisms in the MMP1 ( matrix metalloproteinase 1) and MCP1 ( CCL2 or C-C motif chemokine ligand 2) promoter regions have been shown to portend an increased risk for fibrosis and bronchiectasis after tuberculosis. Given the high prevalence of lung disease after tuberculosis, high tuberculosis-burden settings should be prepared for a substantial burden of lung disease after COVID-19 and resulting disability following the COVID-19 pandemic ( appendix pp 8–9).92Meghji J Simpson H Squire SB Mortimer K A systematic review of the prevalence and pattern of imaging defined post-TB lung disease.PLoS One. 2016; 11e0161176Google Scholar, 93Pasipanodya JG McNabb SJ Hilsenrath P et al.Pulmonary impairment after tuberculosis and its contribution to TB burden.BMC Public Health. 2010; 10: 259Google Scholar The convergence of lung disease after tuberculosis and lung disease after COVID-19 necessitates the follow-up of patients with post-tuberculosis lung disease who had COVID-19 pneumonia and the prioritisation of their linkage to respiratory services for optimal care.94Wang CH Lin HC Lin SM et al.MMP-1 ( -1607G) polymorphism as a risk factor for fibrosis after pulmonary tuberculosis in Taiwan.Int J Tuberc Lung Dis. 2010; 14: 627-634Google Scholar, 95Harries AD Ade S Burney P Hoa NB Schluger NW Castro JL Successfully treated but not fit for purpose: paying attention to chronic lung impairment after TB treatment.Int J Tuberc Lung Dis. 2016; 20: 1010-1014Google Scholar We would advocate for joint or combined services for lung disease after tuberculosis and after COVID-19 in appropriate settings.
Almost one in three ( about 3 million) people with active tuberculosis, even in the pre-COVID-19 era, remained undiagnosed or unreported globally.1WHOGlobal tuberculosis report 2020. World Health Organization, Geneva2020Google Scholar These individuals act as a potential reservoir for transmission. The majority of these so-called missing individuals often reside in peri-urban informal settlements of large cities in Africa and Asia.96WHOWHO consolidated guidelines on tuberculosis module 2: systematic screening for tuberculosis disease. World Health Organization, Geneva2021Google Scholar, 97Dheda K Gumbo T Maartens G et al.The epidemiology, pathogenesis, transmission, diagnosis, and management of multidrug-resistant, extensively drug-resistant, and incurable tuberculosis.Lancet Respir Med. 2017; 5: 291-360Google Scholar Thus, to address the COVID-19-related reduction in case detection and to reduce transmission, disease burden, and mortality, community-based enhanced case detection is required. We need to take tuberculosis testing closer to where people live and work. Active case-finding strategies have always had important implications for tuberculosis prevention and reduced amplification of the epidemic even before the advent of COVID-19.
Instead of annual tuberculosis reports, global and national public-facing dashboards and trackers reporting real-time numbers of tuberculosis cases and deaths, including monitoring of trends over time, would be a useful addition to tuberculosis monitoring. They would keep the public informed and hold services accountable at national, regional, and global levels. Such dashboards have been used very effectively to monitor the COVID-19 pandemic and to evaluate the effect of interventions. It is not widely appreciated by the lay public that although the direct death toll from COVID-19 is estimated to be about 4·5 million people over an approximately 18-month period,98Dong E Du H Gardner L An interactive web-based dashboard to track COVID-19 in real time.Lancet Infect Dis. 2020; 20: 533-534Google Scholar the sustained death toll from tuberculosis over the past decade has been close to about 20 million people.1WHOGlobal tuberculosis report 2020. World Health Organization, Geneva2020Google Scholar A public-facing dashboard for tuberculosis has now been instituted in the Western Cape province of South Africa.99Jeranji T Western Cape to launch Covid-style TB dashboard.https: //www.news24.com/citypress/news/western-cape-to-launch-covid-style-tb-dashboard-20210520Date: May 20, 2021Date accessed: August 21, 2021Google Scholar
Digital tools such as mobile phone-based screening and tracing apps have been used with great effect to manage the COVID-19 pandemic.100Ruhwald M Carmona S Pai M Learning from COVID-19 to reimagine tuberculosis diagnosis.Lancet Microbe. 2021; 2: e169-e170Google Scholar The same methodologies could easily be applied to tuberculosis. In South Africa, the Department of Health has recently introduced a WhatsApp and SMS-based tuberculosis screening app—the TB Health Check app—that requires little cell phone memory, uses a few simple screening questions, and links individuals to tuberculosis testing services. At the time of writing, more than 30 000 screenings had been done, and a staggering 12·8% of those with symptoms who subsequently tested for tuberculosis were positive. Work is underway to integrate the COVID-19 and tuberculosis screening apps. A more sophisticated version of this strategy could link individuals to tuberculosis testing booths in the way individuals have been linked to COVID-19 testing centres. App-based HIV self-testing programmes have already shown great promise,101Pai N Esmail A Saha Chaudhuri P et al.Impact of a personalised, digital, HIV self-testing app-based program on linkages and new infections in the township populations of South Africa.BMJ Glob Health. 2021; 6e006032Google Scholar, 102Diandreth L Jarrett BA Elf JL et al.Secure delivery of HIV-related and tuberculosis laboratory results to patient cell phones: a pilot comparative study.AIDS Behav. 2020; 24: 3511-3521Google Scholar and their potential could be expanded to include tuberculosis testing.
COVID-19 has increased acceptance of the value of universal testing for infectious diseases irrespective of symptoms. WHO recently updated recommendations for systematic screening of people in high-risk tuberculosis groups ( defined as using tests, examinations, or other procedures to identify those most likely to have tuberculosis disease).96WHOWHO consolidated guidelines on tuberculosis module 2: systematic screening for tuberculosis disease. World Health Organization, Geneva2021Google Scholar In most settings, symptom screening fulfils this role for tuberculosis, but there is increasing evidence for the use of WHO-recommended molecular assays, chest radiography, and, for HIV-positive inpatients, CRP and urine LAM assays, either as a standalone or in combination with symptom screening.
In the setting of high tuberculosis burden, people living with HIV are at high risk of tuberculosis, especially those with low CD4 counts103Ellis P Martin W Dodd P CD4 count and tuberculosis risk in HIV-positive adults not on ART: a systematic review and meta-analysis.PeerJ. 2017; 5e4165Google Scholar, 104Gupta A Wood R Kaplan R Bekker LG Lawn SD Tuberculosis incidence rates during 8 years of follow-up of an antiretroviral treatment cohort in South Africa: comparison with rates in the community.PLoS One. 2012; 7e34156Google Scholar and those not receiving suppressive antiretroviral therapy and tuberculosis preventive treatment.105Badje A Moh R Gabillard D et al.Effect of isoniazid preventive therapy on risk of death in west African, HIV-infected adults with high CD4 cell counts: long-term follow-up of the Temprano ANRS 12136 trial.Lancet Glob Health. 2017; 5: e1080-e1089Google Scholar Women who are pregnant and HIV positive bear a dual risk for active tuberculosis,106Salazar-Austin N Cohn S Lala S et al.Isoniazid preventive therapy and pregnancy outcomes in women living with human immunodeficiency virus in the tshepiso cohort.Clin Infect Dis. 2020; 71: 1419-1426Google Scholar given that pregnancy confers additional risk for tuberculosis disease when compared with non-pregnant women.107Jonsson J Kühlmann-Berenzon S Berggren I Bruchfeld J Increased risk of active tuberculosis during pregnancy and postpartum: a register-based cohort study in Sweden.Eur Respir J. 2020; 551901886Google Scholar, 108Odayar J Rangaka MX Zerbe A et al.Burden of tuberculosis in HIV-positive pregnant women in Cape Town, South Africa.Int J Tuberc Lung Dis. 2018; 22: 760-765Google Scholar Patients who have previously had an episode of tuberculosis are at a markedly higher risk of a subsequent episode and warrant additional screening for recurrence.109Reichler MR Khan A Sterling TR et al.Risk and timing of tuberculosis among close contacts of persons with infectious tuberculosis.J Infect Dis. 2018; 218: 1000-1008Google Scholar, 110Hill PC Jackson-Sillah DJ Fox A et al.Incidence of tuberculosis and the predictive value of ELISPOT and Mantoux tests in gambian case contacts.PLoS One. 2008; 3e1379Google Scholar, 111Fox GJ Barry SE Britton WJ Marks GB Contact investigation for tuberculosis: a systematic review and meta-analysis.Eur Respir J. 2013; 41: 140-156Google Scholar, 112Osman M Welte A Dunbar R et al.Morbidity and mortality up to 5 years post tuberculosis treatment in South Africa: a pilot study.Int J Infect Dis. 2019; 85: 57-63Google Scholar Finally, incarcerated adults in virtually every setting have a higher incidence of active tuberculosis than the populations that surround their incarcerating facility.113De Vries G Commandeur S Erkens C et al.Towards selective tuberculosis screening of people in prison in a low-incidence country.Eur Respir J. 2020; 551902209Google Scholar, 114Macedo LR Maciel ELN Struchiner CJ Tuberculosis in the Brazilian imprisoned population, 2007–2013.Epidemiol Serv Saude. 2017; 26: 783-794Google Scholar, 115Cords O Martinez L Warren JL et al.Incidence and prevalence of tuberculosis in incarcerated populations: a systematic review and meta-analysis.Lancet Public Health. 2021; 6: e300-e308Google Scholar
All these populations have a reported tuberculosis prevalence that is markedly higher than the threshold recommended by WHO for systematic screening, and they should be targeted for consent-based universal testing with rapid turnaround tests that have high sensitivity and specificity. Better integration of tuberculosis and COVID-19 molecular testing and optimisation of multidisease testing platforms will greatly help to expand access to testing for both infections. Some countries, such as South Africa, are adopting a targeted universal testing strategy that will test ( regardless of symptoms) all those attending health-care facilities who have HIV, previous tuberculosis, previous tuberculosis contact, or are pregnant. This is an emergency response to the profound reduction in testing since the start of the pandemic and should be considered by other countries.
Symptom screening is often ( and preferably routinely) done for all primary clinic attendees as part of screening for COVID-19. This screening offers an opportunity for systematic tuberculosis screening. There is considerable overlap between symptoms of mild COVID-19 and active tuberculosis, which suggests that dual testing for both pathogens should be done at least in attendees at high risk for tuberculosis, possibly using a single specimen to avoid creating an additional hazard for HCWs or other patients. However, because of safety concerns, there might be a reluctance to collect sputum, and alternative specimens that are safer to collect, such as tongue swabs116Luabeya AK Wood RC Shenje J et al.Noninvasive detection of tuberculosis by oral swab analysis.J Clin Microbiol. 2019; 57: e01847-e01918Google Scholar or saliva, should be explored for SARS-CoV-2 and M tuberculosis testing.117Namuganga AR Chegou NN Mubiri P Walzl G Mayanja-Kizza H Suitability of saliva for Tuberculosis diagnosis: comparing with serum.BMC Infect Dis. 2017; 17: 600Google Scholar, 118Nagura-Ikeda M Imai K Tabata S et al.Clinical evaluation of self-collected saliva by quantitative reverse transcription-PCR ( RT-qPCR), direct RT-qPCR, reverse transcription-loop-mediated isothermal amplification, and a rapid antigen test to diagnose COVID-19.J Clin Microbiol. 2020; 58: e01438-e01520Google Scholar Non-sputum-based tuberculosis diagnosis, however, remains a research challenge.
There are several approaches to community-based active case finding in high-prevalence settings.96WHOWHO consolidated guidelines on tuberculosis module 2: systematic screening for tuberculosis disease. World Health Organization, Geneva2021Google Scholar As noted by WHO, implementation of a population-wide screening programme requires a substantial investment of resources and needs to be judged against the potential for long-term reduction in future tuberculosis incidence. A door-to-door active case-finding or screening strategy has the potential to detect more people with active tuberculosis, but it is more costly and labour intensive than a mobile clinic approach. The door-to-door case-finding strategy, using laboratory-based molecular tools such as Xpert MTB/RIF, has been shown to reduce adult tuberculosis prevalence and have a favourable effect on disease burden in the wider community.119Marks GB Nguyen NV Nguyen PTB et al.Community-wide screening for tuberculosis in a high-prevalence setting.N Engl J Med. 2019; 381: 1347-1357Google Scholar Similarly, reductions in the prevalence of latent tuberculosis infection have been demonstrated among children in clusters in which door-to-door tuberculosis screening was done.119Marks GB Nguyen NV Nguyen PTB et al.Community-wide screening for tuberculosis in a high-prevalence setting.N Engl J Med. 2019; 381: 1347-1357Google Scholar, 120Ayles H Muyoyeta M Du Toit E et al.Effect of household and community interventions on the burden of tuberculosis in southern Africa: the ZAMSTAR community-randomised trial.Lancet. 2013; 382: 1183-1194Google Scholar Compared with door-to-door strategies, a mobile clinic-based approach has been reported to be more effective for case detection.121Corbett EL Bandason T Duong T et al.Comparison of two active case-finding strategies for community-based diagnosis of symptomatic smear-positive tuberculosis and control of infectious tuberculosis in Harare, Zimbabwe ( DETECTB): a cluster-randomised trial.Lancet. 2010; 376: 1244-1253Google Scholar Mobile clinics equipped with point-of-care ( POC) molecular tools provide additional opportunities for community-based active case finding. Indeed, a mobile clinic-based strategy has previously been shown to be feasible and highly effective in detecting people in the community with culture-positive tuberculosis,122Calligaro GL Zijenah LS Peter JG et al.Effect of new tuberculosis diagnostic technologies on community-based intensified case finding: a multicentre randomised controlled trial.Lancet Infect Dis. 2017; 17: 441-450Google Scholar, 123Morishita F Garfin AMCG Lew W et al.Bringing state-of-the-art diagnostics to vulnerable populations: The use of a mobile screening unit in active case finding for tuberculosis in Palawan, the Philippines.PLoS One. 2017; 12e0171310Google Scholar, 124Khanal S Baral S Shrestha P et al.Yield of intensified tuberculosis case-finding activities using Xpert ( ®) MTB/RIF among risk groups in Nepal.Public Health Action. 2016; 6: 136-141Google Scholar although this approach was not readily scalable because of the logistical challenges of running an Xpert platform in the community. Recent advances in technology, however, have enabled the incorporation of portable and battery-operated molecular tools like the GeneXpert systems into active case-finding algorithms. These portable systems enhance the scalability of the mobile clinic-based approaches. A recently completed randomised controlled trial evaluating the effect of a scalable intervention package, including a POC molecular diagnostic tool, on community-based tuberculosis case finding showed the feasibility of such a strategy and its potential to detect the majority of community-based infectious tuberculosis cases ( appendix p 10).125Esmail A Randall P Oelofse S et al.Impact of a scalable intervention package, including a point-of-care molecular diagnostic tool, on community-based active case finding for tuberculosis: a pragmatic randomised controlled trial.Am J Respir Crit Care Med. 2022; ( in press).Google Scholar Such models can also be used to screen at-risk individuals ( eg, close contacts who are HIV negative) for latent tuberculosis infection and link them to preventive therapy.126WHOWHO consolidated guidelines on tuberculosis. Module 1: Prevention–tuberculosis preventive treatment. World Health Organization, Geneva2020Google Scholar
Chest radiography is one of the most sensitive tests for detecting active tuberculosis, particularly in high-burden countries, and is an important inclusion in tuberculosis active case-finding programmes.127Madhani F Maniar RA Burfat A et al.Automated chest radiography and mass systematic screening for tuberculosis.Int J Tuberc Lung Dis. 2020; 24: 665-673Google Scholar, 128Nguyen TBP Nguyen TA Luu BK et al.A comparison of digital chest radiography and Xpert ( ®) MTB/RIF in active case finding for tuberculosis.Int J Tuberc Lung Dis. 2020; 24: 934-940Google Scholar Results from a national survey in South Africa showed that more than half of bacteriologically confirmed tuberculosis survey cases had chest radiography abnormalities without reported symptoms.62South African Medical Research CouncilThe first national TB prevalence survey South Africa 2018.https: //www.knowledgehub.org.za/elibrary/first-national-tb-prevalence-survey-south-africa-2018Date: June 10, 2020Date accessed: August 12, 2021Google Scholar This finding suggests a potential role for screening chest radiography in detecting presymptomatic or minimally symptomatic disease in the community. A major pitfall of using screening chest radiography is its low specificity ( about 50%) in detecting active tuberculosis, especially in a setting of high tuberculosis prevalence in which the prevalence of previous tuberculosis disease is high. Thus, cases that are flagged as active tuberculosis still need to undergo confirmatory bacteriological testing. Furthermore, the use of chest radiography is often hindered by scarcity of resources and trained personnel, technical limitations, high cost of hardware, and intra-reader and inter-reader variability.129Piccazzo R Paparo F Garlaschi G Diagnostic accuracy of chest radiography for the diagnosis of tuberculosis ( TB) and its role in the detection of latent TB infection: a systematic review.J Rheumatol Suppl. 2014; 91: 32-40Google Scholar, 130van't Hoog A Langendam M Mitchell E et al.A systematic review of the sensitivity and specificity of symptom- and chest-radiography screening for active pulmonary tuberculosis in HIV-negative persons and persons with unknown HIV status.https: //www.who.int/tb/Review2Accuracyofscreeningtests.pdfDate: 2013Date accessed: August 27, 2021Google Scholar, 131Pinto LM Pai M Dheda K Schwartzman K Menzies D Steingart KR Scoring systems using chest radiographic features for the diagnosis of pulmonary tuberculosis in adults: a systematic review.Eur Respir J. 2013; 42: 480-494Google Scholar Potential technological answers to these challenges are ultraportable chest radiography machines and artificial intelligence-driven computer-aided detection ( CAD) software packages.132Tavaziva G Harris M Abidi SK et al.Chest X-ray analysis with deep learning-based software as a triage test for pulmonary tuberculosis: an individual patient data meta-analysis of diagnostic accuracy.Clin Infect Dis. 2021; 1ciab639Google Scholar On the basis of available evidence, the WHO recently recommended the use of chest radiography and CAD for pulmonary tuberculosis screening, which has the potential to increase equity in the reach of tuberculosis screening interventions.96WHOWHO consolidated guidelines on tuberculosis module 2: systematic screening for tuberculosis disease. World Health Organization, Geneva2021Google Scholar
The WHO consolidated guidelines on screening recommend systematic ( untargeted) tuberculosis screening for people in the general population when the background tuberculosis prevalence is greater than 500 per 100 000 people, and ( targeted) screening for those with a risk factor for tuberculosis when prevalence is greater than 100 per 100 000 people.96WHOWHO consolidated guidelines on tuberculosis module 2: systematic screening for tuberculosis disease. World Health Organization, Geneva2021Google Scholar Chest radiography was endorsed as a sensitive but non-specific screening tool for the early detection of tuberculosis. CAD software packages had similar performance to human readers but varied across contexts, and WHO's recommendation was thus conditional and based on a low certainty of evidence. CRP testing has been recommended as a screening tool in people who are HIV positive. Molecular rapid diagnostic tests for tuberculosis ( eg, Xpert Ultra) have been recommended by WHO as tuberculosis screening tools for populations in which screening is recommended ( conditional recommendation with a low certainty of evidence). However, how these methods should be deployed remains unclear. We strongly endorse more aggressive tuberculosis screening practices, including the use of chest radiography and molecular tests for people at risk of tuberculosis, as outlined in the guidance. Because of the COVID-19 pandemic, every country has an expanded molecular-testing capacity. This capacity should be leveraged for tuberculosis molecular testing.
It is estimated that between 15% and 40% of patients with active tuberculosis in endemic countries do not initiate treatment after a microbiologically confirmed diagnosis ( known as pretreatment loss to follow-up or PTLF).133MacPherson P Houben RM Glynn JR Corbett EL Kranzer K Pre-treatment loss to follow-up in tuberculosis patients in low- and lower-middle-income countries and high-burden countries: a systematic review and meta-analysis.Bull World Health Organ. 2014; 92: 126-138Google Scholar We assume that COVID-19 would affect people returning to health facilities and exacerbate PTLF ( especially among patients diagnosed at hospital, where mortality is higher because of loss to follow-up).134McQuaid CF Vassall A Cohen T et al.The impact of COVID-19 on TB: a review of the data.Int J Tuberc Lung Dis. 2021; 25: 436-446Google Scholar, 135Osman M Meehan S-A Von Delft A et al.Early mortality in tuberculosis patients initially lost to follow up following diagnosis in provincial hospitals and primary health care facilities in Western Cape, South Africa.PLoS One. 2021; 16e0252084Google Scholar Two studies reported an increase in sputum-smear positivity and more severe clinical and radiological findings as a consequence of diagnostic and pretreatment delays during the COVID-19 pandemic.21Wang X He W Lei J Liu G Huang F Zhao Y Impact of COVID-19 pandemic on pre-treatment delays, detection, and clinical characteristics of tuberculosis patients in Ningxia Hui autonomous region, China.Front Public Health. 2021; 9644536Google Scholar, 136Di Gennaro F Gualano G Timelli L et al.Increase in tuberculosis diagnostic delay during first wave of the COVID-19 pandemic: data from an italian infectious disease referral hospital.Antibiotics. 2021; 10: 272Google Scholar By contrast, a Chinese study documented no increase in pretreatment delay.21Wang X He W Lei J Liu G Huang F Zhao Y Impact of COVID-19 pandemic on pre-treatment delays, detection, and clinical characteristics of tuberculosis patients in Ningxia Hui autonomous region, China.Front Public Health. 2021; 9644536Google Scholar Data-integration systems connecting different levels of the health-care system are important tools to link patients to care and prevent loss to follow-up.
Some developments in health-care system strengthening and person-centred strategies, originally developed for COVID-19, have been integrated into tuberculosis programmes to mitigate the impact of COVID-19 on tuberculosis treatment outcomes as well as knock-on effects, such drug stockouts.137Loveday M Cox H Evans D et al.Opportunities from a new disease for an old threat: extending COVID-19 efforts to address tuberculosis in South Africa.S Afr Med J. 2020; 1101160Google Scholar, 138Zumla A Marais BJ McHugh TD et al.COVID-19 and tuberculosis—threats and opportunities.Int J Tuberc Lung Dis. 2020; 24: 757-760Google Scholar The growing use of digital health, telemedicine, digital adherence technologies ( eg, video-assisted treatment and smart pill boxes), and clinical management with bulk dispensing from decentralised pick-up points or home delivery of medicines are minimising facility visits, limiting nosocomial M tuberculosis and SARS-CoV-2 transmission, and protecting patients with tuberculosis from COVID-19. However, these strategies have been inconsistently implemented in tuberculosis programmes, patients have reported feeling insufficiently supported, and the value of these strategies has not been prospectively evaluated.44The Stop TB PartnershipThe impact of COVID-19 on the TB epidemic: a community perspective.http: //www.stoptb.org/assets/documents/resources/publications/acsm/Civil% 20Society% 20Report% 20on% 20TB% 20and% 20COVID.df? fbclid=IwAR3SOY4kyBs5a 35HIeUhcvwRIWspePA4vVHESqcQxio7G4irivJ90cSU8kDate: 2021Date accessed: September 5, 2021Google Scholar, 134McQuaid CF Vassall A Cohen T et al.The impact of COVID-19 on TB: a review of the data.Int J Tuberc Lung Dis. 2021; 25: 436-446Google Scholar Augmentation of other interventions shown to improve treatment adherence—such as SMS-based reminders, incentives, and enablers ( eg, social grants and incentives with financial value), patient education, counselling, and psychological interventions—will help to facilitate treatment adherence and has become even more relevant in the COVID-19 era.139Alipanah N Jarlsberg L Miller C et al.Adherence interventions and outcomes of tuberculosis treatment: a systematic review and meta-analysis of trials and observational studies.PLoS Med. 2018; 15e1002595Google Scholar
The past 18 months have showcased the crucial role of vaccines in COVID-19 control. Although non-pharmaceutical interventions and other public health measures have helped to mitigate the effects of COVID-19 in many LMICs, vaccine nationalism and vaccine inequity mean that COVID-19 is likely to remain a problem in many of these countries for some time, thus exacerbating suboptimal tuberculosis control. Vaccinating the world, therefore, is not only crucial for ending the pandemic, but also for restoring tuberculosis services. Thus, as a tuberculosis intervention strategy, there must be improved access to SARS-CoV-2 vaccines in LMICs; in many settings, vaccine resistance and hesitancy also have to be overcome.140Cooper S Van Rooyen H Wiysonge CS COVID-19 vaccine hesitancy in South Africa: a complex social phenomenon.S Afr Med J. 2021; 111: 702Google Scholar Lessons learned in design, technological application, testing and fast-tracking of clinical trials, funding, development, and distribution of the SARS-CoV-2 vaccines could also be applied to accelerate tuberculosis vaccine development.
The BCG vaccine was first used about 100 years ago and is now given at birth in several tuberculosis-endemic settings to prevent tuberculous meningitis.141Singh AK Netea MG Bishai WR BCG turns 100: its nontraditional uses against viruses, cancer, and immunologic diseases.J Clin Invest. 2021; 131: 11Google Scholar The impact of COVID-19 in reducing BCG vaccination rates has already been highlighted ( panel 2 and figure 2). However, epidemiological and other studies have shown several non-tuberculosis disease-specific effects of BCG, including protection from respiratory tract infections other than tuberculosis142Moorlag S Arts RJW van Crevel R Netea MG Non-specific effects of BCG vaccine on viral infections.Clin Microbiol Infect. 2019; 25: 1473-1478Google Scholar and enhancement of vaccine responses to yellow fever143Arts RJW Moorlag S Novakovic B et al.BCG vaccination protects against experimental viral infection in humans through the induction of cytokines associated with trained immunity.Cell Host Microbe. 2018; 23: 89-100Google Scholar and influenza.144Leentjens J Kox M Stokman R et al.BCG vaccination enhances the immunogenicity of subsequent influenza vaccination in healthy volunteers: a randomized, placebo-controlled pilot study.J Infect Dis. 2015; 212: 1930-1938Google Scholar Mechanistic studies suggest that these vaccines induce trained innate immunity ( appendix pp 2–3).145Arts RJW Carvalho A La Rocca C et al.Immunometabolic pathways in BCG-induced trained immunity.Cell Rep. 2016; 17: 2562-2571Google Scholar A stronger evidence base to support the clinical application of the heterologous effects of BCG has more recently emerged. The double-blind, placebo-controlled ACTIVATE ( A randomized Clinical trial for enhanced Trained Immune responses through Bacillus Calmette-Guérin VAccination to prevenT infections of the Elderly) trial among 202 European older patients showed a 45% reduction in time to first infection and a 42% reduction in all infections attributed to BCG. The biggest effect was in reducing viral respiratory tract infections; 146Giamarellos-Bourboulis EJ Tsilika M Moorlag S et al.Activate: randomized clinical trial of BCG vaccination against infection in the elderly.Cell. 2020; 183: 315-323Google Scholar findings were consistent with the earlier smaller studies in Indonesia147Wardhana Datau EA Sultana A Mandang VV Jim E The efficacy of Bacillus Calmette-Guerin vaccinations for the prevention of acute upper respiratory tract infection in the elderly.Acta Med Indones. 2011; 43: 185-190Google Scholar and Japan.148Ohrui T Nakayama K Fukushima T Chiba H Sasaki H Prevention of elderly pneumonia by pneumococcal, influenza and BCG vaccinations.Nihon Ronen Igakkai Zasshi. 2005; 42: 34-36Google Scholar
This growing evidence-based and biological understanding of the protective effects of BCG vaccination on respiratory viral infections provides a valid justification for clinical studies to establish the effect, if any, of BCG vaccination on SARS-CoV-2 infections, severe COVID-19, or death.149O'Neill LAJ Netea MG BCG-induced trained immunity: can it offer protection against COVID-19?.Nat Rev Immunol. 2020; 20: 335-337Google Scholar Although early observational, ecological studies suggested a benefit of BCG, more rigorous and updated analyses have shown no effect of BCG on COVID-19.150Chimoyi L Velen K Churchyard GJ Wallis R Lewis JJ Charalambous S An ecological study to evaluate the association of Bacillus Calmette-Guerin ( BCG) vaccination on cases of SARS-CoV2 infection and mortality from COVID-19.PLoS One. 2020; 15e0243707Google Scholar Given the limitations of observational research, as of July 5, 2021, there were more than 20 ongoing clinical trials registered in ClinicalTrials.gov that are evaluating the effects of BCG on SARS-CoV-2 infection ( appendix pp 2–3).151Gonzalez-Perez M Sanchez-Tarjuelo R Shor B Nistal-Villan E Ochando J The BCG vaccine for COVID-19: first verdict and future directions.Front Immunol. 2021; 12632478Google Scholar, 152Bagheri N Montazeri H On BCG vaccine protection from COVID-19: a review.SN Compr Clin Med. 2021; 15: 1-11Google Scholar Although the BCG-PRIME ( Prevention of Respiratory Tract Infection and COVID-19 through BCG Vaccination in Vulnerable Older Adults) trial153Universitair Medisch Centrum UtrechtTuberculosis vaccine does not protect vulnerable elderly people against COVID-19.https: //www.umcutrecht.nl/en/about-us/news/details/jan-18-tuberculosis-vaccine-does-not-protect-vulnerable-elderly-against-covid-19 #: ~: text=Monday% 2018% 20Jan% 202021, -Listen & text=The% 20BCG% 20vaccine% 20does% 20not, patients% 20aged% 2060% 20and% 20overDate: Jan 18, 2021Date accessed: September 5, 2021Google Scholar has shown no benefit, other trials are likely to provide a clear answer about the benefits of BCG vaccination against COVID-19 and other respiratory tract infections in adults.
