Publications by authors named "Firdausi Qadri"

373 Publications

An Assessment of a Rapid SARS-CoV-2 Antigen Test in Bangladesh.

Am J Trop Med Hyg 2022 Aug 15. Epub 2022 Aug 15.

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

Early detection of SARS-CoV-2 infection is crucial to prevent its spread. This study aimed to document test sensitivity/specificity, correlation with cycle threshold value from polymerase chain reaction (PCR), fitness-for-use in different populations and settings, and user perspectives that could inform large-scale implementation. In this study, we evaluated the performance of a rapid antigen detection test, BD Veritor, and compared this (and another rapid test, Standard Q) against reverse transcription PCR (RT-PCR) in terms of sensitivity and specificity in 130 symptomatic and 130 asymptomatic adults. In addition, we evaluated the suitability and ease of use of the BD Veritor test in a subsample of study participants (n = 42) and implementers (n = 5). At 95% confidence interval, the sensitivity of the BD Veritor and Standard Q test were 70% and 63% in symptomatic and 87% and 73% in asymptomatic individuals, respectively, regarding positive SARS-CoV-2 RT-PCR results. Overall, the BD Veritor test was 78% sensitive and 99.5% specific compared with RT-PCR irrespective of the cycle threshold. This warrants large field evaluation as well as use of the rapid antigen test for quick assessment of SARS-CoV-2 for containment of epidemics in the country.
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http://dx.doi.org/10.4269/ajtmh.22-0068DOI Listing
August 2022

Introduction of an Electronic Clinical Decision Support Tool to Inform Prescribing for Pediatric Diarrhea in Bangladesh and Mali: Do Provider Expectations Predict Experiences?

Am J Trop Med Hyg 2022 07 13;107(1):32-34. Epub 2022 Jul 13.

Department of Population Health Sciences, University of Utah School of Medicine, Salt Lake City, Utah.

Nonindicated antibiotics for childhood diarrhea is a major contributor to global antimicrobial resistance. Electronic clinical decision support tools (eCDSTs) may reduce unnecessary antibiotics. This study examined how providers' expectations of an eCDST to predict diarrhea etiology compared with their experiences using the tool. Providers were enrolled from public hospitals in Bangladesh (n = 15) and Mali (n = 15), and surveys were completed at baseline and after using the eCDST. Baseline surveys assessed expectations (utility, ease of use, and threat to autonomy), and post surveys assessed experiences in the same domains. Providers' experiences with ease of use exceeded their baseline expectations, and providers reported less experienced threat to autonomy after use, compared with baseline expectations. Providers' expectations of threat to autonomy significantly predicted their experienced threat to autonomy. Findings suggest that an eCDST to inform antimicrobial prescribing for diarrhea is feasible and acceptable, but training should promote local ownership for sustainability.
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http://dx.doi.org/10.4269/ajtmh.21-1248DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9294706PMC
July 2022

A blueprint for eliminating cholera by 2030.

Nat Med 2022 Jul 22. Epub 2022 Jul 22.

International Center for Diarrhoeal Disease Research, Dhaka, Bangladesh.

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http://dx.doi.org/10.1038/s41591-022-01898-wDOI Listing
July 2022

Development of a Monoclonal Antibody to a Vibriophage as a Proxy for Vibrio cholerae Detection.

Infect Immun 2022 Jul 18:e0016122. Epub 2022 Jul 18.

Department of Environmental and Global Health, University of Floridagrid.15276.37, Gainesville, Florida, USA.

Cholera is an acute watery, diarrheal disease that causes high rates of morbidity and mortality without treatment. Early detection of the etiologic agent of toxigenic Vibrio cholerae is important to mobilize treatment and mitigate outbreaks. Monoclonal antibody (mAb) based rapid diagnostic tests (RDTs) enable early detection in settings without laboratory capacity. However, the odds of an RDT testing positive are reduced by nearly 90% when the common virulent bacteriophage ICP1 is present. We hypothesize that adding a mAb for the common, and specific, virulent bacteriophage ICP1 as a proxy for V. cholerae to an RDT will increase diagnostic sensitivity when virulent ICP1 phage is present. In this study, we used an approach to identify immunogenic ICP1 protein targets that were conserved across disparate time periods and locations. Specificity of targets to cholera patients with known ICP1 was determined, and specific targets were used to produce mAbs in a murine model. Candidate mAbs to the head protein demonstrated specificity to ICP1 by Enzyme linked immunosorbent assay (ELISA) and an ICP1 phage neutralization assay. The limit of detection of the final mAb candidate for ICP1 phage particles spiked into cholera stool matrix was 8 × 10 PFU by Western blotting analysis. This mAb will be incorporated into a RDT prototype for evaluation in a future diagnostic study to test the guiding hypothesis behind this study.
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http://dx.doi.org/10.1128/iai.00161-22DOI Listing
July 2022

Diagnosis, Management, and Future Control of Cholera.

Clin Microbiol Rev 2022 Jun 21:e0021121. Epub 2022 Jun 21.

