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The American Journal of Tropical Medicine and Hygiene - Online First
In order to provide our readers with timely access to new content, papers accepted by the American Journal of Tropical Medicine and Hygiene are posted online ahead of print publication. Papers that have been accepted for publication are peer-reviewed and copy edited but do not incorporate all corrections or constitute the final versions that will appear in the Journal. Final, corrected papers will be published online concurrent with the release of the print issue.
Malaria Infection and Gametocyte Carriage Rates in Preparation for Transmission Blocking Vaccine Trials in Bancoumana, MaliAvailable online: 22 May 2017More Less
The epidemiological characterization of transmission reservoirs is a critical step in preparation for interventional trials for malaria elimination/eradication. Using cluster sampling and households/compounds as units of sampling, we recruited and followed monthly, from June 2011 to June 2012, 250 volunteers 3 months to 50 years of age in Bancoumana, Mali. In July 2012, only participants 5–35 years of age (N = 121) were reenrolled and followed for an additional year. Malaria infection prevalence was highest in October in both 2011 (21.5%, 50/233) and 2012 (38.2%, 26/68). During both years, malaria infection prevalence was highest in children 5–14 years of age (P = 0.01 and P = 0.02, respectively). The gametocyte carriage prevalence was highest in November 2011 (7.6%, 17/225) and in October 2012 (16.2%, 11/68). Gametocyte carriage rates by age did not significantly differ in 2011 and 2012. In Bancoumana, the asexual and sexual parasite carriage rates are relatively high and highly seasonal. Seasonal variation and age differences in parasite and gametocyte carriage provide essential knowledge for the design of transmission blocking assay and vaccine studies in the field.
High Prevalence of Anemia but Low Level of Iron Deficiency in Preschool Children during a Low Transmission Period of Malaria in Rural Kivu, Democratic Republic of the CongoAvailable online: 22 May 2017More Less
Anemia is a worldwide public health concern especially in preschool children in developing countries and iron deficiency (ID) is generally assumed to cause at least 50% of the cases. However, data on this contribution are scarce. To close this gap, we determined in 2013 the contribution of ID in the etiology of anemia and measured others factors associated to noniron deficiency anemia (NIDA) in 900 preschool children randomly selected during a two-stage cluster nutritional survey in the Miti-Murhesa health zone, in eastern Democratic Republic of the Congo. In these children, we collected sociodemographic, clinical, and biological parameters and determined the nutritional status according to the World Health Organization 2006 standards. Anemia was defined as altitude-adjusted hemoglobin < 110 g/L and ID was defined as serum ferritin < 12 μg/L or < 30 μg/L in the absence or presence of inflammation, respectively. Median (interquartile range) age was 29.4 (12–45) months. The prevalence of anemia was 46.6% (391/838) among whom only 16.5% (62/377) had ID. Among children without signs of inflammation, only 4.4% (11/251) met the ferritin-based (unadjusted) definition of ID. Logistic regression analysis identified ID, history of fever during the last 2 weeks and mid-upper arm circumference < 125 mm as the only independent factors associated to anemia. In conclusion, anemia is a severe public health problem in the Miti-Murhesa health zone, but NIDA is mostly predominant and needs to be further studied. Control of infections and prevention of acute undernutrition (wasting) are some of appropriate interventions to reduce the burden anemia in this region.
Sustained High Cure Rate of Artemether–Lumefantrine Against Uncomplicated Plasmodium falciparum Malaria After 8 Years of Its Wide-Scale Use in Bagamoyo District, TanzaniaAvailable online: 15 May 2017More Less
We assessed the temporal trend of artemether–lumefantrine (AL) cure rate after 8 years of its wide-scale use for treatment of uncomplicated Plasmodium falciparum malaria from 2006 to 2014 in Bagamoyo district, Tanzania. Trend analysis was performed for four studies conducted in 2006, 2007–2008, 2012–2013, and 2014. Patients with acute uncomplicated P. falciparum malaria were enrolled, treated with standard AL regimen and followed-up for 3 (2006), 28 (2014), 42 (2012–2013), or 56 (2007–2008) days for clinical and laboratory evaluation. Primary outcome was day 28 polymerase chain reaction (PCR)-adjusted cure rate across years from 2007 to 2014. Parasite clearance was slower for the 2006 and 2007–2008 cohorts with less than 50% of patients cleared of parasitemia on day 1, but was rapid for the 2012–2013 and 2014 cohorts. Day 28 PCR-adjusted cure rate was 168/170 (98.8%) (95% confidence interval [CI], 97.2–100), 122/127 (96.1%) (95% CI, 92.6–99.5), and 206/207 (99.5%) (95% CI, 98.6–100) in 2007–2008, 2012–2013, and 2014, respectively. There was no significant change in the trend of cure rate between 2007 and 2014 (χ2-trend test = 0.06, P = 0.90). Pretreatment P. falciparum multidrug-resistant gene 1 (Pfmdr1) N86 prevalence increased significantly across years from 13/48 (27.1%) in 2006 to 183/213 (85.9%) in 2014 (P < 0.001), and P. falciparum chloroquine resistance transporter gene (Pfcrt) K76 prevalence increased significantly from 24/47 (51.1%) in 2006 to 198/205 (96.6%) in 2014 (P < 0.001). The AL cure rate remained high after 8 years of its wide-scale use in Bagamoyo district for the treatment of uncomplicated P. falciparum malaria despite an increase in prevalence of pretreatment Pfmdr1 N86 and Pfcrt K76 between 2006 and 2014.
A Systematic Review and Meta-Analysis of Practices Exposing Humans to Avian Influenza Viruses, Their Prevalence, and RationaleAuthors: Guillaume Fournié, Erling Høg, Tony Barnett, Dirk U. Pfeiffer and Punam MangtaniAvailable online: 15 May 2017More Less
Almost all human infections by avian influenza viruses (AIVs) are transmitted from poultry. A systematic review was conducted to identify practices associated with human infections, their prevalence, and rationale. Observational studies were identified through database searches. Meta-analysis produced combined odds ratio estimates. The prevalence of practices and rationales for their adoptions were reported. Of the 48,217 records initially identified, 65 articles were included. Direct and indirect exposures to poultry were associated with infection for all investigated viral subtypes and settings. For the most frequently reported practices, association with infection seemed stronger in markets than households, for sick and dead than healthy poultry, and for H7N9 than H5N1. Practices were often described in general terms and their frequency and intensity of contact were not provided. The prevalence of practices was highly variable across studies, and no studies comprehensively explored reasons behind the adoption of practices. Combining epidemiological and targeted anthropological studies would increase the spectrum and detail of practices that could be investigated and should aim to provide insights into the rationale(s) for their existence. A better understanding of these rationales may help to design more realistic and acceptable preventive public health measures and messages.
Consistency of Use and Effectiveness of Household Water Treatment Among Indian Households Claiming to Treat Their WaterAuthors: Ghislaine Rosa and Thomas ClasenAvailable online: 08 May 2017More Less
Household water treatment (HWT) can improve drinking water quality and prevent disease if used correctly and consistently by populations at risk. Current international monitoring estimates by the Joint Monitoring Program for water and sanitation suggest that at least 1.1 billion people practice HWT. These estimates, however, are based on surveys that may overstate the level of consistent use and do not address microbial effectiveness. We sought to assess how HWT is practiced among households identified as HWT users according to these monitoring standards. After a baseline survey (urban: 189 households, rural: 210 households) to identify HWT users, 83 urban and 90 rural households were followed up for 6 weeks. Consistency of reported HWT practices was high in both urban (100%) and rural (93.3%) settings, as was availability of treated water (based on self-report) in all three sampling points (urban: 98.8%, rural: 76.0%). Nevertheless, only 13.7% of urban and 25.8% of rural households identified at baseline as users of adequate HWT had water free of thermotolerant coliforms at all three water sampling points. Our findings raise questions about the value of the data gathered through the international monitoring of HWT as predictors of water quality in the home, as well as questioning the ability of HWT, as actually practiced by vulnerable populations, to reduce exposure to waterborne diseases.
Clinical Usefulness of Real-Time Polymerase Chain Reaction for the Diagnosis of Vibrio vulnificus Infection Using Skin and Soft TissuesAuthors: Jun-Young Lee, Seok Won Kim, Dong-Min Kim, Na Ra Yun, Choon-Mee Kim and Sang-Hong LeeAvailable online: 08 May 2017More Less
Vibrio vulnificus is a halophilic gram-negative bacillus isolated in seawater, fish, and shellfish. Infection by V. vulnificus is the most severe food-borne infection reported in the United States of America. Here, we aimed to examine the clinical usefulness of polymerase chain reaction (PCR) using tissue specimens other than blood samples as a diagnostic tool for V. vulnificus infection. A retrospective study was conducted with patients who underwent real-time PCR of toxR in both blood and skin tissues, including serum, bullae, swab, and operation room specimens, between 2006 and 2009. The median V. vulnificus DNA load of 14 patients in real-time PCR analysis of serum at the time of admission was 638.5 copies/mL blood, which was within the interquartile range (IQR: 37–3,225). In contrast, the median value by real-time PCR using the first tissue specimen at the time of admission was 16,650 copies/mL tissue fluid (IQR: 4,419–832,500). This difference was statistically significant (P = 0.022). DNA copy numbers in tissues were less affected by short-term antibiotic administration than that in blood samples, and antibiotic administration increased the DNA copy number in some patients. We found, for the first time, that DNA copy numbers in tissues of patients infected by V. vulnificus were higher than those in blood samples. Additionally, skin lesions were more useful than blood samples as specimens for PCR analysis in patients administered antibiotics for V. vulnificus infection before admission.
Polymerase Chain Reaction Testing of Tick Bite Site Samples for the Diagnosis of Human Granulocytic AnaplasmosisAvailable online: 08 May 2017More Less
Human granulocytic anaplasmosis (HGA) is a tick-borne infectious disease caused by Anaplasma phagocytophilum, an obligate intracellular bacterium. Until now, the utility of tick-bite site samples for HGA diagnosis has not been reported. Using a patient's buffy coat and tick-bite site crust samples, we performed polymerase chain reaction (PCR) testing using Ehrlichia- or Anaplasma-specific primers. PCR with buffy coat and crust samples obtained before doxycycline administration was positive. Six days after doxycycline administration, PCR with the buffy coat sample was negative but PCR with a crust tissue sample from the tick-bite site remained positive. This is the first case to suggest that crust tissue at the tick-bite site may be useful for early HGA diagnosis in patients who have already been treated with antibiotics such as doxycycline.
Zika Virus Meningoencephalitis and Myelitis and Associated Magnetic Resonance Imaging FindingsAuthors: Faruq Pradhan, Joseph D. Burns, Ahmed Agameya, Avignat Patel, Mohammad Alfaqih, Juan E. Small and Winnie OoiAvailable online: 08 May 2017More Less
Zika virus (ZIKV) has a wide clinical spectrum of associated neurologic disease including microcephaly and Guillain–Barre syndrome but, despite its known neurotropism, ZIKV meningoencephalitis and myelitis have been rare complications. We describe a case of ZIKV meningoencephalitis and probable myelitis and its associated magnetic resonance imaging findings that rapidly resolved during recovery in a previously healthy adult.
Hygienic Behaviors and Risks for Ascariasis Among College Students in Kabul, AfghanistanAvailable online: 08 May 2017More Less
Teenagers have a high prevalence of ascariasis in low-income countries with endemic disease, and their hygienic behaviors and access to proper sanitation may be limited in rapidly urbanizing settings. We studied university students in Kabul to estimate the proportion with ascariasis and determine the prevalence of risk factors for infection. Ascariasis was assessed through microscopy for 520 students attending Kabul Medical University. Overall, 15.8% of students were infected. Living in a hostel (21.2% versus 10.4% in houses) using well water (27.7% versus 9.7% for piped water), eating street food (29.4% versus 3.0% for those who do not), and eating unwashed vegetables (63.6% versus 8.8% for those who do not) were risk factors for infection. Recent city migrants who live in group hostels, including students, are important targets for interventions to reduce ascariasis. Such interventions could include encouraging individuals to prepare their own food and use only potable water.
Differential Vector Competency of Aedes albopictus Populations from the Americas for Zika VirusAuthors: Sasha R. Azar, Christopher M. Roundy, Shannan L. Rossi, Jing H. Huang, Grace Leal, Ruimei Yun, Ildefonso Fernandez-Salas, Christopher J. Vitek, Igor A. D. Paploski, Pamela M. Stark, Jeremy Vela, Mustapha Debboun, Martin R. Nava, Uriel Kitron, Guilherme S. Ribeiro, Kathryn A. Hanley, Nikos Vasilakis and Scott C. WeaverAvailable online: 08 May 2017More Less
To evaluate the potential role of Aedes albopictus (Skuse) as a vector of Zika virus (ZIKV), colonized mosquitoes of low generation number (≤ F5) from Brazil, Houston, and the Rio Grande Valley of Texas engorged on viremic mice infected with ZIKV strains originating from Senegal, Cambodia, Mexico, Brazil, or Puerto Rico. Vector competence was established by monitoring infection, dissemination, and transmission potential after 3, 7, and 14 days extrinsic incubation. Positive saliva samples were assayed for infectious titer. Although all three mosquito populations were susceptible to all ZIKV strains, rates of infection, dissemination, and transmission differed between mosquito and virus strains. Aedes albopictus from Salvador, Brazil, were the least efficient vectors; demonstrating susceptibility to infection to two American strains of ZIKV but failing to transmit virus in saliva. Mosquitoes from the Rio Grande Valley were the most efficient vectors and were capable of transmitting all three tested ZIKV strains into saliva after 14 days of extrinsic incubation. In particular, ZIKV strain DakAR 41525 (Senegal 1954) was significantly more efficient at dissemination and saliva deposition than the others tested in Rio Grande mosquitoes. Overall, our data indicate that, while Ae. albopictus is capable of transmitting ZIKV, its competence is potentially dependent on geographic origin of both the mosquito population and the viral strain.
Clinical Characteristics of Severe Japanese Encephalitis: A Case Series from South KoreaAuthors: Jun-Sang Sunwoo, Soon-Tae Lee, Keun-Hwa Jung, Kyung-Il Park, Jangsup Moon, Ki-Young Jung, Manho Kim, Sang Kun Lee and Kon ChuAvailable online: 08 May 2017More Less
Japanese encephalitis (JE) virus is a major cause of devastating viral encephalitis, especially in Asia. Although a successful vaccination program led to its near-elimination over three decades in South Korea, the incidence of JE has increased since 2010. The present study investigated the clinical manifestations, laboratory findings, and factors affecting neurological outcomes of reemerging JE. We retrospectively reviewed medical records of laboratory-confirmed JE patients who presented with acute encephalitis syndrome at three tertiary hospitals between 2010 and 2015. A total of 17 patients with JE were identified. Their median age was 51 years, and 10 (58.5%) were men. The most common symptoms and signs were fever (94.1%), altered consciousness (94.1%), and headache (80.2%). Hyporeflexia (47.1%), seizures (35.2%), abnormal brainstem reflex (23.5%), and flaccid weakness (17.6%) were also noted. Brain imaging revealed thalamic lesions in all patients, with the hippocampus, midbrain, basal ganglia, and cerebral cortex affected to varying degrees. Sixteen patients (94.1%) required management in the intensive care unit with mechanical ventilation due to neurological deterioration. At the time of discharge, 11 (64.7%) had poor recovery, defined as Glasgow coma scale scores of less than 8, and remained ventilator dependent. Comparison between the two outcome groups indicated that midbrain involvement (P = 0.028) and rapid deterioration (P = 0.005) were associated with severe neurological sequelae. Given that JE is a vaccine-preventable disease, vaccination for adults should be considered in response to the reemergence of JE.