The COVID-19 pandemic has taught the world that epidemics can only be controlled by several interventions, some personal ( eg, masking and vaccinations) and others societal ( eg, social protection and lockdowns). The Swiss cheese respiratory pandemic defence model created by Mackay154Mackay IM Virology Down Under: The Swiss cheese infographic that went viral.https: //virologydownunder.com/the-swiss-cheese-infographic-that-went-viral/Date: Dec 26, 2020Date accessed: September 5, 2021Google Scholar outlines the multiple layers of these personal and shared responsibilities that are needed to prevent the spread of SARS-CoV-2. The model has several layers of Swiss cheese to illustrate the fact that a single layer of protection will not be enough to stop COVID-19. Because of the holes in each slice, the coronavirus will always get through; therefore, multiple layers of protection are needed to halt the pandemic. We need a similar, comprehensive approach for tuberculosis, captured in the tuberculosis Swiss cheese model, with three broad levels: societal, personal, and person-centric health-care systems interventions ( appendix p 11).155Zimmer A Klinton J Omenka C et al.Tuberculosis in times of COVID-19.J Epidemiol Community Health. 2022; 76: 310-316Google Scholar By addressing the multiple layers, including improving the glacial pace of tuberculosis research, correcting suboptimal and deficient research funding, and treating tuberculosis as the global emergency that it is, we could end tuberculosis ( panel 5).156Chaisson RE Frick M Nahid P The scientific response to TB – the other deadly global health emergency.Int J Tuberc Lung Dis. 2022; 26: 186-189Google ScholarPanel 5Research priorities and major challenges that need to be addressedA range of research priorities need to be addressed to restore control efforts and reduce the global burden of tuberculosis. Some of the goals listed here are long-standing priorities; others have become relevant in the time of COVID-19.Diagnosis and care•Improve tuberculosis ( and COVID-19) case finding; for example, through the development of e-health approaches to enable mass triage and targeted screening ( including self-screening) of people with risk factors, with linkage to further investigation and care•Optimise systematic tuberculosis ( and COVID-19) active case finding in high-risk populations; establish how active case finding should be done ( mobile clinics vs door-to-door visits) and how samples should be processed ( on site vs in centralised laboratories) •Develop sensitive and specific point-of-care diagnostics and cost-effective joint screening strategies for tuberculosis and COVID-19•Refine diagnostic algorithms for tuberculosis and COVID-19 that optimise the use of available technologies ( eg, chest radiography with or without computer-aided detection) and are calibrated to the risk profiles of individuals ( eg, previous COVID-19, additional tests for people who are HIV positive, or more frequent testing for people who are incarcerated) •Explore implementational approaches to integrate patient-centred innovations ( such as decentralised dispensing, home delivery, and holistic forms of adherence support) into routine practice, including in resource-constrained settings•Develop methods and algorithms to integrate screening for latent tuberculosis infection ( and COVID-19) and linkage to preventive therapy to all significantly exposed individuals regardless of HIV statusSurveillance and outcomes•Estimate the prevalence and effects of SARS-CoV-2 infection in individuals with active tuberculosis, including on tuberculosis treatment outcomes and long-term health•Characterise impairment in individuals with lung disease after tuberculosis and COVID-19•Establish the prevalence and effects of long COVID in individuals with active tuberculosis•Better monitor adequacy of response to tuberculosis treatment regimens, including those used for preventive therapy•Improve and broaden the use of rapid, direct methods to estimate the impact of COVID-19 on cause-specific mortality ( eg, minimally invasive autopsy) Systems strengthening and pandemic preparedness•Realise a more comprehensive tuberculosis response that simultaneously targets the societal, personal, and health system levels, recognising that many tuberculosis drivers also influence COVID-19•Explore strategies to protect health-care workers against tuberculosis and COVID-19 without compromising on quality of care ( eg, introducing respiratory protection programmes, strengthening occupational health infrastructure, and maintaining reserves of personal protective equipment reserves) •Explore long-term solutions to vaccine hesitancy, recognising that SARS-CoV-2 vaccination will reduce the tuberculosis burden and a viable tuberculosis vaccine is likely to face similar challenges with uptakeMajor challenges•Improve understanding and effectively communicate the cost of tuberculosis, COVID-19, and their interaction, to the economies of tuberculosis-endemic countries in terms of effect on gross domestic product and other metrics of economic development•Substantially increase research funding for translational and operational research, and for innovation and commercialisation activities for tuberculosis interventions ( as has been done for COVID-19) •Improve systems and processes to enable rapid review of proposals and to improve regulatory harmonisation ( thus reducing massive delays in the completion of clinical trials) •Treat tuberculosis ( like COVID-19) as an important entity in any national or global pandemic response strategy•Effectively tackle COVID-19 in countries with high tuberculosis and COVID-19 burden ( predominantly low-income and middle-income countries) without diverting resources and personnel from tuberculosis programmes•Develop strategies to address the effect of COVID-19 on tuberculosis treatment outcomes•Accelerate the development of tuberculosis vaccines through harnessing what has been learned from COVID-19•Increase the level of ambition in terms of what tuberculosis control metrics should be achieved within specific timelines ( using COVID-19 as a benchmark) •Identify and remove sources of structural violence, systemic racism, and discrimination, especially those affecting access to essential services and equitable, high-quality health care
A range of research priorities need to be addressed to restore control efforts and reduce the global burden of tuberculosis. Some of the goals listed here are long-standing priorities; others have become relevant in the time of COVID-19.
COVID-19 has set tuberculosis control efforts back by about a decade. This setback will probably translate into long-term increases in tuberculosis-related deaths and structural lung disease. With low rates of SARS-CoV-2 vaccination in tuberculosis-endemic countries and the emergence of new variants, this trend is likely to continue. New strategies involving triage tools and innovative active case-finding interventions require urgent implementation to reverse these alarming trends. We have provided several examples of the successful use of such interventions in different parts of the world. A more cohesive global approach is now urgently required.
Active tuberculosis and COVID-19 screening should be combined in tuberculosis-endemic settings. False-negative results might occur with both tuberculosis and COVID-19 testing, and better diagnostics, independent of samples obtained from the respiratory tract, are needed for both diseases. The inability to distinguish between acute tuberculosis disease and COVID-19 has implications for strategies of IPC in tuberculosis-endemic settings, including the provision of N95 ( or equivalent) respirators to HCWs. Individuals with active tuberculosis and COVID-19 should be monitored more closely with a lower threshold for referral and intervention.
The vicious cycle of poverty and death is exacerbated by the twin epidemics of tuberculosis and COVID-19 ( with HIV making up a triad of infectious disease epidemics in some settings, and a non-communicable disease epidemic expanding in tandem).157Wong EB Olivier S Gunda R et al.Convergence of infectious and non-communicable disease epidemics in rural South Africa: a cross-sectional, population-based multimorbidity study.Lancet Glob Health. 2021; 9: e967-e976Google Scholar In some settings, disruption of HIV diagnosis and treatment programmes might fuel the tuberculosis pandemic. It is therefore crucial to support and revitalise both tuberculosis and HIV programmes. That airborne and aerosol-based spread is the dominant form of SARS-CoV-2 and M tuberculosis transmission has important implications for interrupting the spread of both diseases and for protecting HCWs. COVID-19 will exacerbate the situation in endemic settings, in which there is already an appreciable burden of pulmonary disability and lung damage caused by tuberculosis. Addressing the mortality and morbidity associated with tuberculosis and COVID-19 will require global unity, political will—addressing global inequalities and power monopolies—improved funding for vaccine development, and enhanced support for preventive and interventional strategies for both diseases.
We did a literature search of PubMed, MEDLINE, and Google Scholar for papers published in the English language from Jan 1, 2000, to Feb 1, 2022, using the search terms “ COVID-19 OR SARS-CoV-2 ” and “ tuberculosis OR TB ”, and “ case detection ” or “ outcomes ” or “ diagnosis ” or “ screening ” or “ impact ”. Articles were selected—on the basis of a critical review of the title, abstract and, when appropriate, full text—if they were regarded as pertinent to our review of the effect of COVID-19 on the global burden of tuberculosis, including patient-level or clinical-level impact, or our discussion of interventions to reverse the deleterious impact of COVID-19. Preprints were considered as applicable. A selection of citations within the original search documents were reviewed and included if relevant. References were also identified through the authors ' own searches online ( up to March 1, 2022) and through searches of the authors ' personal files and the reference lists of landmark papers and selected publications.
We did a literature search of PubMed, MEDLINE, and Google Scholar for papers published in the English language from Jan 1, 2000, to Feb 1, 2022, using the search terms “ COVID-19 OR SARS-CoV-2 ” and “ tuberculosis OR TB ”, and “ case detection ” or “ outcomes ” or “ diagnosis ” or “ screening ” or “ impact ”. Articles were selected—on the basis of a critical review of the title, abstract and, when appropriate, full text—if they were regarded as pertinent to our review of the effect of COVID-19 on the global burden of tuberculosis, including patient-level or clinical-level impact, or our discussion of interventions to reverse the deleterious impact of COVID-19. Preprints were considered as applicable. A selection of citations within the original search documents were reviewed and included if relevant. References were also identified through the authors ' own searches online ( up to March 1, 2022) and through searches of the authors ' personal files and the reference lists of landmark papers and selected publications.
KD, TP, RP, AE, KF, and MP contributed to conceptualisation of this Series paper. KD and TP contributed to formal analysis of the National Institute for Communicable Diseases data, methodology, project administration, resources, visualisation ( panels, tables, and figures), and writing of the original draft, review, and editing of the manuscript. HM contributed to data collection, curation, and formal analysis. RP contributed to writing of the original draft, review, and editing. AE contributed to visualisation ( supplementary figure 5), writing of the original draft, review, and editing. AJS, JP, AvD, DvD, NM, ML, and SC contributed to writing of the original draft, review, and editing. ZU contributed to writing of the original draft. K-CC contributed to visualisation ( supplementary figures), writing of the original draft, review, and editing. AP contributed to visualisation, writing of the original draft, review, and editing. EK contributed to data curation and formal analysis. WJ contributed to data curation, formal analysis, visualisation ( figure 4), and review and editing. CC contributed to data curation, formal analysis, methodology, and review and editing. ST contributed to formal analysis, and review and editing. KF and MP contributed to visualisation, writing of the original draft, review, and editing.
Requests for aggregated laboratory testing data for South Africa should be made in writing by qualifying researchers with valuable research questions to the National Institute for Communicable Diseases, directed to Harry Moultrie ( [ email protected ]). Further information can be obtained from the corresponding author.
NM reports grants from Pfizer and Roche to his institution, outside the submitted work. CC reports research funding from Sanofi Pasteur, awarded to her institution; she is a member of the scientific advisory committee for the BCHW: Burden of COVID-19 Among Health Care Workers project. The other authors declare no competing interests.
KD acknowledges funding from the South African Medical Research Council ( SAMRC; RFA-EMU-02-2017), the European & Developing Countries Clinical Trials Partnership ( EDCTP; TMA-2015SF-1043, TMA-1051-TESAII, TMA-CDF2015, RIA2018D-2505, and RIA2020S-3295), the UK Medical Research Council ( MR/S03563X/1), and the Wellcome Trust ( MR/S027777/1). AP was supported by the EDCTP ( TMA2019CDF-2780). CC acknowledges funding from the Wellcome Trust ( grant number 221003/Z/20/Z), the SAMRC, and the US Centers for Disease Control and Prevention ( co-operative agreement number 6 U01IP001048-04-02), awarded to her institution. KF is supported by the Division of Intramural Research of the National Heart, Lung, and Blood Institute of the National Institutes of Health, Bethesda, MD, USA. MP holds a Canada Research Chair award from the Canadian Institutes of Health Research. We are grateful to Aaron Karat ( independent researcher), who contributed to editing of the manuscript.
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Ending the tuberculosis syndemic: is COVID-19 the ( in) convenient scapegoat for poor progress? Tuberculosis is a syndemic. Elimination requires a syndemic approach that addresses the individual and societal vulnerabilities that determine whether we become infected, get sick, die, or get better with disability and an impact on livelihoods.1 The WHO End TB Strategy, a global initiative launched in 2015, signifies that syndemic approach. End TB outlines fundamentals required to modify determinants of ill health, promote prevention of disease and early diagnosis with prompt treatment to save lives, prevent economic hardships, and reduce transmission. Full-Text PDF The crucial need for tuberculosis translational research in the time of COVID-19The world is still grappling with the devastating effects of COVID-19 more than 2 years into the pandemic. Countries with high COVID-19 vaccination rates are transitioning to the new normal of living with SARS-CoV-2, but low-income and middle-income countries ( LMICs) are struggling to vaccinate their populations while concurrently fighting other communicable diseases, key among them tuberculosis. The burden of tuberculosis, the leading cause of death from an infectious disease before COVID-19 emerged, has been deeply affected by the pandemic. Full-Text PDF | tech |
Safety and immunogenicity of CoronaVac in people living with HIV: a prospective cohort study | Background People living with HIV might have a poor or delayed response to vaccines, mainly when CD4 cell counts are low, and data concerning COVID-19 vaccines in this population are scarce. This prospective cohort study assessed the safety and immunogenicity of the inactivated SARS-CoV-2 vaccine CoronaVac in people with HIV compared with people with no known immunosuppression. Methods In this prospective cohort study, adults ( aged ≥18 years) living with HIV who were regularly followed up at the University of Sao Paulo HIV/AIDS outpatient clinic in Sao Paulo, Brazil, were included in the study. Eligibility for people with HIV was independent of antiretroviral use, HIV viral load, or CD4 cell count. Adults with no known immunosuppression with CoronaVac vaccination history were included as a control group. CoronaVac was given intramuscularly in a two-dose regimen, 28 days apart. Blood was collected before vaccine administration and 6 weeks after the second dose ( day 69). Immunogenicity was assessed at baseline ( day 0), before second vaccine ( day 28), and 6 weeks after second vaccine dose ( day 69) through SARS-CoV-2 IgG titre and seroconversion, neutralising antibody ( NAb) positivity and percentage activity, and factor increase in IgG geometric mean titres ( FI-GMT). We investigated whether HIV status and CD4 count ( < 500 or ≥500 cells per μL) were associated with CoronaVac immunogenicity by use of multivariable models adjusted for age and sex. Findings Between Feb 9, 2021, and March 4, 2021, 776 participants were recruited. Of 511 participants included, 215 ( 42%) were people with HIV and 296 ( 58%) were people with no known immunosuppression. At 6 weeks after the second vaccine dose ( day 69), 185 ( 91%) of 204 participants with HIV and 265 ( 97%) of 274 participants with no known immunosuppression had seroconversion ( p=0·0055). 143 ( 71%) of 202 participants with HIV were NAb positive compared with 229 ( 84%) of 274 participants with no known immunosuppression ( p=0·0008). Median IgG titres were 48·7 AU/mL ( IQR 26·6–88·2) in people with HIV compared with 75·2 AU/mL ( 50·3–112·0) in people with no known immunosuppression ( p < 0·0001); and median NAb activity was 46·2% ( 26·9–69·7) compared with 60·8% ( 39·8–79·9; p < 0·0001). In people with HIV who had CD4 counts less than 500 cells per μL seroconversion rates, NAb positivity, and NAb activity were lower than in those with CD4 counts of at least 500 cells per μL. In multivariable models for seroconversion, NAb positivity, IgG concentration, and NAb activity after a complete two-dose regimen, adjusted for age and sex, people with HIV who had CD4 counts of at least 500 cells per μL and people with no known immunosuppression had higher immunogenicity than did people with HIV with CD4 counts less than 500 cells per μL. No serious adverse reactions were reported during the study. Interpretation Immunogenicity following CoronaVac in people with HIV seems strong but reduced compared with people with no known immunosuppression. Our findings highlight the need for strategies to improve vaccine immunogenicity in people with HIV. Funding Fundação de Amparo à Pesquisa do Estado de São Paulo ( FAPESP), Conselho Nacional de Desenvolvimento Científico e Tecnológico ( CNPq), and B3—Bolsa de Valores do Brasil.
People living with HIV might have a poor or delayed response to vaccines, mainly when CD4 cell counts are low, and data concerning COVID-19 vaccines in this population are scarce. This prospective cohort study assessed the safety and immunogenicity of the inactivated SARS-CoV-2 vaccine CoronaVac in people with HIV compared with people with no known immunosuppression.
In this prospective cohort study, adults ( aged ≥18 years) living with HIV who were regularly followed up at the University of Sao Paulo HIV/AIDS outpatient clinic in Sao Paulo, Brazil, were included in the study. Eligibility for people with HIV was independent of antiretroviral use, HIV viral load, or CD4 cell count. Adults with no known immunosuppression with CoronaVac vaccination history were included as a control group. CoronaVac was given intramuscularly in a two-dose regimen, 28 days apart. Blood was collected before vaccine administration and 6 weeks after the second dose ( day 69). Immunogenicity was assessed at baseline ( day 0), before second vaccine ( day 28), and 6 weeks after second vaccine dose ( day 69) through SARS-CoV-2 IgG titre and seroconversion, neutralising antibody ( NAb) positivity and percentage activity, and factor increase in IgG geometric mean titres ( FI-GMT). We investigated whether HIV status and CD4 count ( < 500 or ≥500 cells per μL) were associated with CoronaVac immunogenicity by use of multivariable models adjusted for age and sex.
Between Feb 9, 2021, and March 4, 2021, 776 participants were recruited. Of 511 participants included, 215 ( 42%) were people with HIV and 296 ( 58%) were people with no known immunosuppression. At 6 weeks after the second vaccine dose ( day 69), 185 ( 91%) of 204 participants with HIV and 265 ( 97%) of 274 participants with no known immunosuppression had seroconversion ( p=0·0055). 143 ( 71%) of 202 participants with HIV were NAb positive compared with 229 ( 84%) of 274 participants with no known immunosuppression ( p=0·0008). Median IgG titres were 48·7 AU/mL ( IQR 26·6–88·2) in people with HIV compared with 75·2 AU/mL ( 50·3–112·0) in people with no known immunosuppression ( p < 0·0001); and median NAb activity was 46·2% ( 26·9–69·7) compared with 60·8% ( 39·8–79·9; p < 0·0001). In people with HIV who had CD4 counts less than 500 cells per μL seroconversion rates, NAb positivity, and NAb activity were lower than in those with CD4 counts of at least 500 cells per μL. In multivariable models for seroconversion, NAb positivity, IgG concentration, and NAb activity after a complete two-dose regimen, adjusted for age and sex, people with HIV who had CD4 counts of at least 500 cells per μL and people with no known immunosuppression had higher immunogenicity than did people with HIV with CD4 counts less than 500 cells per μL. No serious adverse reactions were reported during the study.
Immunogenicity following CoronaVac in people with HIV seems strong but reduced compared with people with no known immunosuppression. Our findings highlight the need for strategies to improve vaccine immunogenicity in people with HIV.
Fundação de Amparo à Pesquisa do Estado de São Paulo ( FAPESP), Conselho Nacional de Desenvolvimento Científico e Tecnológico ( CNPq), and B3—Bolsa de Valores do Brasil. | tech |
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Ending the tuberculosis syndemic: is COVID-19 the ( in) convenient scapegoat for poor progress? - The Lancet Respiratory Medicine | Tuberculosis is a syndemic. Elimination requires a syndemic approach that addresses the individual and societal vulnerabilities that determine whether we become infected, get sick, die, or get better with disability and an impact on livelihoods.1Singer M Syndemics and the biosocial conception of health.Lancet. 2017; 389: 941-950Google Scholar The WHO End TB Strategy, a global initiative launched in 2015, signifies that syndemic approach. End TB outlines fundamentals required to modify determinants of ill health, promote prevention of disease and early diagnosis with prompt treatment to save lives, prevent economic hardships, and reduce transmission. Yet, even before COVID-19 emerged, we were on track to miss all targets.2WHOGlobal tuberculosis report 2021. World Health Organization, Geneva2021Google Scholar The situation is unlikely to improve without a shift in our attitude to tuberculosis elimination.
2 years on from the start of the global response to COVID-19, it is a good time to reflect on what the pandemic has taught us about our elimination efforts and ability to handle threats to tuberculosis control. In a Series of papers published in The Lancet Respiratory Medicine and eBioMedicine to coincide with World TB Day 2022, the authors provide an account of current threats to tuberculosis control. Keertan Dheda and colleagues3Dheda K Perumal T Moultrie H et al.The intersecting pandemics of tuberculosis and COVID-19: population-level and patient-level impact, presentation, and corrective interventions.Lancet Respir Med. 2022; ( published online March 23.) https: //doi.org/10.1016/S2213-2600 ( 22) 00092-3Google Scholar give a painful synopsis of the impact of COVID-19 on tuberculosis, while Ruvandhi Nathavitharana and colleagues4Nathavitharana RR Garcia-Basteiro AL Ruhwald M Cobelens F Theron G Reimagining the status quo: how close are we to rapid sputum-free tuberculosis diagnostics for all?.EBioMedicine. 2022; ( published online March 23.) https: //doi.org/10.1016/j.ebiom.2022.103939Google Scholar and Hanif Esmail and colleagues5Esmail H Macpherson L Coussens AK Houben RMGJ Mind the gap – managing tuberculosis across the disease spectrum.EBioMedicine. 2022; ( published online March 23.) https: //doi.org/10.1016/j.ebiom.2022.103928Google Scholar address the ongoing threat of paucibacillary and subclinical tuberculosis.
Tuberculosis was declared a public health emergency in 1993.6Grange JM Zumla A The global emergency of tuberculosis: what is the cause?.J R Soc Promot Health. 2002; 122: 78-81Google Scholar However, the years that followed this declaration proved tuberculosis to be the most non-urgent emergency. COVID-19, by contrast, was declared an emergency in January, 2020. The new pandemic starkly revealed the impact of underlying health inequalities, but it also demonstrated what can be achieved with sufficient global effort. The response was a model of public health action in an emergency. Within months of the emergence of SARS-CoV-2, we often saw high-quality science informing the response and shaping policy. Nothing was off the table, from use of multidisease big data and multinational collaboration to discover novel diagnostics and therapies, to innovation in service delivery.7Tikkinen KAO Malekzadeh R Schlegel M Rutanen J Glasziou P COVID-19 clinical trials: learning from exceptions in the research chaos.Nat Med. 2020; 26: 1671-1672Google Scholar, 8Zhang Q Gao J Wu JT Cao Z Dajun Zeng D Data science approaches to confronting the COVID-19 pandemic: a narrative review.Philos Trans A Math Phys Eng Sci. 2022; 38020210127Google Scholar
Even when the COVID-19 response has failed, it has provided lessons for future tuberculosis research and control, and an indication of how we should deliver the benefits of research, construct equitable partnerships, and source and share funding. Failure to enact the Trade-Related Aspects of Intellectual Property Rights ( TRIPS) waiver9Hassan F London L Gonsalves G Unequal global vaccine coverage is at the heart of the current covid-19 crisis.BMJ. 2021; 375n3074Google Scholar and the resulting vaccine apartheid provides a clear warning of global health inequalities and threats to the right to benefit from future tuberculosis science. Access to SARS-CoV-2 vaccines has since improved, but when these reach countries in need, roll-out is often hindered by vaccine hesitancy and operational challenges, a poignant lesson in preparedness for novel tuberculosis vaccines and products. COVID-19 also triggered an unprecedented influx of funds for innovation; however, the most value added, with respect to people and expertise, remains in richer countries. US $ 104 billion was spent on COVID-19 research and development in the first 11 months of the pandemic, in contrast to $ 5·5 billion on tuberculosis research and development in the past decade. Less than $ 60 billion has been spent on tuberculosis activities over this period.10Treatment Action GroupTuberculosis research funding trends, 2005–2020.https: //www.stoptb.org/sites/default/files/tb funding 2021 final.pdfDate: 2021Date accessed: March 17, 2022Google Scholar
COVID-19 wiped out 10 years of gains in tuberculosis outcomes in less than 10 months. Evidently, we did not build and prepare resilient health programmes for tuberculosis. Programmes for other diseases appear to be more resilient and were affected less. The number of tuberculosis deaths ( excluding those caused by HIV) rose for the first time in 10 years in 2020–21.3Dheda K Perumal T Moultrie H et al.The intersecting pandemics of tuberculosis and COVID-19: population-level and patient-level impact, presentation, and corrective interventions.Lancet Respir Med. 2022; ( published online March 23.) https: //doi.org/10.1016/S2213-2600 ( 22) 00092-3Google Scholar By contrast, the number of HIV deaths has stayed low. Since 2015, when HIV was announced as the number 1 cause of death from an infectious agent, we have seen better-funded HIV programmes substantially lower mortality to below that of tuberculosis. The HIV response evolved to become patient-centric and offer inspired, decentralised care ( eg, community antiretroviral clubs and HIV self-testing11Jamil MS Eshun-Wilson I Witzel TC et al.Examining the effects of HIV self-testing compared to standard HIV testing services in the general population: a systematic review and meta-analysis.EClinicalMedicine. 2021; 38100991Google Scholar) and robust distribution systems for antiretrovirals, and successfully incorporated its goals within other programmes to reflect HIV priorities.12Bulstra CA Hontelez JAC Otto M et al.Integrating HIV services and other health services: a systematic review and meta-analysis.PLoS Med. 2021; 18e1003836Google Scholar As a result, the delivery of care for HIV has been less affected by COVID-19. The observation by Dheda and colleagues3Dheda K Perumal T Moultrie H et al.The intersecting pandemics of tuberculosis and COVID-19: population-level and patient-level impact, presentation, and corrective interventions.Lancet Respir Med. 2022; ( published online March 23.) https: //doi.org/10.1016/S2213-2600 ( 22) 00092-3Google Scholar that we need similar patient-centric, whole-systems approaches for tuberculosis is on point. The End TB Strategy is the foundation for this, but it needs better funding and a more innovative approach to spending.
Threats to tuberculosis elimination can be inherent to the disease area, but can also come from outside, as observed with the emergence of COVID-19. For example, subclinical tuberculosis has re-emerged as a threat of daunting proportions.13Frascella B Richards AS Sossen B et al.Subclinical tuberculosis disease—a review and analysis of prevalence surveys to inform definitions, burden, associations, and screening methodology.Clin Infect Dis. 2021; 73: e830-e841Google Scholar In their papers, Nathavitharana and colleagues and Esmail and colleagues highlight specific diagnostic and therapeutic research gaps, and propose inspiring solutions for addressing subclinical tuberculosis.4Nathavitharana RR Garcia-Basteiro AL Ruhwald M Cobelens F Theron G Reimagining the status quo: how close are we to rapid sputum-free tuberculosis diagnostics for all?.EBioMedicine. 2022; ( published online March 23.) https: //doi.org/10.1016/j.ebiom.2022.103939Google Scholar, 5Esmail H Macpherson L Coussens AK Houben RMGJ Mind the gap – managing tuberculosis across the disease spectrum.EBioMedicine. 2022; ( published online March 23.) https: //doi.org/10.1016/j.ebiom.2022.103928Google Scholar However, the current research funding gap, US $ 900 million annual expenditure against a target of $ 2 billion, continues to hamper success.
Multimorbidity and failure to develop integrated care pathways is another new threat. Integration is deemed to be complex, needing extensive systems innovation, and therefore costly. This neglect of multimorbidity in poorer countries has resulted in major gaps in care and in data.14Banerjee A Duflo E Goldberg N et al.A multifaceted program causes lasting progress for the very poor: evidence from six countries.Science. 2015; 3481260799Google Scholar COVID-19 revealed how vulnerable both populations and health programmes are to external threats when multimorbidity is neglected. But it also revealed how multidisease platforms and approaches could be used. Pandemic preparedness should not only be about algorithms to predict unknown threats, but equally address prevention and care of prevalent conditions, even during a co-emergency. We need a multidisease framework funded and implemented across multiple disease programmes to achieve this, eventually moving away from a single-disease focus. This would see the tuberculosis community invest in interventions that benefit tuberculosis as well as associated multimorbidities, with the goal to improve health overall. Benefits of the framework would be greater cooperation with other disease sectors, mutual funding, and human resource support.
We have failed to address health inequities and tackle inadequacies in care, systems, and innovation. The global community has fallen short in providing the tools and funding needed to enable us to achieve our goals. As we chart the way forward, we need to reimagine the End TB agenda, and do so within a well-funded, multidisease framework to guarantee resilient systems and better preparedness for future extrinsic threats.
MXR is the recipient of a Wellcome Trust Investigator Award on tuberculosis and diabetes. IA is the recipient of an EU funded award to End-VOC ( End SARS-CoV-2 variants of concern). The authors declare no other competing interests.
The intersecting pandemics of tuberculosis and COVID-19: population-level and patient-level impact, clinical presentation, and corrective interventionsThe global tuberculosis burden remains substantial, with more than 10 million people newly ill per year. Nevertheless, tuberculosis incidence has slowly declined over the past decade, and mortality has decreased by almost a third in tandem. This positive trend was abruptly reversed by the COVID-19 pandemic, which in many parts of the world has resulted in a substantial reduction in tuberculosis testing and case notifications, with an associated increase in mortality, taking global tuberculosis control back by roughly 10 years. Full-Text PDF | tech |
Charleston Luxury Boutique Hampden - Proenza Schouler Pre-fall 22 | Every product on this page was chosen by a Harper's BAZAAR editor. We may earn commission on some of the items you choose to buy.
The South Carolina–based retailer and the iconic New York City label celebrated their anniversaries—together.
When Stacy Smallwood founded her independent luxury boutique Hampden in 2007 on Charleston’ s iconic King Street, she started with just 1,500 square feet and a handful of labels that weren’ t yet in high demand in the city of Southern charm. Now, 15 years later, Hampden has expanded to more than 10,000 square feet of space, is home to more than 175 brands, and boasts a die-hard, loyal following.
“ I was only 27 when I opened the store, and I was just young and dumb enough to take that chance, ” says Smallwood, who successfully moved the needle on what modern style looks like in Charleston by taking a nontraditional, customer-first route. “ Instead of catering to a typical Southern floral customer, I went with my gut, ” Smallwood says, adding that the store’ s top-performing brands are Sacai, Marni, and Proenza Schouler. “ I always look for something different in the market, and then I gauge the interest of my personal shoppers. The city has evolved with Hampden. ” As LVMH begins opening Balenciaga and Gucci stores in small Southern cities, you could argue that Smallwood helped set the stage for a high fashion takeover south of the Mason Dixon.