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

Cholera, caused by Vibrio cholerae, persists in developing countries due to inadequate access to safe water, sanitation, and hygiene. There are approximately 4 million cases and 143,000 deaths each year due to cholera. The disease is transmitted fecally-orally via contaminated food or water. Severe dehydrating cholera can progress to hypovolemic shock due to the rapid loss of fluids and electrolytes, which requires a rapid infusion of intravenous (i.v.) fluids. The case fatality rate exceeds 50% without proper clinical management but can be less than 1% with prompt rehydration and antibiotics. Oral cholera vaccines (OCVs) serve as a major component of an integrated control package during outbreaks or within zones of endemicity. Water, sanitation, and hygiene (WaSH); health education; and prophylactic antibiotic treatment are additional components of the prevention and control of cholera. The World Health Organization (WHO) and the Global Task Force for Cholera Control (GTFCC) have set an ambitious goal of eliminating cholera by 2030 in high-risk areas.
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http://dx.doi.org/10.1128/cmr.00211-21DOI Listing
June 2022

Prevalence of COVID-19 in Bangladesh, April to October 2020-a cross-sectional study.

IJID Reg 2021 Dec 14;1:92-99. Epub 2021 Oct 14.

Directorate General of Health Services (DGHS), Dhaka, Bangladesh.

The aim of this study was to estimate the proportion of symptomatic and asymptomatic laboratory-confirmed coronavirus disease 2019 (COVID-19) cases among the population of Bangladesh. A cross-sectional survey was conducted in Dhaka City and other districts of Bangladesh between April 18 and October 12, 2020. A total of 32 districts outside Dhaka were randomly selected, and one village and one mahalla was selected from each district; 25 mahallas were selected from Dhaka City. From each village or mahalla, 120 households were enrolled through systematic random sampling. A total of 44 865 individuals were interviewed from 10 907 households. The majority (70%,  = 31 488) of the individuals were <40 years of age. Almost half of the individuals (49%,  = 21 888) reported more than four members in their household. It was estimated that 12.6% ( = 160) of the households had one or more severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected individuals, among whom 0.9% ( = 404) of individuals had at least one COVID-19-like symptom, at the national level. The prevalence of COVID-19 in the general population was 6.4%. Among the SARS-CoV-2-positive individuals, 87% were asymptomatic. The substantial high number of asymptomatic cases all over Bangladesh suggests that community-level containment and mitigation measures are required to combat COVID-19. Future studies to understand the transmission capability could help to define mitigation and control measures.
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http://dx.doi.org/10.1016/j.ijregi.2021.10.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8516147PMC
December 2021

Seroprevalence of SARS-CoV-2 antibodies in Bangladesh related to novel coronavirus infection.

IJID Reg 2022 Mar 2;2:198-203. Epub 2022 Feb 2.

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

Design: A cross-sectional study was conducted amongst household members in 32 districts of Bangladesh to build knowledge about disease epidemiology and seroepidemiology of coronavirus disease 2019 (COVID-19).

Objective: Antibody responses to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) were assessed in people between April and October 2020.

Results: The national seroprevalence rates of immunoglobulin G (IgG) and IgM were estimated to be 30.4% and 39.7%, respectively. In Dhaka, the seroprevalence of IgG was 35.4% in non-slum areas and 63.5% in slum areas. In areas outside of Dhaka, the seroprevalence of IgG was 37.5% in urban areas and 28.7% in rural areas. Between April and October 2020, the highest seroprevalence rate (57% for IgG and 64% for IgM) was observed in August. IgM antibody was more prevalent in younger participants, while older participants had more frequent IgG seropositivity. Follow-up specimens from patients with COVID-19 and their household members suggested that both IgG and IgM seropositivity increased significantly at day 14 and day 28 compared with day 1 after enrolment. : SARS-CoV-2 had spread extensively in Bangladesh by October 2020. This highlights the importance of monitoring seroprevalence data, particularly with the emergence of new SARS-CoV-2 variants over time.
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http://dx.doi.org/10.1016/j.ijregi.2022.01.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8809641PMC
March 2022

Covishield vaccine induces robust immune responses in Bangladeshi adults.

IJID Reg 2022 Jun 29;3:211-217. Epub 2022 Apr 29.

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

Objective: To evaluate severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-specific antibody responses after Covishield vaccination for 6 months after vaccination.

Design: SARS-CoV-2-specific antibody responses were assessed by enzyme-linked immunosorbent assay of the recombinant receptor-binding domain of SARS-CoV-2 in 381 adults given the Covishield vaccine at baseline (=119), 1 month (=126) and 2 months (=75) after the first dose, 1 month after the second dose (=161), and monthly for 3 additional months.

Results: Over 51% of participants were seropositive at baseline (before vaccination with Covishield), and almost all participants (159/161) became seropositive 1 month after the second dose. Antibody levels peaked 1 month after receipt of the second dose of vaccine, and decreased by 4 months after the first dose; the lowest responses were found 6 months after the first dose, although antibody responses and responder frequencies remained significantly higher compared with baseline (<0.0001). Compared with younger participants, older participants had lower antibody responses 6 months after the first dose of vaccine (<0.05). Participants who had previous SARS-CoV-2 infection showed robust higher antibody responses after vaccination.