Prevention and Care of Hepatitis B in Senegal; Awareness and Attitudes of Medical PractitionersAvailable online: 08 May 2017More Less
In highly endemic settings for hepatitis B virus (HBV) infection such as Senegal, access to HBV prevention and care is rapidly evolving. In this context, all medical practitioners should have baseline knowledge on HBV infection and promote access to vaccination, screening, and care. A knowledge and attitudes survey on HBV infection was conducted among a randomly selected sample of medical practitioners in Senegal. Participants were asked to fill-out a questionnaire on the HBV epidemiology, prevention, and treatment. A 60-item knowledge score was computed; the lower quartile of the observed score was used to define poor knowledge. Factors associated with poor knowledge were assessed using a logistic regression model. A total of 127 medical practitioners completed the questionnaire. Only 14 (11.0%) participants knew that HBV vaccine could be safely administered to pregnant women and 65 (51.2%) to newborns. Older practitioners (> 40 years) as well as general practitioners (compared with specialists) were more likely to have a poor knowledge score with odds ratios (ORs) of 3.1 (95% confidence interval [CI] 1.0–9.2) and 2.6 (95% CI 1.0–7.3), respectively. Practitioners who declared not to recommend HBV screening frequently during their consultation were more likely to present a poor knowledge score [OR: 3.0; (95% CI 1.1–8.2)]. As universal HBV screening is being promoted in countries with endemic HBV infection, our finding that poor screening attitudes were associated with a poor knowledge is of concern. There is a need to raise awareness of medical practitioners in Senegal toward universal HBV screening and early vaccination of newborns.
Clinical Features of a Case of Suspected Borrelia miyamotoi Disease in Hokkaido, JapanAvailable online: 01 May 2017More Less
We herein report a case of suspected Borrelia miyamotoi disease in Hokkaido, Japan. The patient complained of lassitude, arthralgia, and high fever after a tick bite. Furthermore, at the time of consultation, the patient exhibited momentary loss of consciousness and low blood pressure. Laboratory tests revealed elevation of liver enzymes, thrombocytopenia, and increased C-reactive protein. Seroconversion to B. miyamotoi glycerophosphoryl diester phosphodiesterase antigen suggested the patient was infected with a relapsing fever group Borrelia species.
Spatiotemporal Analysis of the Malaria Epidemic in Mainland China, 2004–2014Authors: Qiang Huang, Lin Hu, Qi-bin Liao, Jing Xia, Qian-ru Wang and Hong-Juan PengAvailable online: 01 May 2017More Less
The purpose of this study is to characterize spatiotemporal heterogeneities in malaria distribution at a provincial level and investigate the association between malaria incidence and climate factors from 2004 to 2014 in China to inform current malaria control efforts. National malaria incidence peaked (4.6/100,000) in 2006 and decreased to a very low level (0.21/100,000) in 2014, and the proportion of imported cases increased from 16.2% in 2004 to 98.2% in 2014. Statistical analyses of global and local spatial autocorrelations and purely spatial scan statistics revealed that malaria was localized in Hainan, Anhui, and Yunnan during 2004–2009 and then gradually shifted and clustered in Yunnan after 2010. Purely temporal clusters shortened to less than 5 months during 2012–2014. The two most likely clusters detected using spatiotemporal analysis occurred in Anhui between July 2005 and November 2007 and Yunnan between January 2010 and June 2012. Correlation coefficients for the association between malaria incidence and climate factors sharply decreased after 2010, and there were zero-month lag effects for climate factors during 2010–2014. Overall, the spatiotemporal distribution of malaria in China changed from relatively scattered (2004–2009) to relatively clustered (2010–2014). As the proportion of imported cases increased, the effect of climate factors on malaria incidence has gradually become weaker since 2011. Therefore, new warning systems should be applied to monitor resurgence and outbreaks of malaria in mainland China, and quarantine at borders should be reinforced to control the increasingly trend of imported malaria cases.
Severity of Pneumonia in Under 5-Year-Old Children from Developing Countries: A Multicenter, Prospective, Observational StudyAuthors: Thomas Bénet, Valentina Sanchez Picot, Shally Awasthi, Nitin Pandey, Ashish Bavdekar, Anand Kawade, Annick Robinson, Mala Rakoto-Andrianarivelo, Maryam Sylla, Souleymane Diallo, Graciela Russomando, Wilma Basualdo, Florence Komurian-Pradel, Hubert Endtz, Philippe Vanhems and Gláucia Paranhos-BaccalàAvailable online: 01 May 2017More Less
Pneumonia is the leading cause of death in children. The objectives were to evaluate the microbiological agents linked with hypoxemia in hospitalized children with pneumonia from developing countries, to identify predictors of hypoxemia, and to characterize factors associated with in-hospital mortality. A multicenter, observational study was conducted in five hospitals, from India (Lucknow, Vadu), Madagascar (Antananarivo), Mali (Bamako), and Paraguay (San Lorenzo). Children aged 2–60 months with radiologically confirmed pneumonia were enrolled prospectively. Respiratory and whole blood specimens were collected, identifying viruses and bacteria by real-time multiplex polymerase chain reaction (PCR). Microbiological agents linked with hypoxemia at admission (oxygen saturation < 90%) were analyzed by multivariate logistic regression, and factors associated with 14-day in-hospital mortality were assessed by bivariate Cox regression. Overall, 405 pneumonia cases (3,338 hospitalization days) were analyzed; 13 patients died within 14 days of hospitalization. Hypoxemia prevalence was 17.3%. Detection of human metapneumovirus (hMPV) and respiratory syncytial virus (RSV) in respiratory samples was independently associated with increased risk of hypoxemia (adjusted odds ratio [aOR] = 2.4, 95% confidence interval [95% CI] = 1.0–5.8 and aOR = 2.5, 95% CI = 1.1–5.3, respectively). Lower chest indrawing and cyanosis were predictive of hypoxemia (positive likelihood ratios = 2.3 and 2.4, respectively). Predictors of death were Streptococcus pneumoniae detection by blood PCR (crude hazard ratio [cHR] = 4.6, 95% CI = 1.5–14.0), procalcitonin ≥ 50 ng/mL (cHR = 22.4, 95% CI = 7.3–68.5) and hypoxemia (cHR = 4.8, 95% CI = 1.6–14.4). These findings were consistent on bivariate analysis. hMPV and RSV in respiratory samples were linked with hypoxemia, and S. pneumoniae in blood was associated with increased risk of death among hospitalized children with pneumonia in developing countries.
Performance of Real-Time Polymerase Chain Reaction Assays for the Detection of 20 Gastrointestinal Parasites in Clinical Samples from SenegalAvailable online: 01 May 2017More Less
Gastrointestinal parasite infections represent one of the biggest public health problems in the world. Therefore, appropriate innovative tools are needed for assessing interventions to control these infections. This study aims to compare the performance of real-time polymerase chain reaction (PCR) assays to microscopic examination for detection of intestinal parasites. A direct microscopic examination and stool concentration was performed on 98 stool samples from patients attending Senegalese hospitals. Negative microscopic control samples were also collected in Nice and Marseille (France). Species-specific primers/probes were used to detect 20 common gastrointestinal protozoans and helminths. Positive frequency and the sensitivity of each real-time PCR assay were compared with conventional microscopic examination. Real-time PCR was positive in 72 of 98 samples (73.5%), whereas microscopic examination was positive in 37 (37.7%) samples (P < 0.001). The real-time PCR assays were more sensitive than microscopy, with 57.4% (31/54) versus 18.5% (10/54), respectively, in the detection of parasites in asymptomatic patients (P < 0.05). In terms of polyparasitism, there were more coinfections detected by real-time PCR assays compared with microscopic methods (25.5% versus 3.06%). In comparison to parasite prevalence on individual samples, the results showed a perfect agreement (100%) between the two techniques for seven species, whereas discrepancies were observed for the others (agreement percentage varying from 64.2% to 98.9%). Real-time PCR appeared to be superior to microscopic examination for the detection of parasites in stool samples. This assay will be useful in diagnostic laboratories and in the field for evaluating the efficacy of mass drug administration programs.
Phosphoproteome of Toxoplasma gondii–Infected Host Cells Reveals Specific Cellular Processes Predominating in Different Phases of InfectionAuthors: Cheng He, Ai-Yuan Chen, Hai-Xia Wei, Xiao-Shuang Feng and Hong-Juan PengAvailable online: 01 May 2017More Less
The invasion of Toxoplasma gondii tachyzoites into the host cell results in extensive host cell signaling activation/deactivation that is usually regulated by the phosphorylation/dephosphorylation. To elucidate how T. gondii regulates host cell signal transduction, the comparative phosphoproteome of stable isotope labeling with amino acids in cell culture–labeled human foreskin fibroblast cells was analyzed. The cells were grouped (Light [L], Medium [M], and Heavy [H] groups) based on the labeling isotope weight and were infected with T. gondii for different lengths of time (L: 0 hour; M: 2 hours; and H: 6 hours). A total of 892 phosphoproteins were identified with 1,872 phosphopeptides and 1,619 phosphorylation sites. The M versus L comparison revealed 694 significantly regulated phosphopeptides (436 upregulated and 258 downregulated). The H versus L comparison revealed 592 significantly regulated phosphopeptides (146 upregulated and 446 downregulated). The H versus M comparison revealed 794 significantly regulated phosphopeptides (149 upregulated and 645 downregulated). At 2 and 6 hours post-T. gondii infection, the most predominant host cell reactions were cell cycle regulation and cytoskeletal reorganization, which might be required for the efficient invasion and multiplication of T. gondii. Similar biological process profiles but different molecular function categories of host cells infected with T. gondii for 2 and 6 hours, which suggested that the host cell processes were not affected significantly by T. gondii infection but emphasized some differences in specific cellular processes at this two time points. Western blotting verification of some significantly regulated phosphoprotein phosphorylation sites was consistent with the mass spectra data. This study provided new insights into and further understanding of pathogen–host interactions from the host cell perspective.
Rickettsia australis and Queensland Tick Typhus: A Rickettsial Spotted Fever Group Infection in AustraliaAuthors: Adam Stewart, Mark Armstrong, Stephen Graves and Krispin HajkowiczAvailable online: 01 May 2017More Less
Rickettsia australis, the etiologic agent of Queensland tick typhus (QTT), is increasingly being recognized as a cause of community-acquired acute febrile illness in eastern Australia. Changing human population demographics, climate change, and increased understanding of expanding vector distribution indicate QTT is an emerging public health threat. This review summarizes the epidemiology, pathogenesis, clinical features, treatment principles, and future directions of this disease. Increased recognition of QTT will enable consideration of and prompt treatment of R. australis infection by clinicians in Australia.
Seasonal Variation in the Epidemiology of Asymptomatic Plasmodium falciparum Infections Across Two Catchment Areas in Bongo District, GhanaAvailable online: 01 May 2017More Less
Understanding the epidemiology of asymptomatic Plasmodium falciparum infections is critical for countries to move toward malaria elimination. Using different methods for parasite detection, we evaluated how seasonality, spatial location, and other factors affect the age-specific epidemiology of asymptomatic malaria in Bongo District, Ghana. Asymptomatic prevalence by microscopy decreased significantly from 42.5% at the end of the wet to 27.5% at the end of the dry season (P < 0.001). Using the 18S rRNA polymerase chain reactions (PCRs), all microscopy-negative samples were screened and prevalence of submicroscopic infections also decreased significantly from the wet (55.4%) to the dry (20.7%) season (P < 0.001). Combining detection methods, 74.4% and 42.5% of the population in the wet and dry seasons, respectively, had evidence of a P. falciparum infection. Interestingly in those > 20 years of age, we found evidence of infection in 64.3% of the population in the wet and 27.0% in the dry season. Using both microscopy and PCR, the asymptomatic P. falciparum reservoir peaks at the end of the wet season and infections in all age groups constitute the reservoir of malaria infection. At the end of the wet season, spatial heterogeneity in the prevalence and density of P. falciparum infections was observed between the two catchment areas surveyed in Bongo District. These results indicate that if elimination is to succeed, interventions will need to target not just P. falciparum infections in children but also in adults, and be implemented toward the end of the dry season in this area of west Africa.
Conventional Wisdom Versus Actual Outcomes: Challenges in the Conduct of an Ebola Vaccine Trial in Liberia During the International Public Health EmergencyAvailable online: 01 May 2017More Less
Clinical trials are challenging endeavors. Planning and implementing an investigational vaccine trial in Liberia, in the midst of an Ebola virus disease (EVD) epidemic that World Health Organization classified a public health emergency of international concern, presented extraordinary challenges. Normally, years of preparation and a litany of tasks lay the groundwork for a successful, randomized, blinded, placebo-controlled trial focused on safety and efficacy. Difficult research settings, unpredictable events, and other unique circumstances can add complexity. The setting in Liberia was especially problematic due to an infrastructure still badly damaged following a lengthy civil war and a very fragile health-care system that was further devastated by the EVD outbreak. The Partnership for Research on Vaccines in Liberia I EVD vaccine trial was planned and implemented in less than 3 months by a Liberian and U.S. research partnership, and its Phase II substudy was fully enrolled 3 months later. Contrasting conventional wisdom with trial outcomes offers an opportunity to compare early assumptions, barriers encountered, and adaptive strategies used, with end results. Understanding what was learned can inform future trial responses when disease outbreaks, especially in resource-poor locations with minimal infrastructure, pose a significant threat to public health.
Burden and Seasonality of Viral Acute Respiratory Tract Infections Among Outpatients in Southern Sri LankaAvailable online: 01 May 2017More Less
In tropical and subtropical settings, the epidemiology of viral acute respiratory tract infections varies widely between countries. We determined the etiology, seasonality, and clinical presentation of viral acute respiratory tract infections among outpatients in southern Sri Lanka. From March 2013 to January 2015, we enrolled outpatients presenting with influenza-like illness (ILI). Nasal/nasopharyngeal samples were tested in duplicate using antigen-based rapid influenza testing and multiplex polymerase chain reaction (PCR) for respiratory viruses. Monthly proportion positive was calculated for each virus. Bivariable and multivariable logistic regression were used to identify associations between sociodemographic/clinical information and viral detection. Of 571 subjects, most (470, 82.3%) were ≥ 5 years of age and 53.1% were male. A respiratory virus was detected by PCR in 63.6% (N = 363). Common viral etiologies included influenza (223, 39%), human enterovirus/rhinovirus (HEV/HRV, 14.5%), respiratory syncytial virus (RSV, 4.2%), and human metapneumovirus (hMPV, 3.9%). Both ILI and influenza showed clear seasonal variation, with peaks from March to June each year. RSV and hMPV activity peaked from May to July, whereas HEV/HRV was seen year-round. Patients with respiratory viruses detected were more likely to report pain with breathing (odds ratio [OR] = 2.60, P = 0.003), anorexia (OR = 2.29, P < 0.001), and fatigue (OR = 2.00, P = 0.002) compared with patients with no respiratory viruses detected. ILI showed clear seasonal variation in southern Sri Lanka, with most activity during March to June; peak activity was largely due to influenza. Targeted infection prevention activities such as influenza vaccination in January–February may have a large public health impact in this region.