To celebrate the store’ s 15-year anniversary, Smallwood partnered with Proenza Schouler on an in-store event, held on March 22, just one day shy of when the pre-fall 2022 collection is available for preorder on Hampden’ s site. The alignment makes sense: Not only is Proenza Schouler celebrating its own anniversary, of 20 years, but Hampden saw nearly $ 1 million in Proenza Schouler sales over the last 12 months. And when you combine the main collection with its White Label line, the brand is now responsible for 5 percent of the store’ s overall business—no small chunk when you consider the breadth of brands Hampden carries.
But how exactly does the label’ s decidedly downtown aesthetic translate to Charleston’ s more feminine-forward fashion scene? “ There’ s a sophistication to Proenza Schouler that you don’ t find elsewhere, ” Smallwood, who’ s been buying heavily into each collection for seven years, says. She began by stocking Proenza Schouler’ s fall 2015 collection—a season of subtly sequined separates and off-the-shoulder, chic, work-ready dresses that helped redefine what modern workwear could be—and customers took notice. “ Most of our clients are established women in their 40s. She’ s cool and wants an element of femininity that Proenza [ Schouler ] is able to provide, because it balances feminine and edge. They’ re designing for women who know what they like, see the value in it, and they look for pieces that you want to have in your wardrobe forever. There’ s an elevated factor that they’ ve been able to maintain—and our clientele has noticed, ” she adds.
The colorful dresses from Proenza Schouler’ s spring 2022 collection have been selling quickly, though Smallwood never thought otherwise. “ Dresses overall are our number one category for the store, ” she shares, “ and the colorful spring 2022 dress in the jersey fabric has been a huge hit. It’ s comfortable but statement making. ”
But it’ s not just one-sided: Proenza Schouler designers Jack McCollough and Lazaro Hernandez never took Hampden’ s business for granted. “ [ Smallwood ] has one of the most successful independent boutiques in the country, and she’ s buying—and selling through—an amazing amount of fashion, ” Hernandez says, adding that the numbers are truly impressive. “ When one store is buying more than 75 percent of any given runway show, you know something special is happening there. ”
When the fashion world closed down due to the COVID-19 pandemic in 2020, the brand hosted an exclusive trunk show for Hampden’ s top clientele—something they repeated only with Moda Operandi that season. McCollough, who called Hampden “ one of the most important resources for luxury designer fashion in the South, ” says the store has been game-changing for its business. “ Hampden is such an important and meaningful store, and Stacy has been so successful in bringing high fashion to Charleston. Stacy’ s love for the Proenza Schouler brand has allowed us to get into the closets of so many wonderful women within Charleston and beyond. ”
That trunk show helped set the stage for how Smallwood has translated her in-store service into a digital experience. For anyone who can’ t make it to Charleston to experience Hampden firsthand, there’ s good news: Every single piece in the store is also available to shop on Hampden’ s website. To enhance the experience, Smallwood just signed on to Shopify Plus’ s Try Now program, which allows customers anywhere in the United States to order up to eight pieces and try them on at home—free of charge. “ That’ s a huge part of our ethos at Hampden, to connect our customer who isn’ t here, ” she says. Shop Hampden’ s selection of Proenza Schouler pre-fall 2022 below. | general |
Vietnam Vets Lose 3rd Circ. Fight Over COVID Crowd Rule | Vietnam veterans in Philadelphia claiming they were unable to have their annual parade failed to show they 'd be irreparably harmed by the city's crowd limit rule during the COVID-19 pandemic, the Third Circuit ruled Wednesday.Third Circuit Judge Joseph Greenaway Jr. wrote in the court's opinion that developments since the filing of the lawsuit in July 2020, such as the moratorium on public gatherings of 50 or more people being rescinded, meant that the veterans were unable to persuade the court that there was a chilling effect on their First Amendment rights.Greenaway said a `` November 23, 2020 Executive Order expressly... | general |
COVID-19 Increases Risk of Type 2 Diabetes | People who have had Covid-19 are at increased risk of developing type 2 diabetes. This is the result of a study by DDZ, DZD and IQVIA, which has now been published in Diabetologia.
Studies show that the human pancreas can also be a target of the SARS-CoV-2 ( severe acute respiratory syndrome coronavirus type 2 virus). Following a Covid-19 infection, reduced numbers of insulin secretory granules in beta cells and impaired glucose-stimulated insulin secretion have been observed. In addition, after Covid-19 disease, some patients developed insulin resistance and had elevated blood glucose levels although they had no previous history of diabetes. SARS-CoV-2 infection may lead to a strong release of pro-inflammatory signaling substances ( cytokines). Activation of the immune system may persist for months after a SARS-CoV-2 infection and impair insulin effectiveness ( muscle, fat cells, liver).
To date, however, it is unclear whether these metabolic changes are transient or whether Covid-19 disease increases the risk of persisting diabetes. To investigate this question, researchers from the German Diabetes Center ( DDZ), German Center for Diabetes Research ( DZD) and IQVIA ( Frankfurt) conducted a retrospective cohort study.
The cohort study included a representative panel of 1,171 physician practices across Germany ( March 2020 to January 2021: 8.8 million patients). Follow-up continued until July 2021. “ The aim of our study was to investigate the incidence of diabetes after infection with SARS-CoV-2, ” said first author Wolfgang Rathmann, head of the Epidemiology Research Group at the DDZ. As a control group, the researchers selected people with acute upper respiratory tract infections ( AURI), which are also frequently caused by viruses. The two cohorts were matched for sex, age, health insurance, month of Covid-19 or AURI diagnosis, and comorbidities ( obesity, hypertension, high cholesterol, heart attack, stroke). Patients on corticosteroid therapy were excluded from the study.
During the study period, 35,865 people were diagnosed with Covid-19. “ Our analyses showed that patients with Covid-19 developed type 2 diabetes more frequently than people with AURI. The incidence of diabetes with Covid-19 infection was 15.8 compared to 12.3 per 1000 people per year with AURI. Statistical analysis resulted in an incidence rate ratio ( IRR) of 1.28. Put simply, this means that the relative risk of developing type 2 diabetes was 28% higher in the Covid-19 group than in the AURI group, ” Rathmann said, summarizing the results.
Although type 2 diabetes is unlikely to be a problem for the vast majority of people with mild Covid-19 disease, the authors recommend that anyone who has recovered from Covid-19 be alert to the warning signs and symptoms, such as fatigue, frequent urination and increased thirst and seek immediate treatment.
For more on this research see Association Found Between Mild COVID-19 Cases and Subsequent Type 2 Diabetes.
Reference: “ Incidence of newly diagnosed diabetes after Covid-19 ” by Wolfgang Rathmann, Oliver Kuss and Karel Kostev, 16 March 2022, Diabetologia. DOI: 10.1007/s00125-022-05670-0 | tech |
Travel Co. Yatra Urges Del. Justices To Revive Ebix Deal Suit | An India-based travel agency that abandoned a merger with a reluctant buyer and then sued for damages told the Delaware Supreme Court Wednesday that the Chancery Court was wrong to dismiss its case because it would have been `` commercially unreasonable '' for the agency to keep negotiating the deal.In oral arguments before a full five-member court, Yatra Online Inc. said would-be acquirer Ebix Inc. had actively tried to undermine their 2019 merger agreement after the COVID-19 pandemic caused Ebix's stock price to drop, making the all-stock deal less appealing.The Chancery Court erred in its August 2021 opinion when it sided... | general |
PayPal Finds Digital Payments Are Key Growth Enablers for UAE Freelancers and SMBs | Conducted between January to February 2022, PayPal’ s UAE and Freelancer Digital Readiness Survey analyses the impact of COVID-19 on small businesses, the key verticals of growth and growing acceptance of digital payments. The results are based on interviews with 300 UAE based SMBs and freelancers.
Despite the uncertainty of business longevity going into the pandemic, the survey highlighted that half of the respondents saw a positive impact of the pandemic on their business. The key factors included an increase in productivity as employees worked from home ( 33%), reduction in overhead costs ( travel, real estate costs) ( 32%) and the ability to access a global customer base outside of the UAE ( 31%). These findings demonstrate that businesses have not only been able to sustain growth without the need for a physical space but have also performed better with 28% of respondents reporting an increase in customer base and 31% reporting an increase in customers from outside of the UAE.
With a rise in sales, nearly half of respondents are looking to build their own e-commerce website and app in the future or to have a presence through a third-party e-commerce marketplace. While online has always been a lucrative option, the pandemic has only increased its role in helping businesses grow. 28% of the UAE entrepreneurs have an online business, while close to half the respondents have a presence both online and offline. 50% said that they are likely to increase their online presence in the future.
Among those who have an online presence, 36% have their own e-commerce website or an app and a similar proportion have a presence through a third-party platform. About 43% have a presence on social media using clickable ads on Instagram, Snapchat, etc. With adoption of digitalisation, 41% of the respondents have seen increased purchases through social media channels with more consumers using online payments ( 39%). With these findings, it’ s no surprise that a staggering 83% are likely to increase their online presence in the future and nearly half of the respondents are looking to have their own e-commerce website or app giving them better control.
A digital-first approach will help both the businesses and consumers as the study shows that the advantages of going digital are:
Among those who have an online presence and use digital payments, 66% claim that it has helped increase their local sales compared to last year. For 56% of the businesses, sales have increased as they were able to reach a global consumer base.
36% of the surveyed entrepreneurs use PayPal, behind 49% of users opting for ‘ cash on delivery and 43% using online bank transfers. As more UAE freelancers and SMBs embrace digital, investment into their digital journey has become a key priority.
Polly is a journalist, content creator and general opinion holder from North Wales. She has written for a number of publications, usually hovering around the topics of fintech, tech, lifestyle and body positivity.
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Ukraine conflict reminds quants that operations matter | The transition from LIBOR to RFR has brought challenges for structured products. There are still legacy IBOR products to consider and at the same time the pricing and risk systems need to be upgraâ¦
To ease the pain associated with meeting compliance targets, global institutions are exploring ways to become more efficient by integrating regulatory and business initiatives.
Wire payment fraud is a major growing risk for financial institutions in the aftermath of the COVID-19 pandemic. These cases of fraud donât just hurt finâ¦
Asia Risk is proud to present Asia Risk Live, a face-to-face event in Hong Kong and Singapore. An opportunity to reconnect in person to learn and exchange new ideas.
View our latest in market leading training courses, both public and in-house.
The Energy Risk Awards recognise the leading firms in energy risk management. Corporates, financial players, technology and data firms, consultancies, brokers and exchanges are all welcome to submit â¦
The Asia Risk Awards recognize best practices in risk management and derivatives use by banks and financial institutions around the region.
Take a look at the wide variety of events and training on offer.
This eBook is based on the 2021 industry research by Acuiti, as well as the FIS Readiness Report. Youâll find plenty of support for a move to AI-powered cloud computing, a modular approach that ensurâ¦
Maximising value from better risk management and deal efficiency This Risk.net survey and white paper, commissioned by SS & C Intralinks, assesses the outlook for the CMBS market in the US and Europe, â¦
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Edited by Bill Coen and D. R. Maurice
For systematic investors, the war in Ukraine has served as a reminder that real-life market frictions can make a fool of even the most carefully designed strategies.
In the wake of the invasion, investors have grappled with the fallout from the economic sanctions imposed on Russia.
Market moves have largely cancelled out, with hits to some assets offset by gains in others, notably commodities. Certain strategies have come unstuck. But others have flourished.
What tripped up most investors were the operational pitfalls posed by the sanctions. The difficulties ranged from pricing anomalies and exchange closures to exploding margin calls on commodities. Such possibilities are rarely considered when quants formulate new alpha strategies, but they have the potential to confound the most elegant ideas.
Much of the “ real ” work in systematic investing, says Joris Tolenaar at quant firm Transtrend, actually has to do with operations. “ It’ s not where you win the game, ” he says, “ but it’ s where you can easily lose. ”
It’ s a time-worn lesson. Margin calls brought down LTCM. ( The consortium that took on the positions of the storied hedge fund turned a profit.)
Frictions of this nature are more common than investors might realise.
In 2021 the US imposed restrictions on US firms trading securities linked to companies believed to have ties to the Chinese military, leading to those instruments also being removed from MSCI’ s global index.
Spain and Italy banned short-selling in some stocks in 2020 as Covid-19 caused equity markets to crash. Sanctions relating to Russia’ s annexation of Crimea in 2014 created problems for banks trading FX futures at the time.
Refco – the world’ s then-biggest independent futures broker – collapsed in 2005, leaving its clients scrambling to transfer business elsewhere. Malaysia effectively froze offshore ringgit assets during the Asian financial crisis in 1998.
The concern for quants is that such market frictions are essentially ignored in the backtests they use to validate strategies. That means strategies that would have been impossible in practice can look promising in tests.
As an extreme example, a quant today might assume that systematic trend following in 2008 was easy, as markets dived. In truth, most investors at the time were concerned about wiring money to counterparties that might not exist the following day. Counterparty risk trumped market risk. Trends were “ on fire ”, Tolenaar says. “ Unfortunately, the banks were on fire too. ”
Likewise, 20 years from now a strategy that in backtests shorted Russian stocks in 2022 might look like a winner. Should that happen, it would be wise to recall that in recent weeks those stocks have been effectively untradeable for most investors.
How might quants try to capture these effects in backtests or build a trading system to handle them? The truth is, they can’ t. Operational problems are a fact of life and inevitably require human intervention.
The war in Ukraine is prompting investors to consider how geopolitics might reshape the international financial system. For systematic investors, it should remind them to trust their backtests a little less.
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To use this feature you will need an individual account. If you have one already please sign in. | general |
Regulators need to go back to fundamentals on fund risks | The transition from LIBOR to RFR has brought challenges for structured products. There are still legacy IBOR products to consider and at the same time the pricing and risk systems need to be upgraâ¦
To ease the pain associated with meeting compliance targets, global institutions are exploring ways to become more efficient by integrating regulatory and business initiatives.
Wire payment fraud is a major growing risk for financial institutions in the aftermath of the COVID-19 pandemic. These cases of fraud donât just hurt finâ¦
Asia Risk is proud to present Asia Risk Live, a face-to-face event in Hong Kong and Singapore. An opportunity to reconnect in person to learn and exchange new ideas.
View our latest in market leading training courses, both public and in-house.
The Energy Risk Awards recognise the leading firms in energy risk management. Corporates, financial players, technology and data firms, consultancies, brokers and exchanges are all welcome to submit â¦
The Asia Risk Awards recognize best practices in risk management and derivatives use by banks and financial institutions around the region.
Take a look at the wide variety of events and training on offer.
This eBook is based on the 2021 industry research by Acuiti, as well as the FIS Readiness Report. Youâll find plenty of support for a move to AI-powered cloud computing, a modular approach that ensurâ¦
Maximising value from better risk management and deal efficiency This Risk.net survey and white paper, commissioned by SS & C Intralinks, assesses the outlook for the CMBS market in the US and Europe, â¦
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Edited by Bill Coen and D. R. Maurice
The March 2020 market turmoil breathed new life into concerns about the systemic risks posed by open-ended funds. Such funds, which have grown substantially in the past decade, saw substantial redemptions that put pressure on the liquidity of some markets.
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Daily Podcast: Wyndham’ s New Budget Extended-Stay Hotel Brand | Get exclusive stories and unlimited access to Skift.com news
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Today’ s edition of Skift’ s daily podcast discusses Wyndham Hotel’ s new brand, Asia’ s tourism rebound, and the ongoing challenge of getting corporate travelers out of Ukraine.
As Asian nations such as Malaysia, Singapore and the Philippines are taking steps to treat Covid as an endemic virus, tourism to the region is expected to make a significant rebound in 2022. But what will it look like? A new report provides three different scenarios for Asia’ s travel recovery, writes Asia Editor Peden Doma Bhutia.
The Pacific Asia Travel Association’ s report, which examines the trends for foreign inbound visitors across the region between 2022 and 2024, envisions mild, medium and severe scenarios in its tourism recovery. The agency’ s special advisor John Koldowksi said the parameters determining the scenarios include containing Covid, keeping borders open without a quarantine-on-arrival and reopening entertainment and hospitality venues.
As for what the scenarios predict, interventional visitor arrivals to Asia are expected to surpass 2019 levels under the mild scenario by 2024 while almost equaling them under the medium scenario. However, the severe scenario predicts visitor numbers to Asia will hit 69 percent of 2019 figures.
We turn now to a big move by Wyndham Hotels & Resorts. The U.S.-based hotel franchising giant is creating an extended-stay brand focused on the budget market, reports Senior Travel Editor Sean O’ Neill.
Wyndham said on Tuesday it has signed deals with two development partners to launch 50 hotels by 2027. The yet-to-be named brand is expected to open its first property next year, and a Wyndham executive said the company projects its average daily rate for those hotels to run between $ 50 and $ 55.
Extended stay caters to travelers staying anywhere from a week to a few months, such as traveling nurses and construction workers. O’ Neill writes developers favor the economy extended-stay segment because it generally performs well during periods of economic boom and bust.
Finally, as the war in Ukraine continues, companies are looking to still evacuate workers from Ukraine, writes Corporate Travel Editor Matthew Parsons, noting that the humanitarian crisis is worsening throughout Eastern Europe as countries in the region grapple with a limited amount of corporate housing available for refugees.
Parsons writes that corporate housing in countries such as Poland and Romania are buckling under pressure from the large numbers of Ukrainian refugees as well as Russians seeking shelter there. One travel executive said the crisis is the worst he’ s seen during his career.
But despite the urgent need to provide accommodation to those fleeing the war, the same executive said companies need to ensure their employees didn’ t apply for refugee status, which he described as a time consuming process. | general |
Europe's Tourism Demand Holds Steady But Ukraine War Anxieties Loom | Get exclusive stories and unlimited access to Skift.com news
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Lebawit Lily Girma, Skift
March 23rd, 2022 at 12:00 PM EDT
A prolonged Russia-Ukraine war could quickly shift this cautious optimism and cause more devastating impacts for Europe's tourism industry. For now, getting ahead of the right messaging and ensuring seamless movement amid an ongoing pandemic will be key in boosting consumer confidence.
Lebawit Lily Girma
The direct and indirect impacts of the Russia-Ukraine war on European tourism are becoming clearer, while also difficult to predict far into the future — and it’ s a mixed bag of both good and bad news for an industry that accounts for approximately 10 percent of gross domestic product in Europe and provides 33 million direct and indirect jobs.
European tourism’ s steady recovery on a global scale has slowed, but it hasn’ t completely stopped it as when the pandemic first hit. Pent-up demand for European travel is helping to mitigate a harsher blow from the Ukraine war, as consumers are adapting to uncertainty and still eager for trips to western Europe. Intra-regional travel demand is holding steady, boosting the sector’ s resilience ahead of Easter and summer, and the bounce back of transatlantic travel continues to stick.
Those were the conclusions drawn by the European Travel Commission on Wednesday in its first official assessment since the start of the Ukraine war, analyzing how Europe’ s tourism recovery will fare amid war, geopolitical shifts, inflation, and supply chain disruptions driving up the cost of travel.
“ We have to be mindful of the impact this war will have on the European economy and on the tourism sector, ” said Luis Araujo, president of the European Travel Commission. “ This crisis will cause another setback in the recovery of our European tourism, especially in eastern European destinations while also threatening the trust and confidence in traveling to Europe. ”
Destinations that are in close geographic proximity to Russia and Ukraine, such as the Baltic countries, as well as Mediterranean coastal towns that were once Russian traveler favorites, will feel more of a direct hit, according to ForwardKeys. But after two years of pandemic restrictions, interest in western European tourism giants, such as Spain, Greece, France and Italy, persists.
“ There’ s been a negative impact; it put a brake on a recovery trend that looked promising, ” said Olivier Ponti, vice president of insights at ForwardKeys, referencing data from the first two weeks of the Ukraine war. “ But recovery is still under way for the leisure segment; in the two weeks following the invasion, bookings were only 22 percent below 2019 and summer also. The resilience of intra-European travel is good news for the sector. ”
Adjusted forecasts for visitor arrivals also show this deferred recovery, but it is not totally derailed, said David Goodger, managing director for Europe and the Middle East at Tourism Economics. “ Western Europe still sees recovery by 2024 with large strides this year though slightly less than previously hoped. ”
Transatlantic travel also holds a firm grip, Forwardkeys’ Ponti agreed.
In other optimistic news, consumer sentiment analysis, based on social conversations, confirms that people continue to see Europe as a safe destination, said Olivier Henry-Biabaud, founder of global travel research firm TCI/TRAVELSAT.
“ One in three social conversations about travel in Europe refer to the Ukraine crisis, but this means two thirds aren’ t, ” said Henry-Biabaud. “ The current situation is showing a drop but it’ s not worse compared to the dramatic decline we had at the start of the covid crisis. ”
Henry-Biabaud added that Europe’ s image so far is most impacted in North America, although it isn’ t a huge impact for now. “ The conversations are more about is it time to postpone, people are questioning if it’ s safe or not to go back to Europe, more than massively canceling. ”
Nevertheless, compared to the rest of the world, Europe is now lagging in its global recovery pace.
“ The European travel sector at large is paying the price already as its competitive situation is deteriorating — a seven percent decrease in bookings since the beginning of war and at same time all other regions were improving, ” said ForwardKeys’ Ponti.
How can tourism offices boost tourism amid the challenge of inflation and rising costs along the travel supply chain?
Boosting confidence with simpler rules on inter-regional travel is key, panelists said, as well as educating consumers and being transparent on the cost of visiting, as well as businesses remaining open to North American travelers.
“ It’ s about informing, not promoting, and then keeping the desire for Europe — making sure people don’ t enter into this ‘ travel is not ethical today’, ” said TCI’ s Henry-Biabaud. “ The message of travel as a peacemaker, and promoting passion-based tourism like art, culture, food, sports, nature, will help escape a bit the anxiety of all these war related conversations. ”
Henry-Biabaud added that the positive images associated with the crisis will help Europe’ s destinations, showing the region as a unified community that’ s opening doors and hearts to refugees.
But it’ s also clear that the longer the conflict lasts, the more pronounced the impact could be on European tourism, and that’ s difficult to predict far ahead.
Perhaps the silver lining is indeed that the war has now given more impetus than the pandemic might have for the European travel sector to unite, collaborate and lean on social sustainability — making it simpler for consumers to travel across borders and give back to local economies in light of the crisis while making a stand against war — as the region must now work harder to reposition itself as the world’ s top destination.
“ Europe is resilient and we will overcome this If we work together, ” said the European Travel Commission’ s Araujo. “ We’ ve seen this inside the European Travel Commission, with a commitment of every national tourism office to not only coordinate a collective answer, but share our experiences in terms of the future of tourism inside Europe and in telling the world that this is not acceptable, that we need to put a stop to the war and we need to start traveling again. ”
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From Alice To Fintiv: Judge O'Malley Dishes On Patent Law | There are very few patent issues that haven't ended up in front of former Federal Circuit Judge Kathleen O'Malley, and now that she's stepped down from the bench, O'Malley's speaking up on the biggest controversies of the moment, from Judge Alan Albright's transfer denials to a recent compromise that waives patents for COVID-19 vaccines.Judge Kathleen O'Malley Judge O'Malley spoke with Law360 in an extensive interview this week, delving into what she would like to see the U.S. Supreme Court change, defending the Federal Circuit's use of Rule 36 orders, and more.Here, the former circuit judge shares her takes on nine major... | general |
MedaSystems Raises $ 1.5M in Pre-Seed Funding | MedaSystems, a Menlo Park, Calif.-based digital health software company, raised $ 1.5m in pre-seed funding.
The round was led by nina capital in conjunction with a group of strategic angel investors.
Led by Fiona Smythe, CEO, MedaSystems has developed a networked platform where pharmaceutical manufacturers and healthcare providers can collaborate on Expanded Access ( also known as Managed Access or Compassionate Use) requests.
Expanded Access allows patients with a serious or life-threatening condition, who have exhausted the standard of care and are not eligible to participate in clinical trials, to request access to investigational therapies that have not yet gained authorization from local regulatory authorities. Expanded Accesses played an essential role in developing novel treatments during the Covid-19 pandemic and historically has been a vital pathway for patients with conditions such as cancer, ALS, Alzheimer’ s disease, and thousands of rare diseases.
The platform enables pharmaceutical companies to respond to Expanded Access requests faster and more efficiently, design more effective clinical trials, enhance pre-approval regulatory submissions and capture real-world data.
FinSMEs
23/03/2022 | business |
Tower in Ontario becomes world's tallest retrofitted Passivhaus structure | used the North American elaboration on European Passivhaus standards for energy efficiency to retrofit the Ken Soble Tower, an 18-storey apartment building constructed in 1967.
Ken Soble tower is the tallest retrofitted Passivehaus in the world. Photo by Codrin Talaba
The largest public housing building in Hamilton, a city southwest of Toronto on Lake Ontario, the tower was in a state of disrepair and selected for renovation by the Canadian National Housing Strategy's Repair and Renewal Fund.
ERA Architects was commissioned to renovate the tower by CityHousing Hamilton. Photo by DoubleSpace
The apartment complex will continue to serve low-income and senior residents under the portfolio of CityHousing Hamilton.
style, the tower is one of the thousands of such buildings built in Canada in the period following the second world war.
The renovation updated the brutalist envelope. Photo by DoubleSpace
The structure is now certified under the Passivhaus EnerPHit category, particular to retrofitted buildings.
In order to achieve the status, ERA updated the cladding of the structure to ensure thermal performance and airtightness. R38 overcladding was used on top of the existing concrete in order to minimise changes to the envelope.
A solarium and garden space were added to the top floor. Photo by DoubleSpace
`` The resulting cladding design includes a 150-millimetre-thick mineral wool EIFS system, not widely used in the local market, complete with an integrated drainage layer and new fluid-applied air barrier membrane, '' said the architects.
Canadian-made, fibreglass-framed, Passivhaus-certified windows were used to maximise the effectiveness of the mechanical systems.
A `` five stage '' cooling system was used throughout the building. This includes the glazing, the
interior shades, ceiling fans, a centralised ventilation system, and decentralised Variable Air Volume Units.
Glazing and cladding was used to increase the effectiveness of the heating and cooling. Photo by Codrin Talaba
The architects acknowledged that centralised cooling systems are not typical for Passivhaus, also known as Passive House in North America.
`` The Passive House standard can at times be at odds with Ontario's humid climate and local building code, '' said ERA.
`` The design team identified a high risk of overheating due to high relative humidity in the regional climate zone, '' the studio continued. `` As such, a centralised air conditioning system was integrated into the design, with resulting impacts on the Passive House energy budget. ''
The ground floor has expanded social areas. Photo by Codrin Talaba
The studio also said that consideration of changing environments due to climate change were factored into the building's design, such as using 2050 projected climate data.
To address the standards of living for an elderly population, ERA implemented a number of socially minded design programs. For example, a new solarium with views over the harbour and a green roof were added along with `` barrier free '' suites, high-contrast wayfinding, and expanded community space on the public ground floor.
The apartment interiors have also been renovated by ERA. Photo is by DoubleSpace
Aspects of the heating design are also geared towards resident well-being.
`` If power and heat were lost on the coldest day of the year, residents could shelter in place for up to four days, as compared to four hours in a building adhering to the minimum requirements of the Ontario Building Code, '' said ERA.
Regarding the aspects of the design informed by the coronavirus pandemic, the studio said that it used `` best-in-class '' individual suite ventilation to account for direct fresh air delivery.
, has been collecting data to work towards national implementation of such restoration processes.
Ken Soble Tower is one of many Canadian postwar social housing towers. Photo is by DoubleSpace
, which, when finished, will become the tallest of its kind building in the world. | business |
Raytheon Says COVID, Not DOJ Probe, Led To Stock Price Dip | Raytheon Technologies Corp. has asked an Arizona federal judge to throw out a proposed class action against it, saying an October 2020 drop in its stock price resulted from the COVID-19 pandemic and not a criminal probe by the U.S. Department of Justice, as investors claim.In a dismissal motion filed Monday, Raytheon argued that its stock prices recovered within a week after the October 2020 drop and that the plaintiffs `` did not wait to see this recovery '' and jumped to the conclusion that the DOJ probe caused the fall. `` The plaintiff hypothesized everything [ Raytheon ] had said about their internal controls and... | general |
Calif. Restaurants Lose Virus Coverage Row With Nationwide | Nationwide Mutual Insurance Co. did not breach its insurance contract with two San Diego restaurants seeking coverage for pandemic-related losses, a California federal judge ruled, saying their claims were barred by a virus exclusion.Mille Fleurs and Bertrand at Mister A's lost their COVID-19 coverage suit on Tuesday based upon the Ninth Circuit's precedent in Mudpie, Inc. v. Travelers Casualty Insurance, according to U.S. District Judge Larry A. Burns.In Mudpie, the Ninth Circuit upheld a lower court's ruling that the children's store operator failed to show how it sustained physical damage from the pandemic, which was necessary to trigger coverage... | general |
Investors shun money market funds despite uncertainty | You are currently accessing Investment Week via your Enterprise account.
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European mutual funds lost net €67.6bn during the second month of the year, while ETFs took in €9.2bn. Overall flows for mutual funds and ETFs were negative at €58.4bn.
Detlef Glow, head of EMEA research at Refinitiv Lipper, said: `` It was not surprising that February 2022 was in general a negative month for the European fund industry given the geopolitical situation in Europe, the still ongoing Covid-19 pandemic, and the sluggish market environment. ''
What did come as a surprise, however, was the fact that investors sold out of money market funds, which are usually seen as a safe haven in times of uncertainty.
Glow said: `` Within this market environment and given the economic uncertainties, one would expect that European investors sold long-term funds and bought money market products. ''
Money market products suffered outflows of nearly €50bn in February. The redemptions `` heavily impacted '' the overall picture, Glow noted.
Mixed asset funds were the best-selling asset type overall with €8.3bn of inflows, followed by equity funds with €4.1bn, commodities ( €1.4bn) and real estate funds ( €0.9bn). Bond funds lost over €23bn while alternative UCITs funds shed €0.6bn.
Switzerland was the fund domicile with the highest net inflows, which totalled €2.9bn followed by Denmark ( €2.4bn) and Spain ( €1.6bn).
