Rotavirus trends and distribution of genotypes before and during COVID-19 pandemic era: Bangladesh, 2017-2021.

Rotavirus gastroenteritis is accountable for an estimated 128 500 deaths among children younger than 5 years worldwide, and the majority occur in low-income countries. Although the clinical trials of rotavirus vaccines in Bangladesh revealed a significant reduction of severe rotavirus disease by around 50%, the vaccines are not yet included in the routine immunization program. The present study was designed to provide data on rotavirus diarrhea with clinical profiles and genotypes before (2017-2019) and during the COVID-19 pandemic period (2020-2021). Fecal samples were collected from 2% of the diarrheal patients at icddr,b Dhaka hospital of all ages between January 2017 and December 2021 and were tested for VP6 rotavirus antigen using ELISA. The clinical manifestations such as fever, duration of diarrhea and hospitalization, number of stools, and dehydration and so on were collected from the surveillance database (n = 3127). Of the positive samples, 10% were randomly selected for genotyping using Sanger sequencing method. A total of 12 705 fecal samples were screened for rotavirus A antigen by enzyme immunoassay. Overall, 3369 (27%) were rotavirus antigen-positive, of whom children <2 years had the highest prevalence (88.6%). The risk of rotavirus A infection was 4.2 times higher in winter than in summer. Overall, G3P[8] was the most prominent genotype (45.3%), followed by G1P[8] (32.1%), G9P[8] (6.8%), and G2P[4] (6.1%). The other unusual combinations, such as G1P[4], G1P[6], G2P[6], G3P[4], G3P[6], and G9P[6], were also present. Genetic analysis on Bangladeshi strains revealed that the selection pressure (dN/dS) was estimated as <1. The number of hospital visits showed a 37% drop during the COVID-19 pandemic relative to the years before the pandemic. Conversely, there was a notable increase in the rate of rotavirus positivity during the pandemic (34%, p < 0.00) compared to the period before COVID-19 (23%). Among the various clinical symptoms, only the occurrence of watery stool significantly increased during the pandemic. The G2P[4] strain showed a sudden rise (19%) in 2020, which then declined in 2021. In the same year, G1P[8] was more prevalent than G3P[8] (40% vs. 38%, respectively). The remaining genotypes were negligible and did not exhibit much fluctuation. This study reveals that the rotavirus burden remained high during the COVID-19 prepandemic and pandemic in Bangladesh. Considering the lack of antigenic variations between the circulating and vaccine-targeted strains, integrating the vaccine into the national immunization program could reduce the prevalence of the disease, the number of hospitalizations, and the severity of cases.

Clinical severity of enteric viruses detected using a quantitative molecular assay compared to conventional assays in the Global Enteric Multicenter Study.

BACKGROUND: Quantitative molecular assays are increasingly used for detection of enteric viruses. METHODS: We compared the clinical severity using modified Vesikari score (mVS) of enteric viruses detected by conventional assays (enzyme immunoassays [EIA] for rotavirus and adenovirus 40/41 and conventional polymerase chain reaction for astrovirus, sapovirus, and norovirus) and a quantitative molecular assay (TaqMan Array Card [TAC]) among children aged 0-59 months in the Global Enteric Multicenter Study. For rotavirus and adenovirus 40/41, we compared severity between EIA-positive and TAC-positive cases assigned etiologies using different cycle threshold (CT) cutoffs. RESULTS: Using conventional assays, the median (interquartile range) mVS was 10 (8, 11) for rotavirus, 9 (7, 11) for adenovirus 40/41, 8 (6, 10) for astrovirus, sapovirus, and norovirus GII, and 7 (6, 9) for norovirus GI. Compared to rotavirus EIA-positive cases, the median mVS was 2 and 3 points lower for EIA-negative/TAC-positive cases with CT<32.6 and 32.6≤CT<35, respectively (p-value<.0001). Adenovirus 40/41 EIA-positive and EIA-negative/TAC-positive cases were similar, regardless of CT cutoff. CONCLUSIONS: Quantitative molecular assays compared to conventional assays, such as EIA, may influence severity of identified cases, especially for rotavirus. Cutoffs to assign etiology for quantitative assays should be considered in the design and interpretation of enteric virus studies.

Impact of Rotaviral Diarrhea on Child Growth in Sub-Saharan Africa and South Asia in the Global Enteric Multicenter Study.