Knowledge and Prevention Practices Among U.S. Pregnant Immigrants from Zika Virus Outbreak AreasAuthors: Abbey B. Berenson, Ha N. Trinh, Jacqueline M. Hirth, Fangjian Guo, Erika L. Fuchs and Scott C. WeaverAvailable online: 01 May 2017More Less
We administered an anonymous survey to assess knowledge, attitudes, and prevention practices related to the Zika virus among pregnant women residing in Texas. Multivariate logistic regression models controlling for age, race/ethnicity, education, and number of years in the United States assessed differences between women born in outbreak areas (N = 390) versus those born in the United States (N = 249). Results demonstrated that most women wanted more information on the Zika virus and desired to obtain it from their physician. The majority did not know that the Zika virus could be spread through sex with an asymptomatic partner or how often those infected were symptomatic. Few women took precautions to avoid mosquito bites. Only 40% reported frequently using repellent; 21% stated that cost was problematic and almost half were concerned about use during pregnancy. Three-fourths stated they would agree to vaccination, if available. Compared with U.S.-born women, those born in outbreak areas were more likely to have already discussed the Zika virus with their doctor (adjusted odds ratio [aOR] = 1.86, 95% confidence interval [CI] = 1.27, 2.71) and identify microcephaly as the most common birth defect (aOR = 2.59, 95% CI = 1.78, 3.76). Moreover, women born in outbreak areas were less likely to desire to keep it a secret if they became infected (aOR = 0.47, 95% CI = 0.31, 0.71). This study found that, regardless of birthplace, pregnant women need more education on the Zika virus disease and assurance regarding the safety of using repellent during pregnancy. They also need financial assistance for repellent, especially if living in states where transmission by mosquitos has been reported.
Rift Valley Fever Seroprevalence in Coastal KenyaAvailable online: 01 May 2017More Less
Rift Valley fever virus (RVFV) causes severe disease in both animals and humans, resulting in significant economic and public health damages. The objective of this study was to measure RVFV seroprevalence in six coastal Kenyan villages between 2009 and 2011, and characterize individual-, household-, and community-level risk factors for prior RVFV exposure. Sera were tested for anti-RVFV IgG via enzyme-linked immunosorbent assay. Overall, 51 (1.8%; confidence interval [CI95] 1.3–2.3) of 2,871 samples were seropositive for RVFV. Seroprevalence differed significantly among villages, and was highest in Jego Village (18/300; 6.0%; CI95 3.6–9.3) and lowest in Magodzoni (0/248). Adults were more likely to be seropositive than children (P < 0.001). Seropositive subjects were less likely to own land or a motor vehicle (P < 0.01), suggesting exposure is associated with lower socioeconomic standing (P = 0.03). RVFV exposure appears to be low in coastal Kenya, although with some variability among villages.
The Cuba–United States Thaw: Building Bridges Through Science and Global HealthAvailable online: 01 May 2017More Less
Beginning in 2014, there has been significant progress in normalization of relations between Cuba and the United States. Herein, we discuss the history and recent progress in scientific collaboration between the two countries as well as the continued challenges. Science and global health diplomacy can be key tools in reestablishing a trusting and productive relationship of mutual and global benefit, bringing about better and healthier lives for people in both Cuba and the United States.
Zika Virus Disease in the Americas: A Storm in the MakingAuthors: Carissa Etienne, Thais dos Santos and Marcos A. EspinalAvailable online: 01 May 2017More Less
More than 700,000 cases of Zika virus (ZIKAV) disease have been officially reported to the Pan American Health Organization (PAHO) from 48 countries and territories of the Americas. The response led by the PAHO and partners suggests major lessons of this outbreak. A seemingly innocuous pathogen became the new villain, causing fear, economic losses and, most importantly, debilitating birth defects and neurological problems, reaffirming the well-known war principle of never to underestimate one's opponent. The ZIKAV tested public health capacities under the International Health Regulations, highlighting the need for continued investment in health security. Last but not least, the lack of appropriate tools was another reminder of the pressing need for innovative solutions to persistent problems. Latin America and the Caribbean have approximately 500 million persons living in areas at risk for transmission of ZIKAV. The fight against ZIKAV is not a 100-m race, but rather a marathon in which science and public health need to work hand in hand for the benefit of our peoples.
A Symptomatic Case of Hymenolepis diminuta Infection in an Urban-Dwelling Adult in MalaysiaAvailable online: 24 April 2017More Less
A case of Hymenolepis diminuta infection in a 43-year-old Malaysian male with persistent abdominal colicky pain is reported. Endoscopy revealed whitish worms in the lumen of the small intestine, which were identified as H. diminuta after microscopy. Patient was successfully treated with a single dose of praziquantel (25 mg/kg).
What is a Hotspot Anyway?Authors: Justin Lessler, Andrew S. Azman, Heather S. McKay and Sean M. MooreAvailable online: 24 April 2017More Less
The importance of spatial clusters, or "hotspots," in infectious disease epidemiology has been increasingly recognized, and targeting hotspots is often seen as an important component of disease-control strategies. However, the precise meaning of "hotspot" varies widely in current research and policy documents. Hotspots have been variously described as areas of elevated incidence or prevalence, higher transmission efficiency or risk, or higher probability of disease emergence. This ambiguity has led to confusion and may result in mistaken inferences regarding the best way to target interventions. We surveyed the literature on epidemiologic hotspots, examining the multitude of ways in which the term is used; and highlight the difference in the geographic scale of hotspots and the properties they are supposed to have. In response to the diversity in the term's usage, we advocate the use of more precise terms, such as "burden hotspot," "transmission hotspot," and "emergence hotspot," as well as explicit specification of the spatiotemporal scale of interest. Increased precision in terminology is needed to ensure clear and effective policies for disease control.
Analysis of Dengue Serotype 4 in Sri Lanka During the 2012–2013 Dengue EpidemicAuthors: Anna Uehara, Hasitha Aravinda Tissera, Champica K. Bodinayake, Ananda Amarasinghe, Ajith Nagahawatte, L. Gayani Tillekeratne, Jie Cui, Megan E. Reller, Paba Palihawadana, Sunethra Gunasena, Aruna Dharshan Desilva, Annelies Wilder-Smith, Duane J. Gubler, Christopher W. Woods and October M. SessionsAvailable online: 24 April 2017More Less
The four serotypes of dengue virus (DENV-1, -2, -3, and -4) have had a rapidly expanding geographic range and are now endemic in over 100 tropical and subtropical countries. Sri Lanka has experienced periodic dengue outbreaks since the 1960s, but since 1989 epidemics have become progressively larger and associated with more severe disease. The dominant virus in the 2012 epidemic was DENV-1, but DENV-4 infections were also commonly observed. DENV-4 transmission was first documented in Sri Lanka when it was isolated from a traveler in 1978, but has been comparatively uncommon since dengue surveillance began in the early 1980s. To better understand the molecular epidemiology of DENV-4 infections in Sri Lanka, we conducted whole-genome sequencing on dengue patient samples from two different geographic locations. Phylogenetic analysis indicates that all sequenced DENV-4 strains belong to genotype 1 and are most closely related to DENV-4 viruses previously found in Sri Lanka and those recently found to be circulating in India and Pakistan.
Experience with a Multinational, Secondary School Education Module with a Focus on Prevention of Virus InfectionsAvailable online: 24 April 2017More Less
Worldwide, virus infections are responsible for many diseases in terms of morbidity and mortality. Vaccinations and therapies are only available for relatively few virus infections and not always where they are needed. However, knowledge of transmission routes can prevent virus infection. In the context of this study, we measured the effects of a secondary school education module, named Viruskenner, on knowledge, attitude, and risk behavior as these relate to virus infections. A nonrandomized intervention study was conducted between April and August 2015 to assess the effect of this 2-month education module on knowledge, attitude, and behavior of 684 secondary school students in the Netherlands, Suriname, and Indonesia. For the Netherlands, a control group of a further 184 students was added. Factor analysis was performed on questions pertaining to attitude and behavior. Comparative analyses between pre- and posttest per country were done using multiple linear regression, independent sample T-tests, and one-way analysis of variance. These showed a significant increase in knowledge about virus infections and the prevention of infectious diseases among the Dutch and Surinamese groups, whereas a trend of increased knowledge was evident among the Indonesian participants. The Dutch control group showed an overall decrease in knowledge. Regression analyses showed that there was a significant interaction effect between participation and time on knowledge, attitude, and awareness and behavior and risk infection. Attitudes improved significantly in the intervention group. Pearson correlation coefficients between knowledge, attitude, and behavior were found to be positive.
Extensive Resistance of Anopheles sinensis to Insecticides in Malaria-Endemic Areas of Hainan Province, ChinaAuthors: Ding-wei Sun, Guang-ze Wang, Lin-hai Zeng, Shan-gan Li, Chang-hua He, Xi-min Hu and Shan-qing WangAvailable online: 24 April 2017More Less
Anopheles sinensis is one of the major malaria vectors and among the dominant species in Hainan Province, China. The resistance of An. sinensis to insecticides is an important threat to malaria control. However, few reports on insecticide resistance of An. sinensis were reported in this area. Eight districts in Hainan Province were selected as the study areas. Insecticide susceptibility bioassays were tested on wild-caught female mosquitoes of An. sinensis to 4% dichlorodiphenyltrichloroethane (DDT), 0.05% deltamethrin, and 5% malathion by using the World Health Organization standard resistance tube assay procedure. All the tested An. sinensis mosquitoes demonstrated resistance to 4% DDT, with less than 72% mortality in the standard assay. The populations from Baisha and Qiongzhong demonstrated possible resistance to 0.05% deltamethrin, with 94–95% mortality, whereas the populations from other districts demonstrated resistance to 0.05% deltamethrin in the standard assay. The populations from Baisha, Qiongzhong, and Dongfang demonstrated susceptibility but the populations from other districts demonstrated resistance. These results facilitate the improvement of effective control strategies for malaria vector mosquitoes in Hainan.
Regional Differences in the Prevalence of Major Opportunistic Infections Among Antiretroviral-Naïve Human Immunodeficiency Virus Patients in Japan, Northern Thailand, Northern Vietnam, and the PhilippinesAvailable online: 24 April 2017More Less
To identify regional differences in the distribution of opportunistic infections (OIs) among human immunodeficiency virus (HIV)-infected patients in Asia, the medical records of antiretroviral therapy (ART)-naïve patients who attended the following tertiary hospitals from 2003 to 2011 were reviewed: Nagoya Medical Center (NMC, Nagoya, Japan), Lampang Hospital (LPH, Lampang, northern Thailand), Bach Mai Hospital (BMH, Hanoi, northern Vietnam), and Philippine General Hospital (PGH, Manila, Philippines). Logistic regression analyses were performed to identify associations between country of origin and risk of major OIs. In total, 1,505 patients were included: NMC, N = 365; LPH, N = 442; BMH, N = 384; and PGH, N = 314. The median age was 32 years, and 73.3% of all patients were male. The median CD4 count was 200 cells/μL. Most patients at NMC and PGH were men who have sex with men. Injection drug users were most common at BMH (35.7%). Mycobacterium tuberculosis (TB) was most common at PGH (N = 75) but was rare at NMC (N = 4). Pneumocystis pneumonia (PCP) prevalence was highest at NMC (N = 74) and lowest at BMH (N = 13). Multivariable logistic regression showed increased odds of TB at PGH (adjusted odds ratio [aOR] = 42.2, 95% confidence interval [CI] = 14.6–122.1), BMH (aOR = 12.6, CI = 3.9–40.3), and LPH (aOR = 6.6, CI = 2.1–21.1) but decreased odds of PCP at BMH (aOR = 0.1, CI = 0.04–0.2) and LPH (aOR = 0.2, CI = 0.1–0.4) compared with those at NMC. The cryptococcosis risk was increased at LPH (aOR = 6.2, CI = 0.9–41.0) compared with that at NMC. Cytomegalovirus (CMV) retinitis prevalences were similar in all countries. OI prevalence remained high among ART-naïve patients in our cohort. The risks of TB, PCP, and cryptococcosis, but not CMV retinitis, differed between countries. Improved early HIV detection is warranted.
Optimizing Household Chlorination Marketing Strategies: A Randomized Controlled Trial on the Effect of Price and Promotion on Adoption in HaitiAvailable online: 24 April 2017More Less
Household water treatment can reduce diarrheal morbidity and mortality in developing countries, but adoption remains low and supply is often unreliable. To test effects of marketing strategies on consumers and suppliers, we randomized 1,798 households in rural Haiti and collected data on purchases of a household chlorination product for 4 months. Households received randomly selected prices ($0.11–$0.56 per chlorine bottle), and half received monthly visits from sales agents. Each $0.22 drop in price increased purchases by 0.10 bottles per household per month (P < 0.001). At the mean price, each 1% drop in price increased purchases by 0.45% (elasticity = 0.45). There is suggestive evidence that household visits by some sales agents increased purchases at mid-range prices; however, the additional revenue did not offset visit cost. Choosing the lowest price and conducting visits maximizes chlorine use, whereas slightly raising the retail price and not conducting visits maximizes cost recovery. For the equivalent cost, price discounts increase purchases 4.2 times as much as adding visits at the current retail price. In this context, price subsidies may be a more cost-effective use of resources than household visits, though all marketing strategies tested offer cost-effective ways to achieve incremental health impact. Decisions about pricing and promotion for health products in developing countries affect health impact, cost recovery, and cost-effectiveness, and tradeoffs between these goals should be made explicit in program design.
Susceptibility of Clinical Isolates of Burkholderia pseudomallei to a Lipid A Biosynthesis InhibitorAvailable online: 24 April 2017More Less
Burkholderia pseudomallei is the causative agent of melioidosis, a serious infection associated with high mortality and relapse. Current antimicrobial therapy using ceftazidime (CAZ) is often ineffective. Inhibitors of LpxC, the enzyme responsible for lipid A biosynthesis, have potential antimicrobial activity against several Gram-negative bacteria in vivo, but their activity against B. pseudomallei is unclear. Herein, we investigated the susceptibility of B. pseudomallei clinical isolates to LpxC-4, an LpxC inhibitor, and LpxC-4 in combination with CAZ. Time-kill assays for bactericidal activity were conducted for B. pseudomallei K96243, revealing growth inhibition and bactericidal effect at LpxC-4 concentrations of 2 μg/mL and 4 μg/mL, respectively. No significant synergistic effect was observed with the combination of LpxC-4 and CAZ. LpxC-4 susceptibility was tested on three groups of clinical isolates: 1) CAZ- and trimethoprim–sulfamethoxazole (SXT)–susceptible (N = 71), 2) CAZ-resistant (N = 14), and 3) SXT-resistant (N = 23) isolates, by broth microdilution. The minimum concentration of LpxC-4 required to inhibit the growth of 90% of organisms was 2 μg/mL for all isolates. The median minimum inhibitory concentration of both the CAZ/SXT-susceptible and CAZ-resistant groups was 1 μg/mL (interquartile range [IQR] = 1–2 μg/mL), compared with 2 μg/mL (IQR = 2–4 μg/mL) for the SXT-resistant group. Cell morphology was observed after drug exposure by immunofluorescent staining, and a change from rod-shaped to cell wall–defective spherical cells was observed in surviving bacteria. LpxC-4 is a potent bactericidal agent against B. pseudomallei and warrants further testing as a new antibiotic to treat melioidosis.