Evergrande faces fresh calls for legal action after $ 2.1bn seized by undisclosed lenders - reports
© Incisive Business Media ( IP) Limited, Published by Incisive Business Media Limited, New London House, 172 Drury Lane, London WC2B 5QR.Registered in England and Wales with company registration numbers 09177174 & 09178013 | business |
Visa Canada and DoorDash deliver real-time payments via Stripe | The new feature, called DoorDash Fast Pay, is facilitated by Stripe's Instant Payouts product, made available through Stripe’ s financial institution partner and powered by Visa Direct, Visa's real-time [ 1 ] push payments platform. The number of Canadians participating in short-term contract work has steadily increased, with 1 in 10 Canadian adults identifying as an independent contractor [ 2 ].Increasingly, independent contractors want fast and efficient access to their wages. In fact, in Visa's survey of gig workers, 89% said they’ re likely to sign up for real-time payments, and 66% said they would select gig companies who offer real-time payments instead of others, showing how fast, on-demand payments can be a powerful tool for gig companies [ 3 ]. “ Increasingly, independent contractors want to be paid on their own terms, ” says Jim Filice, VP and Head of New Payments, Visa Canada. “ Getting access to earned wages in real-time is an expectation for many workers, and companies like DoorDash are helping to meet that demand by leveraging Visa’ s network and implementing solutions like Fast Pay. ” Canadians rely on logistics platforms like DoorDash for flexible, low-barrier-to-entry work and earn when, where and how they want. To help ensure that Dashers are able to access their earnings quickly and effectively, DoorDash is using Instant Payouts with Stripe Connect to handle the U.S. and Canada payments experience, from helping Dashers accept customer payments to directing funds to a Dasher’ s debit cards or bank account. Stripe Connect helps businesses easily create a platform to facilitate purchases and payments between third-party buyers and sellers. `` We're proud to be the payments infrastructure helping Dashers access earnings faster for millions of meals being delivered across North America, '' said Jeanne DeWitt Grosser, Head of Americas Revenue and Growth at Stripe. `` Instant Pay was built for platforms that want to ensure earners and merchants can quickly access funds when they want. Stripe's expansion with Visa and DoorDash in Canada is the latest milestone in making that happen. '' “ We are proud to work with Stripe and Visa to provide Dashers with more flexible earning opportunities, ” said Shilpa Arora, General Manager at DoorDash Canada. “ This is a major step forward in introducing new tools to empower Dashers who count on DoorDash for reliable, independent and flexible work and additional income. `` Now with this new integration with Visa Direct, Dashers who are Visa Debit cardholders will be able to access their earnings in real-time, rather than waiting until the end of the week. Fast Pay has been available to Dashers in the US since 2018. The impact of the current COVID-19 pandemic on Canadians ' finances can make it especially challenging to manage payments during this time. That's why Visa works with Stripe, whose Instant Payouts feature is integrated with Visa Direct to help businesses like DoorDash support Dashers in accessing their earnings in real-time, and other business payment disbursements. | tech |
Ex-Enterprise Worker Asks Court To Approve Layoff Suit Deal | A former Enterprise Rent-A-Car employee who was laid off during the COVID-19 pandemic and hit the company with a class action claiming it failed to notify workers of impending layoffs asked a Florida federal judge to sign off on a settlement.None of the class members nor Enterprise objected to the $ 175,000 deal settling the claims, class representative Elva Benson said in the motion for final approval of the settlement Tuesday, and called the deal an `` excellent outcome '' for the 964 workers included in the class. Continuing the case would have been too risky and expensive, Benson said, as it would... | general |
Feds Can't Nix Suit Over Manila Embassy's Fiancé Visa Delays | Dozens of couples survived the U.S. Department of State's attempt to toss litigation alleging that the Manila embassy was not following department rules by slow-walking fiancé visa applications, after a D.C. federal court said their claims of unreasonable delays were plausible.U.S. District Judge Christopher Cooper on Tuesday tossed claims from the Americans and their noncitizen fiancés that the U.S. Department of State and Secretary of State Antony Blinken had arbitrarily deprioritized processing K-1 fiancé visas throughout the COVID-19 pandemic, agreeing with the department that it had discretion over which visas to prioritize during a state of emergency. But he allowed... | general |
32 Off-the-Rack Wedding Dresses to Shop Now | Every product on this page was chosen by a Harper's BAZAAR editor. We may earn commission on some of the items you choose to buy.
Bridal shopping in record time.
Shopping online for your wedding dress is one of the most efficient, streamlined, and safe shopping experiences to tap when wedding dress shopping during the ongoing COVID-19 pandemic. You 've likely had some time to think about what you want to wear for your civil ceremony, rehearsal dinner, down the aisle, reception, after party, and brunch—and if not, this could be the chance to edit down the many thoughts you have swirling, pinned, and brainstormed. Especially when looking for something to wear for an intimate, outdoor ceremony in 2022 ( or 2023), shopping online with time at home to weigh your options might just get you one step closer to landing on the dress.
Use online shopping as a chance to try on a variety of silhouettes, styles, fabrications, necklines, and more. Ahead, find the best off-the-rack bridal gowns available to shop now. Add one ( or more) of these to your cart for bridal shopping in record time.
Start with a strapless gown that's classic, romantic, and effortless. This dress begs to be worn outdoors.
A slinky halter dress—with the added drama of a leg slit—is ideal for the minimalist looking to be just a little bit extra.
Tiered ruffles make a playful statement yet still feel formal when paired with a strappy heel.
While no party you 'll be hosting is truly `` casual, '' try an upcycled linen dress that feels effortlessly daytime for your not-so-dressy moments.
Side cutouts show off the results of pre-wedding workouts, while floral appliqués add interest to the silhouette.
Ruffles and ruching lend a dreamy vibe to your intimate backyard ceremony or private reception.
A feathery mini may immediately give you after party vibes, but it can also add glam that's apropos for an engagement party or rehearsal dinner. Expert tip: Pair this look with a kitten heeled mule.
For a backyard wedding, choose a romantic look apropos for a secret garden. This satin dress with poet sleeves evokes all things dreamy.
For a classic garden party look, opt for Markarian's embroidered cocktail dress.
Serene and utterly chic: You can't go wrong with a Vivienne Westwood gown.
For civil ceremonies, nod to making it official with a dress that means business—like this piece of bridal suiting.
Opt for full Victorian vibes with a lace neckline and sleeves. Small details, like an ivory ribbon belt, give you options when it comes to styling.
For the bride that's not afraid to make a statement: Enter Alessandra Rich bridal with a midi length and major lace-up details.
Opt for a gown that bears resemblance to spring's trending cutout dresses—and shows off your frame. Looks like this sleek gown set the tone: It's time to party.
A little white dress doesn't always require a short hemline. Sometimes, it's all about the slit. This gown feels bridal top-to-toe, but shows off your legs with a side-slit. It also has removable straps, so you can adjust how much you 'll show off to your heart's content.
Prairie-inspired styles filled the recent bridal runways. Take hints from one of the season's biggest trends with a puff-sleeved, ribbon-belted number that feels just as posh as it does prim.
All-over sequins aren't always for the after party. Done in a dramatic floral motif, this style feels effortlessly elegant.
This classic style nods to '50s shapes and First Lady energy. Update the traditional garden party feel of this frock with platform sandals and a small, top-handle lady bag.
While your wedding events are all about you, dressing for your setting is key. Choose architectural shapes and sleek structure when dressing for an event hosted in a city, industrial space, or a gallery. Pair with an equally sharp pair of pumps.
We 've seen more and more high low hemlines on the bridal runways. If you love the look but it's not a silhouette you 'd opt to wear down a more formal aisle, we suggest you try it for an intimate ceremony at home.
A slip dress is timeless; one with expert draping feels wedding-worthy and fashion-forward.
If all-white isn't for you, try a bridal look with a print or pattern. These touches infuse your personal style into your bridal wardrobe, and make accessorizing that much more simple ( insert black heel and clutch here).
Coverage doesn't always need to fill prim and conservative. This cape neckline is case-in-point. Accent with hair up or a short cut to show off the semi-open back and add a dainty earring.
A semi-sheer organza trench with touches of lace takes simplicity to the next level.
This romantic micro-mini, paired with a super-puff sleeve, calls for a statement shoe—like a platform sandal, an embellished stack heel, or a printed, sky-high wedge.
Khaite's avant-garde gown—complete with waist-defining cutouts and a diamond spine detail—is formal, but doesn't take itself too seriously.
Level up an ivory cloqué mini dress with an exaggerated bow at the back that drapes past the hem.
A sleek maxi always works—be it for the rehearsal dinner, brunch, the aisle, or an engagement celebration. The look gets even stronger when elements of visual interest, like these off-the-shoulder puff sleeves.
All hail the bridal wardrobe hero: the lace dress. Reinvent a classic with a drop waist and sheer paneling. This dress would look stellar for a backyard ceremony. Our tip? Wear this down the aisle this year for an intimate vow exchange, then shorten it to a mini length for a larger brunch or rehearsal dinner come 2023.
If you're not one to wear strapless down the aisle—or even if you are—a nod to a traditional bridal silhouette, with a twist, will suit anything from the engagement party to the rehearsal dinner.
This look has all the ingredients of the best beachfront wedding dresses—thin straps, all-over lace, and a cut-out back—with a '50s inspired silhouette. | general |
Effectiveness of nationwide programmatic testing and treatment for latent tuberculosis infection in migrants in England: a retrospective, population-based cohort study - The Lancet Public Health | BackgroundIn low-incidence countries, tuberculosis mainly affects migrants, mostly resulting from reactivation of latent tuberculosis infection ( LTBI) acquired in high-incidence countries before migration. A nationwide primary care-based LTBI testing and treatment programme for migrants from high-incidence countries was therefore established in high tuberculosis incidence areas in England. We aimed to assess the effectiveness of this programme.MethodsWe did a retrospective, population-based cohort study of migrants who registered in primary care between Jan 1, 2011, and Dec 31, 2018, in 55 high-burden areas with programmatic LTBI testing and treatment. Eligible individuals were aged 16–35 years, born in a high-incidence country, and had entered England in the past 5 years. Individuals who tested interferon-γ release assay ( IGRA) -negative were advised about symptoms of tuberculosis, whereas those who tested IGRA-positive were clinically assessed to rule out active tuberculosis and offered preventive therapy. The primary outcome was incident tuberculosis notified to the national Enhanced Tuberculosis Surveillance system.FindingsOur cohort comprised 368 097 eligible individuals who had registered in primary care, of whom 37 268 ( 10·1%) were tested by the programme. 1446 incident cases of tuberculosis were identified: 166 cases in individuals who had IGRA testing ( incidence 204 cases [ 95% CI 176–238 ] per 100 000 person-years) and 1280 in individuals without IGRA testing ( 82 cases [ 77–86 ] per 100 000 person-years). Overall, in our primary analysis including all diagnosed tuberculosis cases, a time-varying association was identified between LTBI testing and treatment and lower risk of incident tuberculosis ( hazard ratio [ HR ] 0·76 [ 95% CI 0·63–0·91 ]) when compared with no testing. In stratified analysis by follow-up period, the intervention was associated with higher risk of tuberculosis diagnosis during the first 6 months of follow-up ( 9·93 [ 7·63–12·9) and a lower risk after 6 months ( 0·57 [ 0·41–0·79 ]). IGRA-positive individuals had higher risk of tuberculosis diagnosis than IGRA-negative individuals ( 31·9 [ 20·4–49·8 ]). Of 37 268 migrants who were tested, 6640 ( 17·8%) were IGRA-positive, of whom 1740 ( 26·2%) started preventive treatment. LTBI treatment lowered the risk of tuberculosis: of 135 incident cases in the IGRA-positive cohort, seven cases were diagnosed in the treated group ( 1·87 cases [ 95% CI 0·89–3·93 ] per 1000 person-years) and 128 cases were diagnosed in the untreated group ( 10·9 cases [ 9·16–12·9 ] per 1000 person-years; HR 0·14 [ 95% CI 0·06–0·32 ]).InterpretationA low proportion of eligible migrants were tested by the programme and a small proportion of those testing positive started treatment. Despite this, programmatic LTBI testing and treatment of individuals migrating to a low-incidence region is effective at diagnosing active tuberculosis earlier and lowers the long-term risk of progression to tuberculosis. Increasing programme participation and treatment rates for those testing positive could substantially impact national tuberculosis incidence.FundingNational Institute for Health Research Health Protection Research Unit in Respiratory Infections.
In low-incidence countries, tuberculosis mainly affects migrants, mostly resulting from reactivation of latent tuberculosis infection ( LTBI) acquired in high-incidence countries before migration. A nationwide primary care-based LTBI testing and treatment programme for migrants from high-incidence countries was therefore established in high tuberculosis incidence areas in England. We aimed to assess the effectiveness of this programme.
We did a retrospective, population-based cohort study of migrants who registered in primary care between Jan 1, 2011, and Dec 31, 2018, in 55 high-burden areas with programmatic LTBI testing and treatment. Eligible individuals were aged 16–35 years, born in a high-incidence country, and had entered England in the past 5 years. Individuals who tested interferon-γ release assay ( IGRA) -negative were advised about symptoms of tuberculosis, whereas those who tested IGRA-positive were clinically assessed to rule out active tuberculosis and offered preventive therapy. The primary outcome was incident tuberculosis notified to the national Enhanced Tuberculosis Surveillance system.
Our cohort comprised 368 097 eligible individuals who had registered in primary care, of whom 37 268 ( 10·1%) were tested by the programme. 1446 incident cases of tuberculosis were identified: 166 cases in individuals who had IGRA testing ( incidence 204 cases [ 95% CI 176–238 ] per 100 000 person-years) and 1280 in individuals without IGRA testing ( 82 cases [ 77–86 ] per 100 000 person-years). Overall, in our primary analysis including all diagnosed tuberculosis cases, a time-varying association was identified between LTBI testing and treatment and lower risk of incident tuberculosis ( hazard ratio [ HR ] 0·76 [ 95% CI 0·63–0·91 ]) when compared with no testing. In stratified analysis by follow-up period, the intervention was associated with higher risk of tuberculosis diagnosis during the first 6 months of follow-up ( 9·93 [ 7·63–12·9) and a lower risk after 6 months ( 0·57 [ 0·41–0·79 ]). IGRA-positive individuals had higher risk of tuberculosis diagnosis than IGRA-negative individuals ( 31·9 [ 20·4–49·8 ]). Of 37 268 migrants who were tested, 6640 ( 17·8%) were IGRA-positive, of whom 1740 ( 26·2%) started preventive treatment. LTBI treatment lowered the risk of tuberculosis: of 135 incident cases in the IGRA-positive cohort, seven cases were diagnosed in the treated group ( 1·87 cases [ 95% CI 0·89–3·93 ] per 1000 person-years) and 128 cases were diagnosed in the untreated group ( 10·9 cases [ 9·16–12·9 ] per 1000 person-years; HR 0·14 [ 95% CI 0·06–0·32 ]).
A low proportion of eligible migrants were tested by the programme and a small proportion of those testing positive started treatment. Despite this, programmatic LTBI testing and treatment of individuals migrating to a low-incidence region is effective at diagnosing active tuberculosis earlier and lowers the long-term risk of progression to tuberculosis. Increasing programme participation and treatment rates for those testing positive could substantially impact national tuberculosis incidence.
National Institute for Health Research Health Protection Research Unit in Respiratory Infections.
Tuberculosis incidence in high-income countries with a low incidence of the disease is driven disproportionately by cases in specific groups at high risk, particularly migrants from high-incidence countries.1Campbell JR Dowdy D Schwartzman K Treatment of latent infection to achieve tuberculosis elimination in low-incidence countries.PLoS Med. 2019; 16e1002824Google Scholar, 2Lönnroth K Migliori GB Abubakar I et al.Towards tuberculosis elimination: an action framework for low-incidence countries.Eur Respir J. 2015; 45: 928-952Google Scholar In these individuals, tuberculosis usually develops within the first 2–5 years after migration, as a result of reactivation of latent tuberculosis infection ( LTBI) acquired before migration.1Campbell JR Dowdy D Schwartzman K Treatment of latent infection to achieve tuberculosis elimination in low-incidence countries.PLoS Med. 2019; 16e1002824Google Scholar, 3Pareek M Watson JP Ormerod LP et al.Screening of immigrants in the UK for imported latent tuberculosis: a multicentre cohort study and cost-effectiveness analysis.Lancet Infect Dis. 2011; 11: 435-444Google Scholar Risk of progression from LTBI to active tuberculosis can be reduced with preventive treatment, and diagnosis and treatment of LTBI is a mainstay of tuberculosis control in low-incidence countries.3Pareek M Watson JP Ormerod LP et al.Screening of immigrants in the UK for imported latent tuberculosis: a multicentre cohort study and cost-effectiveness analysis.Lancet Infect Dis. 2011; 11: 435-444Google Scholar, 4Rosales-Klintz S Bruchfeld J Haas W et al.Guidance for programmatic management of latent tuberculosis infection in the European Union/European Economic Area.Eur Respir J. 2019; 531802077Google Scholar Systematic testing and treatment of migrants from high-incidence regions might therefore have a large impact on tuberculosis control and elimination.2Lönnroth K Migliori GB Abubakar I et al.Towards tuberculosis elimination: an action framework for low-incidence countries.Eur Respir J. 2015; 45: 928-952Google Scholar, 5European Centre for Disease Prevention and ControlProgrammatic management of latent tuberculosis infection in the European Union.https: //www.ecdc.europa.eu/sites/default/files/documents/October-2018-Programmatic-management-LTBI-EU.pdfDate: 2018Date accessed: February 10, 2020Google Scholar, 6WHOGuidelines on the management of latent tuberculosis infection. World Health Organization, Geneva2015https: //apps.who.int/iris/bitstream/handle/10665/136471/9789241548908 eng.pdf; jsessionid=A098AA6028BDE499F4AAED67C3D7F4DE? sequence=1Date accessed: February 20, 2020Google Scholar
On the basis of the epidemiology of imported LTBI,7Pareek M Baussano I Abubakar I Dye C Lalvani A Evaluation of immigrant tuberculosis screening in industrialized countries.Emerg Infect Dis. 2012; 18: 1422-1429Google Scholar, 8Pareek M Abubakar I White PJ Garnett GP Lalvani A Tuberculosis screening of migrants to low-burden nations: insights from evaluation of UK practice.Eur Respir J. 2011; 37: 1175-1182Google Scholar the risk of progression to active tuberculosis in migrants with a positive interferon-γ release assay ( IGRA),9Abubakar I Lalvani A Southern J et al.Two interferon gamma release assays for predicting active tuberculosis: the UK PREDICT TB prognostic test study.Health Technol Assess. 2018; 22: 1-96Google Scholar health-economic analyses,3Pareek M Watson JP Ormerod LP et al.Screening of immigrants in the UK for imported latent tuberculosis: a multicentre cohort study and cost-effectiveness analysis.Lancet Infect Dis. 2011; 11: 435-444Google Scholar and feasibility studies in primary care and potential screening pathways,10Lalvani A Pareek M Immigrant screening for TB: a missed opportunity to improve TB control in the United Kingdom.Pathog Glob Health. 2012; 106: 5-7Google Scholar, 11Pareek M Bond M Shorey J et al.Community-based evaluation of immigrant tuberculosis screening using interferon γ release assays and tuberculin skin testing: observational study and economic analysis.Thorax. 2013; 68: 230-239Google Scholar in England a primary care-based programme was launched in 2015 for systematic LTBI testing ( by IGRA) and treatment for migrants from high-incidence countries residing in areas with the highest tuberculosis burden.12Public Health EnglandCollaborative tuberculosis strategy for England 2015–2020.https: //assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment data/file/403231/Collaborative TB Strategy for England 2015 2020 .pdfDate: 2015Date accessed: February 23, 2020Google Scholar, 13Public Health EnglandLatent TB testing and treatment for migrants: a practical guide for commissioners and practitioners.https: //assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment data/file/442192/030615 LTBI testing and treatment for migrants 1.pdfDate: 2015Date accessed: February 20, 2020Google Scholar To our knowledge, this is a first, non-obligatory, national public health experiment that individuals can choose to enter if they wish. If successful, this programme would represent an important step towards tuberculosis elimination. Although underpinned by a large evidence base,3Pareek M Watson JP Ormerod LP et al.Screening of immigrants in the UK for imported latent tuberculosis: a multicentre cohort study and cost-effectiveness analysis.Lancet Infect Dis. 2011; 11: 435-444Google Scholar, 7Pareek M Baussano I Abubakar I Dye C Lalvani A Evaluation of immigrant tuberculosis screening in industrialized countries.Emerg Infect Dis. 2012; 18: 1422-1429Google Scholar, 8Pareek M Abubakar I White PJ Garnett GP Lalvani A Tuberculosis screening of migrants to low-burden nations: insights from evaluation of UK practice.Eur Respir J. 2011; 37: 1175-1182Google Scholar, 9Abubakar I Lalvani A Southern J et al.Two interferon gamma release assays for predicting active tuberculosis: the UK PREDICT TB prognostic test study.Health Technol Assess. 2018; 22: 1-96Google Scholar, 10Lalvani A Pareek M Immigrant screening for TB: a missed opportunity to improve TB control in the United Kingdom.Pathog Glob Health. 2012; 106: 5-7Google Scholar, 11Pareek M Bond M Shorey J et al.Community-based evaluation of immigrant tuberculosis screening using interferon γ release assays and tuberculin skin testing: observational study and economic analysis.Thorax. 2013; 68: 230-239Google Scholar the programme has not been evaluated in a randomised controlled trial. In this cohort study, we aimed to pragmatically evaluate the effectiveness of this programme in the real world and to assess the risk of progression to tuberculosis in migrants with a positive IGRA and its mitigation by programmatic preventive treatment.
Research in contextEvidence before this studyWe searched PudMed for articles published in English between Jan 1, 2015, and July 31, 2021, about the effectiveness of programmatic testing and treatment for latent tuberculosis infection ( LTBI) in migrants in high-income countries using the search terms “ TB screening ” AND “ migrant ”. Few studies have assessed the effectiveness of testing and treating migrants for LTBI in a programmatic setting. A systematic review on the effectiveness and cost-effectiveness of screening migrants for LTBI in the EU suggested that the effectiveness of LTBI programmes is limited by poorly predictive tests, long treatment durations, and a weak care cascade ( ie, many individuals are lost to follow-up at each step). A population-based study provided indirect evidence that the reduction in tuberculosis notifications in the UK might be partly explained by the effectiveness of screening interventions, including LTBI testing, in non-EU migrants who had migrated in the past 5 years. England is the only country to have launched a nationwide LTBI testing and treatment programme for new entrants in primary care and its feasibility and effectiveness are of considerable international interest. Preliminary evidence from initial roll-out during the first pilot year of this interferon-γ release assay ( IGRA) -based programme indicated a reduction in tuberculosis incidence among the small number of migrants who were initially tested.Added value of this studyWe assessed whether the UK programme was effective in averting active tuberculosis, the risk of progression to active tuberculosis in new entrants who test positive by IGRA, and the effectiveness of LTBI treatment to prevent active tuberculosis using the 3-month isoniazid and rifampicin regimen. We demonstrated that programmatic nationwide LTBI testing and treatment are feasible and effective to reduce the risk of tuberculosis in foreign-born individuals who had arrived in England in the previous 5 years. Programmatic LTBI testing and treatment is associated with earlier diagnosis of active tuberculosis and an overall lower risk of developing active tuberculosis over time. The risk of developing active tuberculosis was 31 times higher for IGRA-positive individuals than IGRA-negative individuals and LTBI treatment with a 3-month isoniazid and rifampicin regimen reduced this risk by 86%.Implications of all the available evidenceProgrammatic LTBI testing and treatment of new migrants to a low-incidence region is effective at diagnosing active tuberculosis earlier and reduces the long-term risk of progression to tuberculosis. National programmes such as this could therefore be important new public health interventions to enable tuberculosis elimination in low-incidence regions. Such programmes could be especially important to improve tuberculosis control at present considering the widespread disruption to tuberculosis services observed internationally since the start of the COVID-19 pandemic.
We searched PudMed for articles published in English between Jan 1, 2015, and July 31, 2021, about the effectiveness of programmatic testing and treatment for latent tuberculosis infection ( LTBI) in migrants in high-income countries using the search terms “ TB screening ” AND “ migrant ”. Few studies have assessed the effectiveness of testing and treating migrants for LTBI in a programmatic setting. A systematic review on the effectiveness and cost-effectiveness of screening migrants for LTBI in the EU suggested that the effectiveness of LTBI programmes is limited by poorly predictive tests, long treatment durations, and a weak care cascade ( ie, many individuals are lost to follow-up at each step). A population-based study provided indirect evidence that the reduction in tuberculosis notifications in the UK might be partly explained by the effectiveness of screening interventions, including LTBI testing, in non-EU migrants who had migrated in the past 5 years. England is the only country to have launched a nationwide LTBI testing and treatment programme for new entrants in primary care and its feasibility and effectiveness are of considerable international interest. Preliminary evidence from initial roll-out during the first pilot year of this interferon-γ release assay ( IGRA) -based programme indicated a reduction in tuberculosis incidence among the small number of migrants who were initially tested.
We assessed whether the UK programme was effective in averting active tuberculosis, the risk of progression to active tuberculosis in new entrants who test positive by IGRA, and the effectiveness of LTBI treatment to prevent active tuberculosis using the 3-month isoniazid and rifampicin regimen. We demonstrated that programmatic nationwide LTBI testing and treatment are feasible and effective to reduce the risk of tuberculosis in foreign-born individuals who had arrived in England in the previous 5 years. Programmatic LTBI testing and treatment is associated with earlier diagnosis of active tuberculosis and an overall lower risk of developing active tuberculosis over time. The risk of developing active tuberculosis was 31 times higher for IGRA-positive individuals than IGRA-negative individuals and LTBI treatment with a 3-month isoniazid and rifampicin regimen reduced this risk by 86%.
Programmatic LTBI testing and treatment of new migrants to a low-incidence region is effective at diagnosing active tuberculosis earlier and reduces the long-term risk of progression to tuberculosis. National programmes such as this could therefore be important new public health interventions to enable tuberculosis elimination in low-incidence regions. Such programmes could be especially important to improve tuberculosis control at present considering the widespread disruption to tuberculosis services observed internationally since the start of the COVID-19 pandemic.
We did a retrospective, population-based cohort study in individuals who registered in primary care between Jan 1, 2011, and Dec 31, 2018 in 55 high-burden ( tuberculosis incidence > 20 cases per 100 000 population per year) Clinical Commissioning Group areas of England where the LTBI testing and treatment programme was rolled out. Individuals were eligible to participate if they were aged 16–35 years, born in a high-incidence country ( ≥150 cases per 100 000 population per year or any country in sub-Saharan Africa), and had entered England within 5 years of the programme start date.12Public Health EnglandCollaborative tuberculosis strategy for England 2015–2020.https: //assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment data/file/403231/Collaborative TB Strategy for England 2015 2020 .pdfDate: 2015Date accessed: February 23, 2020Google Scholar Participants were excluded if they registered in an area without programmatic LTBI testing or their date of primary care registration was missing and they were not tested for LTBI. The cohort was divided into two groups; individuals who were tested for LTBI and those who were not. The group not tested for LTBI was used as the control group to assess overall programme effectiveness.
A pilot programme started in January, 2014 and was rolled out to all 55 high-burden Clinical Commissioning Group areas by Jan 30, 2015.12Public Health EnglandCollaborative tuberculosis strategy for England 2015–2020.https: //assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment data/file/403231/Collaborative TB Strategy for England 2015 2020 .pdfDate: 2015Date accessed: February 23, 2020Google Scholar IGRA was used to identify tuberculosis infection, which was then investigated to determine whether it represented active tuberculosis disease or LTBI; investigation for active tuberculosis in individuals who tested IGRA-positive was thus part of the screening pathway. Eligible individuals were offered LTBI testing by IGRA in primary care, allowing for alternative suitable settings according to local circumstances.13Public Health EnglandLatent TB testing and treatment for migrants: a practical guide for commissioners and practitioners.https: //assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment data/file/442192/030615 LTBI testing and treatment for migrants 1.pdfDate: 2015Date accessed: February 20, 2020Google Scholar IGRA-negative individuals were advised to be vigilant for symptoms of tuberculosis, and IGRA-positive individuals had clinical assessment including chest radiography, followed by respiratory samples for microscopy and culture if radiographic appearances suggested tuberculosis, to rule out active tuberculosis before referral to local secondary care tuberculosis services for preventive therapy, usually 3 months treatment with isoniazid and rifampicin.13Public Health EnglandLatent TB testing and treatment for migrants: a practical guide for commissioners and practitioners.https: //assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment data/file/442192/030615 LTBI testing and treatment for migrants 1.pdfDate: 2015Date accessed: February 20, 2020Google Scholar, 14National Institute for Health and Care ExcellenceTuberculosis. NICE guideline.https: //www.nice.org.uk/guidance/ng33/resources/tuberculosis-pdf-1837390683589Date: Jan 13, 2016Date accessed: March 26, 2020Google Scholar Individuals identified with active tuberculosis were referred to their local tuberculosis service for standard treatment.13Public Health EnglandLatent TB testing and treatment for migrants: a practical guide for commissioners and practitioners.https: //assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment data/file/442192/030615 LTBI testing and treatment for migrants 1.pdfDate: 2015Date accessed: February 20, 2020Google Scholar, 14National Institute for Health and Care ExcellenceTuberculosis. NICE guideline.https: //www.nice.org.uk/guidance/ng33/resources/tuberculosis-pdf-1837390683589Date: Jan 13, 2016Date accessed: March 26, 2020Google Scholar
We used a validated probabilistic linkage method15Aldridge RW Shaji K Hayward AC Abubakar I Accuracy of probabilistic linkage using the enhanced matching system for public health and epidemiological studies.PLoS One. 2015; 10e0136179Google Scholar to create a cohort of all foreign-born individuals who registered in primary care in England from Jan 1, 2011, to Dec 31, 2018 by linking three different datasets ( appendix p 4). This cohort represents the total number of individuals eligible for the programme; the number invited to participate by their general practitioners was not available. A detailed description of data sources, linkage methods, and all variables used in the analysis is provided in the appendix ( p 4).
