Publications by authors named "Firdausi Qadri"

312 Publications

Genotypic and phenotypic profiles of antibiotic-resistant bacteria isolated from hospitalized patients in Bangladesh.

Trop Med Int Health 2021 Apr 10. Epub 2021 Apr 10.

Infectious Diseases Laboratory, Institute for Developing Science and Health Initiatives, Dhaka, Bangladesh.

Objectives: Characterization of resistance phenotype and genotype is crucial to understanding the burden and transmission of antimicrobial-resistance (AMR). This study aims to determine the spectrum of AMR and associated genes encoding aminoglycoside, macrolide and β-lactam classes of antimicrobials in bacteria isolated from hospitalized patients in Bangladesh.

Methods: 430 bacterial isolates from patients with respiratory, intestinal, wound infections, and typhoid fever, presenting to clinical care from 2015-2019, were examined. They included Escherichia coli (n= 85); Staphylococcus aureus (n= 84); Salmonella typhi (n= 82); Klebsiella pneumoniae (n= 42); Streptococcus pneumoniae (n= 36); coagulase-negative staphylococci (n= 28); Enterococcus faecalis (n= 27); Pseudomonas aeruginosa (n= 26) and Acinetobacter baumannii (n= 20). Reconfirmation of these clinical isolates and antimicrobial susceptibility tests was performed. PCR amplification using resistance gene-specific primers was done and the amplified products were confirmed by Sanger sequencing.

Results: 53% of isolates were multidrug-resistant (MDR), including 97% of Escherichia coli. There was a year-wise gradual increase of MDR isolates from 2015-2018 and there was an almost 2-fold increase in the number of MDR strains isolated in 2019 (P= 0.00058). Among the 5 extended spectrum β-lactamases investigated, CTX-M-1 was the most prevalent (63%) followed by NDM-1 (22%); Escherichia coli was the major reservoir of these genes. The ermB (55%) and aac(6')-Ib (35%) genes were the most frequently detected macrolide and aminoglycoside resistance genes, respectively.

Conclusion: MDR pathogens are highly prevalent in hospital settings of Bangladesh.
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http://dx.doi.org/10.1111/tmi.13584DOI Listing
April 2021

Evaluation of Typhoid Conjugate Vaccine Effectiveness in Ghana (TyVEGHA) Using a Cluster-Randomized Controlled Phase IV Trial: Trial Design and Population Baseline Characteristics.

Vaccines (Basel) 2021 Mar 19;9(3). Epub 2021 Mar 19.

International Vaccine Institute, Seoul 08826, Korea.

Typhoid fever remains a significant health problem in sub-Saharan Africa, with incidence rates of >100 cases per 100,000 person-years of observation. Despite the prequalification of safe and effective typhoid conjugate vaccines (TCV), some uncertainties remain around future demand. Real-life effectiveness data, which inform public health programs on the impact of TCVs in reducing typhoid-related mortality and morbidity, from an African setting may help encourage the introduction of TCVs in high-burden settings. Here, we describe a cluster-randomized trial to investigate population-level protection of TYPBAR-TCV, a Vi-polysaccharide conjugated to a tetanus-toxoid protein carrier (Vi-TT) against blood-culture-confirmed typhoid fever, and the synthesis of health economic evidence to inform policy decisions. A total of 80 geographically distinct clusters are delineated within the Agogo district of the Asante Akim region in Ghana. Clusters are randomized to the intervention arm receiving Vi-TT or a control arm receiving the meningococcal A conjugate vaccine. The primary study endpoint is the total protection of Vi-TT against blood-culture-confirmed typhoid fever. Total, direct, and indirect protection are measured as secondary outcomes. Blood-culture-based enhanced surveillance enables the estimation of incidence rates in the intervention and control clusters. Evaluation of the real-world impact of TCVs and evidence synthesis improve the uptake of prequalified/licensed safe and effective typhoid vaccines in public health programs of high burden settings. This trial is registered at the Pan African Clinical Trial Registry, accessible at Pan African Clinical Trials Registry (ID: PACTR202011804563392).
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http://dx.doi.org/10.3390/vaccines9030281DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8003794PMC
March 2021

Emerging Infectious Diseases - Learning from the Past and Looking to the Future.

N Engl J Med 2021 Apr 27;384(13):1181-1184. Epub 2021 Mar 27.

From the Bill and Melinda Gates Foundation, Seattle (C.E.); the Africa Centres for Disease Control and Prevention, Addis Ababa, Ethiopia (J.N.N.); and the International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh (F.Q.).

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http://dx.doi.org/10.1056/NEJMp2034517DOI Listing
April 2021

Case Report: Typhoid Fever Complicated by Ileal Perforation in an Urban Slum of Dhaka, Bangladesh.

Am J Trop Med Hyg 2021 Mar 22. Epub 2021 Mar 22.

1icddr,b, (International Centre for Diarrhoeal Disease, Research, Bangladesh), Dhaka, Bangladesh.

Intestinal perforation is one of the most dangerous complications of typhoid fever and demands urgent hospitalization, diagnosis, and surgical management to reduce morbidity and prevent mortality. Here, we report a case of typhoidal intestinal perforation in a 19 year-old young man detected by passive surveillance during a cluster-randomized trial with Vi-tetanus toxoid conjugate vaccine (Typhoid Vaccine Acceleration Consortium: TyVAC) in an urban slum area in Mirpur, Dhaka, Bangladesh. The patient presented with a high-grade fever, lower abdominal pain, and vomiting and was admitted to a healthcare facility. Physical examination and preoperative investigations of the patient suggested a presumptive diagnosis of intestinal perforation, and the patient was transferred to a tertiary-level hospital for surgical management. A positive blood culture, intraoperative findings, and histopathology of an intestinal biopsy confirmed ileal perforation due to typhoid fever. This case report highlights the need for prompt diagnosis and appropriate pre- and postoperative management of patients who appear with the symptoms of typhoidal intestinal perforation. This report further demonstrates the importance of systematic surveillance and proper evaluation to determine the true incidence rate of typhoid fever and intestinal perforation in Bangladesh.
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http://dx.doi.org/10.4269/ajtmh.20-1448DOI Listing
March 2021

Author Correction: Vibrio spp. infections.

Nat Rev Dis Primers 2021 Feb 19;7(1):15. Epub 2021 Feb 19.

Centre for Environment, Fisheries and Aquaculture Science (CEFAS), Weymouth, UK.