Molecular Markers for Sensitive Detection of Plasmodium falciparum Asexual Stage Parasites and Their Application in a Malaria Clinical TrialAvailable online: 24 April 2017More Less
Plasmodium falciparum parasite life stages respond differently to antimalarial drugs. Sensitive stage-specific molecular assays may help to examine parasite dynamics at microscopically detectable and submicroscopic parasite densities in epidemiological and clinical studies. In this study, we compared the performance of skeleton-binding protein 1 (SBP1), ring-infected erythrocyte surface antigen, Hyp8, ring-exported protein 1 (REX1), and PHISTb mRNA for detecting ring-stage trophozoite-specific transcripts using quantitative reverse transcriptase polymerase chain reaction. Markers were tested on tightly synchronized in vitro parasites and clinical trial samples alongside established markers of parasite density (18S DNA and rRNA) and gametocyte density (Pfs25 mRNA). SBP1 was the most sensitive marker but showed low-level expression in mature gametocytes. Novel markers REX1 and PHISTb showed lower sensitivity but higher specificity for ring-stage trophozoites. Using in vivo clinical trial samples from gametocyte-negative patients, we observed evidence of persisting trophozoite transcripts for at least 14 days postinitiation of treatment. It is currently not clear if these transcripts represent viable parasites that may have implications for clinical treatment outcome or transmission potential.
Bidirectional Exchange in Global Health: Moving Toward True Global Health PartnershipAuthors: Gitanjili Arora, Christiana Russ, Maneesh Batra, Sabrina Butteris, Jennifer Watts and Michael PittAvailable online: 24 April 2017More Less
Although there has been rapid growth in global health educational experiences over the last two decades, the flow of learners remains overwhelmingly one directional; providers from high-resourced settings travel to limited-resourced environments to participate in clinical care, education, and/or research. Increasingly, there has been a call to promote parity in partnerships, including the development of bidirectional exchanges, where trainees from each institution travel to the partner's setting to learn from and teach each other. As global health educators and steering committee members of the Association of Pediatric Program Directors Global Health Pediatric Education Group, we endorse the belief that we must move away from merely sending learners to international partner sites and instead become true global health partners offering equitable educational experiences. In this article, we summarize the benefits, review common challenges, and highlight solutions to hosting and providing meaningful global health experiences for learners from limited-resourced partner institutions to academic health centers in the United States.
Experimental Infection with and Maintenance of Cell Fusing Agent Virus (Flavivirus) in Aedes aegyptiAvailable online: 24 April 2017More Less
During the past two decades, there has been a dramatic increase in the recognition and characterization of novel insect-specific flaviviruses (ISFVs). Some of these agents are closely related to important mosquito-borne flavivirus pathogens. Results of experimental studies suggest that mosquitoes and mosquito cell cultures infected with some ISFVs are refractory to superinfection with related flavivirus pathogens; and it has been proposed that ISFVs potentially could be used to alter the vector competence of mosquitoes and reduce transmission of specific flavivirus pathogens, such as dengue, West Nile, or Zika viruses. In order for an ISFV to be used in such a control strategy, the virus would have to be vertically transmitted at a high rate in the target vector population to insure its continued maintenance. This study compared the vertical transmission rates of an ISFV, cell fusing agent virus (CFAV), in two Aedes aegypti colonies: one naturally infected with CFAV and the other experimentally infected but previously free of the virus. CFAV filial infection rates in progeny of female mosquitoes from both colonies were > 90% after two generations of selection, indicating the feasibility of introducing an ISFV into a mosquito population. This and other considerations for evaluating the feasibility of using ISFVs as an arbovirus control strategy are discussed.
Endemic Amebiasis in Australia: Implications for Residents, Travelers, and CliniciansAuthors: Simon Smith, Gael E. Phillips, William J. H. McBride and Josh HansonAvailable online: 24 April 2017More Less
Entamoeba histolytica is considered endemic in Australia; however, cases are rare, occurring almost exclusively in high-risk individuals. We describe a series of locally acquired, complicated cases in low-risk individuals from Far North Queensland in whom the diagnosis was delayed. Amebiasis may pose a greater local threat than is currently recognized.
Cognitive Outcomes and Psychiatric Symptoms of Retinopathy-Positive Cerebral Malaria: Cohort Description and Baseline ResultsAvailable online: 24 April 2017More Less
Cerebral malaria (CM) is a common cause of death and disability among children in sub-Saharan Africa. Many prior studies of neuropsychiatric morbidity have been limited by a cross-sectional design or a short duration of follow-up. Most have included subjects who may have presented with coma due to a disease process other than CM. No studies have assessed the relationship between magnetic resonance imaging (MRI) findings and long-term outcomes. The cognitive outcomes and psychiatric symptoms of retinopathy-positive CM cohort is the first large (N = 221) prospectively recruited cohort of stringently defined cases of CM and hospital-based, age-matched, non-CM controls in whom cognitive and psychiatric outcomes are assessed with standardized measures annually for up to 5 years. We report baseline characteristics of the cohort and outcomes at 1 month. At enrollment, CM cases were more likely to come from families with fewer socioeconomic resources and to have health characteristics that increase risk for malaria. In children younger than 5 years, cases were delayed in motor, language, and social development by approximately 6 months, compared with controls. More significant delays occurred in those with MRI abnormalities at the 1-month follow-up visit. There were no differences between cases and controls in inhibitory self-control, nor in cognitive function in children ≥ 5 years of age. The latter finding may be related to the smaller sample size, case-control imbalance in socioeconomic status, or the use of cognitive and behavioral assessments that are less culturally appropriate to this population. Continued follow-up will help determine predictors of long-term outcomes.
Development of a Real-Time Reverse Transcription Polymerase Chain Reaction for O'nyong-nyong Virus and Evaluation with Clinical and Mosquito Specimens from KenyaAvailable online: 24 April 2017More Less
O'nyong-nyong virus (ONNV), an alphavirus closely related to chikungunya virus (CHIKV), has been the documented cause of two large outbreaks in east Africa; however, little is known about the contribution of ONNV to cases of acute febrile illness during interepidemic periods. An ONNV real-time reverse transcription polymerase chain reaction (rRT-PCR) was developed and evaluated using clinical and mosquito pool samples. The ONNV rRT-PCR linear range extended from 8.0 to 2.0 log10 copies/μL, and the lower limit of 95% detection was 22.4 copies/μL. No cases of ONNV infection were identified in serum from 385 Kenyan children who presented with an acute febrile illness. Additionally, ONNV was not detected in 120 mosquito pools collected in coastal and western Kenya. The ONNV rRT-PCR demonstrated good analytical sensitivity when performed in monoplex or as a component of an ONNV–CHIKV duplex assay. This assay should provide a useful diagnostic for the detection of ONNV in surveillance studies.
Malaria-Related Hospitalizations in the United States, 2000–2014Available online: 24 April 2017More Less
Few data are available on the burden of malaria hospitalization in the United States. Study of malaria using hospital-based data can better define the impact of malaria and help inform prevention efforts. U.S. malaria cases identified from hospitalization discharge records in the 2000–2014 Nationwide Inpatient Sample were examined. Frequencies and population rates were reported by demographics, infecting species, clinical, financial, institutional, geographic, and seasonal characteristics, and disparities were identified. Time trends in malaria cases were assessed using negative binomial regression. From 2000 to 2014, there were an estimated 22,029 malaria-related hospitalizations (4.88 per 1 million population) in the United States, including 182 in-hospital deaths and 4,823 severe malaria cases. The rate of malaria-related hospitalizations did not change significantly over the study period. The largest number of malaria-related hospitalizations occurred in August. Malaria-related hospitalizations occurred disproportionately among patients who were male, black, or 25–44 years of age. Plasmodium falciparum accounted for the majority of malaria-related hospitalizations. On average, malaria patients were hospitalized for 4.36 days with charges of $25,789. Patients with a malaria diagnosis were more often hospitalized in the Middle Atlantic and South Atlantic census divisions, urban teaching, private not-for-profit, and large-bed-size hospitals. Malaria imposes a substantial disease burden in the United States. Enhanced primary and secondary prevention measures, including strategies to increase the use of pretravel consultations and prompt diagnosis and treatment are needed.
Climate Influence on Emerging Risk Areas for Rift Valley Fever Epidemics in TanzaniaAuthors: Clement N. Mweya, Leonard E. G. Mboera and Sharadhuli I. KimeraAvailable online: 17 April 2017More Less
Rift Valley Fever (RVF) is a climate-related arboviral infection of animals and humans. Climate is thought to represent a threat toward emerging risk areas for RVF epidemics globally. The objective of this study was to evaluate influence of climate on distribution of suitable breeding habitats for Culex pipiens complex, potential mosquito vector responsible for transmission and distribution of disease epidemics risk areas in Tanzania. We used ecological niche models to estimate potential distribution of disease risk areas based on vectors and disease co-occurrence data approach. Climatic variables for the current and future scenarios were used as model inputs. Changes in mosquito vectors' habitat suitability in relation to disease risk areas were estimated. We used partial receiver operating characteristic and the area under the curves approach to evaluate model predictive performance and significance. Habitat suitability for Cx. pipiens complex indicated broad-scale potential for change and shift in the distribution of the vectors and disease for both 2020 and 2050 climatic scenarios. Risk areas indicated more intensification in the areas surrounding Lake Victoria and northeastern part of the country through 2050 climate scenario. Models show higher probability of emerging risk areas spreading toward the western parts of Tanzania from northeastern areas and decrease in the southern part of the country. Results presented here identified sites for consideration to guide surveillance and control interventions to reduce risk of RVF disease epidemics in Tanzania. A collaborative approach is recommended to develop and adapt climate-related disease control and prevention strategies.
A Fatal Hantavirus Pulmonary Syndrome Misdiagnosed as Dengue: An Investigation Into the First Reported Case in Rio de Janeiro State, BrazilAuthors: Renata Carvalho de Oliveira, Alexandro Guterres, Bernardo Rodrigues Teixeira, Jorlan Fernandes, João Marcos Penna Júnior, Reynaldo de Jesus Oliveira Júnior, Liana Strecht Pereira, João Bosco Júnior, Patrícia Soares Meneguete, Cristina Maria Giordano Dias, Cibele Rodrigues Bonvicino, Paulo Sérgio D'Andrea and Elba Regina Sampaio de LemosAvailable online: 17 April 2017More Less
We report the results of an investigation into a fatal case of hantavirus pulmonary syndrome (HPS) in Rio de Janeiro State, Brazil, where the disease had not been reported previous to 2015. Following the notification of an HPS case, serum samples were collected from the household members and work contacts of the HPS patient and tested for antibody to hantaviruses. Seroprevalence of 22% (10/45) was indicated for hantavirus out of 45 human samples tested. Blood and tissue samples were collected from 72 rodents during fieldwork to evaluate the prevalence of hantavirus infection, by using enzyme-linked immunosorbent assay IgG, and to characterize the rodent hantavirus reservoir(s), by reverse transcription polymerase chain reaction and sequencing. Antibody prevalence was 6.9%. The circulation of a single genotype, the Juquitiba hantavirus, carried by two rodent species, black-footed pigmy rice rat (Oligoryzomys nigripes) and cursor grass mouse (Akodon cursor), was shown by analysis of the nucleotide sequences of the S segment. Juquitiba hantavirus circulates in rodents of various species, but mainly in the black-footed pigmy rice rat. HPS is a newly recognized clinical entity in Rio de Janeiro State and should be considered in patients with febrile illness and acute respiratory distress.
Seroprevalence of Toxoplasma gondii Infection in Refugee and Migrant Pregnant Women Along the Thailand–Myanmar BorderAvailable online: 17 April 2017More Less
Toxoplasma gondii primary infection in pregnancy is associated with poor obstetric outcomes. This study aimed to determine the seroprevalence of Toxoplasma infection in pregnant migrant and refugee women from Myanmar attending antenatal care in Thailand. A random selection of 199 residual blood samples from first antenatal screen in 2014–2015 was tested for Toxoplasma IgG and IgM antibodies. Seroprevalence of Toxoplasma infection was 31.7% (95% confidence interval = 25.6–38.4). Avidity testing in the three positive IgM cases indicated all were past infections. Multiparity (≥ 3 children) was significantly associated with higher Toxoplasma seropositivity rates. Seroprevalence of T. gondii infection in this pregnant population is similar to the only other report from Myanmar, and was significantly associated with multiparity. Toxoplasma infection is important in pregnant women. Nevertheless, in this marginalized population, this infection may be given less priority, due to resource constraints in providing the most basic components of safe motherhood programs.
Disseminated Talaromyces (Penicillium) marneffei and Mycobacterium tuberculosis Coinfection in a Japanese Patient with Acquired Immunodeficiency SyndromeAuthors: Shuji Hatakeyama, Takeshi Yamashita, Toshiyaku Sakai and Katsuhiko KameiAvailable online: 17 April 2017More Less
Talaromyces marneffei is a dimorphic fungus endemic mainly in southeast and south Asia. It causes severe mycosis, usually in immunocompromised individuals, such as those with human immunodeficiency virus (HIV) infection. Concomitant infection with T. marneffei and other opportunistic pathogens is plausible because the majority of T. marneffei infections occur in patients with advanced HIV infection. Nonetheless, coinfection in the same site has rarely been reported, and poses a considerable diagnostic and therapeutic challenge. We report the case of an HIV-infected Japanese patient who had lived in Thailand for 6 years. The patient developed T. marneffei and Mycobacterium tuberculosis coinfection, and both pathogens were isolated from the same sites: a blood specimen and a lymph node aspirate. Clinicians should be aware of concomitant infection with T. marneffei and other pathogens in patients with advanced HIV disease who are living in or who have visited endemic areas.
Analysis of Clinical and Laboratory Alterations Related to Dengue Case Severity: Comparison Between Serotypes 2 and 4 in BrazilAuthors: Nieli Rodrigues da Costa Faria, Victor Edgar Fiestas Solorzano, Luiz José de Souza, Rita Maria Ribeiro Nogueira, Fernanda de Bruycker-Nogueira, Thaís Chouin-Carneiro, Jaqueline Bastos Santos Simões, Monique da Rocha Queiroz Lima, Luzia Maria de Oliveira Pinto, Claire Fernandes Kubelka, Manoela Heringer, Elzinandes Leal de Azeredo and Flavia Barreto dos SantosAvailable online: 10 April 2017More Less
The increase in severe dengue (SD) cases has caused great impact on public health and has concerned authorities of countries where the disease is endemic and epidemics reach high proportions. The recognition of progression signs of this severe disease during the initial febrile phase can be difficult, since the symptoms are often indistinguishable from other febrile diseases. The aim of this study was to evaluate the clinical manifestations and laboratory findings in patients from two dengue outbreaks and their association with the disease. The study was conducted in patients (n = 153) with signs and symptoms consistent with dengue occurred during two distinct epidemics, 2010 and 2013, in the city of Campos dos Goytacazes, Rio de Janeiro, Brazil. According to the 2009 World Health Organization criteria, patients were classified as dengue without warning signs ([DwoWS] 60.6%, 57/94), dengue with warning signs ([DwWS] 30.9%, 29/94), and SD (4.25%, 4/94). Patients with DwWS/SD presented lower platelet and leukocyte counts and higher transaminase levels when compared with the DwoWS ones. Interestingly, patients from the epidemic of 2010 caused by dengue virus 2 (DENV-2) had lower platelet counts than patients of the 2013 epidemic caused by DENV-4. Furthermore, plasma leakage, gastrointestinal bleeding, and pleural effusion, hallmarks for a more severe disease, were also more frequently observed in those cases. Although previous studies may have extensively reported the wide range of the clinical aspects of dengue, the characterization of DENV-4 is desirable considering the burden of the disease during epidemics, especially for the health units and hospitals performing patient's management.