All databases were stored, processed, and analysed at the UK Health Security Agency ( Colindale, UK). Under the UK Health and Social Care Act 2012, the UK Health Security Agency has authority to hold and analyse national surveillance data for public health evaluation purposes. By participating in the pre-entry screening and LTBI testing programmes, individuals consented for their data to be used by the UK Health Security Agency and the National Health Service for monitoring and evaluation and due to the nature of the study the requirement for ethical approval was waived.
The primary outcome measure was new, incident cases of active tuberculosis at any anatomical site, either bacteriologically or clinically diagnosed, notified to the national enhanced tuberculosis surveillance system.16Public Health EnglandGuidance on notifying tuberculosis ( TB) cases.https: //assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment data/file/360263/Guidance on Notifying Tuberculosis TB cases.pdfDate: 2014Date accessed: October 20, 2019Google Scholar
In the primary analysis, we assumed that all individuals with tuberculosis could be identified through the screening pathway and accordingly included all cases diagnosed during the study period; however, cases notified within 21 days of LTBI treatment start date were assumed to be prevalent ( not incident) and excluded from analyses,17Abubakar I Drobniewski F Southern J et al.Prognostic value of interferon-γ release assays and tuberculin skin test in predicting the development of active tuberculosis ( UK PREDICT TB): a prospective cohort study.Lancet Infect Dis. 2018; 18: 1077-1087Google Scholar as were cases notified before roll-out of the programme on Jan 1, 2014. We then did a sensitivity analysis to assess the potential for overestimating the effectiveness of the programme or of LTBI treatment by inclusion of all tuberculosis cases in the analysis. The sensitivity analysis therefore assumed all cases diagnosed within 60 days and 90 days of primary care registration or IGRA testing to be prevalent ( not incident) and these cases were excluded from analysis. Cohort time started on IGRA testing date for the analysis of overall programme effectiveness; for individuals who were not tested, start time was the date of primary care registration plus 99 days ( the median time between primary care registration and IGRA testing for individuals who underwent IGRA testing). For analysis of treatment effectiveness, cohort time started at treatment start date; for individuals who did not start treatment, cohort time started on the date of IGRA testing plus 52 days ( the median time between IGRA testing and treatment start). Cohort time ended at death, development of active tuberculosis, or the end of the study ( Nov 30, 2019), whichever occurred first. We used log-rank tests to assess differences between Kaplan-Meier survival curves for time to tuberculosis diagnosis according to LTBI testing, IGRA positivity, and LTBI treatment. Cox proportional-hazards models were used to assess the effect of the same variables on time to tuberculosis diagnosis after adjustment for covariates. For the survival analysis, univariate models were first fitted for each covariate; we then assessed effect interactions and modifications between the main outcomes and all covariates, after which a multivariable model was fitted including all covariates and significant effect modifications. We did sensitivity analyses to account for the imputation method using complete case analysis, for treatment completion using only participants with confirmed date of treatment completion, and excluding tuberculosis cases diagnosed within 60 and 90 days of primary care registration or LTBI testing. A detailed description of the statistical analysis is provided in the appendix ( p 5).
There are different possible mechanisms that can give rise to variations in the hazard of tuberculosis diagnosis over time in the cohort of individuals who received LTBI testing compared with those who did not. First, by virtue of repeated clinical follow-up, any incident tuberculosis in the tested cohort is likely to be diagnosed and notified more rapidly than in the non-tested cohort. Second, preventive therapy would tend to reduce the incidence of tuberculosis among individuals who are tested and treated. The first mechanism would be expected to lead to a short-term increased hazard of tuberculosis diagnosis, while the second mechanism would cause an overall decrease. To capture the combined effect of these two mechanisms, we estimated the overall effect of LTBI testing and treatment while allowing for a time-varying effect.18Cleves M Gutierrez RG Gould W Marchenko YV Model building using stcox.in: Cleves M Gutierrez RG Gould W Marchenko YV An introduction to survival analysis using Stata. Stata Press, College Station, TX2010: 189-196Google Scholar, 19Zhang Z Reinikainen J Adeleke KA Pieterse ME Groothuis-Oudshoorn CGM Time-varying covariates and coefficients in Cox regression models.Ann Transl Med. 2018; 6: 121Google Scholar This analytical approach considers the two different benefits of the programme: identification of prevalent cases of active tuberculosis through screening and prevention of progression from LTBI to active disease by treatment. We then repeated the analysis stratified by time of follow-up to assess whether the hazard ratio ( HR) varied during follow-up. Missing values were imputed by multiple imputation by chained equations ( appendix p 5).20Rubin DB Multiple imputation for nonresponse in surveys. John Wiley, New York, NY1987Google Scholar, 21He Y Missing data analysis using multiple imputation: getting to the heart of the matter.Circ Cardiovasc Qual Outcomes. 2010; 3: 98-105Google Scholar We used Stata statistical software ( version 15.1) for statistical analyses. The adjusted number needed to treat ( NNT) was calculated using the R package stdReg with R Open software ( version 3.5.3).22Sjölander A Estimation of causal effect measures with the R-package stdReg.Eur J Epidemiol. 2018; 33: 847-858Google Scholar All p values were two-tailed and values of less than 0·05 were considered to indicate a statistically significant difference.
The funder of the study had no role in study design, data collection, analysis, interpretation, or writing of the manuscript.
The cohort comprised 368 097 eligible individuals, of whom 37 268 ( 10·12%) had IGRA testing and 330 829 ( 89·88%) did not ( figure 1). Among the 37 268 individuals who had IGRA testing, 29 892 ( 80·21%) were IGRA-negative and 6640 ( 17·82%) IGRA-positive. Of the 6640 individuals who tested positive, 1740 ( 26·20%) started preventive treatment and 4900 ( 73·80%) did not ( figure 1, table 1). The baseline characteristics of study participants are summarised in table 1.Figure 1Study design and participantsShow full captionLTBI=latent tuberculosis infection. IGRA=interferon-γ release assay. * Participants with indeterminate or no available IGRA results were excluded.View Large Image Figure ViewerDownload Hi-res image Download ( PPT) Table 1Baseline characteristics of study participants ( n=368 097) Tested for LTBI ( n=37 268) Not tested for LTBI ( n=330 829) Age, years16–2516 396/37 051 ( 44·0%) 180 334 ( 54·5%) 26–3520 655/37 051 ( 55·4%) 150 495 ( 45·5%) SexFemale16 518/36 579 ( 45·2%) 162 190/330 823 ( 49·0%) Male20 061/36 579 ( 54·8%) 168 633/330 823 ( 51·0%) ETS region of originAfrica4297/22 546 ( 19·1%) 90 668 ( 27·4%) The Americas or Europe306/22 546 ( 0·8%) 10 153 ( 3·1%) East and southeast Asia606/22 546 ( 2·7%) 25 787 ( 7·8%) South Asia17 337/22 546 ( 76·9%) 204 221 ( 61·7%) Tuberculosis incidence in country of origin ( cases per 100 000) * WHO estimated tuberculosis incidence.1340–1492138/22 546 ( 9·5%) 46 456 ( 14·0%) 150–34919 757/22 546 ( 87·6%) 258 595 ( 78·2%) > 350651/22 546 ( 2·9%) 25 778 ( 7·8%) Tuberculosis incidence in area of residence ( cases per 100 000) †The UK Health Security Agency estimated tuberculosis incidence in Clinical Commissioning Group area of residence.≤9·23132/33 789 ( 9·3%) 35 936/319 090 ( 11·3%) 9·3–31·614 016/33 789 ( 41·5%) 203 003/319 090 ( 63·6%) > 31·616 641/33 789 ( 49·2%) 80 151/319 090 ( 25·1%) Deprivation index1–3 deciles ( most deprived) 21 579/35 948 ( 60·0%) 161 651/323 764 ( 49·9%) 4–6 deciles11 791/35 948 ( 32·8%) 120 217/323 764 ( 37·1%) 7–10 deciles ( least deprived) 2578/35 948 ( 7·2%) 41896/323 764 ( 12·9%) Year of arrival in England or primary care registration2011–121882/22 546 ( 8·3%) 76 342 ( 23·1%) 2013–142610/22 546 ( 11·6%) 58 853 ( 17·8%) 2015–166910/22 546 ( 30·1%) 84 178 ( 25·4%) 2017–1811 144/22 546 ( 49·4%) 111 456 ( 33·7%) Pre-entry screening for active tuberculosisYes7704 ( 20·7%) 80 641 ( 24·4%) No29 564 ( 20·7%) 250 188 ( 75·6%) IGRA for latent tuberculosisPositive6640 ( 17·8%) NANegative29 892 ( 80·2%) NAIndeterminate353 ( 0·9%) NANo result available383 ( 1·0%) NALTBI treatmentYes1740 ( 26·2%) NANo4900 ( 73·8%) NAData are n (%) or n/N (%). ETS=enhanced tuberculosis surveillance system. IGRA= interferon-γ release assay. LTBI=latent tuberculosis infection. NA=not applicable. * WHO estimated tuberculosis incidence.13Public Health EnglandLatent TB testing and treatment for migrants: a practical guide for commissioners and practitioners.https: //assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment data/file/442192/030615 LTBI testing and treatment for migrants 1.pdfDate: 2015Date accessed: February 20, 2020Google Scholar† The UK Health Security Agency estimated tuberculosis incidence in Clinical Commissioning Group area of residence. Open table in a new tab
LTBI=latent tuberculosis infection. IGRA=interferon-γ release assay. * Participants with indeterminate or no available IGRA results were excluded.
Data are n (%) or n/N (%). ETS=enhanced tuberculosis surveillance system. IGRA= interferon-γ release assay. LTBI=latent tuberculosis infection. NA=not applicable.
A total of 1446 tuberculosis cases were identified in the entire cohort during the study period ( figure 1), giving an incidence of 88 cases ( 95% CI 83–92) per 100 000 person-years in a total follow-up time of 1 638 236 person-years, with a median follow-up time of 3·9 years ( IQR 2·29–6·60) per person. In individuals who had IGRA testing, 166 tuberculosis cases were identified ( incidence 204 cases [ 95% CI 176–238 ] per 100 000 person-years, and among individuals without IGRA testing, 1280 cases were identified ( incidence 82 cases [ 95% CI 77–86 ] per 100 000 person-years ( figure 1, table 2). The unadjusted Kaplan-Meier curve indicated that individuals who received an IGRA test had an increased risk of tuberculosis diagnosis compared with those who had no IGRA test ( figure 2); however, the curves converged showing that the increased risk was not sustained as time accrued, indicating that the hazard of tuberculosis diagnosis is not proportional—ie, the HR changes over time.19Zhang Z Reinikainen J Adeleke KA Pieterse ME Groothuis-Oudshoorn CGM Time-varying covariates and coefficients in Cox regression models.Ann Transl Med. 2018; 6: 121Google Scholar For this reason, we estimated the overall effect ( ie, the average effect during the overall follow-up time) of LTBI testing and treatment over time allowing for a time-varying effect.18Cleves M Gutierrez RG Gould W Marchenko YV Model building using stcox.in: Cleves M Gutierrez RG Gould W Marchenko YV An introduction to survival analysis using Stata. Stata Press, College Station, TX2010: 189-196Google Scholar, 19Zhang Z Reinikainen J Adeleke KA Pieterse ME Groothuis-Oudshoorn CGM Time-varying covariates and coefficients in Cox regression models.Ann Transl Med. 2018; 6: 121Google Scholar This analysis showed that overall LTBI testing and treatment is associated with lower risk of tuberculosis diagnosis compared with no testing ( HR 0·76 [ 95% CI 0·63–0·91 ]; table 2). A stratified analysis showed that the intervention was associated with higher risk of tuberculosis diagnosis during the first 6 months of follow-up ( 9·93 [ 7·63–12·9 ]), but after 6 months, the intervention was associated with a significantly lower risk ( 0·57 [ 0·41–0·79 ]; table 2). Of the 1446 tuberculosis cases, 234 were diagnosed during the first 6 months: 124 cases among individuals with IGRA testing ( incidence 4·65 cases [ 95% CI 3·90–5·54 ] per one person-year) and 110 cases among individuals without testing ( incidence 2·59 cases [ 95% CI 2·15–3·13 ] per one person-year). 1212 tuberculosis cases were diagnosed subsequently: 42 in individuals with IGRA testing ( incidence 51·8 cases [ 95% CI 38·3–70·1 ] per 100 000 person-years) and 1170 cases among individuals without testing ( incidence 75·1 cases [ 95% CI 70·9–79·5 ] per 100 000 person-years; table 2).Table 2Multivariable Cox regression model analysis of factors associated with time to tuberculosis diagnosisTuberculosis cases per person-years of follow-up * Included only participants with no missing data for that characteristic.Incidence per 100 000 person-years ( 95% CI) HR ( 95% CI) †HR ( 95% CI) and p value estimates were derived from the total cohort of migrants, excluding those who developed tuberculosis 21 days after starting treatment ( n=368 077), after multiple imputation for missing values by chained equations model.p valueModel 1Age, years16–25773/946 15381 ( 76–87) 0·85 ( 0·76–0·94) 0·00326–35671/691 63597 ( 89–104) 1 ( ref).. SexFemale826/829 16799 ( 93–106) 1 ( ref).. Male618/807 30076 ( 70–82) 0·77 ( 0·69–0·86) < 0·0001ETS region of originAfrica389/423 38791 ( 83–101) 1 ( ref).. The Americas or Europe0/30 89300.. East and southeast Asia49/98 84349 ( 37–65) 0·60 ( 0·45–0·82) 0·001South Asia931/1 051 90188 ( 83–94) 1·16 ( 0·97–1·39) 0·089Tuberculosis incidence in country of origin ( cases per 100 000) ‡WHO estimated tuberculosis incidence.1340–149192/196 67497 ( 84–112) 1 ( ref).. 150–3491105/1 297 87685 ( 80–90) 0·62 ( 0·50–0·77) < 0·0001 > 35072/110 47465 ( 51–82) 0·63 ( 0·47–0·84) 0·002Tuberculosis incidence in area of residence ( cases per 100 000) §The UK Health Security Agency estimated tuberculosis incidence in Clinical Commissioning Group area of residence.≤9·2118/146 62480 ( 67–96) 1 ( ref).. 9·3–31·6855/970 86288 ( 82–94) 1·05 ( 0·86–1·30) 0·583 > 31·6428/460 35892 ( 84–102) 1·16 ( 0·93–1·45) 0·161Deprivation index1–3 deciles ( most deprived) 788/821 58495 ( 89–102) 1 ( ref).. 4–6 deciles495/583 21384 ( 77–92) 0·89 ( 0·79–1·00) 0·0637–10 deciles ( least deprived) 128/196 72765 ( 54–77) 0·73 ( 0·60–0·89) 0·002Year of arrival in England or primary care registration2011–12477/629 97975 ( 69–82) 1 ( ref).. 2013–14340/368 24092 ( 83–102) 1·21 ( 1·03–1·42) 0·0182015–16374/362 069103 ( 93–114) 1·26 ( 1·07–1·48) 0·0042017–18178/244 73672 ( 62–84) 0·78 ( 0·63–0·96) 0·024Pre-entry screening for active tuberculosisYes322/374 03686 ( 77–96) 1·27 ( 1·03–1·56) 0·022No1124/1 264 20088 ( 83–94) 1 ( ref).. Pre-entry screening: year of arrival in England or primary care registration¶Effect modification is shown in the multiplicative scale using pre-entry active tuberculosis screening ( yes) as the baseline group.2011–12.... 1 ( ref).. 2013–14.... 0·92 ( 0·69–1·23) 0·5992015–16.... 0·89 ( 0·67–1·18) 0·4302017–18.... 0·43 ( 0·29–0·63) < 0·0001Time-variant LTBI testing and treatmentYes166/80 995204 ( 176–238) 0·76 ( 0·63–0·91) 0·003No1280/1 557 24182 ( 77–86) 1 ( ref).. LTBI testing and treatment by follow-up periodModel 2 ( < 6 months follow-up) ‖Models 2–6 include the same covariates as model 1 with the addition of the time-variant effect of LTBI testing and treatment.Yes124/26·64·65 ( 3·90–5·54) 9·93 ( 7·63–12·9) < 0·001No110/42·32·59 ( 2·15–3·13) 1 ( ref).. Model 3 ( > 6 months follow-up) * * Rate per one person-year ( 95% CI).Yes42/80 96951·8 ( 38·3–70·1) 0·57 ( 0·41–0·79) 0·001No1170/1 557 19875·1 ( 70·9–79·5) 1 ( ref).. Model 4 ( 1-year follow-up) §The UK Health Security Agency estimated tuberculosis incidence in Clinical Commissioning Group area of residence.Yes18/76 49023·5 ( 14·8–37·3) 0·36 ( 0·22–0·58) < 0·001No977/1 555 58262·8 ( 58·9–66·8) 1 ( ref).. Model 5 ( 2-year follow up) §The UK Health Security Agency estimated tuberculosis incidence in Clinical Commissioning Group area of residence.Yes8/57 54813·9 ( 6·95–27·8) 0·36 ( 0·18–0·73) 0·005No698/1 474 48647·3 ( 43·9–50·9) 1 ( ref).. Model 6 ( 3-year follow-up) §The UK Health Security Agency estimated tuberculosis incidence in Clinical Commissioning Group area of residence.Yes2/30 2966·6 ( 1·65–26·4) 0·29 ( 0·07–1·18) 0·085No464/1 352 52734·3 ( 31·3–37·5) 1 ( ref).. HR=hazard ratio. ETS=enhanced tuberculosis surveillance system. LTBI=latent TB infection. * Included only participants with no missing data for that characteristic.† HR ( 95% CI) and p value estimates were derived from the total cohort of migrants, excluding those who developed tuberculosis 21 days after starting treatment ( n=368 077), after multiple imputation for missing values by chained equations model.‡ WHO estimated tuberculosis incidence.13Public Health EnglandLatent TB testing and treatment for migrants: a practical guide for commissioners and practitioners.https: //assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment data/file/442192/030615 LTBI testing and treatment for migrants 1.pdfDate: 2015Date accessed: February 20, 2020Google Scholar§ The UK Health Security Agency estimated tuberculosis incidence in Clinical Commissioning Group area of residence.¶ Effect modification is shown in the multiplicative scale using pre-entry active tuberculosis screening ( yes) as the baseline group.‖ Models 2–6 include the same covariates as model 1 with the addition of the time-variant effect of LTBI testing and treatment. * * Rate per one person-year ( 95% CI). Open table in a new tab Figure 2Tuberculosis-free survival among migrants tested for LTBI and those not tested for LTBIShow full captionThe unadjusted Kaplan-Meier curve was derived using all study participants, excluding those who developed tuberculosis 21 days after starting treatment ( n=368 077). The inset shows the same data on an enlarged y-axis. LTBI=latent tuberculosis infection.View Large Image Figure ViewerDownload Hi-res image Download ( PPT)
HR=hazard ratio. ETS=enhanced tuberculosis surveillance system. LTBI=latent TB infection.
The unadjusted Kaplan-Meier curve was derived using all study participants, excluding those who developed tuberculosis 21 days after starting treatment ( n=368 077). The inset shows the same data on an enlarged y-axis. LTBI=latent tuberculosis infection.
In the sensitivity analysis, after excluding tuberculosis cases diagnosed within 60 and 90 days of primary care registration or LTBI testing, the overall effectiveness of the LTBI testing and treatment programme was lower, but the association between LTBI testing and a lower risk of tuberculosis diagnosis remained significant ( HR 0·82 [ 95% CI 0·69–0·99 ] when excluding individuals diagnosed within 60 days; 0·81 [ 0·68–0·96 ] when excluding individuals diagnosed within 90 days; appendix pp 14–16). The intervention remained associated with higher risk of tuberculosis diagnosis during the first 6 months of follow-up ( 11·14 [ 8·11–15·30 ] when excluding patients diagnosed with tuberculosis within 60 days; 15·72 [ 10·30–23·90 ] when excluding individuals diagnosed with tuberculosis within 90 days), followed by a significantly lower risk after 6 months ( 0·55 [ 0·38–0·77 ] when excluding individuals diagnosed with tuberculosis within 60 days; 0·56 [ 0·39–0·79 ] when excluding individuals diagnosed with tuberculosis within 90 days; appendix pp 14, 16).
The effect of pre-entry screening for active tuberculosis was included in the analysis as a potential confounder.23Aldridge RW Zenner D White PJ et al.Prevalence of and risk factors for active tuberculosis in migrants screened before entry to the UK: a population-based cross-sectional study.Lancet Infect Dis. 2016; 16: 962-970Google Scholar, 24Berrocal-Almanza LC Harris R Lalor MK et al.Effectiveness of pre-entry active tuberculosis and post-entry latent tuberculosis screening in new entrants to the UK: a retrospective, population-based cohort study.Lancet Infect Dis. 2019; 19: 1191-1201Google Scholar Pre-entry screening was associated with a higher risk of tuberculosis diagnosis than no pre-entry screening ( HR 1·27 [ 95% CI 1·03–1·56 ]; table 2). No interaction was identified ( ie, the effect of pre-entry screening on LTBI testing and treatment did not change, depending on the value of the pre-entry screening) between pre-entry screening and LTBI testing and treatment ( data not shown).25Knol MJ VanderWeele TJ Recommendations for presenting analyses of effect modification and interaction.Int J Epidemiol. 2012; 41: 514-520Google Scholar
Pre-entry screening for active tuberculosis was rolled out in 2012 and LTBI testing and treatment from 2014 onwards.13Public Health EnglandLatent TB testing and treatment for migrants: a practical guide for commissioners and practitioners.https: //assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment data/file/442192/030615 LTBI testing and treatment for migrants 1.pdfDate: 2015Date accessed: February 20, 2020Google Scholar, 23Aldridge RW Zenner D White PJ et al.Prevalence of and risk factors for active tuberculosis in migrants screened before entry to the UK: a population-based cross-sectional study.Lancet Infect Dis. 2016; 16: 962-970Google Scholar We therefore assessed whether the effects of the two interventions were modified by year of entry into England or of primary care registration. No effect modification was identified between LTBI testing and treatment and cohort year ( data not shown), but the effect of pre-entry screening differed by cohort year: the risk of developing tuberculosis was lower in individuals who had pre-entry screening in the cohort year 2017–18 than the cohort year 2011–12 ( HR 0·43 [ 95% CI 0·29–0·63 ]), whereas no effect was observed in earlier years ( table 2; appendix pp 9, 14). The fact that no effect was observed in earlier cohort years is likely to be explained by the exclusion of individuals who developed tuberculosis before January, 2014 when the LTBI programme roll-out began. Hence, the protective effect of pre-entry screening for active tuberculosis in the present study would only be observed in the later cohort years. All associations remained significant after accounting for area-level variation with random effects ( appendix p 17).
128 IGRA-positive individuals who did not start treatment developed tuberculosis ( incidence 1197 cases [ 95% CI 1000–1420 ] per 100 000 person-years), and 24 IGRA-negative individuals developed tuberculosis ( incidence 37 cases [ 95% CI 24–55 ] per 100 000 person-years; HR 31·9 [ 95% CI 20·4–49·8 ]; table 3; appendix pp 10, 18). The risk of tuberculosis was lower in the sensitivity analysis when tuberculosis cases diagnosed within 60 and 90 days of primary care registration or LTBI testing were excluded ( HR 18·6 [ 11·6–29·9 ] when excluding individuals diagnosed within 60 days; 14·6 [ 8·97–23·7 ] when excluding individuals diagnosed within 90 days; appendix pp 19–20). All associations remained significant after accounting for area-level variation with random effects ( appendix p 21).Table 3Multivariable Cox regression model analysis of time to tuberculosis diagnosis according to IGRA statusTuberculosis cases per person-years of follow-up * Included only participants with no missing information for that characteristic.Incidence per 100 000 person-years ( 95% CI) HR ( 95% CI) †HR ( 95% CI) and p value estimates were derived from the total cohort of migrants with a positive IGRA who did not start LTBI treatment, after multiple imputation for missing values by chained equations model ( n=34 792); migrants with indeterminate IGRA results or with no results were excluded.p valueIGRA statusPositive128/10 6841190 ( 1000–1420) 31·9 ( 20·4–49·8) < 0·0001Negative24/64 53737 ( 24–55) 1 ( ref).. Age, years16–2562/33 747183 ( 143–235) 1·04 ( 0·74–1·46) 0·79526–3597/42 849226 ( 185–276) 1 ( ref).. SexFemale94/33 899277 ( 226–339) 1 ( ref).. Male63/41 010153 ( 120–196) 0·65 ( 0·46–0·90) 0·010ETS region of originAfrica24/7598315 ( 211–471) 1 ( ref).. The Americas or Europe0/61400.. East and southeast Asia2/1045191 ( 478–764) 0·78 ( 0·17–3·53) 0·750South Asia58/35 394163 ( 126–211) 0·84 ( 0·42–1·69) 0·616Tuberculosis incidence in country of origin ( cases per 100 000) ‡WHO estimated tuberculosis incidence.1340–14912/3856311 ( 176–547) 1 ( ref).. 150–34967/39 690168 ( 132–214) 0·69 ( 0·33–1·45) 0·305 > 3505/1106451 ( 188–108) 0·81 ( 0·27–2·36) 0·694Tuberculosis incidence in area of residence ( cases per 100 000) §UK Health Security Agency estimated tuberculosis incidence in Clinical Commissioning Group area of residence.≤9·28/5668141 ( 70–282) 1 ( ref).. 9·3–31·661/25 554238 ( 185–306) 1·77 ( 0·83–3·78) 0·135 > 31·669/37 733182 ( 144–231) 1·05 ( 0·49–2·24) 0·885Deprivation index1–3 deciles ( most deprived) 91/45 531199 ( 162–245) 1 ( ref).. 4–6 deciles50/23 543212 ( 160–280) 1·06 ( 0·73–1·54) 0·7507–10 deciles ( least deprived) 11/4965221 ( 122–400) 1·25 ( 0·66–2·36) 0·486Year of arrival in England or primary care registration2011–1212/4684256 ( 145–451) 1 ( ref).. 2013–1416/6923231 ( 141–377) 1·51 ( 0·77–2·97) 0·2242015–1632/17 123186 ( 132–264) 0·74 ( 0·40–1·37) 0·3462017–1824/15 921150 ( 101–224) 0·21 ( 0·10–0·44) < 0·0001IGRA=interferon-γ release assay. HR=hazard ratio. ETS=enhanced tuberculosis surveillance system. LTBI=latent tuberculosis infection. * Included only participants with no missing information for that characteristic.† HR ( 95% CI) and p value estimates were derived from the total cohort of migrants with a positive IGRA who did not start LTBI treatment, after multiple imputation for missing values by chained equations model ( n=34 792); migrants with indeterminate IGRA results or with no results were excluded.‡ WHO estimated tuberculosis incidence.13Public Health EnglandLatent TB testing and treatment for migrants: a practical guide for commissioners and practitioners.https: //assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment data/file/442192/030615 LTBI testing and treatment for migrants 1.pdfDate: 2015Date accessed: February 20, 2020Google Scholar§ UK Health Security Agency estimated tuberculosis incidence in Clinical Commissioning Group area of residence. Open table in a new tab
IGRA=interferon-γ release assay. HR=hazard ratio. ETS=enhanced tuberculosis surveillance system. LTBI=latent tuberculosis infection.
135 tuberculosis cases were diagnosed in the IGRA-positive cohort during 15 470 person-years follow-up, with median follow-up of 2·1 years ( IQR 1·45–5·31) per person. In the group who started LTBI treatment, seven individuals developed active tuberculosis ( incidence 187 cases [ 95% CI 89–393 ] per 100 000 person-years) compared with 128 individuals in the untreated group ( incidence 1090 cases [ 95% CI 916–1290 ] per 100 000 person-years). Thus, LTBI treatment was associated with a substantially lower risk of developing active tuberculosis ( HR 0·14 [ 95% CI 0·06–0·32 ]; table 4; appendix p 10). This effect remained after accounting for area-level variation with random effects ( appendix p 23). The confirmed date of treatment completion was available for 988 ( 56·7%) of 1740 individuals who started treatment. A sensitivity analysis including only individuals who started treatment yielded a higher value for treatment effectiveness ( HR 0·08 [ 95% CI 0·02–0·26 ]; appendix pp 23–24). Thus, the programme would remain effective even if a substantial proportion of individuals had poor compliance. The effectiveness of treatment was lower, but remained significant, in the sensitivity analysis when tuberculosis cases diagnosed within 60 and 90 days of primary care registration or LTBI testing were excluded ( 0·23 [ 0·09–0·57 ] for 60 days; 0·25 [ 0·09–0·67 ] for 90 days; appendix pp 25–26).Table 4Multivariable Cox regression model analysis of time to tuberculosis diagnosis according to treatment statusTuberculosis cases per person-years of follow-up * Included only participants with no missing information for that characteristic.Incidence per 100 000 person-years ( 95% CI) HR ( 95% CI) †HR ( 95% CI) and p value estimates were derived from the total cohort of migrants with a positive interferon-γ release assay after multiple imputation for missing values by chained equations model excluding those who developed tuberculosis 21 days after starting treatment ( n=6620).p valueTreatmentYes7/3728187 ( 89–393) 0·14 ( 0·06–0·32) < 0·0001No128/117421090 ( 916–1296) 1·00.. Age, years16–2550/48921020 ( 774–1340) 1·27 ( 0·88–1·83) 0·19226–3583/10218812 ( 655–1007) 1·00.. SexFemale80/77471032 ( 829–1280) 1·00.. Male53/7415714 ( 546–935) 0·71 ( 0·50–1·01) 0·059ETS region of originAfrica21/2323903 ( 589–1380) 1·00.. The Americas or Europe0/68·5100.. East and southeast Asia2/258772 ( 193–3080) 0·85 ( 0·17–4·12) 0·847South Asia52/6845759 ( 578–996) 0·87 ( 0·45–1·66) 0·655Tuberculosis incidence in country of origin ( cases per 100 000) ‡WHO estimated tuberculosis incidence.1340–1499/988910 ( 473–1750) 1·00.. 150–34961/8157747 ( 581–961) 0·73 ( 0·42–1·26) 0·257 > 3505/3511420 ( 592–3410) 0·93 ( 0·27–3·19) 0·915Tuberculosis incidence in area of residence ( cases per 100 000) §UK Health Security Agency estimated tuberculosis incidence in Clinical Commissioning Group area of residence.≤9·28/1176680 ( 340–1360) 1·00.. 9·3–31·654/5461988 ( 757–1290) 1·72 ( 0·80–3·69) 0·163 > 31·653/7373718 ( 549–940) 0·66 ( 0·31–1·43) 0·300Deprivation index1–3 deciles ( most deprived) 80/9246865 ( 694–1070) 1·00.. 4–6 deciles39/4574852 ( 622–1160) 1·12 ( 0·74–1·69) 0·5647–10 deciles ( least deprived) 9/8581040 ( 545–2010) 1·14 ( 0·56–2·34) 0·708Year of arrival in England or primary care registration2011–1212/9781220 ( 696–2150) 1·00.. 2013–1415/14381042 ( 628–1730) 1·07 ( 0·54–2·10) 0·8332015–1629/3844754 ( 524–1080) 0·90 ( 0·48–1·68) 0·7442017–1819/3235587 ( 374–920) 1·00 ( 0·46–2·15) 0·996HR=hazard ratio. ETS=enhanced tuberculosis surveillance system. * Included only participants with no missing information for that characteristic.† HR ( 95% CI) and p value estimates were derived from the total cohort of migrants with a positive interferon-γ release assay after multiple imputation for missing values by chained equations model excluding those who developed tuberculosis 21 days after starting treatment ( n=6620).‡ WHO estimated tuberculosis incidence.13Public Health EnglandLatent TB testing and treatment for migrants: a practical guide for commissioners and practitioners.https: //assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment data/file/442192/030615 LTBI testing and treatment for migrants 1.pdfDate: 2015Date accessed: February 20, 2020Google Scholar§ UK Health Security Agency estimated tuberculosis incidence in Clinical Commissioning Group area of residence. Open table in a new tab
HR=hazard ratio. ETS=enhanced tuberculosis surveillance system.