Conclusions: These findings help to elucidate the longevity of vaccine-specific antibody responses following vaccination with Covishield, and provide information relevant to the planning of booster doses after the initial two doses of vaccine.
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http://dx.doi.org/10.1016/j.ijregi.2022.04.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9050186PMC
June 2022

Mucosal-Associated Invariant T (MAIT) cells are highly activated in duodenal tissue of humans with Vibrio cholerae O1 infection: A preliminary report.

PLoS Negl Trop Dis 2022 05 12;16(5):e0010411. Epub 2022 May 12.

Division of Infectious Diseases, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, Utah, United States of America.

Mucosal-associated invariant T (MAIT) cells are unconventional T lymphocytes with a semi-conserved TCRα, activated by the presentation of vitamin B metabolites by the MHC-I related protein, MR1, and with diverse innate and adaptive effector functions. The role of MAIT cells in acute intestinal infections, especially at the mucosal level, is not well known. Here, we analyzed the presence and phenotype of MAIT cells in duodenal biopsies and paired peripheral blood samples, in patients during and after culture-confirmed Vibrio cholerae O1 infection. Immunohistochemical staining of duodenal biopsies from cholera patients (n = 5, median age 32 years, range 26-44, 1 female) identified MAIT cells in the lamina propria of the crypts, but not the villi. By flow cytometry (n = 10, median age 31 years, range 23-36, 1 female), we showed that duodenal MAIT cells are more activated than peripheral MAIT cells (p < 0.01 across time points), although there were no significant differences between duodenal MAIT cells at day 2 and day 30. We found fecal markers of intestinal permeability and inflammation to be correlated with the loss of duodenal (but not peripheral) MAIT cells, and single-cell sequencing revealed differing T cell receptor usage between the duodenal and peripheral blood MAIT cells. In this preliminary report limited by a small sample size, we show that MAIT cells are present in the lamina propria of the duodenum during V. cholerae infection, and more activated than those in the blood. Future work into the trafficking and tissue-resident function of MAIT cells is warranted.
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http://dx.doi.org/10.1371/journal.pntd.0010411DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9129025PMC
May 2022

Microbiome Profiling of Enterotoxigenic Escherichia coli (ETEC) Carriers Highlights Signature Differences between Symptomatic and Asymptomatic Individuals.

mBio 2022 06 10;13(3):e0015722. Epub 2022 May 10.

Cambridge Institute for Therapeutic Immunology and Infectious Disease (CITIID), Department of Medicine, University of Cambridge, Cambridge, United Kingdom.

Enterotoxigenic Escherichia coli (ETEC) is an important cause of diarrhea in children in low- and middle-income countries (LMICs). However, large-scale pathogen burden studies in children have identified ETEC in the guts of both symptomatic patients and controls. The factors that influence this balance are poorly understood, but it is postulated that the gut microbiome may play a role in either resistance or progression to disease. In this study, we profiled the microbiomes of children and adults from Bangladesh who were asymptomatically or symptomatically infected with ETEC. Symptomatic patients had significantly higher numbers of sequenced reads mapping to both E. coli and two ETEC toxins, suggesting higher bacterial burden. They were also significantly more likely to be coinfected with enteroaggregative E. coli (EAEC) and had higher proportions of other , including Klebsiella, Salmonella, and Haemophilus. Colonization with ETEC was also associated with increased prevalence of antimicrobial resistance (AMR) genes, most notably those of the β-lactamase class. Taxonomic profiles were distinctly different between all groups in both species richness and composition, although the direction of these changes was different in adults and children. As seen previously, children with high E. coli burdens also had higher proportions of Streptococcus spp., while healthy children were more heavily colonized by spp. Our study provides insight into the microbiome changes that occur upon infection with ETEC in an endemic setting and provides rationale for future studies investigating how the microbiome may protect or predispose individuals to symptomatic infections with gastrointestinal pathogens. Enterotoxigenic Escherichia coli (ETEC) is an important cause of diarrhea in children in low- and middle-income countries. However, these bacteria are often identified in both patients and healthy controls. We do not yet understand why only some people get sick, but it has been suggested that the gut microbiome might play a role. In this study, we used metagenomic sequencing to profile the gut microbiomes of individuals in Bangladesh, with or without a symptomatic ETEC infection. In general, individuals with high levels of ETEC also harbored other pathogenic E. coli strains, higher proportions of such as Salmonella and Klebsiella, and a higher burden of antimicrobial resistance genes in their guts. Healthy children, in contrast, had higher levels of bifidobacteria. These data confirm that the composition of the gut microbiome is different between symptomatic and asymptomatic people and provides important preliminary information on the impact of the gut microbiome in intestinal infections.
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http://dx.doi.org/10.1128/mbio.00157-22DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9239084PMC
June 2022

Transmission of SARS-CoV-2 in the Population Living in High- and Low-Density Gradient Areas in Dhaka, Bangladesh.