Severe Fever with Thrombocytopenia Syndrome Virus in Humans, Domesticated Animals, Ticks, and Mosquitoes, Shaanxi Province, ChinaAuthors: Huaiyu Tian, Pengbo Yu, Gerardo Chowell, Shen Li, Jing Wei, Hui Tian, Wen Lv, Zongqi Han, Jing Yang, Shanqian Huang, Sen Zhou, John S. Brownstein, Jingjun Wang and Bing XuAvailable online: 10 April 2017More Less
The first human infection with severe fever with thrombocytopenia syndrome virus (SFTSV) was detected in Shaanxi Province, China, in 2013, although the virus had been reported in 13 other provinces of China since 2010. We collected and analyzed a total of 4,011 samples, including 936 human serum samples, 155 animal serum samples, 895 ticks, 1,950 mosquitoes, 30 midges, and 20 sandflies. SFTSV antibodies were found in 44 human samples (4.7%) with no significant differences between males and females or across counties. The incidence rate of severe fever with thrombocytopenia syndrome was significantly higher among individuals 20–60 years of age. Moreover, SFTSV-specific antibodies were detected in goats (66.7%), cattle (13.2%), and dogs (15.0%), but not in pigs (0%). We detected the virus in Haemaphysalis concinna ticks with a prevalence rate of 21.3% (17/80 pools). All mosquito, midge, and sandfly samples were negative for SFTSV. These results support wide circulation of the virus in western China. Haemaphysalis concinna ticks may serve as a novel SFTSV vector, and the role of these ticks requires further investigation.
Infective Endocarditis in French West Indies: A 13-Year Observational StudyAuthors: Elisabeth Fernandes, Claude Olive, Jocelyn Inamo, François Roques, André Cabié and Patrick HochedezAvailable online: 10 April 2017More Less
We conducted an observational study to describe the characteristics of infective endocarditis (IE) in French West Indies (FWI) and to identify variables associated with in-hospital case fatality. The records of the patients admitted for IE to the University Hospital of Martinique between 2000 and 2012 were collected using an electronic case report form. Only Duke-Li definite cases were considered for this analysis. Variables associated with in-hospital mortality were tested using univariate logistic regression analysis. The analysis included 201 patients (median age 58 years, sex ratio: two males to one female). There was no previously known heart disease in 45.8%, a prosthetic valve in 21.4%, and previously known native valve disease in 32.8% of the cases. Community-acquired IE represented 59.7% of all cases, health-care-associated IE represented 38.3% and injection-drug-use-acquired IE represented 1.5%. Locations of IE were distributed as follows: 42.3% were mitral valve IE, 34.8% were aortic valve IE, and 7% were right-sided IE. Microorganisms recovered from blood cultures included 30.4% streptococci, 28.9% staphylococci, and 5% enterococci. Blood cultures were negative in 20.9% of the cases. Surgical treatment was performed in 53% of the patients. In-hospital case fatality rate was 19%. Advanced age, Staphylococcus aureus IE, and health-care-associated IE were associated with in-hospital case fatality. The epidemiological and microbiological profile of IE in FWI is in between those observed in developed countries and developing countries: patients were younger, blood cultures were more frequently negative, and IE due to group D streptococci and enterococci were less common than in industrialized countries.
Serologic Monitoring of Public Health Interventions Against Strongyloides stercoralisAvailable online: 10 April 2017More Less
Northwestern Argentina is endemic for soil-transmitted helminths, and annual deworming programs are carried out in prioritized areas. High prevalence of Strongyloides stercoralis was reported in this area; therefore, control programs including ivermectin are being evaluated. The NIE-enzyme linked immunosorbent assay (ELISA) was used for this purpose. In this community trial, two groups of patients, classified according to housing and living conditions were evaluated. Simultaneous with baseline survey, Group 1 was moved to new households with access to improved water and sanitation facilities (W and S), where deworming (MDA, massive drug administration) took place within 1 month; whereas Group 2 received MDA but remained living with unimproved W and S. The mean time interval between baseline and the follow-up was 331 days for Group 1 and 508 for Group 2. Anti-NIE levels were measured for each individual before and after interventions and follow-up optical density (OD) ratios were calculated to quantify the variation. A significant decrease of the anti-NIE levels between baseline and follow-up was observed in both groups. Nonetheless, the number of patients that achieved the cure criteria (OD ratio < 0.6) was higher in Group 1 than Group 2 with values of 72.7% (24/33) and 45.0% (18/40), respectively (P = 0.0197). Our results support the conclusion that a combined intervention including deworming and improvements in life conditions is more effective, in terms of the proportion of subjects cured than deworming alone. Furthermore, we found that NIE-ELISA is a useful test for assessing the response to treatment and to evaluate the outcome of control intervention programs.
Factors Associated with the Duration of Moderate-to-Severe Diarrhea Among Children in Rural Western Kenya Enrolled in the Global Enteric Multicenter Study, 2008–2012Authors: Katharine A. Schilling, Richard Omore, Gordana Derado, Tracy Ayers, Ben J. Ochieng, Tamer H. Farag, Dilruba Nasrin, Sandra Panchalingam, James P. Nataro, Karen L. Kotloff, Myron M. Levine, Joseph Oundo, Michelle B. Parsons, Cheryl Bopp, Kayla Laserson, Christine E. Stauber, Richard Rothenberg, Robert F. Breiman, Ciara E. O'Reilly and Eric D. MintzAvailable online: 10 April 2017More Less
Diarrheal disease is a leading cause of death among young children worldwide. As rates of acute diarrhea (AD; 1–6 days duration) have decreased, persistent diarrhea (PD; > 14 days duration) accounts for a greater proportion of the diarrheal disease burden. We describe factors associated with the duration of moderate-to-severe diarrhea in Kenyan children < 5 years old enrolled in the Global Enteric Multicenter Study. We found 587 (58%) children experienced AD, 360 (35%) had prolonged acute diarrhea (ProAD; 7–13 days duration), and 73 (7%) had PD. We constructed a Cox proportional hazards model to identify factors associated with diarrheal duration. Risk factors independently associated with longer diarrheal duration included infection with Cryptosporidium (hazard ratio [HR]: 0.868, P = 0.035), using an unimproved drinking water source (HR: 0.87, P = 0.035), and being stunted at enrollment (HR: 0.026, P < 0.0001). Diarrheal illness of extended duration appears to be multifactorial; given its association with adverse health and development outcomes, effective strategies should be implemented to reduce the duration and severity of diarrheal illness. Effective treatments for Cryptosporidium should be identified, interventions to improve drinking water are imperative, and nutrition should be improved through exclusive breastfeeding in infants ≤ 6 months and appropriate continued feeding practices for ill children.
Association of Interferon-γ Receptor-1 Gene Polymorphism with Nontuberculous Mycobacterial Lung Infection Among Iranian Pulmonary PatientsAuthors: Poopak Farnia, Jalaledin Ghanavi, Shima Saif, Parissa Farnia and Ali Akbar VelayatiAvailable online: 10 April 2017More Less
Nontuberculous mycobacteria (NTM) cause significant pulmonary infections in humans. Researchers have reported an association between interferon-gamma receptor-1 (IFN-γR1 or IFNGR1) deficiency and susceptibility to NTM, but the relevance of polymorphism within these genes is not yet clear. In this study, a single nucleotide polymorphism (SNP), T to C, at position-56 in NTM pulmonary patients was investigated. Molecular identification of Mycobacterium isolates was performed with hsp65 genes using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). Then, the host genomic DNA from confirmed NTM patients (N = 80) and control subjects (N = 80) were screened for SNPs of IFNGR1 (T-56C) by PCR-RFLP. The results indicated that NTM patients had higher TC (26/80; 32.5%) or CC (46/80; 57.5%) genotypes in comparison with control groups (TC genotypes [22/80, 27.5%]; CC genotypes [6/80, 7.5%]) (P < 0.05). In this regard, all the patients infected with rapid-growing Mycobacterium (RGM, i.e., Mycobacterium chelonae and Mycobacterium fortuitum) had CC genotypes (100%). In contrary, only 50.7% (35/69) of infected patients with slow-growing Mycobacterium (i.e., Mycobacterium simiae, Mycobacterium kansasii, and Mycobacterium avium-intracellulare) had CC genotypes. Thus, patients with CC mutation in IFNGR1 at position-56 are more likely to develop RGM infection. In overall, there is a significant association between SNP of IFNGR1 at position-56 and susceptibility to NTM infection. Based on these data, we propose SNP of IFNGR1 at position-56 as a suitable "biomarker" for identifying populations at higher risk of infection.
Risk Factors for Podoconiosis: Kamwenge District, Western Uganda, September 2015Available online: 10 April 2017More Less
Podoconiosis, a noninfectious elephantiasis, is a disabling neglected tropical disease. In August 2015, an elephantiasis case-cluster was reported in Kamwenge District, western Uganda. We investigated to identify the disease's nature and risk factors. We defined a suspected podoconiosis case as onset in a Kamwenge resident of bilateral asymmetrical lower limb swelling lasting ≥ 1 month, plus ≥ 1 of the following associated symptoms: skin itching, burning sensation, plantar edema, lymph ooze, prominent skin markings, rigid toes, or mossy papillomata. A probable case was a suspected case with negative microfilaria antigen immunochromatographic card test (ruling out filarial elephantiasis). We conducted active case-finding. In a case–control investigation, we tested the hypothesis that the disease was caused by prolonged foot skin exposure to irritant soils, using 40 probable case-persons and 80 asymptomatic village control-persons, individually matched by age and sex. We collected soil samples to characterize irritants. We identified 52 suspected (including 40 probable) cases with onset from 1980 to 2015. Prevalence rates increased with age; annual incidence (by reported onset of disease) was stable over time at 2.9/100,000. We found that 93% (37/40) of cases and 68% (54/80) of controls never wore shoes at work (Mantel–Haenszel odds ratio [ORMH] = 7.7; 95% [confidence interval] CI = 2.0–30); 80% (32/40) of cases and 49% (39/80) of controls never wore shoes at home (ORMH = 5.2; 95% CI = 1.8–15); and 70% (27/39) of cases and 44% (35/79) of controls washed feet at day end (versus immediately after work) (OR = 11; 95% CI = 2.1–56). Soil samples were characterized as rich black-red volcanic clays. In conclusion, this reported elephantiasis is podoconiosis associated with prolonged foot exposure to volcanic soil. We recommended foot hygiene and universal use of protective shoes.
Chikungunya and Zika Virus Cases Detected Against a Backdrop of Endemic Dengue Transmission in VietnamAvailable online: 10 April 2017More Less
Between 2010 and 2014, four chikungunya and two Zika virus infections were identified among 8,105 febrile children in southern Vietnam. Zika viruses were linked to French Polynesian strains, chikungunya to Cambodian strains. Against a backdrop of endemic dengue transmission, chikungunya and Zika present an additional arboviral disease burden in Vietnam.
Microcephaly in Twins Due to the Zika VirusAvailable online: 10 April 2017More Less
Recent studies have demonstrated an association between congenital Zika virus (ZIKV) infection and microcephaly; however, to date, there have been no reports on the consequences of ZIKV infection on fetuses in twin pregnancies. Herein, we reported on the first case of a monochorionic diamniotic (MCDA) twin pregnancy having ZIKV-related microcephaly. Our findings suggested that, in an MCDA twin pregnancy, the ZIKV may cause infection in both fetuses, resulting in severe abnormalities in the central nervous system due to neural cell destruction and the disruption of the normal development processes of the brain. This case report and other similar twin cases may help to understand the pathogenesis and to confirm the etiology of ZIKV as a teratogenic microorganism.
More Evidence on the Effects of Deworming: What Lessons Can We Learn?Authors: Michael Kremer and Kevin CrokeAvailable online: 10 April 2017More Less
In this month's issue, Liu and others present new evidence on the effects of deworming children from a cluster-randomized trial conducted in rural China. This was a useful, well-conducted study. The study found that a program in which school-age children were given deworming pills in school to take at home reduced infection prevalence modestly (end line prevalence of any worm infection was 31.4% in the control group and 27.7% in the treatment group). However, the authors could not reject the hypothesis that the program had no effect on nutrition, cognition, or school performance.
Serological and Molecular Analysis of Leishmania Infection in Healthy Individuals from Two Districts of West Bengal, India, Endemic for Visceral LeishmaniasisAuthors: Himanshu Kaushal, Sujit Kumar Bhattacharya, Sandeep Verma and Poonam SalotraAvailable online: 03 April 2017More Less
Several epidemiological studies have indicated the presence of asymptomatic infections with Leishmania donovani in the Indian subcontinent, where parasite transmission is considered anthroponotic. In India, such asymptomatic Leishmania cases have been identified in the state of Bihar. We explored here, the presence of asymptomatic Leishmania infection among healthy individuals living in two districts in the state of West Bengal, India, using serological and molecular tests. Blood samples of 246 healthy individuals were collected from nine villages of Malda and Murshidabad districts in West Bengal, considered endemic for visceral leishmaniasis (VL). Real-time quantitative polymerase chain reaction (qPCR) was performed for the quantification of parasite load in the blood. In addition, two serological tests were carried out to demonstrate anti-Leishmania antibodies: rK39 strip test and anti-total soluble Leishmania antigen IgG using enzyme-linked immunosorbent assay method. Nearly one-fifth (53/246) of the screened population was positive in qPCR as against 10.97% (27/246) positive in rK39 strip test. A range of parasite load was observed in the blood of identified asymptomatic Leishmania cases with a median value of 7.7 parasites/mL (range = 1–65). There was poor agreement between qPCR and serological tests (κ = 0.089, P = 0.13), and 29.62% and 20.54% of the population were qPCR positive in seropositive and seronegative groups, respectively. Combined molecular and serological tests enhanced the capacity to detect asymptomatic Leishmania infection in healthy individuals residing in the endemic areas of VL. A significant proportion of asymptomatic Leishmania individuals was detected in the examined endemic regions of West Bengal that might play a role in promoting VL transmission.
Mycetoma (Madura Foot) in Israel: Recent Cases and a Systematic Review of the LiteratureAuthors: Ohad Bitan, Yonit Wiener-Well, Rina Segal and Eli SchwartzAvailable online: 03 April 2017More Less
Mycetoma is a chronic soft tissue infection caused by fungal or bacterial pathogens, and is endemic in tropical and subtropical regions. Cases in developed countries outside the mycetoma belt are rare and usually imported by immigrants. Sporadic cases have been reported in Israel. Unpublished cases in the participating medical centers are reported. In addition, a systematic review of the literature was performed. All published mycetoma cases diagnosed in Israel were included with relevant variables collected. Twenty-one cases of mycetoma were diagnosed in Israel between 1942 and 2015, including four unpublished cases and 17 published cases. The mean age at diagnosis was 42 years (range 23–73), and 16 of the patients were male. The foot was the primary involved organ. Fifteen patients were immigrants from Yemen, Ethiopia, and Sudan. Five cases were autochthonous. One case was travel related. Among patients who developed symptoms after immigration, the mean time from exposure to symptom onset was 5.6 years (range 1–10 years). The mean time from symptom onset to diagnosis was 6.6 years (range 0.2–35 years). The autochthonous cases demonstrate that Israel is endemic of mycetoma. The immigrant population represents two distinct waves of immigration to Israel in the past century. Two unpublished cases of Ethiopian immigrants are the first reported cases of mycetoma acquired in Ethiopia. The diagnostic and therapeutic challenges along with the epidemiological data emphasize the need of raising the awareness of physicians to this devastating condition even in developed countries.
