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Possible Impact of Wide-scale Vaccination Against Serogroup B Neisseria Meningitidis on Gonorrhea Incidence Rates in One Region of Quebec, Canada

Abstract Background Owing to a persistent increase of serogroup B Neisseria meningitidis (Nm) invasive infections in the Saguenay-Lac-Saint-Jean (SLSJ) region of the province of Quebec (Canada) since 2006, a wide-scale vaccination campaign of individuals aged 6 months to 20 years was conducted between May and December 2014 using the 4-component protein-based meningococcus serogroup B vaccine (4CMenB). Components of this vaccine have shown to potentially cross-react with Neisseria gonorrhoeae (Ng). The study objective was to assess the impact of the vaccination campaign on Ng incidence rate (IR). Methods Ng cases notified to public health authorities during prevaccination period (January 2006 to June 2014) and postvaccination period (July 2014 to June 2017) were analyzed. The impact of this mass campaign was estimated by a Poisson regression model, including the year (11 July–June categories), age (14–20 vs. 21 years and older), and the intervention (0 by default and 1 in those 14–20 years in the period of July 2014 to June 2017). Results Overall vaccine coverage was 82% in the target group. A total of 231 Ng cases were reported among persons 14 years and older (IR: 8.4/100,000 person-years) of the SLSJ region from January 2006 to June 2017. A decrease in the Ng number of cases and IR among individuals 14–20 years was observed during the post-vaccination period whereas it increased in those 21 years and older (figure). Estimate of vaccination impact was an Ng risk reduction of 59% (95% CI: −22% to 84%; P = 0.1). During the same period, Chlamydia trachomatis (Ct) infections increased among persons of both age groups in the SLSJ region. Conclusion Although the estimate of the impact of the campaign was not statistically significant, possibly due to limited size of the study population and the low incidence of the disease, it is congruent with results of a case–control study in New Zealand showing an OMV-MeNZB vaccine effectiveness of 31%. A higher effectiveness of 4CMenB is a plausible hypothesis as three additional proteins also found in Ng are included in the vaccine used in the SLSJ region. The results of this ecologic study suggest cross-protection of 4CMenB vaccine against Ng infections. Further studies on this topic are warranted. Figure. Ng and Ct infections per quarter and by age group, SLSJ, January 2006 to June 2017. Disclosures P. De Wals, GlaxoSmithKline: Grant Investigator and Scientific Advisor, Grant recipient and travel expenses. Pfizer: Grant Investigator and Scientific Advisor, Grant recipient and travel expenses. Sanofi-Pasteur: Grant Investigator and Scientific Advisor, Grant recipient and travel expenses. Novartis: Grant Investigator and Scientific Advisor, Grant recipient and travel expenses.

Background. Cap-dependent endonuclease (CEN) resides in the PA subunit of influenza virus polymerase and mediates the "cap-snatching" process during viral mRNA biosynthesis. S-033188 is a potent, selective, small molecule inhibitor of CEN. Here we report clinical and virologic outcomes from a global Phase 3 study CAPSTONE-1.
Method. This was a multicenter, randomized, double-blind, placebo-and active-controlled study. Key eligibility criteria included 12-64 years of age, fever (axillary temperature ≥38.0°C), ≥1 general symptom and ≥1 respiratory symptom (moderate to severe), and ≤48 hours from symptom onset. Patients between 20 and 64 years of age were randomized in 2:2:1 ratio to receive a single oral administration of S-033188, placebo, or 75 mg oseltamivir BID for 5 days. Patients between 12 and 19 years of age were randomized in 2:1 ratio to receive either a single oral administration of S-033188 or placebo. The primary efficacy endpoint was time to alleviation of influenza symptoms (TTAS) in the infected intent to treat population. Viral titer and RNA content were determined from pre-and postdose nasal/throat swabs.