The adjusted NNT was estimated using only participants with no missing data ( n=3812). The NNT, with adjustment for all covariates,22Sjölander A Estimation of causal effect measures with the R-package stdReg.Eur J Epidemiol. 2018; 33: 847-858Google Scholar defined as the average number of untreated IGRA-positive individuals who would have had to start LTBI treatment at baseline to prevent one case of tuberculosis before 2 years was 32·5 ( 95% CI 17·0–48·0; table 4) and before 3 years was 26 ( 7·0–45·0). In the sensitivity analysis, the adjusted NNTs were 33·7 ( 19·0–48·4) when excluding individuals diagnosed within 60 days and 34·8 ( 19·8–49·8) when excluding individuals diagnosed within 90 days ( appendix pp 25–26).
Data on treatment regimens were available for 1600 ( 92%) of the 1740 treated individuals; of these 1564 ( 97·8%) were treated with rifampicin and isoniazid for 3 months, 34 ( 2·1%) were treated with isoniazid for 6 months, and two ( 0·1%) were treated with rifampicin for 4 months. 74 ( 4·6%) of 1600 individuals reported adverse reactions, including 11 ( 0·7%) with hepatotoxicity, of whom five were treated with rifampicin and isoniazid for 3 months ( five [ 0·3% ] of 1564 patients on this regimen) and six were treated with isoniazid for 6 months ( six [ 17·6% ] of 34 patients on this regimen; appendix p 29).
The LTBI testing and treatment programme can reduce the risk of being diagnosed with tuberculosis in newly arrived foreign-born individuals in England. Programmatic LTBI testing and treatment is associated with earlier tuberculosis diagnosis and an overall lower risk of tuberculosis. IGRA-positive individuals have a 31-times higher risk of developing active tuberculosis than IGRA-negative individuals and LTBI treatment reduced this risk by 86%. We identified key limitations of the programme. These include a low proportion of eligible migrants who were tested and low uptake of preventive treatment in those testing IGRA-positive. Addressing these limitations would improve the population-level effectiveness of the programme and thereby reduce national tuberculosis incidence.
Our results show that after an initial increase in tuberculosis incidence in the tested group, the intervention reduces the risk of developing tuberculosis in the longer term. The initial increase in tuberculosis incidence is explained by the mandatory clinical and radiographical assessment for active tuberculosis in IGRA-positive individuals.13Public Health EnglandLatent TB testing and treatment for migrants: a practical guide for commissioners and practitioners.https: //assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment data/file/442192/030615 LTBI testing and treatment for migrants 1.pdfDate: 2015Date accessed: February 20, 2020Google Scholar, 26Ho J Fox GJ Marais BJ Passive case finding for tuberculosis is not enough.Int J Mycobacteriol. 2016; 5: 374-378Google Scholar For this reason, our primary analysis included all tuberculosis cases because we assumed that they all could be identified through the screening pathway. However, cases diagnosed early after primary care registration or LTBI testing might instead be asymptomatic prevalent cases,27Kendall EA Shrestha S Dowdy DW The epidemiological importance of subclinical tuberculosis. A critical reappraisal.Am J Respir Crit Care Med. 2021; 203: 168-174Google Scholar detected by programmatic IGRA testing followed by chest radiography if positive. We addressed this through sensitivity analyses that denoted all tuberculosis cases identified within 60 or 90 days as prevalent, thus excluding them from evaluation of the programme's effectiveness in preventing tuberculosis. This further confirmed the programme's effectiveness in preventing progression to tuberculosis and its effect on increasing early case detection of active tuberculosis. Active case finding is a potentially effective, risk-group-based, health-service-initiated screening intervention to detect and treat active tuberculosis.26Ho J Fox GJ Marais BJ Passive case finding for tuberculosis is not enough.Int J Mycobacteriol. 2016; 5: 374-378Google Scholar, 28Lönnroth K Corbett E Golub J et al.Systematic screening for active tuberculosis: rationale, definitions and key considerations.Int J Tuberc Lung Dis. 2013; 17: 289-298Google Scholar Our results suggest that programmatic LTBI testing could be used as an active case finding intervention for this key high-risk group.29Public Health EnglandTuberculosis in England report.https: //webarchive.nationalarchives.gov.uk/ukgwa/20190801150347/https: //www.gov.uk/government/publications/tuberculosis-in-england-annual-reportDate: 2019Date accessed: February 10, 2020Google Scholar The intervention risk stratifies newly arrived foreign-born individuals, who have higher risk of developing tuberculosis compared with the general population.13Public Health EnglandLatent TB testing and treatment for migrants: a practical guide for commissioners and practitioners.https: //assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment data/file/442192/030615 LTBI testing and treatment for migrants 1.pdfDate: 2015Date accessed: February 20, 2020Google Scholar, 29Public Health EnglandTuberculosis in England report.https: //webarchive.nationalarchives.gov.uk/ukgwa/20190801150347/https: //www.gov.uk/government/publications/tuberculosis-in-england-annual-reportDate: 2019Date accessed: February 10, 2020Google Scholar In this model, the confirmatory diagnostic investigation is systematically triggered by a positive IGRA result.13Public Health EnglandLatent TB testing and treatment for migrants: a practical guide for commissioners and practitioners.https: //assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment data/file/442192/030615 LTBI testing and treatment for migrants 1.pdfDate: 2015Date accessed: February 20, 2020Google Scholar Importantly, earlier diagnosis of active tuberculosis through the LTBI testing programme is likely to reduce tuberculosis transmission.26Ho J Fox GJ Marais BJ Passive case finding for tuberculosis is not enough.Int J Mycobacteriol. 2016; 5: 374-378Google Scholar, 28Lönnroth K Corbett E Golub J et al.Systematic screening for active tuberculosis: rationale, definitions and key considerations.Int J Tuberc Lung Dis. 2013; 17: 289-298Google Scholar, 30Azman AS Golub JE Dowdy DW How much is tuberculosis screening worth? Estimating the value of active case finding for tuberculosis in South Africa, China, and India.BMC Med. 2014; 12: 216Google Scholar
The LTBI testing and treatment programme was underpinned by modelling suggesting that it could cost-effectively avert future cases of tuberculosis.3Pareek M Watson JP Ormerod LP et al.Screening of immigrants in the UK for imported latent tuberculosis: a multicentre cohort study and cost-effectiveness analysis.Lancet Infect Dis. 2011; 11: 435-444Google Scholar Tuberculosis incidence in England has significantly reduced since 2013, with the lowest incidence recorded in 2018 ( 8·3 cases per 100 000 population).29Public Health EnglandTuberculosis in England report.https: //webarchive.nationalarchives.gov.uk/ukgwa/20190801150347/https: //www.gov.uk/government/publications/tuberculosis-in-england-annual-reportDate: 2019Date accessed: February 10, 2020Google Scholar This evaluation provides strong evidence that the pre-entry active tuberculosis screening and LTBI testing and treatment programmes are contributing to this reduction, consistent with preliminary data.24Berrocal-Almanza LC Harris R Lalor MK et al.Effectiveness of pre-entry active tuberculosis and post-entry latent tuberculosis screening in new entrants to the UK: a retrospective, population-based cohort study.Lancet Infect Dis. 2019; 19: 1191-1201Google Scholar, 31Thomas HL Harris RJ Muzyamba MC et al.Reduction in tuberculosis incidence in the UK from 2011 to 2015: a population-based study.Thorax. 2018; 73: 769-775Google Scholar As England progresses towards tuberculosis elimination,29Public Health EnglandTuberculosis in England report.https: //webarchive.nationalarchives.gov.uk/ukgwa/20190801150347/https: //www.gov.uk/government/publications/tuberculosis-in-england-annual-reportDate: 2019Date accessed: February 10, 2020Google Scholar the proportion of cases arising in groups not included in the programme, such as migrants resident for more than 5 years or older than 35 years, will increase.29Public Health EnglandTuberculosis in England report.https: //webarchive.nationalarchives.gov.uk/ukgwa/20190801150347/https: //www.gov.uk/government/publications/tuberculosis-in-england-annual-reportDate: 2019Date accessed: February 10, 2020Google Scholar Therefore the LTBI programme will require periodic adjustment to address the epidemiological transition brought about, in part, by its success.
We estimated the risk of tuberculosis stratified by IGRA results in the largest programmatic cohort of foreign-born individuals with the longest follow-up to date, and demonstrate the utility of IGRAs for large-scale risk stratification in a routine setting. Our estimate of tuberculosis incidence among IGRA-positive migrants is similar to that reported in a meta-analysis published in 2020.32Campbell JR Winters N Menzies D Absolute risk of tuberculosis among untreated populations with a positive tuberculin skin test or interferon-gamma release assay result: systematic review and meta-analysis.BMJ. 2020; 368: m549Google Scholar The risk estimate in IGRA-positive individuals compared with IGRA-negative individuals is consistent with a previous estimate in a UK-based cohort of migrants.33Zenner D Loutet MG Harris R Wilson S Ormerod LP Evaluating 17 years of latent tuberculosis infection screening in north-west England: a retrospective cohort study of reactivation.Eur Respir J. 2017; 501602505Google Scholar
We present evidence of effectiveness of a 3-month rifampicin and isoniazid treatment regimen for LTBI, consistent with a 2017 meta-analysis of studies done in people with HIV, and children and adults with silicosis.34Zenner D Beer N Harris RJ Lipman MC Stagg HR van der Werf MJ Treatment of latent tuberculosis infection: an updated network meta-analysis.Ann Intern Med. 2017; 167: 248-255Google Scholar We furthermore observed a low risk of hepatotoxicity, confirming that this regimen is safe and effective.
We provide a programmatic NNT estimate of relevance for national and international policy makers. Our estimates of NNT were similar to other studies in the UK and Norway,35Kruijshaar ME Abubakar I Stagg HR Pedrazzoli D Lipman M Migration and tuberculosis in the UK: targeting screening for latent infection to those at greatest risk of disease.Thorax. 2013; 68: 1172-1174Google Scholar, 36Winje BA Grøneng GM White RA Akre P Aavitsland P Heldal E Immigrant screening for latent tuberculosis infection: numbers needed to test and treat, a Norwegian population-based cohort study.BMJ Open. 2019; 9e023412Google Scholar and lower than modelling-based estimates for the USA.37Rose DN Benefits of screening for latent Mycobacterium tuberculosis infection.Arch Intern Med. 2000; 160: 1513-1521Google Scholar, 38Tasillo A Salomon JA Trikalinos TA Horsburgh Jr, CR Marks SM Linas BP Cost-effectiveness of testing and treatment for latent tuberculosis infection in residents born outside the United States with and without medical comorbidities in a simulation model.JAMA Intern Med. 2017; 177: 1755-1764Google Scholar The high NNT raises important issues because LTBI treatment might be given with no benefit, while exposing individuals to potential adverse events, even if this risk is low.1Campbell JR Dowdy D Schwartzman K Treatment of latent infection to achieve tuberculosis elimination in low-incidence countries.PLoS Med. 2019; 16e1002824Google Scholar WHO guidelines recommend LTBI treatment in risk groups based on direct and surrogate evidence of increased risk and, since tuberculosis is contagious, the disease has public health consequences beyond the individual patients.39Lönnroth K Glaziou P Weil D Floyd K Uplekar M Raviglione M Beyond UHC: monitoring health and social protection coverage in the context of tuberculosis care and prevention.PLoS Med. 2014; 11e1001693Google Scholar Low-incidence countries have set a goal to eliminate tuberculosis,2Lönnroth K Migliori GB Abubakar I et al.Towards tuberculosis elimination: an action framework for low-incidence countries.Eur Respir J. 2015; 45: 928-952Google Scholar but this is not possible without testing and treating LTBI in migrants.4Rosales-Klintz S Bruchfeld J Haas W et al.Guidance for programmatic management of latent tuberculosis infection in the European Union/European Economic Area.Eur Respir J. 2019; 531802077Google Scholar Our evaluation provides evidence to guide policy makers, clinicians, and patients to make informed decisions regarding LTBI treatment, weighing the individual risks and benefits against the overall public health benefit.1Campbell JR Dowdy D Schwartzman K Treatment of latent infection to achieve tuberculosis elimination in low-incidence countries.PLoS Med. 2019; 16e1002824Google Scholar These considerations should inform LTBI testing and treatment programmes, and consideration of the priorities of migrant communities.40Denholm JT Matteelli A Reis A Latent tuberculous infection: ethical considerations in formulating public health policy.Int J Tuberc Lung Dis. 2015; 19: 137-140Google Scholar, 41Berrocal-Almanza LC Botticello J Piotrowski H et al.Engaging with civil society to improve access to LTBI screening for new migrants in England: a qualitative study.Int J Tuberc Lung Dis. 2019; 23: 563-570Google Scholar, 42Mitchell EMH Heumann SG Sprague L Tesfaye DH Van Dam A Spruijt I ‘ Reservoir of infection ' or ‘ fount of knowledge’? Forging equal partnerships and shifting power to address LTBI.Int J Tuberc Lung Dis. 2019; 23: 527-528Google Scholar
The programme is provided free to all migrants from countries with high tuberculosis incidence staying in England for at least 6 months, with the only prerequisite being registration for primary care.41Berrocal-Almanza LC Botticello J Piotrowski H et al.Engaging with civil society to improve access to LTBI screening for new migrants in England: a qualitative study.Int J Tuberc Lung Dis. 2019; 23: 563-570Google Scholar, 43Stagg HR Jones J Bickler G Abubakar I Poor uptake of primary healthcare registration among recent entrants to the UK: a retrospective cohort study.BMJ Open. 2012; 2e001453Google Scholar However, primary care registration among migrants is lower than in UK-born individuals and undocumented migrants do not register.24Berrocal-Almanza LC Harris R Lalor MK et al.Effectiveness of pre-entry active tuberculosis and post-entry latent tuberculosis screening in new entrants to the UK: a retrospective, population-based cohort study.Lancet Infect Dis. 2019; 19: 1191-1201Google Scholar, 41Berrocal-Almanza LC Botticello J Piotrowski H et al.Engaging with civil society to improve access to LTBI screening for new migrants in England: a qualitative study.Int J Tuberc Lung Dis. 2019; 23: 563-570Google Scholar, 43Stagg HR Jones J Bickler G Abubakar I Poor uptake of primary healthcare registration among recent entrants to the UK: a retrospective cohort study.BMJ Open. 2012; 2e001453Google Scholar These individuals are therefore not reached by the programme and thus were not included in our cohort; improving rates of primary care registration among migrants would probably enhance the impact of the programme at the national level and could result in other individual-level and public health benefits. To our knowledge, our study is the first to quantify the losses at individual steps of the LTBI cascade of care for foreign-born individuals in a nationwide programmatic setting. Although only around one in four IGRA-positive individuals started LTBI treatment, the programme was effective. Quantifying the proportion of migrants lost at each stage of the care cascade, and understanding the reasons for this, are important to enable improvements in programme participation. In other settings, migrants are less likely than other groups to complete LTBI screening and start and complete treatment.44Alsdurf H Hill PC Matteelli A Getahun H Menzies D The cascade of care in diagnosis and treatment of latent tuberculosis infection: a systematic review and meta-analysis.Lancet Infect Dis. 2016; 16: 1269-1278Google Scholar Reasons for not completing testing and treatment include language barriers, self-perceived low risk of LTBI or active tuberculosis, stigma, mistrust, and fear of deportation or immigration status.41Berrocal-Almanza LC Botticello J Piotrowski H et al.Engaging with civil society to improve access to LTBI screening for new migrants in England: a qualitative study.Int J Tuberc Lung Dis. 2019; 23: 563-570Google Scholar, 44Alsdurf H Hill PC Matteelli A Getahun H Menzies D The cascade of care in diagnosis and treatment of latent tuberculosis infection: a systematic review and meta-analysis.Lancet Infect Dis. 2016; 16: 1269-1278Google Scholar Addressing such barriers will be pivotal for further increasing the effectiveness of the programme.
Our study had some limitations. We did not attempt to exclude incident cases acquired from transmission within England; however, there would have been few such cases in our cohort considering the local epidemiology of tuberculosis transmission.45Davidson JA Thomas HL Maguire H et al.Understanding tuberculosis transmission in the United Kingdom: findings from 6 years of mycobacterial interspersed repetitive unit-variable number tandem repeats strain typing, 2010–2015.Am J Epidemiol. 2018; 187: 2233-2242Google Scholar Our analysis did not account for the presence of comorbidities, such as HIV or diabetes, which increase risk of tuberculosis, but this would not affect our main findings or implications for low-incidence countries. Our results might be affected by missing information; however, we accounted for the potential bias introduced by missing values by using a multiple imputation model assuming the data was missing at random. We then did sensitivity analysis using only participants with complete information and the results did not vary. The risk of verification, incorporation, and overdiagnosis bias was minimised by using record linkage to establish the final disease status; assignment was based on a quality-assured surveillance system that captures all notifications and de-notifications.16Public Health EnglandGuidance on notifying tuberculosis ( TB) cases.https: //assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment data/file/360263/Guidance on Notifying Tuberculosis TB cases.pdfDate: 2014Date accessed: October 20, 2019Google Scholar The UK Health Security Agency did not have permission to obtain data on individuals who opted not to be tested, hence we could not specifically quantify programme uptake. Our linkage method did not allow us to establish whether the tuberculosis diagnosis was the result of a programmatic positive IGRA test; therefore, we can not ascertain whether cases identified in the first 6 months were diagnosed as a result of programmatic LTBI testing. Moreover, we could not identify IGRA-positive individuals who were not candidates for treatment ( eg, those who might have already been treated). Although clinical assessment of IGRA-positive individuals was mostly done in secondary care, in some areas, such as east London, this was done in primary care. We could not account for the resulting potential heterogeneity in the clinical pathways for exclusion of active tuberculosis. Within our cohort, we could not determine which migrants might have been refugees or asylum seekers. Since our cohort did not include undocumented migrants, our evaluation did not assess the effect of LTBI testing and treatment in this population. It is possible that individuals diagnosed in the early follow-up period differed from those who remained tuberculosis-free during this period, which could introduce selection bias.46Hernán MA Hernández-Díaz S Robins JM A structural approach to selection bias.Epidemiology. 2004; 15: 615-625Google Scholar In our cohort, the only pathway to treatment was through programmatic LTBI testing; thus, no untested individual had treatment and for this reason we could not apply standard statistical methods to account for selection bias, and can not therefore rule out the presence of such bias in the estimate of overall programme effectiveness.46Hernán MA Hernández-Díaz S Robins JM A structural approach to selection bias.Epidemiology. 2004; 15: 615-625Google Scholar However, LTBI treatment was effective at averting tuberculosis in IGRA-positive individuals, suggesting that treatment effectiveness, and not selection bias, was the main contributor to overall programme effectiveness.
In conclusion, this study shows that programmatic LTBI testing and treatment of new migrants is feasible and effective in a nationwide routine setting, lowering the risk of developing tuberculosis and facilitating earlier diagnosis of tuberculosis. The programme would be substantially more effective if a higher proportion of eligible migrants participated, and in particular, if those who test IGRA-positive started treatment. National programmes such as this could therefore be important public health interventions to enable tuberculosis elimination in low-incidence regions.
LCB-A and AL conceived and designed the study. MCM and ODC gathered, processed, and cleaned the data. AM, A-MO and LCB-A did the record linkage. LCB-A, RJH, and SMC analysed the data. LCB-A and AL had full access to all the data in the study. LCB-A wrote the first draft of the manuscript followed by iterative revision with AL. All authors substantially contributed to discussion of content and reviewed and edited the manuscript before submission. All authors were involved in the decision to submit and agreed to publish the paper.
The study protocol and STATA files ( containing the commands used) can be made available upon request. However, the de-identified individual participant data that underlie the results reported in this article are the property of the UK Health Security Agency and can not be made available. Please contact the corresponding author for further information.
AL is named inventor on patents pertaining to T-cell-based diagnosis, including current and second-generation IGRA technologies and flow-cytometric diagnosis and prognosis of tuberculosis infection and disease; some of these patents were assigned by the University of Oxford ( Oxford, UK) to Oxford Immunotec, resulting in the T-SPOT.TB test with royalty entitlements for the University of Oxford and AL. All other authors declare no competing interests.
This research was funded by the National Institute for Health Research ( NIHR) Health Protection Research Unit in Respiratory Infections at Imperial College London ( London, UK) in partnership with the UK Health Security Agency ( London, UK). The views expressed are those of the authors and not necessarily those of the National Health Service, the NIHR, the Department of Health, or the UK Health Security Agency. AL was supported by the NIHR Imperial Biomedical Research Centre. We thank Nirmalan Arinaminpathy whose constructive feedback greatly contributed to the final version of this manuscript and Umar Niazi for his assistance in the calculation of the adjusted number needed to treat.
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Programmatic screening for latent tuberculosis in migrantsWHO has set targets to eliminate tuberculosis as a public health problem globally by 2035. In settings with low tuberculosis incidence, cases have become concentrated among populations born in intermediate and high-incidence countries and susceptible populations.1 To achieve WHO targets in low-incidence countries, identification and treatment of latent tuberculosis infection ( LTBI) among foreign-born individuals will be needed to reduce persistently elevated tuberculosis rates.2,3 In 2016, as part of a new national Collaborative tuberculosis strategy, England implemented the first nationwide migrant LTBI screening programme. Full-Text PDF Open Access | tech |
Financing the future of WHO | WHO has anchored the global health architecture since its founding in 1948, and it is impossible to imagine another institution filling the void if the international community were to let it atrophy. While also confronting and guiding the response to COVID-19, WHO is engaged in the most consequential reforms since its founding, including negotiating a global pandemic agreement and revising the International Health Regulations. Underpinning all these reforms is the need for robust and sustainable financing.
WHO's resources have consistently lagged behind its constitutional mandate. There is a deep misalignment between what governments and the public expect WHO to do and what the organisation is resourced to do. WHO is challenged by low levels of political will to increase its financing, strained government treasuries, and a battle over control of priorities.1WHO Executive BoardSustainable financing: report of the Working Group. EB150/30.https: //apps.who.int/gb/ebwha/pdf files/EB150/B150 30-en.pdfDate: Jan 10, 2022Date accessed: March 17, 2022Google Scholar These tensions were clear when the Working Group on Sustainable Financing, chartered by WHO's Executive Board, did not reach consensus by the January, 2022 deadline.1WHO Executive BoardSustainable financing: report of the Working Group. EB150/30.https: //apps.who.int/gb/ebwha/pdf files/EB150/B150 30-en.pdfDate: Jan 10, 2022Date accessed: March 17, 2022Google Scholar WHO's Executive Board has now charged the Working Group on Sustainable Financing with identifying a viable plan before the World Health Assembly in May, 2022.2WHO Executive BoardWorking Group on Sustainable Financing. EB150 ( 2).https: //apps.who.int/gb/ebwha/pdf files/EB150/B150 ( 2) -en.pdfDate: Jan 25, 2022Date accessed: March 17, 2022Google Scholar
There is no time to lose. WHO's resourcing strategy must match its mission with assured financial support from member states buttressed by proven, innovative financing methods. By defining its priorities, delivering on them, and being transparent and accountable, WHO can more boldly pursue its public health mission.
WHO's revenue model has always been politically contentious with its first budget slashed by 23%, thus “ preventing us from being an operating agency to any extent ”.3WHOFirst World Health Assembly.https: //apps.who.int/iris/bitstream/handle/10665/85592/Official record13 eng.pdfDate: June 24–July 24, 1948Date accessed: March 17, 2022Google Scholar In 2022, WHO is expected to support a world health agenda with a budget less than that of a major research hospital or mid-sized subnational health agency.
The constitution of WHO gives the organisation flexibility to receive voluntary contributions from state and non-state actors to supplement mandatory assessed contributions from member states. That should have augmented its funding. Yet voluntary contributions have skewed WHO's revenue model such that more than 80% of its income now derives from them.4Daugirdas K Burci GL Financing the World Health Organization: what lessons for multilateralism?.Int Organ Law Rev. 2019; 16: 299-338Google Scholar, 5WHOContributors.http: //open.who.int/2018-19/contributors/contributorDate: 2019Date accessed: March 21, 2022Google Scholar Voluntary contributions risk prioritising the parochial interests of major donors over collectively driven all-of-society activities. WHO has little control over its budget, suppressing fiscal predictability, lessening purchasing power, undermining longer-term investments, and diminishing the opportunity to attract and retain world-class scientists consistently.
Former German Chancellor Angela Merkel urged a special session of the World Health Assembly in 2021 to increase assessed contributions from member states to 50% of WHO's base programme budget.6WHOSpecial session of World Health Assembly 29 November 2021 to 1 December 2021.https: //www.who.int/news-room/events/detail/2021/11/29/default-calendar/second-special-session-of-the-world-health-assemblyDate: 2021Date accessed: March 21, 2022Google Scholar Yet despite high-profile advocacy, and that assessed contributions represented roughly half of WHO's budget in 2000,7WHOA proposal for increasing the assessed contribution.https: //www.who.int/about/finances-accountability/funding/financing-dialogue/assessed-contribution.pdfDate: Oct 19, 2016Date accessed: March 17, 2022Google Scholar the Working Group on Sustainable Financing could not reach agreement. Member states variously cited already stretched government budgets, the need for WHO to work within its existing means, and the desire for governance reforms,1WHO Executive BoardSustainable financing: report of the Working Group. EB150/30.https: //apps.who.int/gb/ebwha/pdf files/EB150/B150 30-en.pdfDate: Jan 10, 2022Date accessed: March 17, 2022Google Scholar reflective of the need to ensure fiscal legitimacy, fairness, and justice.8Waris A Tax and development: solving Kenya's fiscal crisis through human rights. Law Africa Publishing Limited, Nairobi2013Google Scholar From a purely financial perspective, however, there is an opportunity to connect increases to assessed contributions with the inevitable tapering of country spending on the acute phase of the COVID-19 pandemic. Such expense substitution is politically easier to accomplish than newly taxing already pressured national budgets.
The tension for control between funders and implementors is nothing new, but a special dynamic exists when underwriting the activities of an intergovernmental organisation. For member states, there is little prospect for a financial return on investment and contributions are made from public treasuries. These realities unsurprisingly cause funders to engage in more risk-averse behaviours than other suppliers of capital, such as company shareholders or charitable foundations. Voluntary contributions, moreover, have become a way to dictate the terms of WHO's activities. The key questions for the future are who gets to set the global health agenda, and will WHO be relegated to an agency that simply implements particular donors ' projects?
If the COVID-19 pandemic has taught us anything, it is that the global health agenda should be elevated above the political fray. Yet as a membership organisation of sovereign nations and thus a political institution, WHO has faced stiff political opposition to achieving ample and sustainable financing. Prominent heads of state must become champions of WHO, expending political capital to generate global will. Finance ministers, who are powerful domestic political figures, must be invited as regular, fully engaged participants in WHO's programmes and financing, and be persuaded assessed contributions could save orders of magnitude of economic pain later.
Organisational credibility underpins any potential long-term commitment to support WHO financially. WHO can achieve that by clearly defining its priorities, delivering on them, and promoting that it did so. Despite WHO's expansive world health remit, prioritisation is necessary and inevitable, even between essential activities and other valuable pursuits. WHO released an investment case9WHOWHO launches first investment case to save up to 30 million lives.https: //www.who.int/news/item/19-09-2018-who-launches-first-investment-case-to-save-up-to-30-million-livesDate: 2018Date accessed: March 21, 2022Google Scholar before COVID-19, a sound method used by other global health actors to articulate goals and financing needs. The organisation must now maintain and refine its mission so that it is transparent about its priorities, successes, shortcomings, and how it incorporates fresh thinking.