Trop Med Infect Dis 2022 Mar 25;7(4). Epub 2022 Mar 25.

Programme for Emerging Infections, Infectious Diseases Division, icddr,b, Dhaka 1212, Bangladesh.

Community transmission of SARS-CoV-2 in densely populated countries has been a topic of concern from the beginning of the pandemic. Evidence of community transmission of SARS-CoV-2 according to population density gradient and socio-economic status (SES) is limited. In June-September 2020, we conducted a descriptive longitudinal study to determine the community transmission of SARS-CoV-2 in high- and low-density areas in Dhaka city. The Secondary Attack Rate (SAR) was 10% in high-density areas compared to 20% in low-density areas. People with high SES had a significantly higher level of SARS-CoV-2-specific Immunoglobulin G (IgG) antibodies on study days 1 ( = 0.01) and 28 ( = 0.03) compared to those with low SES in high-density areas. In contrast, the levels of seropositivity of SARS-CoV-2-specific Immunoglobulin M (IgM) were comparable ( > 0.05) in people with high and low SES on both study days 1 and 28 in both high- and low-density areas. Due to the similar household size, no differences in the seropositivity rates depending on the population gradient were observed. However, people with high SES showed higher seroconversion rates compared to people with low SES. As no difference was observed based on population density, the SES might play a role in SARS-CoV-2 transmission, an issue that calls for further in-depth studies to better understand the community transmission of SARS-CoV-2.
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http://dx.doi.org/10.3390/tropicalmed7040053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9030026PMC
March 2022

Prevention of typhoid by Vi conjugate vaccine and achievable improvements in household WASH: Evidence from a cluster-randomized trial in Dhaka, Bangladesh.

Clin Infect Dis 2022 Apr 12. Epub 2022 Apr 12.

International Vaccine Institute, Seoul, Republic of Korea.

Background: Typhoid fever contributes to approximately 135,000 deaths annually. Achievable improvements in household water-hygiene-sanitation (WASH) combined with vaccination using typhoid conjugate vaccines (TCVs) may be an effective preventive strategy. However, little is known about how improved WASH and vaccination interact to lower the risk of typhoid.

Methods: 61,654 urban Bangladeshi children aged 9 months to <16 years, residing in 150 clusters with a baseline population of 205,760 residents, were randomized 1: 1 by cluster to Vi-tetanus toxoid TCV or Japanese Encephalitis (JE) vaccine. Surveillance for blood culture-confirmed typhoid fever was conducted over two years. Existing household WASH status was assessed at baseline as Better or Not Better using previously validated criteria. The reduction in typhoid risk among all residents associated with living in TCV clusters, Better WASH households, or both was evaluated using mixed-effects Poisson regression models.

Results: The adjusted reduced risk of typhoid among all residents living in the clusters assigned to TCV was 55% (95% confidence interval (CI): 43%,65%; p < 0.001), and that of living in Better WASH households, regardless of cluster, was 37% (95%CI: 24%,48%; p < 0.001). The highest risk of typhoid was observed in persons living in households with Not Better WASH in the JE clusters. In comparison with these persons, those living in households with Better WASH in the TCV clusters had an adjusted reduced risk of 71% (95%CI: 59%, 80%; p < 0.001).

Conclusion: Implementation of TCV programs combined with achievable and culturally acceptable household WASH practices were independently associated with a significant reduction in typhoid risk.
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http://dx.doi.org/10.1093/cid/ciac289DOI Listing
April 2022

Prevention of Typhoid Fever by Existing Improvements in Household Water, Sanitation, and Hygiene, and the Use of the Vi Polysaccharide Typhoid Vaccine in Poor Urban Slums: Results from a Cluster-Randomized Trial.

Am J Trop Med Hyg 2022 03 7;106(4):1149-1155. Epub 2022 Mar 7.

International Vaccine Institute, Seoul, Republic of Korea.

Modest improvements in household water, sanitation, and hygiene (WASH) and typhoid vaccination can reduce typhoid risk in endemic settings. However, empiric evaluation of their combined impact is lacking. A total of 62,756 persons residing in 80 clusters in a Kolkata slum were allocated randomly 1:1 to either the typhoid Vi polysaccharide (ViPS) vaccine or hepatitis A (Hep A) vaccine. Surveillance was conducted for 2 years before and 2 years after vaccination. We classified households as having "better" or "not better" WASH, and calculated the prevalence of better WASH households in clusters using previously validated criteria. We evaluated the protection by better household WASH, better household WASH prevalence, and ViPS vaccination against typhoid in all cluster members present at baseline using Cox proportional hazard models. Overall, ViPS vaccination was associated with a 55% (P < 0.001; 95% CI, 35-69) reduction of typhoid risk and was similar regardless of better WASH in the residence. Living in a better WASH household was associated with a typhoid risk reduction of 31% (P = 0.16; 95% CI, -16 to 59) overall. The reduction was 48% (P = 0.05; 95% CI, -1 to 73) in Hep A clusters, 6% (P = 0.85; 95% CI, -82 to 51) in ViPS clusters, and 57% (P < 0.05; 95% CI, 15-78) in the population during the 2 years preceding the trial. These findings demonstrate a preventive association of better household WASH in the non-ViPS population, but, unexpectedly, an absence of additional protection from ViPS by better WASH in the ViPS population. This analysis highlights the importance of assessing the combination of WASH in conjunction with typhoid vaccines, and has implications for the evaluation of new-generation typhoid conjugate vaccines.
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http://dx.doi.org/10.4269/ajtmh.21-1034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8991341PMC
March 2022

Impact of a human gut microbe on host colonization through biofilm enhancement.