Rotavirus is the leading cause of dehydrating diarrhea among children in developing countries. The impact of rotaviral diarrhea on nutritional status is not well understood. We aimed to determine the association between rotavirus-positive moderate-to-severe diarrhea and nutrition in children under 5 years of age. We analyzed data from the Global Enteric Multicenter Study on children 0-59 months old from South Asia and sub-Saharan Africa. The relationships between explanatory variables and outcome variables were assessed using multiple linear regression; the explanatory variable was the presence of rotavirus in the stool sample, and the outcome variables were z scores [length/height-for-age (LAZ/HAZ), weight-for-age (WAZ), and weight-for-length/height (WLZ/WHZ)] at follow-up (∼60 days). The prevalence of rotaviral diarrhea was 17.3% (905/5,219) in South Asia and 19.95% (842/4,220) in sub-Saharan Africa. Rotavirus was associated with higher LAZ/HAZ (ß: 0.19; 95% CI: 0.12, 0.26; P <0.001) and WAZ (ß: 0.15; 95% CI: 0.79, 0.22; P <0.001) in sub-Saharan Africa and with lower WLZ/WHZ (ß coefficient: -0.08; 95% CI: -0.15, -0.009; P = 0.027) in South Asia. Our study indicates that rotaviral diarrhea is positively associated with nutritional status in sub-Saharan Africa and is negatively associated with nutritional status in South Asia. An expedited implementation policy of ongoing preventive and control strategies, including vaccination against rotavirus, is necessary to reduce the burden of rotaviral diarrhea, which may further help to reduce the potential nutritional ramifications.

Genomic Heterogeneity of Cryptosporidium parvum Isolates From Children in Bangladesh: Implications for Parasite Biology and Human Infection.

Cryptosporidium species are a major cause of diarrhea and associated with growth failure. There is currently only limited knowledge of the parasite's genomic variability. We report a genomic analysis of Cryptosporidium parvum isolated from Bangladeshi infants and reanalysis of sequences from the United Kingdom. Human isolates from both locations shared 154 variants not present in the cattle-derived reference genome, suggesting host-specific adaptation of the parasite. Remarkably 34.6% of single-nucleotide polymorphisms unique to human isolates were nonsynonymous and 8.2% of these were in secreted proteins. Linkage disequilibrium decay indicated frequent recombination. The genetic diversity of C. parvum has potential implications for vaccine and therapeutic design. Clinical Trials Registration. NCT02764918.

Smokeless tobacco consumption and its association with risk factors of chronic kidney disease in rural and peri-urban Bangladesh.

INTRODUCTION: Compared to smoking, which has major consequences in chronic kidney disease (CKD) initiation and progression, smokeless tobacco (SLT) consumption is considered to have fewer health consequences. We investigated the prevalence of SLT consumption and its association with risk factors of CKD in a rural and peri-urban Bangladeshi population. METHODS: Using random sampling we recruited 872 adults in 2020, from the Mirzapur Demographic Surveillance System of Bangladesh, who had resided in the area for at least five years. Interviews using a semi-structured questionnaire, physical examination and anthropometric measurements were done, followed by blood and urine testing. The blood and urine tests were repeated in selected participants after three months as per the CKD Epidemiology Collaboration equation. RESULTS: The prevalence of SLT consumption was 29%. Being aged ≥46 years (OR=7.10; 95% CI: 4.79-10.94), female (OR=1.64; 95% CI: 1.21-2.22), housewife (OR=1.82; 95% CI: 1.35-2.45), farmer (OR=1.71; 95% CI: 1.06-2.76), widow (OR=3.40; 95% CI: 2.24-5.17), and having no formal schooling (OR=4.91; 95% CI: 3.59-6.72), family income of <$100/month (OR=1.66; 95% CI: 1.13-2.43), sleeping duration <7 hours per day (OR=2.33; 95% CI: 1.70-3.19), were associated with a significantly higher odds of SLT consumption. However, being aged 31-45 years (OR=0.25; 95% CI: 0.16-0.38) had significantly lower odds of being an SLT consumer. Among the diseases investigated, undernutrition (OR=1.63; 95% CI: 1.15-2.33), hypertension (OR=1.52; 95% CI: 1.13-2.05), anemia (OR=1.94; 95% CI: 1.39-2.71) and CKD (OR=1.62; 95% CI: 1.15-2.27) were significantly associated with SLT consumption. In the multivariable analysis, being aged 31-45 years (AOR=3.06; 95% CI: 1.91-4.90), ≥46 years (AOR=15.69; 95% CI: 4.64-53.09) and having no formal schooling (AOR=2.47; 95% CI: 1.72-3.55) were found to have a significant association with being an SLT consumer. CONCLUSIONS: SLT consumption is associated with most of the established risk factors of CKD within the studied population.