This approach could lead to additional pools of capital. Public and private actors are more apt to boost funding if they believe their investments can be leveraged. For example, sovereign nations pool their money in multilateral development banks to access attractive capital markets pricing collectively10Kellerman M The proliferation of multilateral development banks.Rev Int Organ. 2019; 14: 111Google Scholar and will partner with the private sector to co-finance and co-research basic biomedical science.11Dolgin E Massive NIH-industry project opens portals to target validation.Nat Rev Drug Discov. 2019; 18: 240-242Google Scholar As the Humanitarian Finance Forum has proposed, there are also “ leaders in humanitarian institutions, international organisations, investment banks, insurance companies and government ” who may be interested in championing WHO's mission and could “ assist in the development of sustainable financing tools at scale ”.12Humanitarian Finance ForumWhat we aim to do.https: //www.hfforum.org/about # what-we-aim-to-doDate: 2022Date accessed: March 17, 2022Google Scholar
Holding a periodic replenishment conference would boost resources and gain support from civil society and stakeholder communities. Such a meeting could syphon potential contributions to WHO's overall strategic plan. Alternatively, replenishment goals could be geared towards acute priorities in WHO's budget to address one-off investments, such as supporting the new mRNA vaccine hubs in Africa,13WHOThe mRNA vaccine technology transfer hub.https: //www.who.int/initiatives/the-mrna-vaccine-technology-transfer-hubDate: 2021Date accessed: March 17, 2022Google Scholar thus ensuring that assessed contributions are reserved for ongoing activities.
More tactically, WHO could pursue new in-kind services, refine its purchasing methods, partner with other actors to achieve concessionary pricing, or design an incrementally more aggressive investment policy. Additionally, the self-imposed 13% cap on programme support cost fees that WHO charges should be reconsidered.14WHO34th World Health Assembly. Programme support costs.https: //www.who.int/tdr/about/governance/basic documents/wha34 17/en/Date: May, 1981Date accessed: March 17, 2022Google Scholar A meaningful increase, combined with smart application, such as only applying them to voluntary contributions, could release some pressure.
All these proposals involve risk, but there is an existential risk of doing nothing and backsliding into irrelevance. Björn Kümmel, Chairperson of the Working Group on Sustainable Financing, told WHO's Executive Board in January, 2022 that “ what we are discussing is not just the financing of WHO. It is the future of WHO ”.15WHO Executive BoardItem 19.3, sustainable financing: report of the working group.https: //www.who.int/about/governance/executive-board/executive-board-150th-sessionDate: Jan 25, 2022Date accessed: March 17, 2022Google Scholar It is also a choice between integration and fragmentation, higher or lower health outcomes, and thriving or pressured economies. The world needs an empowered, well financed WHO at the centre of the global health architecture. WHO is an essential investment.
LOG and KAK lead the O'Neill Institute and Foundation for the National Institutes of Health ( FNIH) project on an international instrument for pandemic prevention and preparedness. The FNIH provided funding to the O'Neill Institute for the project. LOG is the Director of the WHO Collaborating Center on National and Global Health Law. WHO is an intellectual non-financial partner to the FNIH-managed GeneConvene Global Collaborative. HC was Co-Chair of the Independent Panel for Pandemic Preparedness and Response. The other authors declare no competing interests. The views in this Comment are those of the authors and do not necessarily reflect the views of the FNIH. | tech |
SARS-CoV-2-specific antibody and T-cell responses 1 year after infection in people recovered from COVID-19: a longitudinal cohort study | BackgroundThe memory immune response is crucial for preventing reinfection or reducing disease severity. However, the robustness and functionality of the humoral and T-cell response to SARS-CoV-2 remains unknown 12 months after initial infection. The aim of this study is to investigate the durability and functionality of the humoral and T-cell response to the original SARS-CoV-2 strain and variants in recovered patients 12 months after infection.MethodsIn this longitudinal cohort study, we recruited participants who had recovered from COVID-19 and who were discharged from the Wuhan Research Center for Communicable Disease Diagnosis and Treatment at the Chinese Academy of Medical Sciences, Wuhan, China, between Jan 7 and May 29, 2020. Patients received a follow-up visit between Dec 16, 2020, and Jan 27, 2021. We evaluated the presence of IgM, IgA, and IgG antibodies against the SARS-CoV-2 nucleoprotein, Spike protein, and the receptor-binding domain 12 months after initial infection, using ELISA. Neutralising antibodies against the original SARS-CoV-2 strain, and the D614G, beta ( B.1.351), and delta ( B.1.617.2) variants were analysed using a microneutralisation assay in a subset of plasma samples. We analysed the magnitude and breadth of the SARS-CoV-2-specific memory T-cell responses using the interferon γ ( IFNγ) enzyme-linked immune absorbent spot ( ELISpot) assay and intracellular cytokine staining ( ICS) assay. The antibody response and T-cell response ( ie, IFN-γ, interleukin-2 [ IL-2 ], and tumour necrosis factor α [ TNFα ]) were analysed by age and disease severity. Antibody titres were also analysed according to sequelae symptoms.FindingsWe enrolled 1096 patients, including 289 ( 26·4%) patients with moderate initial disease, 734 ( 67·0%) with severe initial disease, and 73 ( 6·7%) with critical initial disease. Paired plasma samples were collected from 141 patients during the follow-up visits for the microneutralisation assay. PBMCs were collected from 92 of 141 individuals at the 12-month follow-up visit, of which 80 were analysed by ELISpot and 92 by ICS assay to detect the SARS-CoV-2-specific memory T-cell responses. N-IgG ( 899 [ 82·0% ]), S-IgG ( 1043 [ 95·2% ]), RBD-IgG ( 1032 [ 94·2% ]), and neutralising ( 115 [ 81·6% ] of 141) antibodies were detectable 12 months after initial infection in most individuals. Neutralising antibodies remained stable 6 and 12 months after initial infection in most individuals younger than 60 years. Multifunctional T-cell responses were detected for all SARS-CoV-2 viral proteins tested. There was no difference in the magnitude of T-cell responses or cytokine profiles in individuals with different symptom severity. Moreover, we evaluated both antibody and T-cell responses to the D614G, beta, and delta viral strains. The degree of reduced in-vitro neutralising antibody responses to the D614G and delta variants, but not to the beta variant, was associated with the neutralising antibody titres after SARS-CoV-2 infection. We also found poor neutralising antibody responses to the beta variant; 83 ( 72·2%) of 115 patients showed no response at all. Moreover, the neutralising antibody titre reduction of the recovered patient plasma against the delta variant was similar to that of the D614G variant and lower than that of the beta variant. By contrast, T-cell responses were cross-reactive to the beta variant in most individuals. Importantly, T-cell responses could be detected in all individuals who had lost the neutralising antibody response to SARS-CoV-2 12 months after the initial infection.InterpretationSARS-CoV-2-specific neutralising antibody and T-cell responses were retained 12 months after initial infection. Neutralising antibodies to the D614G, beta, and delta viral strains were reduced compared with those for the original strain, and were diminished in general. Memory T-cell responses to the original strain were not disrupted by new variants. This study suggests that cross-reactive SARS-CoV-2-specific T-cell responses could be particularly important in the protection against severe disease caused by variants of concern whereas neutralising antibody responses seem to reduce over time.FundingChinese Academy of Medical Sciences, National Natural Science Foundation, and UK Medical Research Council.
The memory immune response is crucial for preventing reinfection or reducing disease severity. However, the robustness and functionality of the humoral and T-cell response to SARS-CoV-2 remains unknown 12 months after initial infection. The aim of this study is to investigate the durability and functionality of the humoral and T-cell response to the original SARS-CoV-2 strain and variants in recovered patients 12 months after infection.
In this longitudinal cohort study, we recruited participants who had recovered from COVID-19 and who were discharged from the Wuhan Research Center for Communicable Disease Diagnosis and Treatment at the Chinese Academy of Medical Sciences, Wuhan, China, between Jan 7 and May 29, 2020. Patients received a follow-up visit between Dec 16, 2020, and Jan 27, 2021. We evaluated the presence of IgM, IgA, and IgG antibodies against the SARS-CoV-2 nucleoprotein, Spike protein, and the receptor-binding domain 12 months after initial infection, using ELISA. Neutralising antibodies against the original SARS-CoV-2 strain, and the D614G, beta ( B.1.351), and delta ( B.1.617.2) variants were analysed using a microneutralisation assay in a subset of plasma samples. We analysed the magnitude and breadth of the SARS-CoV-2-specific memory T-cell responses using the interferon γ ( IFNγ) enzyme-linked immune absorbent spot ( ELISpot) assay and intracellular cytokine staining ( ICS) assay. The antibody response and T-cell response ( ie, IFN-γ, interleukin-2 [ IL-2 ], and tumour necrosis factor α [ TNFα ]) were analysed by age and disease severity. Antibody titres were also analysed according to sequelae symptoms.
We enrolled 1096 patients, including 289 ( 26·4%) patients with moderate initial disease, 734 ( 67·0%) with severe initial disease, and 73 ( 6·7%) with critical initial disease. Paired plasma samples were collected from 141 patients during the follow-up visits for the microneutralisation assay. PBMCs were collected from 92 of 141 individuals at the 12-month follow-up visit, of which 80 were analysed by ELISpot and 92 by ICS assay to detect the SARS-CoV-2-specific memory T-cell responses. N-IgG ( 899 [ 82·0% ]), S-IgG ( 1043 [ 95·2% ]), RBD-IgG ( 1032 [ 94·2% ]), and neutralising ( 115 [ 81·6% ] of 141) antibodies were detectable 12 months after initial infection in most individuals. Neutralising antibodies remained stable 6 and 12 months after initial infection in most individuals younger than 60 years. Multifunctional T-cell responses were detected for all SARS-CoV-2 viral proteins tested. There was no difference in the magnitude of T-cell responses or cytokine profiles in individuals with different symptom severity. Moreover, we evaluated both antibody and T-cell responses to the D614G, beta, and delta viral strains. The degree of reduced in-vitro neutralising antibody responses to the D614G and delta variants, but not to the beta variant, was associated with the neutralising antibody titres after SARS-CoV-2 infection. We also found poor neutralising antibody responses to the beta variant; 83 ( 72·2%) of 115 patients showed no response at all. Moreover, the neutralising antibody titre reduction of the recovered patient plasma against the delta variant was similar to that of the D614G variant and lower than that of the beta variant. By contrast, T-cell responses were cross-reactive to the beta variant in most individuals. Importantly, T-cell responses could be detected in all individuals who had lost the neutralising antibody response to SARS-CoV-2 12 months after the initial infection.
SARS-CoV-2-specific neutralising antibody and T-cell responses were retained 12 months after initial infection. Neutralising antibodies to the D614G, beta, and delta viral strains were reduced compared with those for the original strain, and were diminished in general. Memory T-cell responses to the original strain were not disrupted by new variants. This study suggests that cross-reactive SARS-CoV-2-specific T-cell responses could be particularly important in the protection against severe disease caused by variants of concern whereas neutralising antibody responses seem to reduce over time.
Chinese Academy of Medical Sciences, National Natural Science Foundation, and UK Medical Research Council.
Research in contextEvidence before this studyWe searched PubMed on Nov 2, 2021, using the following search terms [ ( “ SARS-CoV-2 ” OR “ COVID-19 ” OR “ Coronavirus Disease 2019 Virus ” OR “ 2019 Novel Coronavirus ”) AND ( “ Adaptive Immunity ” OR “ Adoptive Immunity ” OR “ Immunity, Cellular ” OR “ Cellular Immunity ” OR “ Humoral Immunity ” OR “ Immunity, Humoral ”) ], with no date or language restrictions, and identified 793 results. Studies identified by the search reported that SARS-CoV-2-specific antibodies gradually decreased over several months. However, analyses of lymphocytes from COVID-19-convalescent individuals indicate that B cells and CD4 or CD8 T cells play an important role in mediating memory responses after natural infection. Therefore, it is important to explore these pathways to improve vaccination efficacy. The longest study spanned 12 months. However, the characteristics of adaptive immunity in patients 12 months after they contracted COVID-19 was not well understood. Given the rapid emergence of variants of concern, the ability of immunological memory to protect previously infected individuals from new variants has been examined, but no firm conclusions were reached.Added value of this studyTo our knowledge, this is the first comprehensive evaluation on the durability and robustness of antibody and T-cell responses against the SARS-CoV-2 original strain and its variants in recovered patients 1 year after natural infection without repeat exposure or vaccination in Wuhan, China. Our findings show that robust antibody and T-cell immunity against SARS-CoV-2 is present in the majority of recovered patients 12 months after moderate-to-critical infection. Total SARS-CoV-2-specific T-cell responses remain effective against variants, but neutralising antibodies diminish by 12 months.Implications of all the available evidenceThese data have important implications for vaccine efficacy against SARS-CoV-2 variants; the presence of cellular immune responses to SARS-CoV-2 variants and patients who lost their neutralising antibody responses provide additional important information on broad B-cell and T-cell immunity for future vaccine strategies targeting SARS-CoV-2. In particular, when neutralising antibody responses are reduced, cross-reactive SARS-CoV-2-specific T-cell responses could be important in protection against severe disease caused by variants of concern. Continuous surveillance is required to assess the duration of infection-induced immunity and the antibody and T-cell responses to these variants.
We searched PubMed on Nov 2, 2021, using the following search terms [ ( “ SARS-CoV-2 ” OR “ COVID-19 ” OR “ Coronavirus Disease 2019 Virus ” OR “ 2019 Novel Coronavirus ”) AND ( “ Adaptive Immunity ” OR “ Adoptive Immunity ” OR “ Immunity, Cellular ” OR “ Cellular Immunity ” OR “ Humoral Immunity ” OR “ Immunity, Humoral ”) ], with no date or language restrictions, and identified 793 results. Studies identified by the search reported that SARS-CoV-2-specific antibodies gradually decreased over several months. However, analyses of lymphocytes from COVID-19-convalescent individuals indicate that B cells and CD4 or CD8 T cells play an important role in mediating memory responses after natural infection. Therefore, it is important to explore these pathways to improve vaccination efficacy. The longest study spanned 12 months. However, the characteristics of adaptive immunity in patients 12 months after they contracted COVID-19 was not well understood. Given the rapid emergence of variants of concern, the ability of immunological memory to protect previously infected individuals from new variants has been examined, but no firm conclusions were reached.
To our knowledge, this is the first comprehensive evaluation on the durability and robustness of antibody and T-cell responses against the SARS-CoV-2 original strain and its variants in recovered patients 1 year after natural infection without repeat exposure or vaccination in Wuhan, China. Our findings show that robust antibody and T-cell immunity against SARS-CoV-2 is present in the majority of recovered patients 12 months after moderate-to-critical infection. Total SARS-CoV-2-specific T-cell responses remain effective against variants, but neutralising antibodies diminish by 12 months.
These data have important implications for vaccine efficacy against SARS-CoV-2 variants; the presence of cellular immune responses to SARS-CoV-2 variants and patients who lost their neutralising antibody responses provide additional important information on broad B-cell and T-cell immunity for future vaccine strategies targeting SARS-CoV-2. In particular, when neutralising antibody responses are reduced, cross-reactive SARS-CoV-2-specific T-cell responses could be important in protection against severe disease caused by variants of concern. Continuous surveillance is required to assess the duration of infection-induced immunity and the antibody and T-cell responses to these variants.
The SARS-CoV-2 pandemic remains a serious public health threat to the global population.1Ren LL Wang YM Wu ZQ et al.Identification of a novel coronavirus causing severe pneumonia in human: a descriptive study.Chin Med J ( Engl). 2020; 133: 1015-1024Google Scholar Consistent with other viral infections, there is evidence that humans develop SARS-CoV-2-specific humoral and cellular immunity that mediates viral clearance and inhibits viral dissemination. A study of patients with COVID-19 suggests that CD4 and CD8 T cells play a dominant role in reducing disease severity during initial SARS-CoV-2 infection.2Karlsson AC Humbert M Buggert M The known unknowns of T cell immunity to COVID-19.Sci Immunol. 2020; 5eabe8063Google Scholar In terms of neutralising antibodies, the data are inconclusive; one study suggested that neutralising antibodies against SARS-CoV-2 did not generally correlate with reduced disease severity in initial infections,3Sette A Crotty S Adaptive immunity to SARS-CoV-2 and COVID-19.Cell. 2021; 184: 861-880Google Scholar but in another study, they seemed to have an important role in vaccination against and treatment of COVID-19.4Du L Yang Y Zhang X Neutralizing antibodies for the prevention and treatment of COVID-19.Cell Mol Immunol. 2021; 18: 2293-2306Google Scholar To date, few data are available on long-term immunity against SARS-CoV-2. Available reports mainly suggest that the titres of antibodies against SARS-CoV-2 decline over time after clearance of COVID-19 infection.5Huang C Huang L Wang Y et al.6-month consequences of COVID-19 in patients discharged from hospital: a cohort study.Lancet. 2021; 397: 220-232Google Scholar, 6He Z Ren L Yang J et al.Seroprevalence and humoral immune durability of anti-SARS-CoV-2 antibodies in Wuhan, China: a longitudinal, population-level, cross-sectional study.Lancet. 2021; 397: 1075-1084Google Scholar Studies have shown that SARS-CoV-2-specific cellular immune responses developed in patients with COVID-197Braun J Loyal L Frentsch M et al.SARS-CoV-2-reactive T cells in healthy donors and patients with COVID-19.Nature. 2020; 587: 270-274Google Scholar, 8Sekine T Perez-Potti A Rivera-Ballesteros O et al.Robust T cell immunity in convalescent individuals with asymptomatic or mild COVID-19.Cell. 2020; 183: 158-168Google Scholar and remained detectable 8 months after infection.9Dan JM Mateus J Kato Y et al.Immunological memory to SARS-CoV-2 assessed for up to 8 months after infection.Science. 2021; 371eabf4063Google Scholar Studies on patients who have recovered from SARS-CoV indicated that cellular immune responses were maintained for nearly two decades, whereas memory B cells and antibody responses could not be detected in most individuals at that point.10Jarjour NN Masopust D Jameson SC T cell memory: understanding COVID-19.Immunity. 2021; 54: 14-18Google Scholar However, the durability of antibody and T-cell memory against SARS-CoV-2 in recovered individuals remains poorly characterised.
Emerging SARS-CoV-2 variants are a major public health concern. SARS-CoV-2 variants of concern ( VOCs), including the alpha ( B.1.1.7), beta ( B.1.351), gamma ( P.1), delta ( B.1.617.2), and omicron ( B.1.1.529) variants, spread more efficiently11Krause PR Fleming TR Longini IM et al.SARS-CoV-2 variants and vaccines.N Engl J Med. 2021; 385: 179-186Google Scholar and lead to a substantial loss of neutralising activity by vaccine-elicited and monoclonal antibodies.12Chen X Chen Z Azman AS et al.Neutralizing antibodies against SARS-CoV-2 variants induced by natural infection or vaccination: a systematic review and pooled meta-analysis.Clin Infect Dis. 2021; ( published online July 24.) https: //doi.org/10.1093/cid/ciab646Google Scholar However, the impact of VOCs on the durability of SARS-CoV-2 immunity, and whether these VOCs evolved to escape from natural infection-elicited immunity, is not well understood.
In this study, we characterised SARS-CoV-2-specific humoral and cellular immune responses in a follow-up cohort of patients recovered from COVID-19 12 months after infection, without repeat exposure or SARS-CoV-2 vaccination, in Wuhan, China. We also tested in vitro the impact of SARS-CoV-2 variants on B-cell and T-cell responses 12 months after infection in this cohort.
In this longitudinal cohort study, we recruited participants who had recovered from laboratory-confirmed COVID-19 and who were discharged from the Wuhan Research Center for Communicable Disease Diagnosis and Treatment at the Chinese Academy of Medical Sciences, Wuhan, China, between Jan 7 and May 29, 2020.5Huang C Huang L Wang Y et al.6-month consequences of COVID-19 in patients discharged from hospital: a cohort study.Lancet. 2021; 397: 220-232Google Scholar Patients were asked to attend a follow-up visit at the research centre between Dec 16, 2020, and Jan 27, 2021. Inclusion and exclusion criteria are provided in the appendix ( p 2). The individuals studied are part of a larger longitudinal cohort study, whose outcomes were described in detail elsewhere.5Huang C Huang L Wang Y et al.6-month consequences of COVID-19 in patients discharged from hospital: a cohort study.Lancet. 2021; 397: 220-232Google Scholar, 13Huang L Yao Q Gu X et al.1-year outcomes in hospital survivors with COVID-19: a longitudinal cohort study.Lancet. 2021; 398: 747-758Google Scholar Written informed consent was obtained from each individual. The study was approved by the Institutional Review Boards of the Wuhan Research Center for Communicable Disease Diagnosis and Treatment, Chinese Academy of Medical Sciences ( KY-2020-80.01).
Disease severity was characterised by clinicians using the highest seven-category scale during hospital stay ( appendix p 2); for this study, patients in the third category ( admitted to hospital but who did not require supplemental oxygen) were categorised as moderate, patients in the fourth category ( admitted to hospital requiring supplemental oxygen) were categorised as severe, and patients in the fifth and sixth categories ( admitted to hospital requiring high-flow nasal cannula, non-invasive mechanical ventilation, extracorporeal membrane oxygenation, or invasive mechanical ventilation) were categorised as critical.5Huang C Huang L Wang Y et al.6-month consequences of COVID-19 in patients discharged from hospital: a cohort study.Lancet. 2021; 397: 220-232Google Scholar 10 mL of venous blood was collected from participants by clinicians when they attended the 12-month follow-up visit and processed within 12 h to isolate plasma ( for the antibody assays) and peripheral blood mononuclear cells ( PBMCs; for the T-cell response assays; appendix p 2). Titres of IgM, IgA, and IgG antibodies against the nucleoprotein, Spike protein, and receptor-binding domain of SARS-CoV-2 were evaluated using ELISA ( appendix pp 2–3). The neutralising antibodies against the original, beta, and delta SARS-CoV-2 strains were titred on Vero cells using a microneutralisation assay ( appendix p 3). SARS-CoV-2-specific memory T-cell responses to overlapping peptides spanning the SARS-CoV-2 Spike protein, nucleoprotein, membrane protein, and envelope protein–open reading frame ( E/ORF) were detected using both cryopreserved ( ex vivo) and cultured PBMCs ( in vitro) and assessed using the interferon enzyme-linked immune absorbent spot ( ELISpot) and intracellular cytokine staining ( ICS) assays ( appendix pp 3–4). The antibody and T-cell responses ( ie, interferon γ [ IFNγ ], interleukin-2 [ IL-2 ], and tumour necrosis factor α [ TNFα ]) were analysed by age and disease severity. Antibody titres were also analysed according to sequelae symptoms.
The primary outcomes were neutralising antibody titres and T-cell responses. The cutoff for neutralising antibody titre was 1/10. T-cell responses were expressed as the magnitude of IFNγ production and proportion of IL-2, IFNγ, and TNFα produced by SARS-CoV-2-specific CD4 and CD8 T cells. Secondary outcomes included IgM antibodies against the nucleoprotein ( N-IgM), Spike protein ( S-IgM), and receptor-binding domain ( RBD-IgM), and IgA and IgG antibodies, which were expressed as optical density at 450 nm. Further secondary outcomes were the demographic characteristics of recovered patients, such as age, sex, days after infection, and sequelae symptoms.
Demographic characteristics and sequelae symptoms of COVID-19 in patients are presented as median ( IQR) for continuous variables and n (%) for categorical variables. The comparison of seropositivity of IgM, IgA, IgG, and neutralising antibodies, and the escape percentage of the D614G, beta, and delta variants from neutralising antibodies was done with the χ2 test, or Fisher's exact test when appropriate. Single comparisons between other metrics were done using the Mann-Whitney U test. Multiple comparisons of antibody titres and memory T-cell responses were done using the Kruskal-Wallis test followed by a post-hoc Dunn's correction. Paired plasma antibody titres and T-cell responses were compared using a two-tailed Wilcoxon matched-pairs signed-rank test. Spearman correlation analysis was done for single continuous variate correlation analyses. A two-sided p value less than 0·05 was considered to be statistically significant. All statistical analyses were done using GraphPad Prism 9.1 ( GraphPad Software, San Diego, CA, USA) and SAS ( version 9.4).
The funders of the study had no role in the study design, data collection, data analysis, data interpretation, or writing of this report.
We assessed 1107 patients for eligibility, of whom 1096 patients who had recovered from COVID-19 and for whom 12 months had passed after the initial infection were enrolled. Demographic characteristics of recovered COVID-19 patients recruited in the 12-month follow-up visit are listed in the table; the baseline characteristics of these individuals are listed in the appendix ( p 6). Participants included 289 ( 26·4%) patients with moderate initial disease, 734 ( 67·0%) with severe disease, and 73 ( 6·7%) with critical disease. The median duration from symptom onset to the follow-up visit was 347 days ( IQR 336–358). The median age of the patients was 58 years ( range 21–95; IQR 48–65), and 587 ( 53·6%) were male. In this cohort, 514 ( 46·9%) of 1096 patients reported at least one symptom at the 12-month follow-up visit, with fatigue, sleep difficulties, and muscle weakness being the most common self-reported symptoms ( table).TableDemographic characteristics of study patients recovered from COVID-19Total ( n=1096) Moderate ( n=289) Severe ( n=734) Critical ( n=73) Age, years58 ( 48–65) 59 ( 48–66) 58 ( 48–65) 53 ( 47–64) SexMale587 ( 53·6%) 146 ( 50·5%) 393 ( 53·5%) 48 ( 65·8%) Female509 ( 46·4%) 143 ( 49·5%) 341 ( 46·5%) 25 ( 34·2%) Days after infection347 ( 336–358) 345 ( 335–355) 347 ( 336–358) 360 ( 351–372) Sequelae symptomsOverall514 ( 46·9%) 131 ( 45·3%) 345 ( 47·0%) 38 ( 52·1%) Fatigue202 ( 18·4%) 51 ( 17·6%) 136 ( 18·5%) 15 ( 20·5%) Sleep difficulties183 ( 16·7%) 45 ( 15·6%) 128 ( 17·4%) 10 ( 13·7%) Muscle weakness147 ( 13·4%) 39 ( 13·5%) 98 ( 13·4% 10 ( 13·7%) Joint pain138 ( 12·6%) 35 ( 12·1%) 88 ( 12·0%) 15/58 ( 25·9%) Palpitations117 ( 10·7%) 24 ( 8·3%) 86 ( 11·7%) 7 ( 9·6%) Hair loss114 ( 10·4%) 26 ( 9·0%) 83 ( 11·3%) 5 ( 6·8%) Chest pain91 ( 8·3%) 23 ( 8·0%) 63 ( 8·6%) 5 ( 6·8%) Cough80 ( 7·3%) 25 ( 8·7%) 48 ( 6·5%) 7 ( 9·6%) Dizziness74 ( 6·8%) 18 ( 6·2%) 47 ( 6·4%) 9 ( 12·3%) Headache69 ( 6·3%) 17 ( 5·9%) 45 ( 6·1%) 7 ( 9·6%) Skin rash62 ( 5·7%) 14 ( 4·8%) 46 ( 6·3%) 2 ( 2·7%) Myalgia53 ( 4·8%) 14 ( 4·8%) 32 ( 4·4%) 7 ( 9·6%) Smell disorder45 ( 4·1%) 13 ( 4·5%) 28 ( 3·8%) 4 ( 5·5%) Sore throat or difficult to swallow43 ( 3·9%) 13 ( 4·5%) 26 ( 3·5%) 4 ( 5·5%) Decreased appetite33 ( 3·0%) 5 ( 1·7%) 24 ( 3·3) 4 ( 5·5%) Taste disorder33 ( 3·0%) 4 ( 1·4%) 29 ( 4·0%) 0Diarrhoea or vomiting10 ( 0·9%) 4 ( 1·4%) 4 ( 0·5%) 2/71 ( 2·8%) Data are n (%), n/N (%), or median ( IQR). Open table in a new tab
Data are n (%), n/N (%), or median ( IQR).
Plasma samples were taken from all 1096 patients to perform the ELISA assay. 141 paired plasmas were collected from 141 patients during the follow-up visits 6 ( between June 16 and Sept 3, 2020) and 12 months after infection for the microneutralisation assay. PBMCs were collected from 92 of 141 individuals at the 12-month follow-up visit, of which 80 were analysed by ELISpot and 92 by ICS assay to detect the SARS-CoV-2-specific memory T-cell responses ( appendix p 7).
Seropositivity for N-IgM, N-IgA, S-IgM, S-IgA, RBD-IgM, and RBD-IgA ranged from 11 ( 1·0%) to 49 ( 4·5%; appendix p 8). 899 ( 82·0%) were seropositive for N-IgG, 1043 ( 95·2%) were seropositive for S-IgG, and 1032 ( 94·2%) were seropositive for RBD-IgG ( appendix p 8). S-IgG antibody titres were higher in those with severe symptoms ( 0·63 [ IQR 0·44–0·83 ]) than in those with moderate symptoms ( 0·59 [ 0·42–0·75 ]; p=0·017). The IgG titres against SARS-CoV-2 increased with age at the 12-month follow-up visit ( appendix p 11). We found that SARS-CoV-2-specific antibody titres for some age groups were higher in patients with muscle weakness, hair loss, and headache than in patients with no related symptoms reported at the 12-month follow-up visit ( appendix p 12).