Elife 2022 Mar 28;11. Epub 2022 Mar 28.

Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, United States.

Recent studies indicate that the human intestinal microbiota could impact the outcome of infection by the etiological agent of the diarrheal disease cholera. A commensal bacterium, was previously identified in high abundance in stool collected from individuals infected with when compared to stool from uninfected persons. However, if and how interacts with has not been experimentally determined; moreover, whether any association between this bacterium alters the behaviors of to affect the disease outcome is unclear. Here, we show that and together form dual-species biofilm structure at the air-liquid interface, with previously uncharacterized novel features. Importantly, the presence of within the murine small intestine enhances colonization in the same niche that is dependent on the exopolysaccharide and other major components of mature biofilm. These studies illustrate that multispecies biofilm formation is a plausible mechanism used by a gut microbe to increase the virulence of the pathogen, and this interaction may alter outcomes in enteric infections.
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http://dx.doi.org/10.7554/eLife.73010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8993218PMC
March 2022

Toward Typhoid Fever Elimination.

Int J Infect Dis 2022 Jun 23;119:41-43. Epub 2022 Mar 23.

International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh.

Salmonella enterica serotype Typhi (S Typhi) causes typhoid fever and is responsible for an estimated 9 million cases and 110,000 deaths globally per annum. Typhoid fever is endemic in areas where water, sanitation, and hygiene (WaSH) infrastructure is poor. Serious complications develop in approximately 10%-15% of patients if left untreated, and this is driven by inadequate diagnostic methods and the high burden of antibiotic-resistant strains, complicating clinical management and ultimately prognosis. Asymptomatic chronic carriers, in addition to acutely infected patients, contribute to continued transmission through the shedding of the organism in the feces. The high morbidity and mortality of typhoid fever in low- and middle-income countries reinforce the need for an integrated control approach, which may ultimately lead to elimination of the disease in the 21 century. Here we discuss the challenges faced in pursuit of typhoid fever elimination.
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http://dx.doi.org/10.1016/j.ijid.2022.03.036DOI Listing
June 2022

Genome Sequences of 25 SARS-CoV-2 Sublineage B.1.1.529 Omicron Strains in Bangladesh.

Microbiol Resour Announc 2022 Apr 24;11(4):e0011922. Epub 2022 Mar 24.

Institute of Epidemiology, Disease Control, and Research, Dhaka, Bangladesh.

We report the coding-complete genome sequences of 25 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sublineage B.1.1.529 Omicron strains obtained from Bangladeshi individuals in samples collected between December 2021 and January 2022. Genomic data were generated by Nanopore sequencing using the amplicon sequencing approach developed by the ARTIC Network.
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http://dx.doi.org/10.1128/mra.00119-22DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9022525PMC
April 2022

Virus-like Particle Display of -Specific Polysaccharide as a Potential Vaccine against Cholera.

ACS Infect Dis 2022 03 16;8(3):574-583. Epub 2022 Feb 16.

Department of Chemistry, Michigan State University, East Lansing, Michigan 48824, United States.

, a noninvasive mucosal pathogen, is endemic in more than 50 countries. Oral cholera vaccines, based on killed whole-cell strains of , can provide significant protection in adults and children for 2-5 years. However, they have relatively limited direct protection in young children. To overcome current challenges, in this study, a potential conjugate vaccine was developed by linking -specific polysaccharide (OSP) antigen purified from O1 El Tor Inaba strain PIC018 with Qβ virus-like particles efficiently via squarate chemistry. The Qβ-OSP conjugate was characterized with mass photometry (MP) on the whole particle level. Pertinent immunologic display of OSP was confirmed by immunoreactivity of the conjugate with convalescent phase samples from humans with cholera. Mouse immunization with the Qβ-OSP conjugate showed that the construct generated prominent and long-lasting IgG antibody responses against OSP, and the resulting antibodies could recognize the native lipopolysaccharide from O1 Inaba. This was the first time that Qβ was conjugated with a bacterial polysaccharide for vaccine development, broadening the scope of this powerful carrier.
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http://dx.doi.org/10.1021/acsinfecdis.1c00585DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9119010PMC
March 2022

COVID-19 and dengue infection in Bangladesh: A case of coinfection where hemoptysis as first presentation.

Clin Case Rep 2022 Jan 20;10(1):e05252. Epub 2022 Jan 20.