Reduced Diarrhea Prevalence and Improvements in Handwashing with Soap and Stored Drinking Water Quality Associated with Diarrheal Disease Awareness Measured by Interactive Voice Response Messages in the CHoBI7 Mobile Health Program.

The Cholera-Hospital-Based-Intervention-for-7-Days (CHoBI7) mobile health program promotes water, sanitation, and hygiene (WASH) behaviors through interactive voice response (IVR), voice, and text messages to reduce diarrheal diseases in Bangladesh. The objective of this study was to investigate the relationship between responses to CHoBI7 WASH IVR quiz messages and subsequent diarrhea and WASH behaviors. Fourteen CHoBI7 IVR quiz messages on handwashing with soap and treatment of stored water were sent to 517 households with 1,777 participants during the 12-month program period. IVR message responses were classified as correct answer, incorrect answer, no response (did not press 1 or 2), and failed (did not answer the phone). Diarrhea prevalence was assessed through self-reported monthly clinical surveillance visits. Handwashing with soap was assessed by a 5-hour structured observation, and stored water quality was defined by Escherichia coli concentration. Households that responded correctly to a CHoBI7 IVR quiz message had significantly lower odds of diarrhea for all age groups (adults and children) at the subsequent visit 1 month later (odds ratio [OR], 0.73; 95% CI, 0.54-0.98), and significantly greater odds of handwashing with soap after stool-related events (OR, 2.48; 95% CI, 1.12-5.49) and E. coli levels < 100 colony forming units (CFU)/100 mL (World Health Organization high-risk cutoff) in the stored household water (OR, 2.04; 95% CI, 1.25-3.33) compared with households that did not answer CHoBI7 IVR quiz calls. Correct responses to CHoBI7 IVR quizzes were associated with decreased diarrhea prevalence and improved stored drinking water quality and handwashing with soap behaviors at the subsequent visits. These findings suggest engagement in the CHoBI7 mobile health (mHealth) program and awareness of diarrheal disease prevention can reduce diarrhea and facilitate changes in WASH behaviors.

Spatiotemporal variation in risk of Shigella infection in childhood: a global risk mapping and prediction model using individual participant data.

BACKGROUND: Diarrhoeal disease is a leading cause of childhood illness and death globally, and Shigella is a major aetiological contributor for which a vaccine might soon be available. The primary objective of this study was to model the spatiotemporal variation in paediatric Shigella infection and map its predicted prevalence across low-income and middle-income countries (LMICs). METHODS: Individual participant data for Shigella positivity in stool samples were sourced from multiple LMIC-based studies of children aged 59 months or younger. Covariates included household-level and participant-level factors ascertained by study investigators and environmental and hydrometeorological variables extracted from various data products at georeferenced child locations. Multivariate models were fitted and prevalence predictions obtained by syndrome and age stratum. FINDINGS: 20 studies from 23 countries (including locations in Central America and South America, sub-Saharan Africa, and south and southeast Asia) contributed 66 563 sample results. Age, symptom status, and study design contributed most to model performance followed by temperature, wind speed, relative humidity, and soil moisture. Probability of Shigella infection exceeded 20% when both precipitation and soil moisture were above average and had a 43% peak in uncomplicated diarrhoea cases at 33°C temperatures, above which it decreased. Compared with unimproved sanitation, improved sanitation decreased the odds of Shigella infection by 19% (odds ratio [OR]=0·81 [95% CI 0·76-0·86]) and open defecation decreased them by 18% (OR=0·82 [0·76-0·88]). INTERPRETATION: The distribution of Shigella is more sensitive to climatological factors, such as temperature, than previously recognised. Conditions in much of sub-Saharan Africa are particularly propitious for Shigella transmission, although hotspots also occur in South America and Central America, the Ganges-Brahmaputra Delta, and the island of New Guinea. These findings can inform prioritisation of populations for future vaccine trials and campaigns. FUNDING: NASA, National Institutes of Health-The National Institute of Allergy and Infectious Diseases, and Bill & Melinda Gates Foundation.

Feasibility of MinION Nanopore Rapid Sequencing in the Detection of Common Diarrhea Pathogens in Fecal Specimen.