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http://dx.doi.org/10.1038/s41572-021-00250-9DOI Listing
February 2021

Frequency of Hepatitis B, C and HIV Infections among Transfusion-Dependent Beta Thalassemia Patients in Dhaka.

Infect Dis Rep 2021 Jan 15;13(1):89-95. Epub 2021 Jan 15.

Infectious Diseases Laboratory, Institute for Developing Science and Health Initiatives, Mohakhali, Dhaka-1212, Bangladesh.

Transfusion transmitted infections have remained a major deterrent to public health, particularly among the patients with transfusion-dependent Beta thalassemia in developing countries. Although proper donor selection through adoption of WHO-advised infection panel has lowered the rate of infections, the multi-transfused patients are not free of risk. In this study, we screened 148 transfusion-dependent Beta thalassemia patients to determine the frequency of Hepatitis C Virus (HCV), Hepatitis B Virus (HBV) and Human Immunodeficiency Virus (HIV) using the ELISA method. Among them, infected cases with HCV, HBV and HIV were 13.51%, 3.37% and 0%, respectively. Moreover, 2% of the patients were found to be co-infected with both HBV and HCV. The percentage of infections in the patients with frequent transfusion interval (≤30 days) was significantly higher ( < 0.0005) than that in the patients with less frequent transfusion intervals (>30 days). Immunochromatography (ICT)-based rapid test kits are usually used to screen and confirm these infections in the blood of the patients. However, ICT-based tests are not sensitive enough to detect the infections. So, a combination of both Nucleic Acid testing (NAT) and serological testing are suggested to significantly reduce the risk of viral infections during blood transfusion.
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http://dx.doi.org/10.3390/idr13010011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7838932PMC
January 2021

IgG antibody response demonstrates inverse correlation with viral load in Bangladeshi women with acute hepatitis E virus genotype 1 infection.

Int J Infect Dis 2021 Mar 15;104:482-490. Epub 2021 Jan 15.

Laboratory of Infectious Diseases, Institute for Developing Science and Health Initiatives, Mohakhali, Dhaka 1212, Bangladesh; Laboratory of Genetics and Genomics, Institute for Developing Science and Health Initiatives, Mohakhali, Dhaka 1212, Bangladesh. Electronic address:

Objectives: To determine IgG immune responses and hepatitis E virus (HEV) viral load, and to explore the associations with pregnancy.

Methods: A total of 121 HEV-infected women (57 pregnant, 64 non-pregnant) were analysed. Quantitative reverse transcription PCR (RT-qPCR) was done for 78 HEV IgM-positive patients to determine viral load, and Sanger sequencing was performed for 62 HEV-RNA-positive patients to confirm genotyping. ELISA was conducted to determine HEV antibody and avidity indices.

Results: The HEV genotype was identified as variant 1. Significant negative correlations were observed between log HEV copy number and log hepatitis E virus IgG antibody index in the late acute phase of jaundice for both pregnant women (r = -0.7971, p = 0.0002) and non-pregnant women (r = -0.9117, p = 0.0002). Pregnant women had significantly higher serum log viral copy numbers and lower IgG antibody indices than non-pregnant women in the late acute phase of HEV-induced jaundice (p = 0.0196 and p = 0.0303, respectively). Moreover, pregnant women with acute HEV hepatitis had higher cross-reactive IgG antibodies compared to the non-pregnant women (p = 0.0017). Five patients with HEV hepatitis died, of whom four were pregnant.

Conclusions: Pregnancy might be associated with higher viral loads and a lower IgG response in the HEV-induced late acute phase of jaundice.
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http://dx.doi.org/10.1016/j.ijid.2020.12.081DOI Listing
March 2021

O1 transmission in Bangladesh: insights from a nationally representative serosurvey.

Lancet Microbe 2020 Dec;1(8):e336-e343

Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.

Background: Pandemic from cholera-endemic countries around the Bay of Bengal regularly seed epidemics globally. Without reducing cholera in these countries, including Bangladesh, global cholera control might never be achieved. Little is known about the geographical distribution and magnitude of O1 transmission nationally. We aimed to describe infection risk across Bangladesh, making use of advances in cholera seroepidemiology, therefore overcoming many of the limitations of current clinic-based surveillance.

Methods: We tested serum samples from a nationally representative serosurvey in Bangladesh with eight -specific assays. Using these data with a machine-learning model previously validated within a cohort of confirmed cholera cases and their household contacts, we estimated the proportion of the population with evidence of infection by O1 in the previous year (annual seroincidence) and used Bayesian geostatistical models to create high-resolution national maps of infection risk.

Findings: Between Oct 16, 2015, and Jan 24, 2016, we obtained and tested serum samples from 2930 participants (707 households) in 70 communities across Bangladesh. We estimated national annual seroincidence of O1 infection of 17·3% (95% CI 10·5-24·1). Our high-resolution maps showed large heterogeneity of infection risk, with community-level annual infection risk within the sampled population ranging from 4·3% to 62·9%. Across Bangladesh, we estimated that 28·1 (95% CI 17·1-39·2) million infections occurred in the year before the survey. Despite having an annual seroincidence of O1 infection lower than much of Bangladesh, Dhaka (the capital of Bangladesh and largest city in the country) had 2·0 (95% CI 0·6-3·9) million infections during the same year, primarily because of its large population.

Interpretation: Serosurveillance provides an avenue for identifying areas with high O1 transmission and investigating key risk factors for infection across geographical scales. Serosurveillance could serve as an important method for countries to plan and monitor progress towards 2030 cholera elimination goals.

Funding: The Bill & Melinda Gates Foundation, National Institutes of Health, and US Centers for Disease Control and Prevention.
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http://dx.doi.org/10.1016/S2666-5247(20)30141-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7738617PMC
December 2020

Electronic decision support and diarrhoeal disease guideline adherence (mHDM): a cluster randomised controlled trial.

Lancet Digit Health 2020 05;2(5):e250-e258

Department of Pediatrics, University of Florida, Gainesville, FL, USA; Department of Environmental and Global Health, University of Florida, Gainesville, FL, USA; Emerging Pathogens Institute, University of Florida, Gainesville, FL, USA; Department of Pediatrics, Stanford University School of Medicine, Stanford University, Stanford, CA, USA. Electronic address:

Background: Acute diarrhoeal disease management often requires rehydration alone without antibiotics. However, non-indicated antibiotics are frequently ordered and this is an important driver of antimicrobial resistance. The mHealth Diarrhoea Management (mHDM) trial aimed to establish whether electronic decision support improves rehydration and antibiotic guideline adherence in resource-limited settings.