Therapeutic Dilemma of Refractory Erythema Nodosum LeprosumAuthors: Jianyu Zhu, Degang Yang, Chao Shi and Zhichun JingAvailable online: 27 March 2017More Less
Erythema nodosum leprosum (ENL), also known as type II leprosy reaction, is a severe immune-mediated complication of multibacillary leprosy. For ENL, corticosteroids and thalidomide are the mainstays of treatment. Other immunosuppressants, such as clofazimine, cyclosporine, and azathioprine have also been used. Although most patients with ENL respond well to conventional treatments, a small number are refractory to these therapies and have severe morbidity or mortality. We report the case of a 24-year-old man with refractory ENL treated with high-dose corticosteroids for 15 months. The patient developed steroid-dependence and serious adverse effects, and died of an intracranial infection.
Travelers' Diarrhea and Other Gastrointestinal Symptoms Among Boston-Area International TravelersAvailable online: 27 March 2017More Less
This prospective cohort study describes travelers' diarrhea (TD) and non-TD gastrointestinal (GI) symptoms among international travelers from the Boston area, the association of TD with traveler characteristics and dietary practices, use of prescribed antidiarrheal medications, and the impact of TD and non-TD GI symptoms on planned activities during and after travel. We included adults who received a pretravel consultation at three Boston-area travel clinics and who completed a three-part survey: pretravel, during travel, and posttravel (2–4 weeks after return). TD was defined as self-reported diarrhea with or without nausea/vomiting, abdominal pain, or fever. Demographic and travel characteristics were evaluated by χ2 test for categorical and Wilcoxon rank-sum test for continuous variables. Analysis of dietary practices used logistic generalized estimating equation models or logistic regression models. Of 628 travelers, 208 (33%) experienced TD and 45 (7%) experienced non-TD GI symptoms. Of 208 with TD, 128 (64%), 71 (36%), and 123 (62%) were prescribed ciprofloxacin, azithromycin, and/or loperamide before travel, respectively. Thirty-nine (36%) of 108 took ciprofloxacin, 20 (38%) of 55 took azithromycin, and 28 (28%) of 99 took loperamide during travel. Of 172 with TD during travel, 24% stopped planned activities, and 2% were hospitalized. Of 31 with non-TD GI symptoms during travel, six (13%) stopped planned activities. International travelers continue to experience diarrhea and other GI symptoms, resulting in disruption of planned activities and health-care visits for some. Although these illnesses resulted in interruption of travel plans, a relatively small proportion took prescribed antibiotics.
High Hepatitis E Seroprevalence Among Displaced Persons in South SudanAvailable online: 27 March 2017More Less
Large protracted outbreaks of hepatitis E virus (HEV) have been documented in displaced populations in Africa over the past decade though data are limited outside these exceptional settings. Serological studies can provide insights useful for improving surveillance and disease control. We conducted an age-stratified serological survey using samples previously collected for another research study from 206 residents of an internally displaced person camp in Juba, South Sudan. We tested serum for anti-HEV antibodies (IgM and IgG) and estimated the prevalence of recent and historical exposure to the virus. Using data on individuals' serostatus, camp arrival date, and state of origin, we used catalytic transmission models to estimate the relative risk of HEV infection in the camp compared with that in the participants' home states. The age-adjusted seroprevalence of anti-HEV IgG was 71% (95% confidence interval = 63–78), and 4% had evidence of recent exposure (IgM). We estimated HEV exposure rates to be more than 2-fold (hazard ratio = 2.3, 95% credible interval = 0.3–5.8) higher in the camp than in the participants' home states, although this difference was not statistically significant. HEV transmission may be higher than previously appreciated, even in the absence of reported cases. Improved surveillance in similar settings is needed to understand the burden of disease and minimize epidemic impact through early detection and response.
Multiplex Serologic Assessment of Schistosomiasis in Western Kenya: Antibody Responses in Preschool Age Children as a Measure of Reduced TransmissionAvailable online: 27 March 2017More Less
Currently, impact of schistosomiasis control programs in Schistosoma mansoni–endemic areas is monitored primarily by assessment of parasitologic indicators only. Our study was conducted to evaluate the use of antibody responses as a way to measure the impact of schistosomiasis control programs. A total of 3,612 serum samples collected at three time points from children 1–5 years of age were tested for antibody responses to two schistosome antigens (soluble egg antigen [SEA] and Sm25) by multiplex bead assay. The overall prevalence of antibody responses to SEA was high at baseline (50.0%). After one round of mass drug administration (MDA), there was minimal change in odds of SEA positivity (odds ratio [OR] = 1.02, confidence interval [CI] = 0.79–1.32, P = 0.89). However, after two rounds of treatment, there was a slight decrease in odds of SEA positivity (OR = 0.80, CI = 0.63–1.02, P = 0.08). In contrast to the SEA results, prevalence of antibody responses to Sm25 was lowest at baseline (14.1%) and higher in years 2 (19.8%) and 3 (18.4%). After one round of MDA, odds of Sm25 positivity increased significantly (OR = 1.51, CI = 1.14–2.02, P = 0.005) and remained significantly higher than baseline after two rounds of MDA (OR = 1.37, CI = 1.07–1.76, P = 0.01). There was a significant decrease in the proportion of 1-year-olds with positive SEA responses from 33.1% in year 1 to 13.2% in year 3 and a corresponding decrease in the odds (OR = 3.25, CI = 1.75–6.08, P < 0.001). These results provide preliminary evidence that schistosomiasis program impact can be monitored using serologic responses.
Reducing Uncertainty for Acute Febrile Illness in Resource-Limited Settings: The Current Diagnostic LandscapeAuthors: Matthew L. Robinson and Yukari C. ManabeAvailable online: 27 March 2017More Less
Diagnosing the cause of acute febrile illness in resource-limited settings is important—to give the correct antimicrobials to patients who need them, to prevent unnecessary antimicrobial use, to detect emerging infectious diseases early, and to guide vaccine deployment. A variety of approaches are yielding more rapid and accurate tests that can detect more pathogens in a wider variety of settings. After decades of slow progress in diagnostics for acute febrile illness in resource-limited settings, a wave of converging advancements will enable clinicians in resource-limited settings to reduce uncertainty for the diagnosis of acute febrile illness.
The Economic Value of Long-Lasting Insecticidal Nets and Indoor Residual Spraying Implementation in MozambiqueAvailable online: 27 March 2017More Less
Malaria-endemic countries have to decide how much of their limited resources for vector control to allocate toward implementing long-lasting insecticidal nets (LLINs) versus indoor residual spraying (IRS). To help the Mozambique Ministry of Health use an evidence-based approach to determine funding allocation toward various malaria control strategies, the Global Fund convened the Mozambique Modeling Working Group which then used JANUS, a software platform that includes integrated computational economic, operational, and clinical outcome models that can link with different transmission models (in this case, OpenMalaria) to determine the economic value of vector control strategies. Any increase in LLINs (from 80% baseline coverage) or IRS (from 80% baseline coverage) would be cost-effective (incremental cost-effectiveness ratios ≤ $114/disability-adjusted life year averted). However, LLIN coverage increases tend to be more cost-effective than similar IRS coverage increases, except where both pyrethroid resistance is high and LLIN usage is low. In high-transmission northern regions, increasing LLIN coverage would be more cost-effective than increasing IRS coverage. In medium-transmission central regions, changing from LLINs to IRS would be more costly and less effective. In low-transmission southern regions, LLINs were more costly and less effective than IRS, due to low LLIN usage. In regions where LLINs are more cost-effective than IRS, it is worth considering prioritizing LLIN coverage and use. However, IRS may have an important role in insecticide resistance management and epidemic control. Malaria intervention campaigns are not a one-size-fits-all solution, and tailored approaches are necessary to account for the heterogeneity of malaria epidemiology.
Risk Factors for Household Transmission of Vibrio cholerae in Dhaka, Bangladesh (CHoBI7 Trial)Authors: Vanessa Burrowes, Jamie Perin, Shirajum Monira, David A. Sack, Mahamud-ur Rashid, Toslim Mahamud, Zillur Rahman, Munshi Mustafiz, Sazzadul I. Bhuyian, Farzana Begum, Fatema Zohura, Shwapon Biswas, Tahmina Parvin, Tasdik Hasan, Xiaotong Zhang, Bradley R. Sack, K. M. Saif-Ur-Rahman, Munirul Alam and Christine M. GeorgeAvailable online: 27 March 2017More Less
Household contacts of cholera patients are at a 100 times higher risk of a Vibrio cholerae infection than the general population. To examine risk factors for V. cholerae infections and investigate intervention strategies among this population, we followed household contacts of cholera patients for the 1-week high-risk period after the index patient obtained care. This study was nested within a randomized controlled trial of the Cholera-Hospital-Based-Intervention-for-7-days (CHoBI7), a handwashing with soap and water treatment intervention in Dhaka, Bangladesh. Rectal swab results were available from 320 household contacts of cholera patients at five time points over a 1-week period. Fecal and water samples were analyzed for V. cholerae by culture. All analyses were stratified by study arm. Within the intervention arm, a household median free chlorine concentration below 0.5 mg/L was associated with an increased odds of a three times higher odds of a cholera infection (odds ratio [OR]: 3.0; 95 confidence interval [CI]: 1.32, 6.63), and each 0.5 mg/L decrease in free chlorine was associated with a 1.95 times higher odds of a cholera infection (95% CI: 1.2, 3.1). In the control arm, having V. cholerae in stored water was associated with a higher odds of a symptomatic cholera infection (OR: 8.66; 95% CI: 2.11, 35.48). No association was found between observed handwashing with soap at food and stool-related events and V. cholerae infections. Household water quality and treatment practices were found to be important risk factors for cholera infection among household contacts of cholera patients. These findings emphasize the need for water treatment interventions targeting this high risk population.
Prevalence and Risk Factors for Human Cystic Echinococcosis in the Cusco Region of the Peruvian Highlands Diagnosed Using Focused Abdominal UltrasoundAvailable online: 27 March 2017More Less
Latin America is among the highly endemic regions for cystic echinococcosis (CE). In Peru, an estimated 1,139 disability-adjusted life years are lost annually from surgical treatment of CE. This is comparable with the combined total for Argentina, Brazil, Uruguay, and Chile. The prevalence of human infection has been investigated in the central Peruvian Andes, but there are no community-based screening data from other regions of Peru. We carried out a population survey in January 2015 using abdominal ultrasound to estimate the prevalence of abdominal CE in the Canas and Canchis provinces, in the Cusco region of Peru. Among 1,351 subjects screened, 41 (3%) had CE. There was significant variation between communities with similar socioeconomic features in a small geographical area. A history of CE was reported by 4.1% of the screened subjects, among whom 30.3% still had CE on ultrasound. Among patients reporting previous CE treatment, 14.9% had CE in active stages. Limited education, community of residence, and knowing people with CE in the community were associated with CE. These results demonstrate a significant burden of CE in the region and suggest the need for further investigations, control activities, and optimization of clinical management for CE in this area.
Evaluation of the Field Performance of ImmunoCard STAT!® Rapid Diagnostic Tests for Rotavirus in Dadaab Refugee Camp and at the Kenya–Somalia BorderAuthors: Maurice Ope, Raymond Nyoka, Ahmed Unshur, Fredrick O. Oyier, Shafe A. Mowlid, Brian Owino, Steve B. Ochieng, Charles I. Okello, Joel M. Montgomery, Burton Wagacha, Aleksandar Galev, Abdikadir Abdow, Mathew D. Esona, Jacqueline Tate, David Fitter, Susan T. Cookson, Balajee Arunmozhi and Nina MaranoAvailable online: 27 March 2017More Less
Rotavirus commonly causes diarrhea in children, leading to hospitalization and even death. Rapid diagnostic tests are feasible alternatives for determining rotavirus outbreaks in refugee camps that have inadequate laboratory capacity. We evaluated the field performance of ImmunoCard STAT!® Rotavirus (ICS-RV) in Dadaab Refugee Camp and at the Kenya–Somalia border. From May to December 2014, we prospectively enrolled children aged < 5 years hospitalized with acute diarrhea, defined as ≥ 3 episodes of loose stool in 24 hours for < 7 days. Stool samples were collected and tested by trained surveillance clerks using ICS-RV per manufacturer's instructions. The field performance characteristics of ICS-RV were evaluated against the gold standard test, Premier™ Rotaclone® enzyme immunoassay. The operational characteristics were evaluated using World Health Organization (WHO) ASSURED criteria to determine whether ICS-RV is appropriate as a point-of-care test by administering a standard questionnaire and observing surveillance clerks performing the test. We enrolled 213 patients with a median age of 10 months (range = 1–48); 58.2% were male. A total of 71 (33.3%) and 60 (28.2%) patients tested positive for rotavirus infection by immunoassay and ICS-RV, respectively. The sensitivity, specificity, and positive and negative predictive values of ICS-RV compared with the immunoassay were 83.1% (95% confidence interval [CI] = 72.3–91.0), 99.3% (95% CI = 96.1–100), 98.3% (95% CI = 91.1–100), and 92.1% (95% CI = 86.6–95.9), respectively. The ICS-RV fulfilled the WHO ASSURED criteria for point-of-care testing. ICS-RV is a field-ready point-of-care test with good field performance and operational characteristics. It can be useful in determining rotavirus outbreaks in resource-limited settings.
Molecular Epidemiology of Malaria in Cameroon and Côte d'Ivoire. XXXI. Kelch 13 Propeller Sequences in Plasmodium falciparum Isolates Before and After Implementation of Artemisinin-Based Combination TherapyAvailable online: 27 March 2017More Less
Artemisinin-resistant malaria has not been reported from Africa, but resistance can possibly spread from Asia or arise independently in Africa. The emergence of artemisinin resistance in Africa can be monitored by molecular assay of Kelch 13 (K13) propeller sequences. A total of 251 archived DNA samples of Plasmodium falciparum isolates collected in 2002, 2003, and 2006 in Yaounde, Cameroon, and 47 samples collected in 2006 and 2013 in Abidjan, Côte d'Ivoire, were analyzed for K13-propeller sequence polymorphism. Only one isolate carried a mutant K13-propeller allele (E602D). None of the isolates carried the key mutant alleles (Y493H, R539T, I543T, and C580Y) associated with artemisinin resistance in Cambodia. The presence of the mutant allele was not correlated with in vitro response to dihydroartemisinin determined by the classical hypoxanthine incorporation assay. There was no evidence of K13 mutations associated with artemisinin resistance before and soon after the introduction of artemisinin-based combination therapies in Cameroon and Côte d'Ivoire.
Evaluation of a Mobile Phone–Based Microscope for Screening of Schistosoma haematobium Infection in Rural GhanaAvailable online: 27 March 2017More Less
Schistosomiasis affects over 170 million people in Africa. Here we compare a novel, low-cost mobile phone microscope to a conventional light microscope for the label-free diagnosis of Schistosoma haematobium infections in a rural Ghanaian school setting. We tested the performance of our handheld microscope using 60 slides that were randomly chosen from an ongoing epidemiologic study in school-aged children. The mobile phone microscope had a sensitivity of 72.1% (95% confidence interval [CI]: 56.1–84.2), specificity of 100% (95% CI: 75.9–100), positive predictive value of 100% (95% CI: 86.3–100), and a negative predictive value of 57.1% (95% CI: 37.4–75.0). With its modest sensitivity and high specificity, this handheld and cost-effective mobile phone–based microscope is a stepping-stone toward developing a powerful tool in clinical and public health settings where there is limited access to conventional laboratory diagnostic support.