The need for fast detection of etiological agents outside the narrow target range of pathogens that may cause an event of an infectious disease epidemic necessitates rapid sequencing technologies to be implemented in routine diagnostic procedures. We tested the performance of a PCR-free rapid nanopore barcoding assay to detect microbial species by analyzing genomic contents extracted from acute diarrheal case specimens. Sequenced reads were processed in an automated analysis module for species identification, whereas pathogenic subspecies detection was aided by a sequence similarity search against a gene-specific database. Evaluation of assay and analysis parameters (e.g., run-time, sequence length, and species hit abundance level) was carried out using a standard bacterial community for assessing detection accuracy. It was observed that longer sequence length (≥500 nucleotides) along with higher species abundance level (≥1%) can be critical for exclusion of false-negative outcomes, while increased sequencing run-time can affect the proportional abundance of true-positive species. Under optimal parameters, the sensitivity of the rapid assay remained 100% for the detection of a target species in a background of nontarget fecal (diarrheal) DNA that weighed up to 64 times the DNA of the target species. The method was applied to acute diarrheal samples. Among these, 62.5% (5/8) were in agreement with target-specific traditional diagnosis methods for the presence/absence of pathogenic agent(s), 12.5% (1/8) were in disagreement, and pathogenic agents that were not targeted by the traditional methods were revealed by sequencing for 25% (2/8) of samples. These observations suggest that further optimization and evaluation of the rapid nanopore sequencing method could potentiate the widening of the range of pathogens that can be detected in acute diarrheal samples in the context of regular diagnostic needs as well as epidemics.

Formative Research for the Development of the CHoBI7 Cholera Rapid Response Program for Cholera Hotspots in Bangladesh.

Cholera is a severe form of acute watery diarrhea that if left untreated can result in death. Globally, there are 2.9 million cholera cases annually. Individuals living in close proximity to cholera cases are at a higher risk for developing cholera compared to the general population. Targeted water, sanitation, and hygiene (WASH) interventions have the potential to reduce cholera transmission in cholera hotspots around cholera cases. The objective of this study was to expand the scope of the Cholera-Hospital-Based-Intervention-for-7-Days (CHoBI7) program, focused on cholera patient households, for delivery in cholera hotspots in urban slums in Dhaka, Bangladesh. Thirty-one semi-structured interviews were conducted in cholera hotspots around cholera patients, and three intervention planning workshops were conducted to inform modifications needed to the CHoBI7 program. After exploratory interviews, a two-phase, iterative pilot study was conducted for 9 months to test the developed CHoBI7 Cholera Rapid Response program among 180 participants to further inform modifications to intervention content and delivery. Findings from pilot participant interviews highlighted the need to adapt intervention content for delivery at the compound-rather than household-level, given an environment with multiple households sharing a water source, toilets, and kitchen facilities. This was addressed by conducting a "ring session" for intervention delivery in cholera hotspots for households to discuss how to improve their shared facilities together and encourage a compound-level commitment to promoted WASH behaviors and placement of soapy water bottles in shared spaces. Based on the low number of soapy water bottles observed in communal spaces during the first iteration of the pilot, we also added context-specific examples using the narratives of families in mobile messages to encourage WASH behavioral recommendations. Formative research identified important considerations for the modifications needed to tailor the CHoBI7 program for delivery in cholera hotspots in urban Bangladesh.

Incidence of Asymptomatic Shigella Infection and Association with the Composite Index of Anthropometric Failure among Children Aged 1-24 Months in Low-Resource Settings.

Asymptomatic or subclinical infection by diarrheal enteropathogens during childhood has been linked to poor health and nutritional outcomes. In this study, we aimed to assess the impact of asymptomatic Shigella infection on different forms of childhood malnutrition including the composite index of anthropometric failure (CIAF). We used data from 1715 children enrolled in the multi-country birth cohort study, MAL-ED, from November 2009 to February 2012. Monthly non-diarrheal stools were collected and assessed using TaqMan Array Cards (TAC). Poisson regression was used to calculate incidence rates of asymptomatic Shigella infection. Generalized estimating equations (GEE) were used to assess the association between asymptomatic Shigella infection and nutritional indicators after adjusting for relevant covariates. Incidence rates per 100 child-months were higher in Tanzania, Bangladesh and Peru. Overall, after adjusting for relevant covariates, asymptomatic Shigella infection was significantly associated with stunting (aOR 1.60; 95% CI: 1.50, 1.70), wasting (aOR 1.26; 95% CI: 1.09, 1.46), underweight (aOR 1.45; 95% CI: 1.35, 1.56), and CIAF (aOR 1.55; 95% CI: 1.46, 1.65) in all the study sites except for Brazil. The high incidence rates of asymptomatic Shigella infection underscore the immediate need for Shigella vaccines to avert the long-term sequelae involving childhood growth.

Low Fruit and Vegetable Consumption Associated with Linear Growth Faltering among Children in Urban Bangladesh.