Methods: A cluster randomised controlled trial was done at ten district hospitals in Bangladesh. Inclusion criteria were patients aged 2 months or older with uncomplicated acute diarrhoea. Admission orders were observed without intervention in the pre-intervention period, followed by randomisation to electronic (rehydration calculator) or paper formatted WHO guidelines for the intervention period. The primary outcome was rate of intravenous fluid ordered as a binary variable. Generalised linear mixed-effect models, accounting for hospital clustering, served as the analytical framework; the analysis was intention to treat. The trial is registered with ClinicalTrials.gov (NCT03154229) and is completed.

Findings: From March 11 to Sept 10, 2018, 4975 patients (75·6%) of 6577 screened patients were enrolled. The intervention effect for the primary outcome showed no significant differences in rates of intravenous fluids ordered as a function of decision-support type. Intravenous fluid orders decreased by 0·9 percentage points for paper electronic decision support and 4·2 percentage points for electronic decision support, with a 4·2-point difference between decision-support types in the intervention period (paper 98·7% [95% CI 91·8-99·8] vs electronic 94·5% [72·2-99·1]; p=0·31). Adverse events such as complications and mortality events were uncommon and could not be statistically estimated.

Interpretation: Although intravenous fluid orders did not change, electronic decision support was associated with increases in the volume of intravenous fluid ordered and decreases in antibiotics ordered, which are consistent with WHO guidelines.

Funding: US National Institutes of Health.
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http://dx.doi.org/10.1016/S2589-7500(20)30062-5DOI Listing
May 2020

Humans Surviving Cholera Develop Antibodies against Vibrio cholerae O-Specific Polysaccharide That Inhibit Pathogen Motility.

mBio 2020 11 17;11(6). Epub 2020 Nov 17.

Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, USA

The mechanism of protection against cholera afforded by previous illness or vaccination is currently unknown. We have recently shown that antibodies targeting O-specific polysaccharide (OSP) of correlate highly with protection against cholera. is highly motile and possesses a flagellum sheathed in OSP, and motility of correlates with virulence. Using high-speed video microscopy and building upon previous animal-related work, we demonstrate that sera, polyclonal antibody fractions, and OSP-specific monoclonal antibodies recovered from humans surviving cholera block motility at both subagglutinating and agglutinating concentrations. This antimotility effect is reversed by preadsorbing sera and polyclonal antibody fractions with purified OSP and is associated with OSP-specific but not flagellin-specific monoclonal antibodies. Fab fragments of OSP-specific polyclonal antibodies do not inhibit motility, suggesting a requirement for antibody-mediated cross-linking in motility inhibition. We show that OSP-specific antibodies do not directly affect viability, but that OSP-specific monoclonal antibody highly protects against death in the murine cholera model. We used competitive index studies to demonstrate that OSP-specific antibodies impede colonization and survival of in intestinal tissues and that this impact is motility dependent. Our findings suggest that the impedance of motility by antibodies targeting OSP contributes to protection against cholera. Cholera is a severe dehydrating illness of humans caused by is a highly motile bacterium that has a single flagellum covered in lipopolysaccharide (LPS) displaying O-specific polysaccharide (OSP), and motility correlates with its ability to cause disease. The mechanisms of protection against cholera are not well understood; however, since is a noninvasive intestinal pathogen, it is likely that antibodies that bind the pathogen or its products in the intestinal lumen contribute to protection from infection. Here, we demonstrate that OSP-specific antibodies isolated from humans surviving cholera in Bangladesh inhibit motility and are associated with protection against challenge in a motility-dependent manner.
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http://dx.doi.org/10.1128/mBio.02847-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7683404PMC
November 2020

CEACAMs serve as toxin-stimulated receptors for enterotoxigenic .

Proc Natl Acad Sci U S A 2020 11 2;117(46):29055-29062. Epub 2020 Nov 2.

Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO 63110;

The enterotoxigenic (ETEC) are among the most common causes of diarrheal illness and death due to diarrhea among young children in low-/middle-income countries (LMICs). ETEC have also been associated with important sequelae including malnutrition and stunting, placing children at further risk of death from diarrhea and other infections. Our understanding of the molecular pathogenesis of acute diarrheal disease as well as the sequelae linked to ETEC are still evolving. It has long been known that ETEC heat-labile toxin (LT) activates production of cAMP in the cell, signaling the modulation of cellular ion channels that results in a net efflux of salt and water into the intestinal lumen, culminating in watery diarrhea. However, as LT also promotes ETEC adhesion to intestinal epithelial cells, we postulated that increases in cAMP, a critical cellular "second messenger," may be linked to changes in cellular architecture that favor pathogen-host interactions. Indeed, here we show that ETEC use LT to up-regulate carcinoembryonic antigenrelated cell adhesion molecules (CEACAMs) on the surface of small intestinal epithelia, where they serve as critical bacterial receptors. Moreover, we show that bacteria are specifically recruited to areas of CEACAM expression, in particular CEACAM6, and that deletion of this CEACAM abrogates both bacterial adhesion and toxin delivery. Collectively, these results provide a paradigm for the molecular pathogenesis of ETEC in which the bacteria use toxin to drive up-regulation of cellular targets that enhances subsequent pathogen-host interactions.
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http://dx.doi.org/10.1073/pnas.2012480117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7682567PMC
November 2020

Antibody responses after COVID-19 infection in patients who are mildly symptomatic or asymptomatic in Bangladesh.

Int J Infect Dis 2020 Dec 5;101:220-225. Epub 2020 Oct 5.

Infectious Diseases Division, icddr,b, Mohakhali, Dhaka, Bangladesh. Electronic address:

Objectives: Studies on serological responses following coronavirus disease-2019 (COVID-19) have been published primarily in individuals who are moderately or severely symptomatic, but there are few data from individuals who are mildly symptomatic or asymptomatic.

Methods: We measured IgG, IgM, and IgA to the receptor-binding domain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by using enzyme-linked immunosorbent assay in mildly symptomatic (n = 108) and asymptomatic (n = 63) on days 1, 7, 14, and 30 following RT-PCR confirmation in Bangladesh and when compared with pre-pandemic samples, including healthy controls (n = 73) and individuals infected with other viruses (n = 79).