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

Bangladesh recently faced large outbreaks of both COVID-19 and dengue. We present a case of COVID-19 and dengue coinfection in a patient who presented with hemoptysis. Our results demonstrate that COVID-19 and dengue fever are both public health issues in Bangladesh and other dengue-endemic nations and that they can coexist.
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http://dx.doi.org/10.1002/ccr3.5252DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8777161PMC
January 2022

SARS-CoV-2 Seroprevalence before Delta Variant Surge, Chattogram, Bangladesh, March-June 2021.

Emerg Infect Dis 2022 02;28(2):429-431

A March-June 2021 representative serosurvey among Sitakunda subdistrict (Chattogram, Bangladesh) residents found an adjusted prevalence of severe acute respiratory syndrome coronavirus 2 antibodies of 64.1% (95% credible interval 60.0%-68.1%). Before the Delta variant surge, most residents had been infected, although cumulative confirmed coronavirus disease incidence was low.
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http://dx.doi.org/10.3201/eid2802.211689DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8798688PMC
February 2022

Disease characteristics and serological responses in patients with differing severity of COVID-19 infection: A longitudinal cohort study in Dhaka, Bangladesh.

PLoS Negl Trop Dis 2022 01 4;16(1):e0010102. Epub 2022 Jan 4.

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

Background: COVID-19 caused by SARS-CoV-2 ranges from asymptomatic to severe disease and can cause fatal and devastating outcome in many cases. In this study, we have compared the clinical, biochemical and immunological parameters across the different disease spectrum of COVID-19 in Bangladeshi patients.

Methodology/principal Findings: This longitudinal study was conducted in two COVID-19 hospitals and also around the community in Dhaka city in Bangladesh between November 2020 to March 2021. A total of 100 patients with COVID-19 infection were enrolled and classified into asymptomatic, mild, moderate and severe cases (n = 25/group). In addition, thirty age and sex matched healthy participants were enrolled and 21 were analyzed as controls based on exclusion criteria. After enrollment (study day1), follow-up visits were conducted on day 7, 14 and 28 for the cases. Older age, male gender and co-morbid conditions were the risk factors for severe COVID-19 disease. Those with moderate and severe cases of infection had low lymphocyte counts, high neutrophil counts along with a higher neutrophil-lymphocyte ratio (NLR) at enrollment; this decreased to normal range within 42 days after the onset of symptom. At enrollment, D-dimer, CRP and ferritin levels were elevated among moderate and severe cases. The mild, moderate, and severe cases were seropositive for IgG antibody by day 14 after enrollment. Moderate and severe cases showed significantly higher IgM and IgG levels of antibodies to SARS-CoV-2 compared to mild and asymptomatic cases.

Conclusion/significance: We report on the clinical, biochemical, and hematological parameters associated with the different severity of COVID-19 infection. We also show different profile of antibody response against SARS-CoV-2 in relation to disease severity, especially in those with moderate and severe disease manifestations compared to the mild and asymptomatic infection.
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http://dx.doi.org/10.1371/journal.pntd.0010102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8759637PMC
January 2022

A non-inferiority trial comparing two killed, whole cell, oral cholera vaccines (Cholvax vs. Shanchol) in Dhaka, Bangladesh.

Vaccine 2022 01 27;40(4):640-649. Epub 2021 Dec 27.

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

Bangladesh remains cholera endemic with biannual seasonal peaks causing epidemics. At least 300,000 severe cases and over 4,500 deaths occur each year. The available oral cholera vaccineshave not yet been adopted for cholera control in Bangladesh due to insufficient number of doses available for endemic control. With a public private partnership, icddr,b initiated a collaboration between vaccine manufacturers in Bangladesh and abroad. A locally manufactured Oral Cholera Vaccine (OCV) named Cholvax became available for testing in Bangladesh. We evaluated the safety and immunogenicity of this locally produced Cholvax (Incepta Vaccine Ltd) inexpensive OCV comparatively to Shanchol (Shantha Biotechnics-Sanofi Pasteur) which is licensed in several countries. We conducted a randomized non-inferiority clinical trial of bivalent, killed oral whole-cell cholera vaccine Cholvax vs. Shanchol in the cholera-endemic area of Mirpur, Dhaka, among three different age cohorts (1-5, 6-17 and 18-45 years) between April 2016 and April 2017. Two vaccine doses were given at 14 days apart to 2,052 healthy participants. No vaccine-related serious adverse events were reported. There were no significant differences in the frequency of solicited (7.31% vs. 6.73%) and unsolicited (1.46% vs. 1.07%) adverse events reported between the Cholvax and Shanchol groups. Vibriocidal antibody responses among the overall population for O1 Ogawa (81% vs. 77%) and O1 Inaba (83% vs. 84%) serotypes showed that Cholvax was non-inferior to Shanchol, with the non-inferiority margin of -10%. For O1 Inaba, GMT was 462.60 (Test group), 450.84 (Comparator group) with GMR 1.02(95% CI: 0.92, 1.13). For O1 Ogawa, GMT was 419.64 (Test group), 387.22 (Comparator group) with GMR 1.12 (95% CI: 1.02, 1.23). Cholvax was safe and non-inferior to Shanchol in terms of immunogenicity in the different age groups. These results support public use of Cholvax to contribute for reduction of the cholera burden in Bangladesh. ClinicalTrials.gov number: NCT027425581.
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http://dx.doi.org/10.1016/j.vaccine.2021.12.015DOI Listing
January 2022

Systemic, Mucosal, and Memory Immune Responses following Cholera.