The objective of this study was to examine the association between dietary diversity and child growth among children 6 to 23 months of age in urban slums of Bangladesh. This prospective cohort study enrolled 192 participants 6 to 23 months of age in Dhaka, Bangladesh. A total of 170 children with follow-up anthropometric data were included in the analysis. To collect dietary intake information for children 6 to 23 months of age, consumption of five or more of the following eight minimum dietary diversity food groups was recorded using 24-hour dietary recall at enrollment provided by the child's caregiver: 1) breast milk; 2) grains, roots, and tubers; 3) legumes and nuts; 4) dairy products; 5) flesh foods; 6) eggs; 7) vitamin A-rich fruits and vegetables; and 8) other fruits and vegetables. Height and weight were measured at baseline and at a 12-month follow-up. Fifty-five percent of children (106 of 192) consumed five or more of the eight minimum dietary diversity food groups during their first visit to assess dietary intake. Eighty-two percent of children (157 of 192) had a report of consuming an animal source of food (e.g., eggs, diary, flesh foods) in the past 24 hours, 85% (164 of 192) consumed any source of protein (e.g., eggs, diary, flesh foods, nuts, and legumes), and 65% of children (125 of 192) were reported to consume any fruits and vegetables. Child consumption of fruits and vegetables was associated positively with change in length-for-age z-scores from baseline to the 12-month follow-up (coefficient, 0.86; 95% CI, 0.03-1.68). Inadequate fruit and vegetable consumption was associated with linear growth faltering among the young children residing in urban Dhaka, Bangladesh. These findings demonstrate the need for effective interventions to increase fruit and vegetable consumption in this susceptible pediatric population.

Factors associated with community acquired severe pneumonia among under five children in Dhaka, Bangladesh: A case control analysis.

BACKGROUND: Pneumonia is the leading cause of death in children globally with the majority of these deaths observed in resource-limited settings. Globally, the annual incidence of clinical pneumonia in under-five children is approximately 152 million, mostly in the low- and middle-income countries. Of these, 8.7% progressed to severe pneumonia requiring hospitalization. However, data to predict children at the greatest risk to develop severe pneumonia from pneumonia are limited. METHOD: Secondary data analysis was performed after extracting relevant data from a prospective cluster randomized controlled clinical trial; children of either sex, aged two months to five years with pneumonia or severe pneumonia acquired in the community were enrolled over a period of three years in 16 clusters in urban Dhaka city. RESULTS: The analysis comprised of 2,597 children aged 2-59 months. Of these, 904 and 1693 were categorized as pneumonia (controls) and severe pneumonia (cases), respectively based on WHO criteria. The median age of children was 9.2 months (inter quartile range, 5.1-17.1) and 1,576 (60%) were male. After adjustment for covariates, children with temperature ≥38°C, duration of illness ≥3 days, male sex, received prior medical care and severe stunting showed a significantly increased likelihood of developing severe pneumonia compared to those with pneumonia. Severe pneumonia in children occurred more often in older children who presented commonly from wealthy quintile families, and who often sought care from private facilities in urban settings. CONCLUSION AND RECOMMENDATION: Male sex, longer duration of illness, fever, received prior medical care, and severe stunting were significantly associated with development of WHO-defined severe childhood pneumonia in our population. The results of this study may help to develop interventions target to reduce childhood morbidity and mortality of children suffering from severe pneumonia.

Associations Between Eight Earth Observation-Derived Climate Variables and Enteropathogen Infection: An Independent Participant Data Meta-Analysis of Surveillance Studies With Broad Spectrum Nucleic Acid Diagnostics.

Diarrheal disease, still a major cause of childhood illness, is caused by numerous, diverse infectious microorganisms, which are differentially sensitive to environmental conditions. Enteropathogen-specific impacts of climate remain underexplored. Results from 15 studies that diagnosed enteropathogens in 64,788 stool samples from 20,760 children in 19 countries were combined. Infection status for 10 common enteropathogens-adenovirus, astrovirus, norovirus, rotavirus, sapovirus, Campylobacter, ETEC, Shigella, Cryptosporidium and Giardia-was matched by date with hydrometeorological variables from a global Earth observation dataset-precipitation and runoff volume, humidity, soil moisture, solar radiation, air pressure, temperature, and wind speed. Models were fitted for each pathogen, accounting for lags, nonlinearity, confounders, and threshold effects. Different variables showed complex, non-linear associations with infection risk varying in magnitude and direction depending on pathogen species. Rotavirus infection decreased markedly following increasing 7-day average temperatures-a relative risk of 0.76 (95% confidence interval: 0.69-0.85) above 28°C-while ETEC risk increased by almost half, 1.43 (1.36-1.50), in the 20-35°C range. Risk for all pathogens was highest following soil moistures in the upper range. Humidity was associated with increases in bacterial infections and decreases in most viral infections. Several virus species' risk increased following lower-than-average rainfall, while rotavirus and ETEC increased with heavier runoff. Temperature, soil moisture, and humidity are particularly influential parameters across all enteropathogens, likely impacting pathogen survival outside the host. Precipitation and runoff have divergent associations with different enteric viruses. These effects may engender shifts in the relative burden of diarrhea-causing agents as the global climate changes.