Bungarus multicinctus multicinctus Snakebite in TaiwanAuthors: Yan-Chiao Mao, Po-Yu Liu, Liao-Chun Chiang, Shu-Chen Liao, Hung-Yuan Su, Szu-Yin Hsieh and Chen-Chang YangAvailable online: 27 March 2017More Less
Although specific antivenom is available in Taiwan, respiratory failure and general pain frequently accompany Bungarus multicinctus envenomation and there have been few reports on the management of B. multicinctus envenomation. We retrospectively analyzed 44 cases of B. multicinctus bite admitted to Taichung Veterans General Hospital (VGH) or to Taipei VGH. Demographic data, treatment, and outcome of patients with and without respiratory failure were compared. In this study, 20.5% patients had bites without noticeable signs or symptoms of significant envenoming, 27.3% developed respiratory failure, and 27.3% experienced general pain. Bivalent specific antivenom for B. multicinctus and N. atra was administered in all envenomed cases. Respiratory failure occurred 1.5–6.5 hours post-bite and general pain occurred 1–12 hours post-bite. Specific antivenom for B. multicinctus and N. atra at the recommended dose (i.e., 2–4 vials) might not effectively prevent respiratory failure and pain. Respiratory failure, general pain, and autonomic effects after B. multicinctus bite were probably caused, at least partly, by β-bungarotoxin. Although general weakness, ptosis, dysarthria, and dilated pupils were significantly associated with respiratory failure, their predictive value could not be accurately determined in such a retrospective study. Due to the rapid onset of respiratory failure, every suspected envenomed case thus should be closely monitored in the first few hours. We recommend the initial administration of four vials of antivenom in all envenomation cases, and a subsequent four vials be considered if the patient's condition is deteriorating. Prospective evaluation of the antivenom dosing regimen is urgently needed to improve B. multicinctus envenomation treatment.
Symptomatic Falciparum Malaria After Living in a Nonendemic Area for 10 Years: Recrudescence or Indigenous Transmission?Available online: 27 March 2017More Less
We report the case of a patient from Mali who, after 10 years of living in Spain, presented with symptomatic Plasmodium falciparum malaria without having visited an endemic area during that time. We cannot completely rule out the possibility of indigenous transmission, but this case most likely represents recrudescence of an infection acquired over 10 years earlier.
Patient-Reported Adverse Effects Associated with Combination Antiretroviral Therapy and Coadministered Enzyme-Inducing Antiepileptic DrugsAvailable online: 20 March 2017More Less
Concurrent treatment with combination antiretroviral therapy (cART) and an enzyme‐inducing antiepileptic drug (EI‐AED) is common in resource‐limited settings; however, the incidence and impact of adverse effects in cotreated patients is largely unknown. Symptoms of adverse effects were assessed by both spontaneous report and checklist for 145 human immunodeficiency virus (HIV)–infected Zambian adults initiating various treatment combinations, such as cART with an EI‐AED (N = 20), cART only (N = 43), or neither drug (untreated; N = 82). At study baseline, the cART + EI‐AED group reported more headache, generalized fatigue, problems with concentration, and depression than the untreated group (P < 0.01 for all). At 2 weeks, a greater proportion of cART + EI‐AED participants reported increased nausea or vomiting compared with baseline (P < 0.05). Adverse effects did not appear to impact self‐reported adherence at 2 weeks as 100% cART adherence was reported in 19 of 20 (95%) and 42 of 43 (98%) cART + EI‐AED and cART‐only participants, respectively; 100% EI‐AED adherence was reported in 19 of 20 (95%) participants. However, adherence at 6 months was suboptimal in both groups with 18 of 33 (56%) participants on cART experiencing greater than 1‐week lapse in pharmacy‐reported medication supply. Our results highlight the need to educate patients about the increased potential for nausea and vomiting with cART + EI‐AED cotreatment. Although adherence was high early during treatment, adherence should be reinforced overtime to minimize the potential for HIV and/or epilepsy treatment failure.
The Influence of Household- and Community-Level Sanitation and Fecal Sludge Management on Urban Fecal Contamination in Households and Drains and Enteric Infection in ChildrenAvailable online: 20 March 2017More Less
Urban sanitation necessitates management of fecal sludge inside and outside the household. This study examined associations between household sanitation, fecal contamination, and enteric infection in two low‐income neighborhoods in Vellore, India. Surveys and spatial analysis assessed the presence and clustering of toilets and fecal sludge management (FSM) practices in 200 households. Fecal contamination was measured in environmental samples from 50 households and household drains. Enteric infection was assessed from stool specimens from children under 5 years of age in these households. The two neighborhoods differed significantly in toilet coverage (78% versus 33%) and spatial clustering. Overall, 49% of toilets discharged directly into open drains ("poor FSM"). Children in households with poor FSM had 3.78 times higher prevalence of enteric infection when compared with children in other households, even those without toilets. In the neighborhood with high coverage of household toilets, children in households with poor FSM had 10 times higher prevalence of enteric infection than other children in the neighborhood and drains in poor FSM clusters who had significantly higher concentrations of genogroup II norovirus. Conversely, children in households with a toilet that contained excreta in a tank onsite had 55% lower prevalence of enteric infection compared with the rest of the study area. Notably, households with a toilet in the neighborhood with low toilet coverage had more fecal contamination on floors where children played compared with those without a toilet. Overall, both toilet coverage levels and FSM were associated with environmental fecal contamination and, subsequently, enteric infection prevalence in this urban setting.
Evaluation of the Protective Effect of Deoxyribonucleic Acid Vaccines Encoding Granule Antigen 2 and 5 against Acute Toxoplasmosis in BALB/c MiceAuthors: Xiao Teng Ching, Mun Yik Fong and Yee Ling LauAvailable online: 20 March 2017More Less
Toxoplasma gondii infects a broad range of warm‐blooded hosts, including humans. Important clinical manifestations include encephalitis in immunocompromised patients as well as miscarriage and fetal damage during early pregnancy. Toxoplasma gondii dense granule antigen 2 and 5 (GRA2 and GRA5) are essential for parasitophorous vacuole development of the parasite. To evaluate the potential of GRA2 and GRA5 as recombinant DNA vaccine candidates, these antigens were cloned into eukaryotic expression vector (pcDNA 3.1C) and evaluated in vaccination experiments. Recombinant DNA vaccines constructed with genes encoding GRAs were validated in Chinese hamster ovary cells before evaluation using lethal challenge of the virulent T. gondii RH strain in BALB/c mice. The DNA vaccines of pcGRA2 and pcGRA5 elicited cellular‐mediated immune response with significantly higher levels of interferon‐gamma, interleukin‐2 (IL‐2), IL‐4, and IL‐10 (P < 0.05) compared with controls. A mixed T‐helper cell 1 (Th1)/Th2 response was associated with slightly prolonged survival. These findings provide evidence that DNA vaccination with GRA2 and GRA5 is associated with Th1‐like cell‐mediated immune responses. It will be worthwhile to construct recombinant multiantigen combining full‐length GRA2 or/and GRA5 with various antigenic proteins such as the surface antigens and rhoptry antigens to improve vaccination efficacy.
Nonacademic Attributes Predict Medical and Nursing Student Intentions to Emigrate or to Work Rurally: An Eight-Country Survey in Asia and AfricaAvailable online: 20 March 2017More Less
We sought to identify independent, nonacademic predictors of medical and nursing student intent to migrate abroad or from rural to urban areas after graduation in low‐ and middle‐income countries (LMIC). This was a cross‐sectional survey of 3,199 first‐ and final‐year medical and nursing students at 16 training institutions in eight LMIC. Questionnaires assessed demographics, career intentions, and preferences regarding selected career, location, and work‐related attributes. Using principal component analysis, student preferences were reduced into four discrete categories of priorities: 1) work environment resources, 2) location livability, 3) altruistic job values, and 4) individualistic job values. Students' preferences were scored in each category. Using students' characteristics and priority scores, multivariable proportional odds models were used to derive independent predictors of intentions to emigrate for work outside the country, or to work in a rural area in their native country. Students prioritizing individualistic values more often planned international careers (adjusted odds ratio [aOR] = 1.44, 95% confidence interval [CI] = 1.16–1.78), whereas those prioritizing altruistic values preferred rural careers (aOR = 1.82, 95% CI = 1.50–2.21). Trainees prioritizing high‐resource environments preferentially planned careers abroad (aOR = 1.38, 95% CI = 1.12–1.69) and were unlikely to seek rural work (aOR = 0.60, 95% CI = 0.49–0.73). Independent of their priorities, students with prolonged prior rural residence were unlikely to plan emigration (aOR = 0.67, 95% CI = 0.50–0.90) and were more likely to plan a rural career (aOR = 1.53, 95% CI = 1.16–2.03). We conclude that use of nonacademic attributes in medical and nursing admissions processes would likely increase retention in high‐need rural areas and reduce emigration "brain drain" in LMIC.
Serosurvey of Crimean–Congo Hemorrhagic Fever Virus in Cattle, Mali, West AfricaAvailable online: 20 March 2017More Less
Crimean–Congo hemorrhagic fever is a tick‐borne disease caused by the arbovirus Crimean–Congo hemorrhagic fever virus (CCHFV, family Bunyaviridae, genus Nairovirus). CCHFV can cause a severe hemorrhagic fever with high‐case fatality rates in humans. CCHFV has a wide geographic range and has been described in around 30 countries in the Middle East, Asia, Europe, and Africa including Mali and neighboring countries. To date, little is known about the prevalence rates of CCHFV in Mali. Here, using banked bovine serum samples from across the country, we describe the results of a seroepidemiological study for CCHFV aimed at identifying regions of circulation in Mali. In total, 1,074 serum samples were tested by a modified in‐house CCHFV‐IgG‐enzyme‐linked immunosorbent assay (ELISA) with confirmatory testing by commercial ELISA and immunofluorescence assay. Overall, 66% of samples tested were positive for CCHFV‐specific IgG antibodies. Regional seroprevalence rates ranged from 15% to 95% and seemed to correlate with cattle density. Our results demonstrate that CCHFV prevalence is high in many regions in Mali and suggest that CCHFV surveillance should be established.
No Serologic Evidence of Middle East Respiratory Syndrome Coronavirus Infection among Camel Farmers Exposed to Highly Seropositive Camel Herds: A Household Linked Study, Kenya, 2013Available online: 20 March 2017More Less
High seroprevalence of Middle East respiratory syndrome coronavirus (MERS‐CoV) among camels has been reported in Kenya and other countries in Africa. To date, the only report of MERS-CoV seropositivity among humans in Kenya is of two livestock keepers with no known contact with camels. We assessed whether persons exposed to seropositive camels at household level had serological evidence of infection. In 2013, 760 human and 879 camel sera were collected from 265 households in Marsabit County. Data on human and animal demographics and type of contact with camels were collected. Human and camel sera were tested for anti‐MERS‐CoV IgG using a commercial enzyme‐linked immunosorbent assay (ELISA) test. Human samples were confirmed by plaque reduction neutralization test (PRNT). Logistic regression was used to identify factors associated with seropositivity. The median age of persons sampled was 30 years (range: 5–90) and 50% were males. A quarter (197/760) of the participants reported having had contact with camels defined as milking, feeding, watering, slaughtering, or herding. Of the human sera, 18 (2.4%) were positive on ELISA but negative by PRNT. Of the camel sera, 791 (90%) were positive on ELISA. On univariate analysis, higher prevalence was observed in female and older camels over 4 years of age (P < 0.05). On multivariate analysis, only age remained significantly associated with increased odds of seropositivity. Despite high seroprevalence among camels, there was no serological confirmation of MERS‐CoV infection among camel pastoralists in Marsabit County. The high seropositivity suggests that MERS‐CoV or other closely related virus continues to circulate in camels and highlights ongoing potential for animal‐to‐human transmission.
Differences in Inflammation Patterns Induced by African and Asian Burkholderia pseudomallei Isolates in MiceAvailable online: 13 March 2017More Less
Burkholderia pseudomallei is the causative agent of melioidosis, an emerging tropical disease of high mortality. Sub‐Saharan Africa represents potential melioidosis "hotspots"; however, to date, only a few cases have been reported. Herein, we compared the inflammatory patterns induced by a B. pseudomallei strain recently isolated from a fatal Gabonese case with the Thai reference strain B. pseudomallei‐1026b and Burkholderia thailandensis‐E264. Ex vivo, no differences were observed in terms of cellular responsiveness between strains. However, when compared with the B. pseudomallei‐1026b strain, the Gabonese isolate was significantly less virulent in terms of bacterial dissemination, inflammatory response, and organ damage in mice. Genomic comparison between strains showed differences in regions containing a fimbriae/adhesion virulence protein. In addition to a lack of microbiology facilities, differences in virulence of Burkholderia strains might contribute to the diverse global clinical occurrence of melioidosis.
Impact of a Food Safety Campaign on Streptococcus suis Infection in Humans in ThailandAuthors: Dan Takeuchi, Anusak Kerdsin, Yukihiro Akeda, Piphat Chiranairadul, Phacharaphan Loetthong, Nutchada Tanburawong, Prasanee Areeratana, Panarat Puangmali, Kasean Khamisara, Wirasinee Pinyo, Rapeepun Anukul, Sutit Samerchea, Punpong Lekhalula, Tatsuya Nakayama, Kouji Yamamoto, Masayo Hirose, Shigeyuki Hamada, Surang Dejsirilert and Kazunori OishiAvailable online: 13 March 2017More Less
Streptococcus suis is an important zoonotic pathogen in swine and humans that causes sepsis and meningitis. Our previous study in Thailand showed that the prevalence of S. suis infection in humans, especially in northern areas of Thailand, and the transmission of the pathogen occurred mainly through the consumption of traditional raw pork products. Considering the high incidence proportion and mortality rate of the disease as an important public health problem, we implemented a food safety campaign in the Phayao Province in northern Thailand in 2011. We evaluated the effects of a food safety campaign by comparing the sociodemographic, clinical, and bacteriological characteristics of cases before and after the campaign. The follow‐up study showed a marked decrease of the incidence proportion in the first 2 years, indicating the effectiveness of the campaign. In the third year, however, the incidence proportion slightly increased again, indicating the existence of deep‐rooted cultural behaviors and the necessity of continuous public health intervention. Furthermore, epidemiological analysis of the cases made it possible to estimate the infectivity of the pathogen via the oral route of infection. In the present study, we showed the effectiveness of the food safety campaign for controlling the S. suis infection, and we present a role model public health intervention for prevalent areas affected by S. suis infection in humans.
Clinical Characteristics and Prognosis of Penicilliosis among Human Immunodeficiency Virus–Infected Patients in Eastern ChinaAuthors: Jun Chen, Renfang Zhang, Yinzhong Shen, Li Liu, Tangkai Qi, Zhenyan Wang, Wei Song, Yang Tang and Hongzhou LuAvailable online: 13 March 2017More Less
Talaromyces marneffei infection is increasingly observed in people living with human immunodeficiency virus (HIV) in eastern China, a nonendemic area. This study aimed to draw the clinician's attention to this disease by presenting the clinical characteristics and prognosis of penicilliosis among HIV‐infected patients from this region. We retrospectively analyzed HIV‐infected patients with culture‐proven T. marneffei infection admitted during January 1, 2014–December 31, 2015, at the Shanghai Public Health Clinical Center. A total of 48 patients with confirmed HIV infection and penicilliosis were enrolled, which accounted for a mean of 3.2% (95% confidence interval: 2.4–4.2%) of yearly HIV infection admissions among patients from eastern China. Symptoms included fever, cough, and gastrointestinal complaints, whereas the most common sign was skin lesions. Anemia occurred in 87.5% (42/48) of the patients. The overall mortality rate was 16.7%. Low CD4 T‐cell count and hemoglobin level were correlated with mortality. Based on these results, we concluded that penicilliosis should be considered in HIV‐infected patients from eastern China who present with fever, cutaneous lesions, and anemia. The clinical characters and the prognosis of patients with penicilliosis are similar to those in endemic areas. More attention should be paid to penicilliosis patients with low CD4 T‐cell count and/or low hemoglobin level.
