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Objectives: The severity of the diarrhea disease is exacerbated by co-infections that involve Enterotoxigenic Escherichia coli (ETEC) and other enteric pathogens, which complicate the diagnosis and treatment. This study explores the prevalence, clinical manifestations, and risk factors of ETEC and its co-infections in Dhaka, Bangladesh., Methods: The study used data from the Diarrheal Disease Surveillance System at Dhaka Hospital, involving 16,276 patients from 2017 to 2022. We identified 1404 ETEC-positive patients from the 16,276 data points to investigate the association between ETEC infections, co-infections, and clinical outcomes., Results: ETEC was identified in 1404 (8.6%) of cases, representing the most common infection among adults (56.6%). ETEC co-infection occurred combined with V. cholerae (23%), Aeromonas (14.6%), rotavirus (11.8%), Campylobacter (6.5%), and Shigella spp. (1.7%), respectively. Adults were more likely to develop co-infections with ETEC and V. cholerae, while children under five were more likely to develop ETEC co-infections with rotavirus. Co-infections with V. cholerae, rotavirus, and Salmonella spp. increased the likelihood of fever, while ETEC co-infections with V. cholerae increased risks of vomiting, dehydration, and intravenous fluids., Conclusions: ETEC and co-infections exacerbate illness severity and overburden healthcare systems. Policymakers should prioritize resilient healthcare strategies for ETEC and co-infections., Competing Interests: Declarations of competing interest The authors affirm that the research was carried out without any commercial or financial associations that could be seen as a possible conflict of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: When delivered through vaccination Vi-polysaccharide antigen of Salmonella enterica serotype Typhi protects against typhoid by inducing IgG anti-Vi antibodies. We aimed to determine whether the presence of antibodies following natural infection is associated with a lower incidence of typhoid fever in endemic regions., Methods: We analyzed data from a cohort study of typhoid fever conducted in Dhaka, Bangladesh. Plasma IgG anti-Vi antibodies were measured using a standard enzyme-linked immunosorbent assay in random serosurveys of a population that had not previously received typhoid vaccination. Participants were followed for up to 20 months for culture-confirmed typhoid fever. The receiver operating characteristic (ROC) curve and Cox proportional hazard models were used to evaluate the associations between antibody levels and typhoid risk., Results: The ROC analysis revealed that IgG anti-Vi antibody titers were predictive of typhoid risk among the 8,261 serosurvey participants (area under the curve: 0·63; 95% confidence interval (CI): 0·58─0·67). Detection of any antibodies was associated with a lower risk of typhoid in crude analyses (hazard ratio (HR): 0·13; 95% CI: 0·03─0·52), though this association declined after adjustment (HR: 0·32; 95% CI: 0·07─1·40). A positive correlation was observed between IgG anti-Vi titers and age (correlation coefficient 0·35; p < 0·001), with a stepwise increase in detectable antibodies by age, ranging from 12·0% (280/2,333) in children under 5 years to 54·2% (463/854) in individuals 50 years and older (p < 0·001)., Conclusions: In typhoid-endemic populations, IgG anti-Vi antibodies may indicate natural immunity to typhoid. The increasing seroprevalence with age suggests that these antibodies could serve as markers of cumulative past typhoid infections. Future research should explore these possibilities., Clinical Trial Number: Not applicable., Competing Interests: Declarations. Ethics approval and consent to participate: The study was conducted under the provisions of the Helsinki Declaration. The study protocol was approved by the research review committee and ethical review committee of the International Centre for Diarrhoeal Disease Research, Bangladesh. Informed written consent was obtained for all study participants, or from a parent or guardian for minors, and informed written assent was obtained from individuals aged 11–17 years. Anonymized data were obtained from all study participants. Consent for publication: Not applicable. Competing interests: FQ and XL are members of the WHO SAGE typhoid working group. XL is a member of the WHO TAG on Salmonella vaccines. AJP is chair of the UK Department of Health and Social Care’s Joint Committee on Vaccination, and he was a member of the WHO’s Strategic Advisory Group of Experts until 2022 and is chair of WHO’s TAG on Salmonella vaccines. All other authors declare no competing interests., (© 2025. The Author(s).)