Small Intestine Bacterial Overgrowth in Bangladeshi Infants Is Associated With Growth Stunting in a Longitudinal Cohort.

INTRODUCTION: Small intestine bacterial overgrowth (SIBO) is common in children from low-income countries and has been cross-sectionally associated with growth stunting. We sought to determine whether SIBO was associated with poor growth and neurodevelopmental in a longitudinal analysis. METHODS: We measured SIBO by glucose hydrogen breath test (GHBT) at 18, 52, 78, and 104 weeks of life in a prospective longitudinal birth cohort of Bangladeshi children. Sociodemographic information and measures of enteric inflammation were analyzed as covariates. Diarrheal samples were tested for enteropathogens using polymerase chain reaction. Regression models were created using standardized mean GHBT area under the H2 curve (AUC) to determine associations with linear growth and cognitive, language, and motor scores on the Bayley-III Scales of Infant and Toddler Development at 2 years. We also investigated associations between GHBT AUC and enteropathogen exposure. RESULTS: A 1-ppm increase in standardized mean GHBT AUC was associated with a 0.01-SD decrease in length-for-age Z score (P = 0.03) and a 0.11-point decrease in Bayley language score (P = 0.05) at 2 years of age in adjusted analysis. Enteroaggregative Escherichia coli, Enteropathogenic Escherichia coli, Giardia, and Enterocytozoon bieneusi were associated with increased GHBT AUC, whereas Clostridium difficile, norovirus GI, sapovirus, rotavirus, and Cryptosporidium were associated with decreased GHBT AUC. None were consistent across all 4 time points. DISCUSSION: SIBO in the first 2 years of life is associated with growth stunting and decreased language ability in Bangladeshi infants and may represent a modifiable risk factor in poor growth and neurodevelopment in low-income countries.

Characteristics of Rotavirus, ETEC, and Vibrio Cholerae Among Under 2-year Children Attending an Urban Diarrheal Disease Hospital in Bangladesh.

BACKGROUND: Information on comparative clinical and host characteristics of under-2 children with watery diarrhea caused by rotavirus, Enterotoxigenic Escherichia coli (ETEC), and Vibrio cholerae as single pathogens is lacking. We sought to investigate the sociodemographic, clinical, and host characteristics of under-2 children hospitalized due to these pathogens. METHODOLOGY: We conducted a hospital-based case-control study using the icddr,b Diarrheal Diseases Surveillance System. Children of either sex, <2 years with diarrhea, who attended the hospital during 2014 to 2018, constituted the study population. Stool specimens having a single pathogen like rotavirus, ETEC, or Vibrio cholerae constituted the cases and stool specimens having no detectable common enteropathogens comprised the controls. Multinomial logistic regression analysis was done where control was the reference group. RESULTS: A total of 14 889 patients were enrolled, 6939 of whom were under-2 children, and 5245 (76%) constituted our study population. Among them 48% (n = 2532), 3% (n = 148) and 1% (n = 49) had rotavirus, ETEC, and Vibrio cholera, respectively. A control group (diarrhea without these 3 or Shigella, Salmonella, Aeromonas) accounted for 48% (n = 2516). In multinomial regression model, children with rotavirus (adjusted odds ratio [aOR], 1.36; 95% confidence interval [95% CI], 1.19-1.55) less often presented with dehydrating diarrhea compared to those with ETEC (aOR, 1.54; 95% CI, 1.05-2.26) and cholera (aOR, 2.25; 95% CI, 1.11-4.57). Rotavirus diarrhea was associated (aOR, 1.25; 95% CI, 1.07-1.46) with those who received antimicrobials prior to hospital admission and protectively associated with drinking tap water (aOR, 0.84; 95% CI, 0.73-0.95); however, ETEC diarrhea had protective association (aOR, 0.62; 95% CI, 0.43-0.92) with children who received antimicrobials prior to hospital admission and was associated with drinking tap water (aOR, 1.78; 95% CI, 1.19-2.66). Use of intravenous fluid was associated with cholera (aOR, 10.36; 95% CI, 4.85-22.16) and had protective association with rotavirus episodes (aOR, 0.64; 95% CI, 0.45-0.91). CONCLUSIONS: Clinical presentations and host characteristics of rotavirus, ETEC, and Vibrio cholerae diarrhea differed from each other and the information may be helpful for clinicians for better understanding and proper management of these children.