Results: Mildly symptomatic individuals developed IgM and IgA responses by day 14 in 72% and 83% of individuals, respectively, while 95% of individuals developed IgG response, and rose to 100% by day 30. In contrast, individuals infected with SARS-CoV-2 but who remained asymptomatic developed antibody responses significantly less frequently, with only 20% positive for IgA and 22% positive for IgM by day 14, and 45% positive for IgG by day 30 after infection.

Conclusions: These results confirm immune responses are generated following COVID-19 who develop mildly symptomatic illness. However, those with asymptomatic infection do not respond or have lower antibody levels. These results will impact modeling needed for determining herd immunity generated by natural infection or vaccination.
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http://dx.doi.org/10.1016/j.ijid.2020.09.1484DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7534791PMC
December 2020

Can existing improvements of water, sanitation, and hygiene (WASH) in urban slums reduce the burden of typhoid fever in these settings?

Clin Infect Dis 2020 Sep 22. Epub 2020 Sep 22.

International Centre for Diarrheal Disease Research, Bangladesh, Dhaka, Bangladesh.

Background: Sustained investment in water, sanitation and hygiene (WASH) has lagged in resource-poor settings; incremental WASH improvements may, nonetheless, prevent diseases such as typhoid in disease-endemic populations.

Methods: Using prospective data from a large cohort in urban Kolkata, India, we evaluated whether baseline WASH variables predicted typhoid risk in a training subpopulation (n=28470). We applied a machine learning algorithm to the training subset to create a composite, dichotomous ("good", "not good") WASH variable based on four variables and evaluated sensitivity and specificity of this variable in a validation subset (n=28470). We evaluated in Cox regression models whether residents of "good" WASH households experienced lower typhoid risk after controlling for potential confounders. We constructed virtual clusters (radius 50m) surrounding each household to evaluate whether "good" WASH prevalence modified typhoid risk in central household members.

Results: "Good" WASH was associated with protection in analyses of all households (Hazard ratio (HR)=0.57, 95% CI: 0.37-0.90, p=0.015). This protection was evident in persons ≥5 years at baseline (HR=0.47, 95% CI: 0.34-0.93, p=0.005) and was suggestive, though not statistically significant, in younger age groups (HR=0.61, 95% CI: 0.27-1.38, p=0.235). The level of surrounding household "good" WASH coverage was also associated with protection (HR=0.988, 95% CI: 0.979-0.996, p=0.004, for each percent coverage increase). However, collinearity between household WASH and WASH coverage prevented assessment of their independent predictive contributions.

Conclusion: In this typhoid-endemic setting, natural variation in household WASH was associated with typhoid risk. If replicated elsewhere, these findings suggest that WASH improvements short of major infrastructural investments may enhance typhoid control.
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http://dx.doi.org/10.1093/cid/ciaa1429DOI Listing
September 2020

High-Dose Neonatal Vitamin A Supplementation to Bangladeshi Infants Increases the Percentage of CCR9-Positive Treg Cells in Infants with Lower Birthweight in Early Infancy, and Decreases Plasma sCD14 Concentration and the Prevalence of Vitamin A Deficiency at Two Years of Age.

J Nutr 2020 11;150(11):3005-3012

USDA Western Human Nutrition Research Center at University of California, Davis, CA, USA.

Background: Vitamin A (VA) stores are low in early infancy and may impair development of the immune system.

Objective: This study determined if neonatal VA supplementation (VAS) affects the following: 1) development of regulatory T (Treg) cells; 2) chemokine receptor 9 (CCR9) expression, which directs mucosal targeting of immune cells; and 3) systemic endotoxin exposure as indicated by changed plasma concentrations of soluble CD14 (sCD14). Secondarily, VA status, growth, and systemic inflammation were investigated.

Methods: In total, 306 Bangladeshi infants were randomly assigned to receive 50,000 IU VA or placebo (PL) within 48 h of birth, and immune function was assessed at 6 wk, 15 wk, and 2 y. Primary outcomes included the following: 1) peripheral blood Treg cells; 2) percentage of Treg, T, and B cells expressing CCR9; and 3) plasma sCD14. Secondary outcomes included the following: 4) VA status measured using the modified relative dose-response (MRDR) test and plasma retinol; 5) infant growth; and 6) plasma C-reactive protein (CRP). Statistical analysis identified group differences and interactions with sex and birthweight.

Results: VAS increased (P = 0.004) the percentage of CCR9+ Treg cells (13.2 ± 1.37%) relative to PL (9.17 ± 1.15%) in children below the median birthweight but had the opposite effect (P = 0.04) in those with higher birthweight (VA, 9.13 ± 0.89; PL, 12.1 ± 1.31%) at 6 and 15 wk (values are combined mean ± SE). VAS decreased (P = 0.003) plasma sCD14 (1.56 ± 0.025 mg/L) relative to PL (1.67 ± 0.032 mg/L) and decreased (P = 0.034) the prevalence of VA deficiency (2.3%) relative to PL (9.2%) at 2 y.

Conclusions: Neonatal VAS enhanced mucosal targeting of Treg cells in low-birthweight infants. The decreased systemic exposure to endotoxin and improved VA status at 2 y may have been due to VA-mediated improvements in gut development resulting in improved barrier function and nutrient absorption. This trial was registered at clinicaltrials.gov as NCT01583972 and NCT02027610.
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http://dx.doi.org/10.1093/jn/nxaa260DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7675026PMC
November 2020

Protection conferred by typhoid fever against recurrent typhoid fever in urban Kolkata.

PLoS Negl Trop Dis 2020 08 17;14(8):e0008530. Epub 2020 Aug 17.

International Centre for Diarrheal Disease Research, Bangladesh, Dhaka, Bangladesh.

We evaluated the protection conferred by a first documented visit for clinical care of typhoid fever against recurrent typhoid fever prompting a visit. This study takes advantage of multi-year follow-up of a population with endemic typhoid participating in a cluster-randomized control trial of Vi capsular polysaccharide typhoid vaccine in Kolkata, India. A population of 70,566 individuals, of whom 37,673 were vaccinated with one dose of either Vi vaccine or a control (Hepatitis A) vaccine, were observed for four years. Surveillance detected 315 first typhoid visits, among whom 4 developed subsequent typhoid, 3 due to reinfection, defined using genomic criteria and corresponding to -124% (95% CI: -599, 28) protection by the initial illness. Point estimates of protection conferred by an initial illness were negative or negligible in both vaccinated and non-vaccinated subjects, though confidence intervals around the point estimates were wide. These data provide little support for a protective immunizing effect of clinically treated typhoid illness, though modest levels of protection cannot be excluded.
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http://dx.doi.org/10.1371/journal.pntd.0008530DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7430703PMC
August 2020

Early Insights From Clinical Trials of Typhoid Conjugate Vaccine.