Trop Med Infect Dis 2021 Oct 27;6(4). Epub 2021 Oct 27.

Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA 02114, USA.

O1, the major causative agent of cholera, remains a significant public health threat. Although there are available vaccines for cholera, the protection provided by killed whole-cell cholera vaccines in young children is poor. An obstacle to the development of improved cholera vaccines is the need for a better understanding of the primary mechanisms of cholera immunity and identification of improved correlates of protection. Considerable progress has been made over the last decade in understanding the adaptive and innate immune responses to cholera disease as well as infection. This review will assess what is currently known about the systemic, mucosal, memory, and innate immune responses to clinical cholera, as well as recent advances in our understanding of the mechanisms and correlates of protection against O1 infection.
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http://dx.doi.org/10.3390/tropicalmed6040192DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8628923PMC
October 2021

Clinical evaluation of SARS-CoV-2 antigen-based rapid diagnostic test kit for detection of COVID-19 cases in Bangladesh.

Heliyon 2021 Nov 22;7(11):e08455. Epub 2021 Nov 22.

Infectious Diseases Division (IDD), icddr,b, 68, Shaheed Tajuddin Ahmed Sarani, Mohakhali, Dhaka, 1212, Bangladesh.

The rapid and early detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections is key to control the current Coronavirus disease 2019 (COVID-19) pandemic. The present study was conducted to clinically evaluate a rapid diagnostic test (RDT) kit, Standard Q COVID-19 Ag Test (SD Biosensor®, Republic of Korea), with reference to the standard real-time RT-PCR for detection of COVID-19 cases in Bangladesh. Nasopharyngeal swabs were taken from 900 COVID-19 suspected patients. Among them, 34.11% (n = 307) were diagnosed as COVID-19 cases by RT-PCR assay, of which 85% (n = 261) were also detectable using the RDT. The overall sensitivity and specificity of the RDT compared to RT-PCR were 85.02% and 100%, respectively, regardless of age, sex, and type of SARS-CoV-2 variants. Most of the RT-PCR positive cases (94%) were found within the first five days of disease onset, and the sensitivity of RDT was 85.91% for the same samples. The positive predictive value (PPV) of the RDT was 100%, and the negative predictive value (NPV) was 92.8%. The Cohen's kappa value of 0.882 indicated excellent agreement between the RDT and RT-PCR assays. The findings of this study showed the potential use of SARS-CoV-2 antigen-based RDT to expedite the diagnostic process and onward COVID-19 management in Bangladesh.
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http://dx.doi.org/10.1016/j.heliyon.2021.e08455DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8606316PMC
November 2021

Burden of enteric fever at three urban sites in Africa and Asia: a multicentre population-based study.

Lancet Glob Health 2021 12;9(12):e1688-e1696

Oxford Vaccine Group, Department of Paediatrics, University of Oxford, and the NIHR Oxford Biomedical Research Centre, Oxford, UK.

Background: Enteric fever is a serious public health concern in many low-income and middle-income countries. Numerous data gaps exist concerning the epidemiology of Salmonella enterica serotype Typhi (S Typhi) and Salmonella enterica serotype Paratyphi (S Paratyphi), which are the causative agents of enteric fever. We aimed to determine the burden of enteric fever in three urban sites in Africa and Asia.

Methods: In this multicentre population-based study, we did a demographic census at three urban sites in Africa (Blantyre, Malawi) and Asia (Kathmandu, Nepal and Dhaka, Bangladesh) between June 1, 2016, and Sept 25, 2018. Households were selected randomly from the demographic census. Participants from within the geographical census area presenting to study health-care facilities were approached for recruitment if they had a history of fever for 72 h or more (later changed to >48 h) or temperature of 38·0°C or higher. Facility-based passive surveillance was done between Nov 11, 2016, and Dec 31, 2018, with blood-culture collection for febrile illness. We also did a community-based serological survey to obtain data on Vi-antibody defined infections. We calculated crude incidence for blood-culture-confirmed S Typhi and S Paratyphi infection, and calculated adjusted incidence and seroincidence of S Typhi blood-culture-confirmed infection.