Cholera outbreak in Forcibly Displaced Myanmar National (FDMN) from a small population segment in Cox's Bazar, Bangladesh, 2019.

BACKGROUND: Bangladesh experienced a sudden, large influx of forcibly displaced persons from Myanmar in August 2017. A cholera outbreak occurred in the displaced population during September-December 2019. This study aims to describe the epidemiologic characteristics of cholera patients who were hospitalized in diarrhea treatment centers (DTCs) and sought care from settlements of Forcibly Displaced Myanmar Nationals (FDMN) as well as host country nationals during the cholera outbreak. METHODS: Diarrhea Treatment Center (DTC) based surveillance was carried out among the FDMN and host population in Teknaf and Leda DTCs hospitalized for cholera during September-December 2019. RESULTS: During the study period, 147 individuals with cholera were hospitalized. The majority, 72% of patients reported to Leda DTC. Nearly 65% sought care from FDMN settlements. About 47% of the cholera individuals were children less than 5 years old and 42% were aged 15 years and more. Half of the cholera patients were females. FDMN often reported from Camp # 26 (45%), followed by Camp # 24 (36%), and Camp # 27 (12%). Eighty-two percent of the cholera patients reported watery diarrhea. Some or severe dehydration was observed in 65% of cholera individuals. Eighty-one percent of people with cholera received pre-packaged ORS at home. About 88% of FDMN cholera patients reported consumption of public tap water. Pit latrine without water seal was often used by FDMN cholera individuals (78%). CONCLUSION: Vigilance for cholera patients by routine surveillance, preparedness, and response readiness for surges and oral cholera vaccination campaigns can alleviate the threats of cholera.

Pathogens Associated With Linear Growth Faltering in Children With Diarrhea and Impact of Antibiotic Treatment: The Global Enteric Multicenter Study.

BACKGROUND: The association between childhood diarrheal disease and linear growth faltering in developing countries is well described. However, the impact attributed to specific pathogens has not been elucidated, nor has the impact of recommended antibiotic treatment. METHODS: The Global Enteric Multicenter Study enrolled children with moderate to severe diarrhea (MSD) seeking healthcare at 7 sites in sub-Saharan Africa and South Asia. At enrollment, we collected stool samples to identify enteropathogens. Length/height was measured at enrollment and follow-up, approximately 60 days later, to calculate change in height-for-age z scores (ΔHAZ). The association of pathogens with ΔHAZ was tested using linear mixed effects regression models. RESULTS: Among 8077 MSD cases analyzed, the proportion with stunting (HAZ below -1) increased from 59% at enrollment to 65% at follow-up (P < .0001). Pathogens significantly associated with linear growth decline included Cryptosporidium (P < .001), typical enteropathogenic Escherichia coli (P = .01), and untreated Shigella (P = .009) among infants (aged 0-11 months) and enterotoxigenic E. coli encoding heat-stable toxin (P < .001) and Cryptosporidium (P = .03) among toddlers (aged 12-23 months). Shigella-infected toddlers given antibiotics had improved linear growth (P = .02). CONCLUSIONS: Linear growth faltering among children aged 0-23 months with MSD is associated with specific pathogens and can be mitigated with targeted treatment strategies, as demonstrated for Shigella.

Diarrhea treatment center (DTC) based diarrheal disease surveillance in settlements in the wake of the mass influx of forcibly displaced Myanmar national (FDMN) in Cox's Bazar, Bangladesh, 2018.