Clin Infect Dis 2020 Jul;71(Supplement_2):S155-S159

Infectious Diseases Division, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh.

Clinical trials of typhoid conjugate vaccine (TCV) are ongoing in 4 countries. Early data confirm safety, tolerability, and immunogenicity of typhoid conjugate vaccine, and early efficacy results are promising. These data support World Health Organization recommendations and planned country introductions. Forthcoming trial data will continue to inform programmatic use of typhoid conjugate vaccine.
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http://dx.doi.org/10.1093/cid/ciaa370DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7388715PMC
July 2020

The Surveillance for Enteric Fever in Asia Project (SEAP), Severe Typhoid Fever Surveillance in Africa (SETA), Surveillance of Enteric Fever in India (SEFI), and Strategic Typhoid Alliance Across Africa and Asia (STRATAA) Population-based Enteric Fever Studies: A Review of Methodological Similarities and Differences.

Clin Infect Dis 2020 Jul;71(Supplement_2):S102-S110

Department of Medicine, University of Cambridge, Cambridge, United Kingdom.

Building on previous multicountry surveillance studies of typhoid and others salmonelloses such as the Diseases of the Most Impoverished program and the Typhoid Surveillance in Africa Project, several ongoing blood culture surveillance studies are generating important data about incidence, severity, transmission, and clinical features of invasive Salmonella infections in sub-Saharan Africa and South Asia. These studies are also characterizing drug resistance patterns in their respective study sites. Each study answers a different set of research questions and employs slightly different methodologies, and the geographies under surveillance differ in size, population density, physician practices, access to healthcare facilities, and access to microbiologically safe water and improved sanitation. These differences in part reflect the heterogeneity of the epidemiology of invasive salmonellosis globally, and thus enable generation of data that are useful to policymakers in decision-making for the introduction of typhoid conjugate vaccines (TCVs). Moreover, each study is evaluating the large-scale deployment of TCVs, and may ultimately be used to assess post-introduction vaccine impact. The data generated by these studies will also be used to refine global disease burden estimates. It is important to ensure that lessons learned from these studies not only inform vaccination policy, but also are incorporated into sustainable, low-cost, integrated vaccine-preventable disease surveillance systems.
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http://dx.doi.org/10.1093/cid/ciaa367DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7388711PMC
July 2020

Transcutaneous Vaccination with Conjugate Typhoid Vaccine Vi-DT Induces Systemic, Mucosal, and Memory Anti-Polysaccharide Responses.

Am J Trop Med Hyg 2020 09;103(3):1032-1038

Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts.

Transcutaneous vaccination can induce both mucosal and systemic immune responses. However, there are few data on anti-polysaccharide responses following transcutaneous vaccination of polysaccharides, despite the role that anti-polysaccharide responses play in protecting against intestinal mucosal and respiratory pathogens. Whether transcutaneous vaccination with a conjugate polysaccharide vaccine would be able to induce memory responses is also unknown. To address this, we transcutaneously vaccinated mice with virulence antigen (Vi) polysaccharide of serovar Typhi (the cause of typhoid fever), either in unconjugated or conjugated form (the latter as a Vi-DT conjugate). We also assessed the ability of the immunoadjuvant cholera toxin to impact responses following vaccination. We found that presenting Vi in a conjugate versus nonconjugate form transcutaneously resulted in comparable serum IgG responses but higher serum and lamina propria lymphocyte IgA anti-Vi responses, as well as increased IgG memory responses. The addition of immunoadjuvant did not further increase these responses; however, it boosted fecal IgA and serum IgG anti-Vi responses. Our results suggest that transcutaneous vaccination of a conjugate vaccine can induce systemic as well as enhanced mucosal and memory B-cell anti-polysaccharide responses.
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http://dx.doi.org/10.4269/ajtmh.19-0798DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7470581PMC
September 2020

An ethnographic exploration of diarrheal disease management in public hospitals in Bangladesh: From problems to solutions.

Soc Sci Med 2020 09 10;260:113185. Epub 2020 Jul 10.

Departments of Pediatrics and Environmental and Global Health, Emerging Pathogens Institute, University of Florida, USA. Electronic address:

Introduction: Diarrheal disease is one of the most common causes of hospital admission globally. The barriers that influence guideline-adherent care at resource limited hospitals are poorly defined, especially during diarrheal disease outbreaks. The objective of this study was to characterize challenges faced in diarrheal disease management in resource-limited hospitals and identify opportunities to improve care.

Methods: The study was conducted during a diarrheal disease outbreak period at ten public district hospitals distributed across Bangladesh. A rapid ethnographic approach included observations and informal interviews with clinicians, staff nurses and patients. In the first phase, observations identified common and unique challenges in diarrheal management at the ten sites. In the second phase, four hospitals were purposively selected for additional ethnographic study. Systematic observations over 420 total hours were collected from patient-clinician interactions (n = 76) and informal interviews (n = 138). Applied thematic analysis identified factors that influenced hospitalbased diarrhea management.

Results: Normalization of guideline deviation was observed at all ten sites, including prescription of non-indicated antibiotics and intravenous (IV) fluids. Conflict between 'what should be done' and 'what can be done' was the most common challenge identified. Clinical assessments and patient treatment plans were established at admission in a median of 2 minutes (n = 76), often without a physical examination (57%; n=43/76). Factors that prevented adherence to clinical guidelines included human resource constraints, conflicts of interests, overcrowding, and inadequate hygiene and sanitation in the emergency department and wards.

Conclusion: This study identified challenges in hospital-based management of diarrheal disease and opportunities to improve care in seemingly change-resilient hospital settings. The results reveal important areas for intervention and policy engagement that may have additive benefit for both hospitals and their patients. These interventions include targeting barriers to clean-water, sanitation and hygiene that prevent clinicians from adopting guidelines out of concern for hospital acquired infections.
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http://dx.doi.org/10.1016/j.socscimed.2020.113185DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7502197PMC
September 2020

Predicting Vibrio cholerae Infection and Disease Severity Using Metagenomics in a Prospective Cohort Study.