Result. A total of 1436 patients were randomized. TTAS was significantly shorter in the S-033188 group than that in the placebo group (median TTAS: 53.7 hours vs. 80.2 hours, P < 0.0001). Median time to cessation of viral shedding was 24 hours in patients treated with S-033188, compared with 72 hours in those treated with oseltamivir (P < 0.0001) and 96 hours for placebo (P < 0.0001). Patients in the S-033188 group had significantly greater reductions from baseline in both viral titer and RNA content than those in oseltamivir or placebo groups at all time-points until Day 3 (compared with oseltamivir) or Day 5 (compared with placebo). S-033188 was generally well tolerated, with overall incidence of treatment-emergent adverse events lower than that seen with oseltamivir.
Conclusion. Treatment with S-033188 was superior to placebo in alleviating influenza symptoms, and superior to both oseltamivir and placebo in virologic outcomes. Safety profile of S-033188 compared favorably with that of oseltamivir.
Disclosures Results. Overall vaccine coverage was 82% in the target group. A total of 231 Ng cases were reported among persons 14 years and older (IR: 8.4/100,000 person-years) of the SLSJ region from January 2006 to June 2017. A decrease in the Ng number of cases and IR among individuals 14-20 years was observed during the post-vaccination period whereas it increased in those 21 years and older (figure). Estimate of vaccination impact was an Ng risk reduction of 59% (95% CI: −22% to 84%; P = 0.1). During the same period, Chlamydia trachomatis (Ct) infections increased among persons of both age groups in the SLSJ region.
Conclusion. Although the estimate of the impact of the campaign was not statistically significant, possibly due to limited size of the study population and the low incidence of the disease, it is congruent with results of a case-control study in New Zealand showing an OMV-MeNZB vaccine effectiveness of 31%. A higher effectiveness of 4CMenB is a plausible hypothesis as three additional proteins also found in Ng are included in the vaccine used in the SLSJ region. The results of this ecologic study suggest cross-protection of 4CMenB vaccine against Ng infections. Further studies on this topic are warranted. Background. Sepsis is a leading cause of death and can be caused by a wide range of potential pathogens. In up to 40% of cases, a causative pathogen is never identified. There is a need for improved diagnostic tests that can accurately identify the breadth of potential pathogens to inform effective antimicrobial therapy.
Methods. We enrolled a prospective cohort of patients presenting to the hospital with signs and symptoms of sepsis. Plasma samples were collected for NGS testing at time of initial blood culture. Extracted plasma cell-free DNA was sequenced, human sequences removed and remaining reads aligned against a pathogen database consisting of viruses, bacteria, and eukaryotic pathogens. Relative abundance was estimated; pathogens present at high statistical significance were identified. NGS results were compared with a composite reference standard of all microbiology testing performed within 7 days of admission and clinical diagnosis.
Results. Of 286 patients enrolled, plasma NGS identified potential pathogens in 60.1% (172 of 286) of septic subjects including DNA viruses, bacteria (including fastidious/unculturable bacteria like Mycobacterium tuberculosis), and fungi. In contrast, 15.7% (45 of 286) subjects had a positive initial blood culture and 38.1% (109 of 286) had a potential infectious etiology identified using a composite microbiology laboratory standard. The NGS plasma assay had a positive agreement of 86.7% (39 of 45) and 79.5% (78 of 98) compared with initial blood culture (after excluding contaminants) and the composite laboratory reference standard, respectively. After clinical adjudication, 81.4% (140 of 172) of the positive plasma NGS results were deemed to be consistent with the septic event. Of the remaining 32 subjects, 15 had NGS results that were plausible causes of sepsis but clinical were insufficient to confirm this.
Conclusions. With a single blood draw, the Karius plasma NGS assay identified a broad range of pathogens in septic patients three times more often than blood culture and more often than all microbiology tests combined. This plasma NGS test can identify a viruses, bacteria, and eukaryotic pathogens which can provide valuable information to help clinicians better target antimicrobial therapy for patients with sepsis. Disclosures