Background: Shigella spp are among the notable causes of global diarrheal disease and death, accounting for 13.2% of deaths in 2016. Antimicrobial resistance complicates shigellosis management. Understanding local disease epidemiology is crucial for developing effective preventive strategies, including vaccine use., Methods: We investigated antimicrobial resistance, risk factors (socioeconomic, behavioral, and water, sanitation and hygiene (WaSH), and clinical characteristics of Shigella diarrhea in Mukuru informal settlement and surrounding villages in Nairobi, Kenya. Patients presenting with diarrhea, fever, or both in treatment centers had stool or rectal swab samples cultured, and bacteria was identified through biochemical and serologic tests., Results: The rate of Shigella isolation among the 4689 individuals presenting with diarrhea was 1.4% across all ages, with a similar isolation rate (1.5%) among children <5 years of age. The majority of the Shigella spp (40 [59.7%]) were Shigella flexneri, and the majority of S flexneri (34 of 40 [85%]) were resistant to trimethoprim-sulfamethoxazole; however, all were sensitive to amoxicillin-clavulanate, ceftazidime, ceftriaxone, and cefpodoxime. The rate of multidrug resistance was higher in Shigella sonnei (13 [48.1%]) than in S flexneri (3 [7.5%]). Shigella positivity was associated with bloody diarrhea, severe/moderate dehydration, coated tongue, and high fever. Consumption of street food was also associated with Shigella diarrhea., Conclusions: Despite low prevalence, shigellosis still poses a significant burden of diarrheal disease, warranting future incidence studies. First-line antibiotics against Shigella remain effective, but intermediate resistance to azithromycin and ciprofloxacin is a concerning trend. Improving household food preparation and handling could potentially reduce Shigella infections., Competing Interests: Potential conflicts of interest. The authors declare no competing interests., (© The Author(s) 2025. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Patients with cholera have been shown to be protected against subsequent cholera for 3 years after their initial episode. We aimed to assess protection at 10 years of follow-up., Methods: In this retrospective cohort study, cohorts of patients treated for cholera (index patients) and contemporaneously selected age-matched individuals without cholera (controls), randomly selected from the population of Matlab, Bangladesh, were assembled between 1990 and 2009 and followed for up to 10 years. Selection of participants who had no history of cholera in the 5 years before selection proceeded in secular sequence, and selection was done without replacement. Protection against subsequent treated cholera was assessed in proportional hazards models and waning of protection was assessed non-parametrically with use of smoothing of protection curves., Findings: We included 3925 index patients and 23 550 matched controls. Patients with El Tor cholera (26 subsequent episodes among 3619 index patients) had a 48·6% (95% CI 23·1 to 65·7; p=0·0012) lower risk of El Tor cholera than controls, with no evidence of waning during up to 10 years of follow-up (p=0·87). Index patients aged 5 years and older with El Tor cholera (nine subsequent episodes among 2279 index patients) were at a 61·7% (23·6 to 80·8; p=0·0065) lower risk of El Tor cholera, whereas index patients younger than 5 years with El Tor cholera (17 subsequent episodes among 1340 index patients) had a 36·2% (-5·0 to 61·3; p=0·077) lower risk (p=0·26 for the difference by age)., Interpretation: Protection against El Tor cholera associated with previous El Tor cholera was moderate in magnitude and sustained over 10 years of follow-up. These findings suggest the potential for sustained, long-term protection by oral cholera vaccines in populations with endemic cholera and help inform models of cholera in endemic settings., Funding: Bill & Melinda Gates Foundation., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Diarrheal diseases, especially cholera, can be a serious threat to Rohingya refugees in Cox's Bazar due to overcrowding and inadequate hygiene infrastructure. Assessing the risk, cholera surveillance network was established with the aim to identify the outbreak of diarrhea and cholera and help to take appropriate preventive measures including a vaccination campaign. The surveillance network has been ongoing for 6 years (2017-2023) in 17 health facilities. Diarrhea patients from Rohingya Myanmar nationals matched with case definition were enrolled and stool samples were tested by Rapid diagnostic test (RDT) for early cholera detection Multiple Logistic regression models were fitted to examine the