Trial of a Novel Intervention to Improve Multiple Food Hygiene Behaviors in NepalAuthors: Om Prasad Gautam, Wolf-Peter Schmidt, Sandy Cairncross, Sue Cavill and Valerie CurtisAvailable online: 13 March 2017More Less
In this study, we report on the results of a trial of an intervention to improve five food hygiene behaviors among mothers of young children in rural Nepal. This novel intervention targeted five behaviors; cleanliness of serving utensils, handwashing with soap before feeding, proper storage of cooked food, and thorough reheating and water treatment. Based on formative research and a creative process using the Behavior‐Centered Design approach, an innovative intervention package was designed and delivered over a period of 3 months. The intervention activities included local rallies, games, rewards, storytelling, drama, competitions linking with emotional drivers of behavior, and "kitchen makeovers" to disrupt behavior settings. The effect of the package on behavior was evaluated via a cluster‐randomized before–after study in four villages with four villages serving as controls. The primary outcome was the difference in the mean cluster level proportions of mothers directly observed practicing all five food hygiene behaviors. The five targeted food hygiene behaviors were rare at baseline (composite performance of all five behaviors in intervention 1% [standard deviation (SD) = 2%] and in control groups 2% [SD = 2%]). Six weeks after the intervention, the target behaviors were more common in the intervention than in the control group (43% [SD = 14%] versus 2% [SD = 2%], P = 0.02) during follow-up. The intervention appeared to be equally effective in improving all five behaviors in all intervention clusters. This study shows that a theory-driven, systematic approach employing emotional motivators and modifying behavior settings was capable of substantially improving multiple food hygiene behaviors in Nepal.
Comparison of Cytokine Responses in Ecuadorian Children Infected with Giardia, Ascaris, or Both ParasitesAvailable online: 13 March 2017More Less
More than 2 billion people are infected with parasites globally, and the majority have coinfections. Intestinal protozoa and helminths induce polarizing CD4+ T‐helper cell 1 (Th1) mediated cytokine responses within the host. Such immune polarization may inhibit the ability of the host to mount an adequate immune response for pathogen clearance to concurrent pathogens. The current study evaluated the plasma cytokine profile in Ascaris and Giardia coinfected children compared with Giardia‐ and Ascaris‐only infected children. Fecal samples and blood samples were collected from asymptomatic 3‐year‐old children living in the district of Quininde, Ecuador. Stool samples that tested positive for Giardia lamblia‐only, Ascaris lumbricoides‐only, or G. lamblia and A. lumbricoides coinfections were confirmed by quantitative real‐time polymerase chain reaction. Plasma samples from the study subjects were used to quantitate cytokines. A total of 39 patients were evaluated. Children with coinfection had a significant decrease in Th1 cytokine production, interleukin 2 (IL‐2) (P < 0.05), IL‐12 (P < 0.05), and tumor necrosis factor alpha (P < 0.05) compared with Giardia‐only infected children. Coinfected children had an increase in IL‐10/interferon gamma (IFN‐γ) ratio compared with uninfected (P < 0.05) and Ascaris alone (P < 0.05). The increased IL‐10/IFN‐γ ratio in the setting of decreased Th1 cytokine response indicates Th2 polarization in the coinfected group. Reduced Th1 cytokines in children coinfected with Ascaris and Giardia may impair the host's ability to eradicate Giardia infection leading to chronic giardiasis.
Phase 1 Randomized Study of a Tetravalent Dengue Purified Inactivated Vaccine in Healthy Adults in the United StatesAvailable online: 13 March 2017More Less
The safety and immunogenicity of four formulations of an investigational tetravalent dengue purified inactivated vaccine (DPIV), formulated at 1 or 4 μg with aluminum hydroxide (alum) or at 1 μg with an adjuvant system (AS01E or AS03B), were evaluated in a first‐time‐in‐human, placebo‐controlled, randomized, observer‐blind, phase 1 trial in the continental United States. Two doses of vaccine or placebo were administered intramuscularly 4 weeks apart to 100 healthy adults 18–39 years of age, randomized 1:1:1:1:1 to receive one of four DPIV formulations or saline placebo. The response to a third dose was evaluated in a subset of nine participants remote from primary vaccination. Humoral immunogenicity was assessed using a 50% microneutralization assay. All DPIV formulations were well tolerated. No vaccine‐related serious adverse events were observed through 12 months after the second vaccine dose. In all DPIV groups, geometric mean antibody titers peaked at Day 56, waned through 6 months after the second vaccine dose, and then stabilized. In the nine subjects where boosting was evaluated, a strong anamnestic response was observed. These results support continuation of the clinical development of this dengue vaccine candidate (clinicaltrials.gov: NCT01666652).
Cost-Effectiveness Evaluation of a Novel Integrated Bite Case Management Program for the Control of Human Rabies, Haiti 2014–2015Available online: 13 March 2017More Less
Haiti has the highest burden of rabies in the Western hemisphere, with 130 estimated annual deaths. We present the cost‐effectiveness evaluation of an integrated bite case management program combining community bite investigations and passive animal rabies surveillance, using a governmental perspective. The Haiti Animal Rabies Surveillance Program (HARSP) was first implemented in three communes of the West Department, Haiti. Our evaluation encompassed all individuals exposed to rabies in the study area (N = 2,289) in 2014–2015. Costs (2014 U.S. dollars) included diagnostic laboratory development, training of surveillance officers, operational costs, and postexposure prophylaxis (PEP). We used estimated deaths averted and years of life gained (YLG) from prevented rabies as health outcomes. HARSP had higher overall costs (range: $39,568–$80,290) than the no‐bite‐case‐management (NBCM) scenario ($15,988–$26,976), partly from an increased number receiving PEP. But HARSP had better health outcomes than NBCM, with estimated 11 additional annual averted deaths in 2014 and nine in 2015, and 654 additional YLG in 2014 and 535 in 2015. Overall, HARSP was more cost-effective (US$ per death averted) than NBCM (2014, HARSP: $2,891–$4,735, NBCM: $5,980–$8,453; 2015, HARSP: $3,534–$7,171, NBCM: $7,298–$12,284). HARSP offers a cost‐effective human rabies prevention solution for countries transitioning from reactive to preventive strategies (i.e., comprehensive dog vaccination).
High Triatoma brasiliensis Densities and Trypanosoma cruzi Prevalence in Domestic and Peridomestic Habitats in the State of Rio Grande do Norte, Brazil: The Source for Chagas Disease Outbreaks?Available online: 13 March 2017More Less
A total of 2,431 Triatoma brasiliensis were collected from 39 populations of Paraíba (PB) and Rio Grande do Norte (RN) states, Brazil. In PB, Trypanosoma cruzi infection was not detected in either peridomestic or domestic vector populations. In contrast, in RN, T. brasiliensis was detected with high parasite prevalence in these ecotopes (30.7–40.0%). Moreover, peridomicile insect population densities were more than double the average densities of all other settings evaluated (19.17 versus < 8.94 triatomine/man-hour). Genotyped parasites evidenced a mix of T. cruzi lineages circulating in both peridomestic and sylvatic populations. Although vector control efforts have dramatically decreased Chagas disease transmission to humans, recent outbreaks have been detected in four municipalities of RN state. Our results clearly evidence a worrisome proximity between infected vectors and humans in RN. Indeed, finding of infected T. brasiliensis inside homes is routinely recorded by local vector control surveillance staff around the outbreak area, challenging the current and conventional view that vector transmissions are controlled in northeastern Brazil. This scenario calls for strengthening vector control surveillance and interventions to prevent further Chagas transmission, especially in RN State.
Burden of Disease Attributed to Waterborne Transmission of Selected Enteric Pathogens, Australia, 2010Authors: Katherine B. Gibney, Joanne O'Toole, Martha Sinclair and Karin LederAvailable online: 13 March 2017More Less
Universal access to safe drinking water is a global priority. To estimate the annual disease burden of campylobacteriosis, nontyphoidal salmonellosis, cryptosporidiosis, giardiasis, and norovirus attributable to waterborne transmission in Australia, we multiplied regional World Health Organization (WHO) estimates of the proportion of cases attributable to waterborne transmission by estimates of all-source disease burden for each study pathogen. Norovirus was attributed as causing the most waterborne disease cases (479,632; 95% uncertainly interval [UI]: 0–1,111,874) followed by giardiasis and campylobacteriosis. The estimated waterborne disability-adjusted life year (DALY) burden for campylobacteriosis (2,004; 95% UI: 0–5,831) was 7-fold greater than other study pathogens and exceeded the WHO guidelines for drinking water quality (1 × 10−6 DALY per person per year) by 90-fold. However, these estimates include disease transmitted via either drinking or recreational water exposure. More precise country-specific and drinking water–specific attribution estimates would better define the health burden from drinking water and inform changes to treatment requirements.
Trachomatous Scar Ranking: A Novel Outcome for Trachoma StudiesAvailable online: 13 March 2017More Less
We evaluated a new trachoma scarring ranking system with potential use in clinical research. The upper right tarsal conjunctivas of 427 individuals from Ethiopian villages with hyperendemic trachoma were photographed. An expert grader first assigned a scar grade to each photograph using the 1981 World Health Organization (WHO) grading system. Then, all photographs were ranked from least (rank = 1) to most scarring (rank = 427). Photographic grading found 79 (18.5%) conjunctivae without scarring (C0), 191 (44.7%) with minimal scarring (C1), 105 (24.6%) with moderate scarring (C2), and 52 (12.2%) with severe scarring (C3). The ranking method demonstrated good internal validity, exhibiting a monotonic increase in the median rank across the levels of the 1981 WHO grading system. Intrarater repeatability was also better for the ranking method (intraclass correlation coefficient = 0.84, 95% CI = 0.74–0.94). Exhibiting better internal and external validity, this ranking method is ideal for evaluating the difference in scarring between groups of individuals.
American Aedes vexans Mosquitoes are Competent Vectors of Zika VirusAvailable online: 13 March 2017More Less
Starting in 2013–2014, the Americas have experienced a massive outbreak of Zika virus (ZIKV) which has now reached at least 49 countries. Although most cases have occurred in South America and the Caribbean, imported and autochthonous cases have occurred in the United States. Aedes aegypti and Aedes albopictus mosquitoes are known vectors of ZIKV. Little is known about the potential for temperate Aedes mosquitoes to transmit ZIKV. Aedes vexans has a worldwide distribution, is highly abundant in particular localities, aggressively bites humans, and is a competent vector of several arboviruses. However, it is not clear whether Ae. vexans mosquitoes are competent to transmit ZIKV. To determine the vector competence of Ae. vexans for ZIKV, wild‐caught mosquitoes were exposed to an infectious bloodmeal containing a ZIKV strain isolated during the current outbreak. Approximately 80% of 148 mosquitoes tested became infected by ZIKV, and approximately 5% transmitted infectious virus after 14 days of extrinsic incubation. These results establish that Ae. vexans are competent ZIKV vectors. Their relative importance as vectors (i.e., their vectorial capacity) depends on feeding behavior, longevity, and other factors that are likely to vary in ecologically distinct environments.
The Human Microbiome in the Fight against TuberculosisAuthors: Madeleine R. Wood, Elaine A. Yu and Saurabh MehtaAvailable online: 27 February 2017More Less
The human microbiome is an intriguing potentially modifiable risk factor in our arsenal against Mycobacterium tuberculosis, the leading infectious disease killer globally. Previous studies have shown associations between the human microbiome and pulmonary disease states; however, etiological links between the microbiome and tuberculosis (TB) infection or disease remain unclear. Immunomodulatory roles of the microbiome may prove to be a critical asset in the host response against TB, including in preventing TB infection, reducing progression from latency, mitigating disease severity, and lowering the incidence of drug resistance and coinfections. This review examined the associations between TB and the gut and lung microbiome. Eight studies were identified through a PubMed database search, including one animal study (N = 1), case report (N = 1), and case–control studies (N = 6). TB infection and disease were associated with reduced gastrointestinal microbial diversity in a murine model and human case report. Sputum microbial diversity differed by TB status in case–control studies, although some reported heterogeneous findings. Current evidence suggests that the gut and lung microbiome are associated with TB infection and disease. However, as studies are limited, etiological and longitudinal research is needed to determine clinical relevance.
Effect of Deworming on Indices of Health, Cognition, and Education among Schoolchildren in Rural China: A Cluster-Randomized Controlled TrialAvailable online: 16 January 2017More Less
Soil‐transmitted helminths (STHs) infect over one billion people worldwide. There is concern that chronic infection with STHs among school‐aged children may detrimentally affect their development, including their health, cognition, and education. However, two recent Cochrane reviews examining the impact of deworming drugs for STH on nutrition, hemoglobin, and school performance found that randomized controlled trials (RCTs) in the literature provide an insufficient evidence base to draw reliable conclusions. This study uses a cluster‐RCT to add to existing evidence by assessing the impact of a deworming intervention on nutrition, cognition, and school performance among schoolchildren in rural China. The intervention, implemented by local health practitioners in a setting with a baseline infection prevalence of 41.9% (95% confidence interval [CI] = 39.8%, 43.9%) and infection intensity of 599.5 eggs per gram of feces among positive‐tested schoolchildren (95% CI = 473.2, 725.8), consisted of distributing a 400‐mg dose of albendazole accompanied with educational training about STH infection, treatment, and prevention. The intervention was conducted twice over the course of the study—at baseline in May 2013 and later in November 2013. We found that the deworming intervention reduced both infection prevalence and infection intensity, but these declines in infection were not accompanied by an impact on outcomes of nutrition, cognition, or school performance. Our interpretation is that the impact of deworming was attenuated by the light infection intensity in our sample population. Evidence from future RCTs is needed to assess the effect of deworming on key outcomes in areas with moderate and severe worm infections.
Assessing the Contribution of Malaria Vector Control and Other Maternal and Child Health Interventions in Reducing All-Cause Under-Five Mortality in ZambiaAvailable online: 15 February 2016More Less
Under-five mortality in Zambia has declined since 1990, with reductions accelerating after 2000. Zambia's scale-up of malaria control is viewed as the driver of these gains, but past studies have not fully accounted for other potential factors. This study sought to systematically evaluate the impact of malaria vector control on under-five mortality. Using a mixed-effects regression model, we quantified the relationship between malaria vector control, other priority health interventions, and socioeconomic indicators and district-level under-five mortality trends from 1990 to 2010. We then conducted counterfactual analyses to estimate under-five mortality in the absence of scaling up malaria vector control. Throughout Zambia, increased malaria vector control coverage coincided with scaling up three other interventions: the pentavalent vaccine, exclusive breast-feeding, and prevention of mother-to-child transmission of HIV services. This simultaneous scale-up made statistically isolating intervention-specific impact infeasible. Instead, in combination, these interventions jointly accelerated declines in under-five mortality by 11% between 2000 and 2010. Zambia's scale-up of multiple interventions is notable, yet our findings highlight challenges in quantifying program-specific impact without better health data and information systems. As countries aim to further improve health outcomes, there is even greater need—and opportunity—to strengthen routine data systems and to develop more rigorous evaluation strategies.
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