J Infect Dis 2021 Feb;223(2):342-351

Division of Allergy and Infectious Diseases, University of Washington, Seattle, Washington, USA.

Background: Susceptibility to Vibrio cholerae infection is affected by blood group, age, and preexisting immunity, but these factors only partially explain who becomes infected. A recent study used 16S ribosomal RNA amplicon sequencing to quantify the composition of the gut microbiome and identify predictive biomarkers of infection with limited taxonomic resolution.

Methods: To achieve increased resolution of gut microbial factors associated with V. cholerae susceptibility and identify predictors of symptomatic disease, we applied deep shotgun metagenomic sequencing to a cohort of household contacts of patients with cholera.

Results: Using machine learning, we resolved species, strains, gene families, and cellular pathways in the microbiome at the time of exposure to V. cholerae to identify markers that predict infection and symptoms. Use of metagenomic features improved the precision and accuracy of prediction relative to 16S sequencing. We also predicted disease severity, although with greater uncertainty than our infection prediction. Species within the genera Prevotella and Bifidobacterium predicted protection from infection, and genes involved in iron metabolism were also correlated with protection.

Conclusion: Our results highlight the power of metagenomics to predict disease outcomes and suggest specific species and genes for experimental testing to investigate mechanisms of microbiome-related protection from cholera.
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http://dx.doi.org/10.1093/infdis/jiaa358DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7857355PMC
February 2021

Etiology of diarrhea requiring hospitalization in Bangladesh by quantitative PCR, 2014-2018.

Clin Infect Dis 2020 Jun 27. Epub 2020 Jun 27.

Mucosal Immunology and Vaccinology Unit, Infectious Diseases Division, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Mohakhali Dhaka, Bangladesh.

Background: Diarrhea remains a major public health problem and characterization of etiology is needed to prioritize interventions. However, most data are from single-site studies of children. We tested samples from participants of any age from 11 geographically diverse hospitals in Bangladesh to describe pathogen-specific burdens of diarrhea.

Methods: We utilized two existing diarrhea surveillance systems: a Nationwide network at 10 sentinel hospitals and at the icddr,b hospital. We tested stools from enrolled participants and non-diarrheal controls for enteropathogens using quantitative PCR and calculated pathogen-specific attributable fractions (AFs) of diarrhea.

Results: We analyzed 5516 diarrheal patients and 735 controls. Overall, rotavirus had the highest attributable burden of diarrhea (Nationwide AF 17.7%, 95% confidence interval: 14.3, 20.9; icddr,b AF 39.9%; 38.0, 41.8), followed by adenovirus 40/41 (Nationwide AF 17.9%, CI: 13.9, 21.9; icddr,b AF 16.6%; CI: 14.4, 19.4) and Vibrio cholerae (Nationwide AF 10.2%, CI: 9.1, 11.3; icddr,b AF 13.3%, CI: 11.9, 15.1). Rotavirus was the leading pathogen in children under 5 years of age and was consistent across the sites (coefficient of variation = 56.3%). Adenovirus 40/41 was the second leading pathogen in both children and adults. V. cholerae was the leading pathogen in individuals above 5 years old but was more geographically variable (coefficient of variation = 71.5%). Other attributable pathogens included astrovirus, norovirus, Shigella, Salmonella, ETEC, sapovirus, and typical EPEC.

Conclusions: Rotavirus, adenovirus 40/41, and V. cholerae were the leading etiologies of infectious diarrhea requiring hospitalization in Bangladesh. Other pathogens were important in certain age groups or sites.
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http://dx.doi.org/10.1093/cid/ciaa840DOI Listing
June 2020

Use of Typhoid Vi-Polysaccharide Vaccine as a Vaccine Probe to Delineate Clinical Criteria for Typhoid Fever.

Am J Trop Med Hyg 2020 08 18;103(2):665-671. Epub 2020 Jun 18.

Korea University College of Medicine, Seoul, South Korea.

Blood cultures (BCs) detect an estimated 50% of typhoid fever cases. There is need for validated clinical criteria to define cases that are BC negative, both to help direct empiric antibiotic treatment and to better evaluate the magnitude of protection conferred by typhoid vaccines. To derive and validate a clinical rule for defining BC-negative typhoid fever, we assessed, in a cluster-randomized effectiveness trial of Vi-polysaccharide (ViPS) typhoid vaccine in Kolkata, India, 14,797 episodes of fever lasting at least 3 days during 4 years of comprehensive, BC-based surveillance of 70,865 persons. A recursive partitioning algorithm was used to develop a decision rule to predict BC-proven typhoid cases with a diagnostic specificity of 97-98%. To validate this rule as a definition for BC-negative typhoid fever, we assessed whether the rule defined culture-negative syndromes prevented by ViPS vaccine. In a training subset of individuals, we identified the following two rules: rule 1: patients aged < 15 years with prolonged fever accompanied by a measured body temperature ≥ 100°F, headache, and nausea; rule 2: patients aged ≥ 15 years with prolonged fever accompanied by nausea and palpable liver but without constipation. The adjusted protective efficacy of ViPS against clinical typhoid defined by these rules in persons aged ≥ 2 years in a separate validation subset was 33% (95% CI: 4-53%). We have defined and validated a clinical rule for predicting BC-negative typhoid fever using a novel vaccine probe approach. If validated in other settings, this rule may be useful to guide clinical care and to enhance typhoid vaccine evaluations.
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http://dx.doi.org/10.4269/ajtmh.19-0968DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7410438PMC
August 2020

Evaluation of a standardised Vi poly-l-lysine ELISA for serology of Vi capsular polysaccharide antibodies.

Biologicals 2020 Jul 20;66:21-29. Epub 2020 Jun 20.