associations of risk factors among cholera cases. A total of 17,252 stool samples were collected through surveillance. Among the tested samples, 588 (3.5 %) were detected positive by RDT, and 239 (1.4 %) Vibrio cholerae were isolated by microbiological culture. Between 2021 and 2023, the number of culture-confirmed cases exceeded that in the period from 2017 to 2020. In addition to V. cholerae ; high positivity was identified for ETEC (11.8 %) followed by Salmonella (3.9 %) and Shigella (2.7 %). Most of the cholera cases were presented with vomiting, dehydration and loose watery and rice watery nature of stool ( p value = <0.001). Major risk factors for cholera were 2-4 years age group (OR = 5.72; 95 % CI, 3.84-8.53.14; P  = .001), process of water treatment (OR = 1.54; 95 % CI, 1.01-2.37; P = .046) and hand washing with soap before taking meals (OR = 0.6; 95 % CI, 0.39-0.92; P  = .020. This study highlights the epidemiology of cholera among the Rohingya population and underscores the effectiveness of integrating surveillance data with early warning, alert, and response systems (EWARS) system, along with oral cholera vaccine (OCV) campaigns, in preventing major cholera outbreak., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Dr. Firdausi Qadri reports administrative support and statistical analysis were provided by International Centre for Diarrhoeal Disease Research Bangladesh. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

Background: Salmonella enterica serotype Typhi (Salmonella Typhi) causes severe and occasionally life-threatening disease, transmitted through contaminated food and water. Humans are the only reservoir, inadequate water, sanitation, and hygiene infrastructure increases risk of typhoid. High-quality data to assess spatial and temporal relationships in disease dynamics are scarce., Methods: We analyzed data from a prospective cohort conducted in an urban slum area of Dhaka City, Bangladesh. Passive surveillance at study centers identified typhoid cases by microbiological culture. Each incident case (index case) was matched to two randomly selected index controls, and we measured typhoid incidence in the population residing in a geographically defined region surrounding each case and control. Spatial clustering was evaluated by comparing the typhoid incidence in residents of geometric rings of increasing radii surrounding the index cases and controls over 28 days. Temporal clustering was evaluated by separately measuring incidence in the first and second 14-day periods following selection. Incidence rate ratios (IRRs) were calculated using Poisson regression models., Results: We evaluated 141 typhoid index cases. The overall typhoid incidence was 0.44 per 100,000 person-days (PDs) (95% CI: 0.40, 0.49). In the 28 days following selection, the highest typhoid incidence (1.2 per 100,000 PDs [95% CI: 0.8, 1.6]) was in the innermost cluster surrounding index cases. The IRR in this innermost cluster was 4.9 (95% CI: 2.4, 10.3) relative to the innermost control clusters. Neither typhoid incidence rates nor relative IRR between index case and control populations showed substantive differences in the first and second 14-day periods after selection., Conclusion: In the absence of routine immunization programs, geographic clustering of typhoid cases suggests a higher intensity of typhoid risk in the population immediately surrounding identified cases. Further studies are needed to understand spatial and temporal trends and to evaluate the effectiveness of targeted vaccination in disrupting typhoid transmission., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ahmmed et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Oral cholera vaccine (OCV) and incremental improvements in household water, sanitation, and hygiene (WASH) within cholera-endemic areas can reduce cholera risk. However, we lack empiric evaluation of their combined impact., Methods: We evaluated a cluster-randomized, placebo-controlled trial of OCV (Shanchol) in Kolkata, India. The study population included 108 777 individuals, and 106 879 nonpregnant individuals >1 year of age were eligible to receive 2 doses of OCV or placebo. We measured cholera risk in all household members assigned to OCV vs placebo and in all members of households with "Better" vs "Not Better" WASH, where WASH was classified according to validated criteria. Protection was measured by Cox proportional hazard models., Results: Residence in an OCV household was associated with protective effectiveness (PE) of 54% (95% CI, 42%-64%; P < .001) and was similar regardless of Better (PE, 57%; 95% CI, 26%-75%; P = .002) or Not Better (PE, 53%; 95% CI, 40%-64%; P < .001) household WASH. Better WASH household residence