Findings: 423 618 individuals were included in the demographic census, contributing 626 219 person-years of observation for febrile illness surveillance. 624 S Typhi and 108 S Paratyphi A isolates were collected from the blood of 12 082 febrile patients. Multidrug resistance was observed in 44% S Typhi isolates and fluoroquinolone resistance in 61% of S Typhi isolates. In Blantyre, the overall crude incidence of blood-culture confirmed S Typhi was 58 cases per 100 000 person-years of observation (95% CI 48-70); the adjusted incidence was 444 cases per 100 000 person-years of observation (95% credible interval [CrI] 347-717). The corresponding rates were 74 (95% CI 62-87) and 1062 (95% CrI 683-1839) in Kathmandu, and 161 (95% CI 145-179) and 1135 (95% CrI 898-1480) in Dhaka. S Paratyphi was not found in Blantyre; overall crude incidence of blood-culture-confirmed S Paratyphi A infection was 6 cases per 100 000 person-years of observation (95% CI 3-11) in Kathmandu and 42 (95% CI 34-52) in Dhaka. Seroconversion rates for S Typhi infection per 100 000 person-years estimated from anti-Vi seroconversion episodes in serological surveillance were 2505 episodes (95% CI 1605-3727) in Blantyre, 7631 (95% CI 5913-9691) in Kathmandu, and 3256 (95% CI 2432-4270) in Dhaka.

Interpretation: High disease incidence and rates of antimicrobial resistance were observed across three different transmission settings and thus necessitate multiple intervention strategies to achieve global control of these pathogens.

Funding: Wellcome Trust and the Bill & Melinda Gates Foundation.
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http://dx.doi.org/10.1016/S2214-109X(21)00370-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8609278PMC
December 2021

Induction of mucosal and systemic immune responses against the common O78 antigen of an oral inactivated ETEC vaccine in Bangladeshi children and infants.

Vaccine 2022 01 10;40(2):380-389. Epub 2021 Nov 10.

PATH, Washington, DC, USA.

We tested an oral enterotoxigenic Escherichia coli (ETEC) vaccine, ETVAX, consisting of inactivated E. coli overexpressing the most prevalent ETEC colonization factors (CFs) and a toxoid (LCTBA), in Bangladeshi children for capacity to induce mucosal and plasma immune responses against O78 lipopolysaccharide (LPS) expressed on the vaccine strains. The vaccine was given ± double-mutant heat-labile toxin (dmLT) adjuvant. We evaluated the impact of dmLT on anti-O78 LPS immune responses and whether such responses can predict responses against the CFs as a marker for vaccine "take". Two fractionated doses of ETVAX ± different amounts of dmLT were administered biweekly to groups of children 24-59 (n = 125), 12-23 (n = 97) and 6-11 (n = 158) months of age. Immune responses were evaluated in antibody in lymphocyte supernatants (ALS), fecal extracts and plasma. ALS IgA responses against O78 LPS were induced in 44-49% of the children aged 12-59 months. The magnitudes of the ALS responses were significantly higher in children receiving a half-dose (5 × 10 bacteria) of ETVAX ± dmLT than in placebo recipients. <10% of the vaccinees aged 6-11 months mounted ALS responses against O78 LPS. However, 49% of the infants developed fecal secretory IgA responses which were significantly more frequent in those receiving a quarter-dose (2.5 × 10 bacteria) of vaccine + dmLT (62%) compared to a quarter-dose alone (36%). Plasma IgA antibody responses were induced in 80% of older children and 36% of infants. The frequencies of O78 LPS responses in plasma and feces were comparable or higher than against the vaccine CFs in infants. Our findings show that ETVAX induced mucosal and systemic immune responses against O78 LPS in all age groups and that dmLT improved intestinal immune responses among infants. These observations may have implications for more successful use of other oral vaccines based on O antigens in children.
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http://dx.doi.org/10.1016/j.vaccine.2021.10.056DOI Listing
January 2022

Scalable production and immunogenicity of a cholera conjugate vaccine.

Vaccine 2021 11 27;39(47):6936-6946. Epub 2021 Oct 27.

Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA; Department of Medicine, Harvard Medical School, Boston, MA, USA; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA. Electronic address:

There is a need to develop cholera vaccines that are protective in young children under 5 years of age, which induce long-term immunity, and which can be incorporated into the Expanded Programme of Immunization (EPI) in cholera-endemic countries. The degree of protection afforded by currently available oral cholera vaccines (OCV) to young children is significantly lower than that induced by vaccination of older vaccine recipients. Immune responses that protect against cholera target the O-specific polysaccharide (OSP) of Vibrio cholerae, and young children have poor immunological responses to bacterial polysaccharides, which are T cell independent antigens. To overcome this, we have developed a cholera conjugate vaccine (CCV) containing the OSP of V. cholerae O1, the main cause of endemic and epidemic cholera. Here, we describe production of CCV through a scalable manufacturing process and preclinical evaluation of immunogenicity in the presence and absence of aluminum phosphate (alum) as an adjuvant. The vaccine displays V. cholerae O1 Inaba OSP in sun-burst display via single point attachment of core oligosaccharide to a recombinant tetanus toxoid heavy chain fragment (rTTHc). Two different pilot-scale production batches of non-GMP CCV were manufactured and characterized in terms of physico-chemical properties and immunogenicity. In preclinical testing, the vaccine induced OSP- and lipopolysaccharide (LPS)-specific IgG and IgM responses, vibriocidal responses, memory B cell responses, and protection in a V. cholerae O1 challenge model. The addition of alum to the administered vaccine increased OSP-specific immune responses. These results support evaluation of CCV in humans.
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http://dx.doi.org/10.1016/j.vaccine.2021.10.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8609181PMC
November 2021
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