Division of Bacteriology, National Institute for Biological Standards and Control, Potters Bar, Hertfordshire, EN6 3QG, UK. Electronic address:

Typhoid vaccines based on protein-conjugated capsular Vi polysaccharide (TCVs) prevent typhoid in infants and young children. Analysis of the serum anti-Vi IgG response following immunisation against typhoid confirms the immunogenicity of TCVs and forms an important part of the pathway to licensing. Comparative studies could expedite the licencing process, and the availability of a standardised ELISA method alongside the 1st International Standard (IS) 16/138 for anti-typhoid capsular Vi polysaccharide IgG (human) will facilitate this process. To this end, a non-commercial ELISA based on a coat of Vi and poly-l-lysine (Vi-PLL ELISA) was evaluated by 10 laboratories. Eight serum samples, including IS 16/138, were tested in the standardised Vi-PLL ELISA (n = 10), a commercial Vi ELISA (n = 3) and a biotinylated Vi ELISA (n = 1). Valid estimates of potencies relative to IS 16/138 were obtained for all samples in the Vi-PLL ELISA and the commercial ELISA, with good repeatability and reproducibility evident from the study results and concordant estimates obtained by the two ELISA methods. The study demonstrates that the Vi-PLL ELISA can be used in clinical trial studies to determine the immunogenicity of TCVs.
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http://dx.doi.org/10.1016/j.biologicals.2020.05.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7391004PMC
July 2020

Impact of DNA Extraction Method on Variation in Human and Built Environment Microbial Community and Functional Profiles Assessed by Shotgun Metagenomics Sequencing.

Front Microbiol 2020 25;11:953. Epub 2020 May 25.

Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital, Boston, MA, United States.

Both the host microbiome and the microbiome of the built environment can have profound impacts on human health. While prior studies have suggested that the variability introduced by DNA extraction method is less than typical biologic variation, most studies have focused on 16S rRNA amplicon sequencing or on high biomass fecal samples. Shotgun metagenomic sequencing provides advantages over amplicon sequencing for surveying the microbiome, but is a challenge to perform in lower microbial biomass samples with high human DNA content such as sputum or vacuumed dust. Here we systematically evaluate the impact of four different extraction methods (phenol:choloroform, and three high-throughput kit-based approaches, the Promega Maxwell gDNA, Qiagen MagAttract PowerSoil DNA, and ZymoBIOMICS 96 MagBead). We report the variation in microbial community structure and predicted microbial function assessed by shotgun metagenomics sequencing in human stool, sputum, and vacuumed dust obtained from ongoing cohort studies or clinical trials. The same beadbeating protocol was used for all samples to focus our evaluation on the impact of kit chemistries on sequencing results. DNA yield was overall highest in the phenol:choloroform and Promega approaches. Only the phenol:choloroform approach showed evidence of contamination in negative controls. Bias was evaluated using mock community controls, and was noted across all extraction methods, although Promega exhibited the least amount of bias. The extraction method did not impact the proportion of human reads, although stool had the lowest proportion of human reads (0.1%) as compared to dust (44.1%) and sputum (80%). We calculated Bray-Curtis dissimilarity and Aitchison distances to evaluate the impact of extraction method on microbial community structure by sample type. Extraction method had the lowest impact in stool (extraction method responsible for 3.0-3.9% of the variability), the most impact in vacuumed dust (12-16% of the variability) and intermediate values for sputum (9.2-12% variability). Similar differences were noted when evaluating microbial community function. Our results will inform investigators planning microbiome studies using diverse sample types in large clinical studies. A consistent DNA extraction approach across all sample types is recommended, particularly with lower microbial biomass samples that are more heavily influenced by extraction method.
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http://dx.doi.org/10.3389/fmicb.2020.00953DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7262970PMC
May 2020

Evaluation of a Rapid Point-of-Care Multiplex Immunochromatographic Assay for the Diagnosis of Enteric Fever.

mSphere 2020 06 10;5(3). Epub 2020 Jun 10.

Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, USA

There is a critical need for an improved rapid diagnostic for enteric fever. We have previously demonstrated that serum IgA responses targeting serovar Typhi hemolysin E (HlyE) and lipopolysaccharide (LPS) are able to discriminate patients with acute typhoid from healthy controls in areas where enteric fever is endemic (healthy endemic controls) and from patients with other bacterial infections. We now have data demonstrating that IgA antibody responses against these antigens also work well for identifying patients with acute Paratyphi A infection. To develop a test for acute enteric fever detection, we have adapted a point-of-care immunochromatographic dual-path platform technology (DPP), which improves on the traditional lateral flow technology by using separate sample and conjugate paths and a compact, portable reader, resulting in diagnostics with higher sensitivity and multiplexing abilities. In this analysis, we have compared our standard enzyme-linked immunosorbent assay (ELISA) method to the DPP method in detecting acute phase plasma/serum anti-HlyE and anti-LPS IgA antibodies in a cohort of patients with culture-confirmed Typhi ( = 30) and Paratyphi A infection ( = 20), healthy endemic controls ( = 25), and febrile endemic controls ( = 25). We found that the DPP measurements highly correlated with ELISA results, and both antigens had an area under the curve (AUC) of 0.98 (sensitivity of 92%, specificity of 94%) with all controls and an AUC of 0.98 (sensitivity of 90%, specificity of 96%) with febrile endemic controls. Our results suggest that the point-of-care DPP Typhoid System has high diagnostic accuracy for the rapid detection of enteric fever and warrants further evaluation. Enteric fever remains a significant global problem, and control programs are significantly limited by the lack of an optimal assay for identifying individuals with acute infection. This is especially critical considering the recently released World Health Organization (WHO) position paper endorsing the role of the typhoid conjugate vaccine in communities where enteric fever is endemic. A reliable diagnostic test is needed to assess and evaluate typhoid intervention strategies and determine which high-burden areas may benefit most from a vaccine intervention. Our collaborative team has developed and evaluated a point-of-care serodiagnostic assay based on detection of anti-HlyE and LPS IgA. Our finding of the high diagnostic accuracy of the DPP Typhoid System for the rapid detection of enteric fever has the potential to have significant public health impact by allowing for improved surveillance and for control and prevention programs in areas with limited laboratory capacity.
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http://dx.doi.org/10.1128/mSphere.00253-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7289704PMC
June 2020

Case Report: Serovar Paratyphi B Infection in a Febrile Ill Child during Enhanced Passive Surveillance in an Urban Slum in Mirpur, Dhaka.

Am J Trop Med Hyg 2020 07 21;103(1):231-233. Epub 2020 May 21.

icddr,b, (International Centre for Diarrhoeal Disease Research, Bangladesh), Dhaka, Bangladesh.