was associated with PE of 30% (95% CI, 5%-48%; P = .023) and was similar in OCV (PE, 24%; 95% CI, -26% to 54%; P = .293) and placebo (PE, 29%; 95% CI, -3% to 51%; P = .069) households. When assessed conjointly, residence in OCV households with Better WASH was associated with the greatest PE against cholera at 69% (95% CI, 49%-81%; P < .001)., Conclusions: These findings suggest that the combination of a vaccine policy and improved WASH reduces cholera risk more than either would alone, although the magnitude of either intervention was not affected by the other. Future randomized trials investigating OCV and WASH interventions separately and together are recommended to further understand the interaction between OCV and WASH., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Global cholera control efforts rely heavily on effective water, sanitation, and hygiene (WASH) interventions in cholera-endemic settings., Methods: Using data from a large, randomized controlled trial of oral cholera vaccine conducted in Kolkata, India, we evaluated whether natural variations in WASH in an urban slum setting were predictive of cholera risk. From the control population (n = 55 086), baseline WASH data from a randomly selected "training subpopulation" (n = 27 634) were analyzed with recursive partitioning to develop a dichotomous ("better" vs "not better") composite household WASH variable from several WASH features collected at baseline, and this composite variable was then evaluated in a mutually exclusive "validation population" (n = 27 452). We then evaluated whether residents of better WASH households in the entire population (n = 55 086) experienced lower cholera risk using Cox regression models. Better WASH was defined by a combination of 4 dichotomized WASH characteristics including safe source of water for daily use, safe source of drinking water, private or shared flush toilet use, and always handwashing with soap after defecation., Results: Residence in better WASH households was associated with a 30% reduction in risk of cholera over a 5-year period (adjusted hazard ratio, 0.70 [95% confidence interval, .49-.99]; P = .048). We also found that the impact of better WASH households on reducing cholera risk was greatest in young children (0-4 years) and this effect progressively declined with age., Conclusions: The evidence suggests that modest improvements in WASH facilities and behaviors significantly modify cholera risk and may be an important component of cholera prevention and elimination strategies in endemic settings. Clinical Trials Registration. NCT00289224., Competing Interests: Potential conflicts of interest. The authors: No reported conflicts of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background and Objectives : The morbidity and mortality associated with COVID-19 have burdened worldwide healthcare systems beyond their capacities, forcing them to promptly investigate the virus characteristics and its associated outcomes. This clinical analysis aimed to explore the key factors related to the fatal outcome of severe COVID-19 cases. Materials and Methods : Thirty-five adult severe COVID-19 patients were enrolled from two COVID-19 hospitals in Dhaka, Bangladesh. Clinical manifestation, comorbid conditions, medications, SARS-CoV-2 RT-PCR related cycle threshold (CT) value, hematology, biochemical parameters with SARS-CoV-2 specific IgG and IgM responses at enrollment were compared between the survivors and deceased participants. Results : Total 27 patients survived and 8 patients died within 3 months of disease onset. Deceased patients suffered longer from shortness of breath than the survived ( p = 0.049). Among the severe cases, 62% of the deceased patients had multiple comorbid condition compared to 48% of those who survived. Interestingly, the anti-viral was initiated earlier among the deceased patients [median day of 1 (IQR: 0, 1.5) versus 6.5 (IQR: 6.25, 6.75)]. Most of the survivors (55%) received a combination of anticoagulant ( p = 0.034). Liver enzymes, creatinine kinase, and procalcitonin were higher among the deceased patients during enrollment. The median CT value among the deceased was significantly lower than the survivors ( p = 0.025). A significant difference for initial IgG ( p = 0.013) and IgM ( p = 0.030) responses was found between the survivor and the deceased groups. Conclusions: The factors including older age, male gender, early onset of respiratory distress, multiple comorbidities, low CT value, and poor antibody response may contribute to the fatal outcome in severe COVID-19 patients. Early initiation of anti-viral and a combination of anticoagulant treatment may prevent or lower the fatality among severe COVID-19 cases.