Among 141 paired plasmas, 121 ( 85·8%) were positive for neutralising antibodies at the 6-month follow-up visit and 115 ( 81·6%) were positive for neutralising antibodies at the 12-month follow-up visit ( p=0·33; figure 1A). There were no significant differences in neutralising antibody titres between critical, moderate, and severe individuals at the 6-month ( p=0·088) and 12-month ( p=0·53) visits, as well as between age groups of 18–44, 45–59, and 60–95 years at 6 months ( p=0·48) and 12 months ( p=0·73). When comparing overall titres, neutralising antibody titres decreased between the 6-month ( median 1/25·1 [ IQR 1/12·6 to 1/40 ]) and 12-month visits ( 1/25·1 [ 1/13·4 to 1/50·1 ]; p=0·024; figure 1B). Neutralising antibody titres did not differ significantly between the 6-month and 12-month visits in moderate ( p=0·67) and severe ( p=0·31) patients, or in the groups aged 18–44 ( p=0·59) and 45–59 ( p=0·58) years ( figure 1C–D). However, neutralising antibody titres did decrease in the critical group ( from 1/29·5 [ 1/22·4 to 1/56·2 ] at 6 months to 1/28·2 [ 1/15·8 to 1/35·1 ] at 12 months; p=0·038) and the group aged 60 years or older ( from 1/31·6 [ 1/15·9 to 1/50·1 ] at 6 months to 1/24·3 [ 1/11·3 to 1/40·0 ] at 12 months; p=0·0008; figure 1C–D). Seropositivity for neutralising antibodies did not differ significantly between the 6-month and 12-month visits in cohorts with different disease severity and across age groups ( appendix p 13).Figure 1Neutralising antibody titres 6 and 12 months after SARS-CoV-2 infectionShow full caption ( A) Seropositivity of neutralising antibodies against the original SARS-CoV-2 strain from Wuhan, China. ( B) Neutralising antibody titres against the original SARS-CoV-2 strain ( IPBCAMS-WH-01/2019, number EPI ISL 402123). ( C) Neutralising antibody titres against the original SARS-CoV-2 strain in moderate, severe, and critical patients. ( D) Neutralising antibody titres against the original SARS-CoV-2 strain in different age groups. The dotted line denotes the cutoff value for positive neutralising antibody titre. The solid lines denote the median value.View Large Image Figure ViewerDownload Hi-res image Download ( PPT)
( A) Seropositivity of neutralising antibodies against the original SARS-CoV-2 strain from Wuhan, China. ( B) Neutralising antibody titres against the original SARS-CoV-2 strain ( IPBCAMS-WH-01/2019, number EPI ISL 402123). ( C) Neutralising antibody titres against the original SARS-CoV-2 strain in moderate, severe, and critical patients. ( D) Neutralising antibody titres against the original SARS-CoV-2 strain in different age groups. The dotted line denotes the cutoff value for positive neutralising antibody titre. The solid lines denote the median value.
ELISpot responses against SARS-CoV-2 were measured in five ( 26%) of 19 healthy individuals sampled between October and December, 2018 ( appendix p 14). The overall magnitude and breadth of SARS-CoV-2-specific IFNγ responses against viral peptides is shown in figure 2A and the appendix ( p 15). Memory T-cell responses were detected in 72 ( 90%) of 80 recovered patients, showing SARS-CoV-2-specific T-cell responses to at least one of the SARS-CoV-2 peptide pools. However, there was high interindividual heterogeneity in the magnitude of SARS-CoV-2-specific T-cell responses ( figure 2A). No significant correlations were observed between the magnitude of SARS-CoV-2-specific memory T-cell responses and disease severity ( p=0·42; figure 2B). Differences in the magnitude of IFNγ T-cell responses to the Spike ( p=0·62), nucleoprotein ( p=0·82), and membrane protein ( p=0·80) peptide pools were not significant ( figure 2C). However, the IFNγ T-cell responses to the E/ORF peptide pool were lower than those to nucleoprotein peptide pools ( p=0·0045; figure 2C).Figure 2Memory T-cell responses to SARS-CoV-2 peptides measured by IFNγ ELISpotShow full caption ( A) Magnitude of IFNγ T-cell responses for each individual. Each bar shows the total T-cell response of each individual specific to all the SARS-CoV-2 protein peptide pools tested. Each coloured segment represents the source protein corresponding to peptide pools eliciting the IFNγ T-cell responses. ( B) Magnitude of IFNγ T-cell responses in individuals with different disease severity. ( C) Magnitude of IFNγ T-cell responses against different peptide pools. The solid lines in panels B and C denote the median of magnitude of IFNγ T-cell responses. ELISpot=enzyme-linked immune absorbent spot assay. IFNγ=interferon γ. PBMC=peripheral blood mononuclear cells.View Large Image Figure ViewerDownload Hi-res image Download ( PPT)
( A) Magnitude of IFNγ T-cell responses for each individual. Each bar shows the total T-cell response of each individual specific to all the SARS-CoV-2 protein peptide pools tested. Each coloured segment represents the source protein corresponding to peptide pools eliciting the IFNγ T-cell responses. ( B) Magnitude of IFNγ T-cell responses in individuals with different disease severity. ( C) Magnitude of IFNγ T-cell responses against different peptide pools. The solid lines in panels B and C denote the median of magnitude of IFNγ T-cell responses. ELISpot=enzyme-linked immune absorbent spot assay. IFNγ=interferon γ. PBMC=peripheral blood mononuclear cells.
Ex-vivo ELISpot assays for T-cell responses to the Spike and nucleoprotein peptide pools were performed on 37 individuals ( 15 moderate and 22 severe patients; appendix p 16). We did not see any significant difference between Spike protein and nucleoprotein T-cell responses overall, or between severe versus moderate patients, in line with data from the expanded ( in vitro) patient T-cells ( figure 2).
To assess functional SARS-CoV-2-specific memory T-cell responses in COVID-19-convalescent individuals, we isolated PBMCs and exposed them to overlapping Spike, nucleoprotein, and membrane or E/ORF peptide pools. We then measured the production of IFNγ, IL-2, and TNFα by SARS-CoV-2-reactive T cells ( appendix pp 17–18). For 92 individuals tested, both CD4 and CD8 antigen-specific T cells produced at least one of these three cytokines. The proportion of CD4 and CD8 T-cell responses to the Spike protein and the membrane and E/ORF protein peptide pools showed no significant differences among moderate, severe, and critical patients ( figure 3A–B). However, there was a lower proportion of CD4 ( p=0·0032 for severe vs moderate and p=0·0017 for severe vs critical) and CD8 ( p=0·019 for severe vs moderate and p=0·0034 for severe vs critical) T-cell responses to the nucleoprotein in severe patients than in moderate and critical patients ( figure 3A–B). Spike and nucleoprotein peptide pools expressed more IL-2 and TNFα than did membrane and E/ORF peptide pools ( figure 3C–D).Figure 3Functional characteristics of SARS-CoV-2-specific T cells in recovered COVID-19 patientsShow full captionCytokine-producing T cells were detected by ICS after incubation with SARS-CoV-2 peptides in 92 recovered patients. Comparison of the relative proportion of SARS-CoV-2 peptide-pool-reactive CD4 ( A) and CD8 ( B) T cells among moderate ( n=35), severe ( n=29), and critical ( n=28) patients recovered from COVID-19. The SARS-CoV-2 peptide-pool-reactive CD4 or CD8 T cells were identified with at least one of the three cytokines ( IFNγ, TNFα, and IL-2) detected. Bar graphs summarise the distribution of multifunctional cytokines against different peptide pools among SARS-CoV-2-specific CD4 ( C) and CD8 ( D) T cells in 92 recovered patients. Data are presented as median ( IQR). ICS=intracellular cytokine staining. IFNγ=interferon γ. IL-2=interleukin 2. TNFα=tumour necrosis factor α.View Large Image Figure ViewerDownload Hi-res image Download ( PPT)
Cytokine-producing T cells were detected by ICS after incubation with SARS-CoV-2 peptides in 92 recovered patients. Comparison of the relative proportion of SARS-CoV-2 peptide-pool-reactive CD4 ( A) and CD8 ( B) T cells among moderate ( n=35), severe ( n=29), and critical ( n=28) patients recovered from COVID-19. The SARS-CoV-2 peptide-pool-reactive CD4 or CD8 T cells were identified with at least one of the three cytokines ( IFNγ, TNFα, and IL-2) detected. Bar graphs summarise the distribution of multifunctional cytokines against different peptide pools among SARS-CoV-2-specific CD4 ( C) and CD8 ( D) T cells in 92 recovered patients. Data are presented as median ( IQR). ICS=intracellular cytokine staining. IFNγ=interferon γ. IL-2=interleukin 2. TNFα=tumour necrosis factor α.
To establish whether plasma from recovered patients can neutralise circulating SARS-CoV-2 variants, we tested plasma from 141 recovered patients against authentic viruses of the D614G, beta, and delta variants using microneutralisation assays. 12 months after infection, 115 ( 82%) of 141 individuals had neutralising antibodies against the original strain from Wuhan, China. By contrast, only 68 ( 48%) had neutralising antibodies against D614G, 32 ( 23%) had neutralising antibodies against the beta variant, and 69 ( 49%) had neutralising antibody responses against the delta variant ( all p < 0·0001; figure 4A). The neutralising antibody titres were significantly lower for the D614G ( median 1/5·0 [ IQR 1/5·0–1/14·1 ]; p < 0·0001), beta ( 1/5·0 [ 1/5·0–1/5·0 ]; p < 0·0001), and delta ( 1/5·0 [ 1/5·0–1/15·8 ]; p < 0·0001) variants than for the original strain ( 1/25·1 [ 1/12·6–1/40·0 ]). Moreover, the neutralising antibody titres against the D614G and delta variants were similar ( p=0·42), and both were higher than those against the beta variant ( p=0·036 for D614G vs beta and p=0·0019 for delta vs beta; figure 4A).Figure 4Humoral and cellular immune responses to the original SARS-CoV-2 strain, and the D614G, beta, and delta variants, in recovered patients 12 months after infectionShow full caption ( A) Neutralising antibody titres against the original SARS-CoV-2 strain from Wuhan, China ( IPBCAMS-WH-01/2019, number EPI ISL 402123), and the D614G, beta ( B.1.351), and delta ( B.1.617.2) variants in 141 patients. The lines denote the median of neutralising antibody titres. ( B) Magnitude of IFNγ T-cell responses to the original SARS-CoV-2 strain, and the beta variant Spike protein peptide pool, plotted pairwise in 80 individuals. ( C–D) Comparison of the relative proportion of multifunctional cytokines between the original SARS-CoV-2 strain and the beta variant Spike protein peptide-pool-reactive CD4 ( C) and CD8 ( D) T cells in 92 recovered patients. The lines denote the median proportion of T-cell responses. IFNγ=interferon γ. IL-2=interleukin 2. TNFα=tumour necrosis factor α.View Large Image Figure ViewerDownload Hi-res image Download ( PPT)
( A) Neutralising antibody titres against the original SARS-CoV-2 strain from Wuhan, China ( IPBCAMS-WH-01/2019, number EPI ISL 402123), and the D614G, beta ( B.1.351), and delta ( B.1.617.2) variants in 141 patients. The lines denote the median of neutralising antibody titres. ( B) Magnitude of IFNγ T-cell responses to the original SARS-CoV-2 strain, and the beta variant Spike protein peptide pool, plotted pairwise in 80 individuals. ( C–D) Comparison of the relative proportion of multifunctional cytokines between the original SARS-CoV-2 strain and the beta variant Spike protein peptide-pool-reactive CD4 ( C) and CD8 ( D) T cells in 92 recovered patients. The lines denote the median proportion of T-cell responses. IFNγ=interferon γ. IL-2=interleukin 2. TNFα=tumour necrosis factor α.
Of the 115 samples positive for neutralising antibodies to the original strain, 28 ( 24%) had a titre of 1/10 to 1/20, 43 ( 37%) had a titre of 1/20 to 1/32, and 44 ( 38%) had a titre of 1/32 or more. 21 ( 75%) of 28 patients with a titre of 1/10 to 1/20 ( p=0·047), 21 ( 49%) of 43 patients with a titre of 1/20 to 1/32 ( p < 0·0001), and five ( 11%) of 44 patients with a titre of 1/32 or more ( p=0·0001) lost neutralising activity to the D614G variant at 12 months. 19 ( 68%) of 28 patients with a titre of 1/10 to 1/20 ( p=0·32), 23 ( 53%) of 43 with a titre of 1/20 to 1/32 ( p < 0·0001), and seven ( 16%) of 44 with a titre of 1/32 or more ( p=0·0003) lost neutralising activity against the delta variant at 12 months ( appendix p 19). By contrast, 22 ( 79%) of 28 patients with a titre of 1/10 to 1/20, 34 ( 79%) of 43 with a titre of 1/20 to 1/32, and 27 ( 61%) of 44 with a titre of 1/32 or more lost neutralising activity against the beta variant ( p=0·13; appendix p 19). The D614G ( p=0·36) and beta ( p=0·82) variants escaped from neutralising antibodies against the original strain, and there were no differences between age cohorts ( appendix p 19). However, the escape percentage of the delta variant was higher in those aged 18–44 years ( p=0·020) and 45–59 years ( p=0·021) than in those aged 60–95 years ( appendix p 19).
To investigate the difference in T-cell recognition between the original strain and the beta variant, we did IFNγ ELISpot and ICS assays using the original strain and the beta variant peptide pools spanning the full length of the Spike protein. The SARS-CoV-2-specific IFNγ responses were heterogeneous. However, the overall SARS-CoV-2-specific IFNγ responses in ELISpot showed no differences between the original strain and the beta variant peptide pool ( p=0·70; figure 4B) and showed a strong correlation in the magnitude of IFNγ responses ( Spearman r=0·85, p < 0·0001; appendix p 19). Furthermore, we examined whether there was T-cell immune deviation between the original strain and the beta variant using ICS. The beta variant induced a stronger TNFα response in CD4 T-cell responses ( p=0·012), and stronger IFNγ ( p=0·024) and TNFα ( p=0·013) responses in CD8 T-cell responses ( figure 4C–D).
No correlation was observed between the magnitude of the T-cell ELISpot responses and the neutralising antibody ( Spearman r=0·10, p=0·34), S-IgG ( Spearman r=–0·062, p=0·59), N-IgG ( Spearman r=–0·052, p=0·65), and RBD-IgG ( Spearman r=0·14, p=0·23) titres 12 months after infection ( appendix p 20). To assess the persistence of the T-cell response, we measured the SARS-CoV-2-specific cellular immune response in 16 patients who were negative for neutralising antibodies after 12 months, selected from 26 ( 18%) of 141 recovered patients. We found that 15 ( 94%) of 16 individuals showed memory IFNγ responses in the ELISpot assay. All 16 samples produced at least one of the three cytokines ( IL-2, IFNγ, and TNFα) in combination in CD4 and CD8 specific T-cell responses in the ICS assay ( appendix p 21).
The data presented here show that 82·0% of recovered COVID-19 patients had N-IgG antibodies, 95·2% had S-IgG antibodies, 94·2% had RBD-IgG antibodies, and 81·6% had neutralising antibodies 12 months after a SARS-CoV-2 infection. Although the decline in neutralising antibody titres between 6 and 12 months after infection mainly occurred in older people and critical patients, seropositivity of neutralising antibodies was stable in this population. Virus-specific T cells were detectable in all patients that had recovered from COVID-19. Both the D614G and the delta variants escape from the neutralising antibodies against the original strain, an effect that depends on neutralising antibody titres. By contrast, an absence of response to the beta variant is not related to neutralising antibody titres against the original strain. Importantly, although neutralising antibody responses are less efficient to this variant, T-cell responses are cross-reactive to the beta variant in patients recovered from infection. Memory T cells retained the ability to mediate cellular immunity in patients who had lost their neutralising antibody responses.
At present, long-term immune responses in recovered patients have been investigated. Cohen and colleagues observed that broad and effective antibody responses, and memory B-cell and T-cell responses, might persist for 8 months following SARS-CoV-2 infection.14Cohen KW Linderman SL Moodie Z et al.Longitudinal analysis shows durable and broad immune memory after SARS-CoV-2 infection with persisting antibody responses and memory B and T cells.Cell Rep Med. 2021; 2100354Google Scholar Li and colleagues found that the positive rate of RBD-IgG exceeded 70% 12 months after diagnosis.15Li C Yu D Wu X et al.Twelve-month specific IgG response to SARS-CoV-2 receptor-binding domain among COVID-19 convalescent plasma donors in Wuhan.Nat Commun. 2021; 124144Google Scholar However, they did not evaluate the T-cell responses to SARS-CoV-2 and neutralising antibody responses to variants. Rank and colleagues found that about two-thirds of participants maintained IFNγ-specific T-cell responses at the 12-month follow-up. The antiviral T cells were lower in frequency than those in this study.16Rank A Tzortzini A Kling E et al.One year after mild COVID-19: the majority of patients maintain specific immunity, but one in four still suffer from long-term symptoms.J Clin Med. 2021; 103305Google Scholar The major reason for this discrepancy might be because we used in-vitro expanded short-term T-cell lines after peptide pool stimulation. Recently, Zhang and colleagues reported that SARS-CoV-2-specific cellular and humoral immunities are durable 1 year after disease onset, and PBMCs were expanded for 9 days in vitro.17Zhang J Lin H Ye B et al.One-year sustained cellular and humoral immunities of COVID-19 convalescents.Clin Infect Dis. 2021; ( published online Oct 5.) https: //doi.org/10.1093/cid/ciab884Google Scholar The results were similar to our findings. However, the neutralising antibody and T-cell responses to SARS-CoV-2 variants were not assessed in the study by Zhang and colleagues.
SARS-CoV-2 variants, especially alpha, beta, gamma, delta, and omicron, have been associated with rapid increases in cases at multiple locations.18Galloway SE Paul P MacCannell DR et al.Emergence of SARS-CoV-2 B.1.1.7 lineage—United States, December 29, 2020–January 12, 2021.MMWR Morb Mortal Wkly Rep. 2021; 70: 95-99Google Scholar, 19Tegally H Wilkinson E Giovanetti M et al.Detection of a SARS-CoV-2 variant of concern in South Africa.Nature. 2021; 592: 438-443Google Scholar, 20Faria NR Mellan TA Whittaker C et al.Genomics and epidemiology of the P.1 SARS-CoV-2 lineage in Manaus, Brazil.Science. 2021; 372: 815-821Google Scholar, 21Vaidyanathan G Coronavirus variants are spreading in India—what scientists know so far.Nature. 2021; 593: 321-322Google Scholar, 22Torjesen I Covid-19: omicron may be more transmissible than other variants and partly resistant to existing vaccines, scientists fear.BMJ. 2021; 375n2943Google Scholar These variants harbour mutations in the Spike protein that might alter virus–host cell interactions and escape neutralising antibody responses. Because beta is the most probable variant to escape the approved vaccines in comparison with the alpha, gamma, and delta variants,23Khateeb J Li Y Zhang H Emerging SARS-CoV-2 variants of concern and potential intervention approaches.Crit Care. 2021; 25: 244Google Scholar we evaluate the neutralising antibody and T-cell responses to the beta variant in this study. Our data showed that neutralising antibodies from individuals who had recovered from natural infection against the original strain are less able to neutralise effectively the D614G, beta, and delta variants. However, higher neutralising antibody titres against the original strain contributed to the protection from infection of D614G and delta variants in vitro. Neutralising antibodies against the original strain had a lower ability to neutralise the beta variant than the D614G and delta variants. The ability to escape from the neutralising antibodies against the original strain has no association to antibody titres, suggesting that the beta variant affects the binding of neutralising antibodies to the viral Spike protein. Structural information provides a basis for how SARS-CoV-2 variants have evolved to evade the immune system. The three mutations characterising the beta variant ( K417N, E484K, and N501Y) are located at the receptor-binding domain, making the variant resistant to some potent neutralising antibodies.24Cai Y Zhang J Xiao T et al.Structural basis for enhanced infectivity and immune evasion of SARS-CoV-2 variants.Science. 2021; 373: 642-648Google Scholar However, the D614G variant enhances infectivity mainly through increasing the stability of the trimer, rather than through more exposed receptor-binding domains.25Zhang J Cai Y Xiao T et al.Structural impact on SARS-CoV-2 spike protein by D614G substitution.Science. 2021; 372: 525-530Google Scholar Recently, a new SARS-CoV-2 variant ( omicron [ B.1.1.529 ]) was reported.22Torjesen I Covid-19: omicron may be more transmissible than other variants and partly resistant to existing vaccines, scientists fear.BMJ. 2021; 375n2943Google Scholar How it interacts with immune cells needs to be assessed.
Current SARS-CoV-2 vaccines are mainly focused on neutralising antibodies induced by the viral Spike or receptor-binding domain protein. However, mutations in the Spike protein can cause epitope changes, potentially resulting in the virus escaping from neutralising antibodies. It has been reported that the beta and gamma variants could not be efficiently blocked by plasma from convalescent patients with COVID-19 and serum from individuals vaccinated with the BNT162b2 vaccine ( tozinameran, Pfizer–BioNTech),26Hoffmann M Arora P Groß R et al.SARS-CoV-2 variants B.1.351 and P.1 escape from neutralizing antibodies.Cell. 2021; 184: 2384-2393Google Scholar indicating that vaccine efficacy could be compromised by the emergence of viral variants. Although neutralising antibodies were less efficient at mediating in-vitro protection in naturally infected individuals, we found that the beta variant seemed to have no substantial impact on cellular immune responses 12 months after infection. Thus, the lack of sufficient neutralising antibodies against SARS-CoV-2 variants in individuals recovered from previous SARS-CoV-2 infection could be mitigated by T-cell responses. Despite the existence of cellular immune responses, it is urgent to use viral targets that are less likely to mutate for future SARS-CoV-2 vaccine platforms.
Our findings indicate that SARS-CoV-2 cellular immunity decays more slowly over time than neutralising antibody titres. In addition, SARS-CoV memory T cells have been detected 17 years after infection in individuals who recovered from SARS, and displayed robust cross-reactivity to SARS-CoV-2.27Le Bert N Tan AT Kunasegaran K et al.SARS-CoV-2-specific T cell immunity in cases of COVID-19 and SARS, and uninfected controls.Nature. 2020; 584: 457-462Google Scholar It has been reported that in the absence of neutralising antibodies, T-cell memory correlates with protection from influenza disease severity in humans.28Sridhar S Begom S Bermingham A et al.Cellular immune correlates of protection against symptomatic pandemic influenza.Nat Med. 2013; 19: 1305-1312Google Scholar Future studies are needed to evaluate the role of T-cell memory of SARS-CoV-2 in protection against reinfections.
Our study has several limitations. First, we did not obtain consecutive samples. Longitudinal data from cohorts will help to further analyse the SARS-CoV-2 humoral and cellular immunity in individuals recovered from COVID-19. Second, because moderate-to-critical cases represent most inpatients, asymptomatic and mild cases are not included here. Third, we evaluated neutralising antibody responses to the D614G, beta, and delta variants, and the cellular responses to the beta variant. Further studies should be done to characterise humoral and cellular immunity against other SARS-CoV-2 VOCs. In addition, because of the ethical limitations to sampling, we were not able to obtain enough samples for T-cell analysis. Instead, we cultured PBMCs in vitro before analysing T-cell responses in ELISpot assays, as described previously.17Zhang J Lin H Ye B et al.One-year sustained cellular and humoral immunities of COVID-19 convalescents.Clin Infect Dis. 2021; ( published online Oct 5.) https: //doi.org/10.1093/cid/ciab884Google Scholar This expansion protocol could potentially alter both the magnitude and polyfunctionality of the T cells due to differences in the proliferative capacity of different antigen-specific T cells.
In summary, we evaluated antibody and cellular immunity in COVID-19-convalescent individuals 12 months after infection. Our findings show that humoral and cellular immunity against SARS-CoV-2 is present in most recovered patients 12 months after moderate-to-critical infection. Neutralising antibody responses to the D614G, beta, and delta variants are much poorer than those to the original strain from Wuhan, China. Our results also showed the presence of cellular immune responses to SARS-CoV-2 variants and patients who lost their neutralising antibody responses. These data underline the importance of broad B-cell and T-cell immunity for future vaccine strategies targeting SARS-CoV-2.
JW and BC conceived and designed the study, had full access to all the data in the study, and take responsibility for the integrity of the data and the accuracy of the data analysis. LG, GW, QZ, and TH did the literature review. LG, GW, QZ, YP, TH, JZ, LX, CW, LC, and XX did the laboratory analysis. LG, TD, JW, GW, JCK, QZ, and LR drafted the paper. YeW, XG, JZ, YiW, XW, and LH completed the follow-up work. YeW, XG, YiW, XW, GW, QZ, LG, and LR collected the data. LG, GW, QZ, and TH verified the underlying data in the study. All authors read and edited the manuscript. All authors approved the final version, had full access to all the data, and had final responsibility for the decision to submit for publication.
Restrictions apply to the availability of these data and so are not publicly available. However, data are available from JW upon reasonable request and with the permission of the institution.
We declare no competing interests.
This study was funded by the Chinese Academy of Medical Sciences ( CAMS) Innovation Fund for Medical Sciences ( 2020-I2M-2-015, 2018-I2M-2-002), the National Natural Science Foundation ( 81930063), and the UK Medical Research Council. We are grateful to all individuals who participated in this study and their families. We also would like to thank all staff of the follow-up study team at Wuhan Research Center for Communicable Disease Diagnosis and Treatment, Chinese Academy of Medical Sciences.
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GUINEA: World Bank takes interest in Robert Friedland's Nimba iron ore project | The International Union for Conservation of Nature will help Guinea's ministry of the environment define a policy to develop the country's key minerals bauxite and gold in a way that respects its biodiversity. [... ]
UNESCO is concerned about the consequences for biodiversity from iron ore mining in Guinea's Nimba mountains. The company that owns the site plans to submit the first version of its study in 2022. This study is supposed to explain how to develop the site without causing any damage to the area. [... ]
Rio Tinto and Chinalco, co-owners of blocks 3 and 4 of the Simandou iron ore project in Guinea, are recruiting a team they hope will soothe relations with locals and shield the firms from accusations of damaging biodiversity. [... ]
Solway, a firm which steel giant ArcelorMittal accuses of encroaching on its iron ore concessions in Liberia, is headed by Estonian multimillionaire businessman Aleksandr Bronstein, who seems to enjoy the blessings of George Weah's administration. [... ]
The former Guinean prime minister, who is today in charge of the Nimba project, considers that prospects for the development of the iron ore deposit there have been damaged by the coronavirus pandemic after having been already called into question by UNESCO on environmental grounds. [... ]
In 2020, Unesco should assess what impact Robert Friedland and Aboubacar Sampil's iron ore projects could have on the Mount Nimba nature reserve that was inscribed on the world heritage list in 1981. [... ]
Miners operating in southeast Guinea are hammering the Conakry authorities with demands to be allowed to evacuate their output via Liberia. The region boasts some of the world's largest deposits of iron ore and battery metals but is landlocked, with [. [... ]
The difficult negotiations between Canadian mining magnate Robert Friedland's High Power Exploration ( HPX) and the Guinean state for control of the Nimba iron ore project is only a small part of its US parent company I-Pulse's African strategy. [... ]
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MALI: Transitional government begins to take shape after coup d'état | After the coup d'état of 18 August in Mali, the UN Panel of Experts for Mali was tasked with gauging the new authorities ' will to implement the Algiers accord. In the event of obstruction, those now in power in Bamako know that the United Nations is serious about imposing sanctions. [... ]
Following the formation of a new government on 5 October, Bamako is to set up a provisional parliament which the putschists are hoping to preside over. [... ]
Umaro Sissoco Embalo was the only foreign head of state to attend the inauguration of Mali's transitional president Bah N'Daw on 25 September. Embalo is trying to strengthen his relationship with Bamako - with Malian businessman Aliou Boubacar Diallo's help. [... ]
Already negatively impacted by the Covid-19 pandemic, the prospects for fertiliser sales in Mali, one of the leading markets in West Africa, have deteriorated further. The recent coup d'état has increased uncertainty among international commodities producers and local blenders. [... ]
With only days to go before the expected appointment of the transitional president, CNSP officers are still divided over who should have the job. The coup-makers are divided between former generals Moussa Sinko Coulibaly and Mahamane Touré. [... ]
As ECOWAS puts pressure on the putschists to appoint a civilian to lead the transition period, two names keep popping up. Expect a compromise in the coming days. [... ]
Some within ECOWAS are becoming increasingly critical of how the former Nigieran president has handled the Malian crisis and would like to see it taken off his hands. [... ]
Ever since the military seized power in Mali on 18 August, Morocco has been building ties with the coup leaders as Algiers, wanting to retain its influence in Bamako, looks on with a wary eye. [... ]
After being forced to resign by part of the army on 18 August, the former Malian president could be allowed to go to the United Arab Emirates, where he has been receiving medical care for months. [... ]
Mali's top boss Mamadou Sinsy Coulibaly is going all out to pressure President Ibrahim Boubacar Keita to free anti-corruption campaigner Clément Dembélé. [... ]
Anti-corruption dossiers have been piling up in the in tray of the justice minister Malick Coulibaly since his appointment in [... ]
Africa Intelligence uses cookies to provide reliable and secure features, measure and analyse website traffic and provide support to the website users.Apart from those essential for the proper operation of the website, you can choose which cookies you accept to have stored on your device.Either “ Accept and close ” to agree to all cookies or go to “ Manage cookies ” to review your options. You can change these settings at any time by going to our Cookie management page.
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A pioneer on the web since 1996, Africa Intelligence is the leading news site on Africa for professionals. | general |
Ardian Weighs Sale of $ 3.3 Billion Health-Care IT Firm | The information you requested is not available at this time, please check back again soon.
( Bloomberg) -- Ardian SAS is considering options for Dedalus, including a sale that could value the Italian health-care software provider at more than 3 billion euros ( $ 3.3 billion), according to people familiar with the matter.
The Paris-based private equity firm is working with financial advisers as it explores options to exit its controlling stake in Dedalus, the people said, asking not to be identified discussing confidential information.
The business is likely to draw interest from financial investors, as well as strategic bidders keen to gain exposure in the sector, the people said. Deliberations are in the early stages and there’ s no certainty they’ ll lead to a sale, according to the people. A representative for Ardian declined to comment, while a spokesperson for Dedalus couldn’ t immediately be reached for comment.
Dedalus provides information and clinical and administrative software to hospitals, clinics and laboratories in 40 countries. The company has expanded rapidly through acquisitions since being bought by Ardian in 2016. Sovereign wealth fund Abu Dhabi Investment Authority took a minority stake in Dedalus for an undisclosed amount last year.
Private equity firms and other financial investors have been very active in the health-care sector throughout the Covid-19 pandemic. They were involved in acquisitions of health-care companies valued at $ 148 billion last year, almost double the previous annual record, data compiled by Bloomberg show.
With more than $ 125 billion under management, mid-market specialist Ardian is one of Europe’ s largest houses investing across private equity, growth and debt strategies. The buyout firm has begun internal preparations for a possible initial public offering, Bloomberg News reported last year.
A new report from Capital Economics is warning the expected magnitude of interest rate increases from the Bank of Canada could “ topple ” the domestic housing market.
The Trudeau Liberals and federal NDP's shared ambition for a national pharmacare program could shave at least two per cent off annual earnings for owners of some top pharmacy chains, according to an analyst.
Global stocks drifted lower Wednesday as the bond market stabilized from an unprecedented rout. | general |
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