Paratyphoid fever is one of the major causes of morbidity of febrile illnesses in endemic regions. We report a case of high-grade fever in an infant who was positive for serovar Paratyphi B (. Paratyphi B) both in blood and stool cultures. The baby was enrolled in the passive surveillance of multicenter, multicomponent epidemiological study of enteric fever (Strategic Typhoid alliance across Africa and Asia; STRATAA) conducted in a population of 110,000 residents over 2 years in an urban slum, Dhaka, Bangladesh. This is the only patient who was positive for . Paratyphi B in blood and stool among more than 6,000 febrile ill patients enrolled in the passive surveillance. The report shows the significance of surveillance to identify changes in the epidemiology of enteric fever.
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http://dx.doi.org/10.4269/ajtmh.19-0958DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7356450PMC
July 2020

Willingness to pay for oral cholera vaccines in urban Bangladesh.

PLoS One 2020 30;15(4):e0232600. Epub 2020 Apr 30.

Karolinska Institute, Solna, Stockholm, Sweden.

Introduction: Cholera is a highly infectious disease and remains a serious public health burden in Bangladesh. The objective of the study was to measure the private demand for oral cholera vaccines (OCV) in Bangladesh and to investigate the key determinants of this demand, reflected in the household's willingness to pay (WTP) for oral cholera vaccine.

Methods: A contingent valuation method was employed in an urban setting of Bangladesh during December 2015 to January 2016. All respondents (N = 1051) received a description of World Health Organization (WHO) prequalified OCV, Shanchol™. Interviews were conducted with either the head of households or their spouse or a major economic contributor of the households. Respondents were asked about how much at maximum they were willing to pay for OCV for their own and their household members' protection. Results are presented as the average and median of the reported maximum WTP of the respondents with standard deviations and 95% confidence interval. Natural log-linear regression model was employed to examine the factors influencing participants' WTP for OCV.

Results: About 99% of the respondents expressed WTP for OCV with a maximum mean and median WTP per vaccination (2 doses) of US$ 2.23 and US$ 1.92 respectively. On the household level with an average number of 4.62 members, the estimated mean WTP was US$ 10 (median: US$ 7.69) which represents the perceived demand for OCV of a household to vaccinate against cholera.

Conclusions: The demand of vaccination further indicates that there is a potential scope for recovering a certain portion of the expenditure of immunization program by introducing direct user fees for future cholera vaccination in Bangladesh. Findings from this study will be useful for the policy-makers to make decision on cost-recovery in future oral cholera vaccination programs in Bangladesh and in similar countries.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0232600PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7192494PMC
July 2020

Nationwide Hospital-Based Seroprevalence of Hepatitis A and Hepatitis E Virus in Bangladesh.

Ann Glob Health 2020 03 16;86(1):29. Epub 2020 Mar 16.

icddr,b (International Centre for Diarrheal Disease Research, Bangladesh), Dhaka, BD.

Background: Hepatitis A virus (HAV) and hepatitis E virus (HEV) are transmitted by the fecal-oral route and are responsible for epidemic and sporadic outbreaks of acute hepatitis in low-income countries like Bangladesh.

Objective: The purpose of this study was to describe the seroprevalence of acute hepatitis due to HAV and HEV infection in Bangladesh.

Methods: The nationwide food-borne illness surveillance started in 2014 at 10 different hospitals which covered seven divisions of Bangladesh. Blood samples were collected from suspected acute hepatitis cases and screened for the anti-HAV IgM and anti-HEV IgM using enzyme-linked immunosorbent assay (ELISA). Participants' socioeconomic status, clinical, sanitation and food history were recorded. Multivariate logistic regression was performed to determine the risk factors associated with HAV and HEV infection.

Findings: A total of 998 patients were enrolled and tested for both HAV and HEV. Among these, 19% (191/998) were identified as HAV positive and 10% (103/998) were HEV positive. The median age was 12 years and 25 years for HAV and HEV positive patients, respectively. The prevalence of HAV was higher among the females (24.9%), whereas HEV was higher among males (11.2%). The highest occurrence of HAV was observed among children while HEV was most prevalent in the 15-60 years age group (12.4%).

Conclusion: Through our nationwide surveillance, it is evident that hepatitis A and hepatitis E infection is common in Bangladesh. These data will be useful towards planning preventive and control measures by strengthening the sanitation programs and vaccination strategies in Bangladesh.
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http://dx.doi.org/10.5334/aogh.2574DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7082825PMC
March 2020

Immunogenicity of a killed bivalent whole cell oral cholera vaccine in forcibly displaced Myanmar nationals in Cox's Bazar, Bangladesh.

PLoS Negl Trop Dis 2020 03 16;14(3):e0007989. Epub 2020 Mar 16.

Infectious Diseases Division, International Centre for Diarrhoeal Disease Research Bangladesh (icddr,b), Dhaka, Bangladesh.

After the large influx of Rohingya nationals (termed Forcibly Displaced Myanmar National; FDMN) from Rakhine State of Myanmar to Cox's Bazar in Bangladesh, it was apparent that outbreaks of cholera was very likely in this setting where people were living under adverse water and sanitation conditions. Large campaigns of oral cholera vaccine (OCV) were carried out as a preemptive measure to control cholera epidemics. The aim of the study was to evaluate the immune responses of healthy adults and children after administration of two doses of OCV at 14 days interval in FDMN population and compare with the response observed in Bangladeshi's vaccinated earlier. A cross-sectional immunogenicity study was conducted among FDMNs of three age cohort; in adults (18+years; n = 83), in older children (6-17 years; n = 63) and in younger children (1-5 years; n = 80). Capillary blood was collected at three time points to measure vibriocidal antibodies using either plasma or dried blood spot (DBS) specimens. There was a significant increase of responder frequency of vibriocidal antibody titer at day 14 in all groups for Vibrio cholerae O1 (Ogawa/Inaba: adults-64%/64%, older children-70%/89% and younger children-51%/75%). There was no overall difference of vibriocidal antibody titer between FDMN and Bangladeshi population at baseline (p = 0.07-0.08) and at day 14, day 28 in all age groups for both serotypes. The seroconversion rate and geometric mean titer (GMT) of either serotype were comparable using both plasma and DBS specimens. These results showed that OCV is capable of inducing robust immune responses in adults and children among the FDMN population which is comparable to that seen in Bangladeshi participants in different age groups or that reported from other cholera endemic countries. Our results also suggest that the displaced population were exposed to V. cholerae prior to seeking shelter in Bangladesh.
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http://dx.doi.org/10.1371/journal.pntd.0007989DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7075546PMC
March 2020