Background: Enterotoxigenic Escherichia coli (ETEC) and Vibrio cholerae O1 are most common bacterial causes of diarrheal diseases in Bangladesh. This analysis projected distribution of ETEC and V. cholerae O1 among diarrheal patients of icddr,b, Dhaka hospital in two diarrheal peaks of 2022., Methodology: Under the 2% systematic surveillance system, stool samples collected from diarrheal patients of icddr,b hospital were cultured and diagnostic testing was done for ETEC and V. cholerae O1. Comparison of positive cases was done between first peak (March-April) and second peak (October-November) in 2022., Results: A total of 2,937 stool specimens were tested of which 12% were ETEC and 20% were V. cholerae O1. About 40% of the severe dehydration cases were infected with V. cholerae O1. Predominant ETEC enterotoxin type was 'LT/ST' (41%). The LT enterotoxin significantly increased from 13% to 28% in the second peak ( p  = 0.015). The predominant colonization factors (CFs) on ETEC were CS5 + CS6 (23%), followed by CS6 (15%). CF-positive isolates was significantly higher in the second peak (36%) than in the first peak (22%) ( p  = 0.043). Total 14% cases were co-infected with ETEC and V. cholerae O1. Significant differences in the distribution of enterotoxin types were observed ( p  = 0.029) among the co-infection cases., Conclusion: Changing patterns of enterotoxin and CFs observed in ETEC pathogens should be taken into consideration for ETEC vaccine development. Considering cholera and ETEC biannual trends in causing diarrheal epidemics and outbreaks, emphasizes the need for thoughts on combination vaccine strategies for preventing acute watery diarrhea due to the two major bacterial pathogens., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Tauheed, Ahmed, Akter, Firoj, Ahmmed, Rahman, Afrad, Islam, Rahman, Khan, Alam, Bhuiyan, Chowdhury and Qadri.)

Background: Immune responses that target sialidase occur following natural cholera and have been associated with protection against cholera. Sialidase is a neuraminidase that facilitates the binding of cholera toxin (CT) to intestinal epithelial cells. Despite this, little is known about age-related sialidase-specific immune responses and the impact of nutritional status and co-infection on sialidase-specific immunity., Methods: We enrolled 50 culture-confirmed Vibrio cholerae O1 cholera cases presenting to the icddr,b Dhaka hospital with moderate to severe dehydration. We evaluated antibody responses out to 18 months (day 540) following cholera. We assessed immune responses targeting sialidase, lipopolysaccharide (LPS), cholera toxin B subunit (CtxB), and vibriocidal responses. We also explored the association of sialidase-specific immune responses to nutritional parameters and parasitic co-infection of cases., Results: This longitudinal cohort study showed age-dependent differences in anti-sialidase immune response after natural cholera infection. Adult patients developed plasma anti-sialidase IgA and IgG responses after acute infection (P<0.05), which gradually decreased from day 30 on. In children, no significant anti-sialidase IgA, IgM, and IgG response was seen with the exception of a late IgG response at study day 540 (p=0.05 compared to adults). There was a correlation between anti-sialidase IgA with vibriocidal titers, as well as anti-sialidase IgA and IgG with anti-LPS and anti-CtxB antibody responses in adult patients, whereas in children, a significant positive correlation was seen only between anti-sialidase IgA and CtxB IgA responses. Stunted children showed significantly lower anti-sialidase IgA, IgG, and IgM antibody responses and higher LPS IgG and IgM antibody responses than healthy children. The anti-sialidase IgA and IgG responses were significantly higher in cases with concomitant parasitic infection., Conclusion: Our data suggest that cholera patients develop age-distinct systemic and mucosal immune responses against sialidase. The stunted children have a lower anti-sialidase antibody response which may be associated with gut enteropathy and the neuraminidase plays an important role in augmented immune response in cholera patients infected with parasites., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chowdhury, Akter, Bhuiyan, Biswas, Firoj, Tauheed, Harris, Larocque, Ross, McMillan, Charles, Ryan, Calderwood and Qadri.)