BACKGROUND: In August 2017, after a large influx of forcibly displaced Myanmar nationals (FDMN) in Cox's Bazar, Bangladesh diarrhea treatment centers (DTCs) were deployed. This study aims to report the clinical, epidemiological, and laboratory characteristics of the hospitalized patients. METHODS: The study followed cross-sectional design. In total 1792 individuals were studied. Other than data, a single, stool specimen was subjected to one step rapid visual diagnostic test for Vibrio cholerae. The provisionally diagnosed specimens of cholera cases were inoculated into Cary-Blair Transport Medium; then sent to the laboratory of icddr,b in Dhaka to isolate the colony as well as perform antibiotic susceptibility tests. Data were analyzed by STATA and analyses included descriptive as well as analytic methods. RESULTS: Of the total 1792 admissions in 5 DTCs, 729 (41%) were from FDMN settlements; children <5 years contributed the most (n = 981; 55%). Forty percent (n = 716) were aged 15 years and above, and females were predominant (n = 453; 63%). Twenty-eight percent (n = 502) sought treatment within 24h of the onset of diarrhea. FDMN admissions within 24h were low compared to host hospitalization (n = 172, 24% vs. n = 330, 31%; p<0.001). Seventy-two percent (n = 1295) had watery diarrhea; more common among host population than FDMN (n = 802; 75% vs. n = 493; 68%; p<0.001). Forty-four percent admissions (n = 796) had some or severe dehydration, the later was common in FDMN (n = 46; 6% vs. n = 36; 3%, p = 0.005). FDMN often used public taps (n = 263; 36%), deep tube-well (n = 243; 33%), and shallow tube well (n = 188; 26%) as the source of drinking water. Nearly 96% (n = 698) of the admitted FDMN used pit latrines as opposed to 79% (n = 842) from the host community (p<0.001). FDMN children were often malnourished. None of the FDMN reported cholera. CONCLUSION: No diarrhea outbreak was detected, but preparedness for surges and response readiness are warranted in this emergency and crisis setting.

Epidemiology and genetic characterization of human sapovirus among hospitalized acute diarrhea patients in Bangladesh, 2012-2015.

Human sapovirus, which causes acute gastroenteritis, is not well studied and poorly understood. This study aims to investigate the contribution of sapovirus in diarrhea, their clinical association, and genotypic diversity. Fecal specimens (n = 871) were randomly selected from diarrheal patients who attended International Centre for Diarrhoeal Disease Research, Bangladesh hospital in Dhaka, Bangladesh during January 2012-December 2015 and tested for the presence of sapovirus RNA using real-time polymerase chain reaction. Sapovirus RNA was identified in 2.3% (n = 20) of the samples. Seventy-five percent of the sapovirus positive cases were coinfected with other pathogens, such as rotavirus, norovirus, enterotoxigenic Escherichia coli, adenovirus, Shigella spp., and Vibrio cholerae. A vast genetic diversity was observed among sapovirus with at least seven common genotypes (GI.1, GI.2, GI.7, GII.1, GII.4, GII.6, and GIV), and a new genotype GII.NA1. Some of the GI.1 strains detected were similar to GI.4 in the polymerase region sequence and were confirmed as recombinant strains. Our findings suggest that the overall contribution of sapovirus in hospitalized diarrheal illness is low but highlight enormous genetic diversity.

Characteristics of Salmonella Recovered From Stools of Children Enrolled in the Global Enteric Multicenter Study.

BACKGROUND: The Global Enteric Multicenter Study (GEMS) determined the etiologic agents of moderate-to-severe diarrhea (MSD) in children under 5 years old in Africa and Asia. Here, we describe the prevalence and antimicrobial susceptibility of nontyphoidal Salmonella (NTS) serovars in GEMS and examine the phylogenetics of Salmonella Typhimurium ST313 isolates. METHODS: Salmonella isolated from children with MSD or diarrhea-free controls were identified by classical clinical microbiology and serotyped using antisera and/or whole-genome sequence data. We evaluated antimicrobial susceptibility using the Kirby-Bauer disk-diffusion method. Salmonella Typhimurium sequence types were determined using multi-locus sequence typing, and whole-genome sequencing was performed to assess the phylogeny of ST313. RESULTS: Of 370 Salmonella-positive individuals, 190 (51.4%) were MSD cases and 180 (48.6%) were diarrhea-free controls. The most frequent Salmonella serovars identified were Salmonella Typhimurium, serogroup O:8 (C2-C3), serogroup O:6,7 (C1), Salmonella Paratyphi B Java, and serogroup O:4 (B). The prevalence of NTS was low but similar across sites, regardless of age, and was similar among both cases and controls except in Kenya, where Salmonella Typhimurium was more commonly associated with cases than controls. Phylogenetic analysis showed that these Salmonella Typhimurium isolates, all ST313, were highly genetically related to isolates from controls. Generally, Salmonella isolates from Asia were resistant to ciprofloxacin and ceftriaxone, but African isolates were susceptible to these antibiotics. CONCLUSIONS: Our data confirm that NTS is prevalent, albeit at low levels, in Africa and South Asia. Our findings provide further evidence that multidrug-resistant Salmonella Typhimurium ST313 can be carried asymptomatically by humans in sub-Saharan Africa.