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.

Correction: Evaluation of community based surveillance in the Rohingya refugee camps in Cox's Bazar, Bangladesh, 2019.

[This corrects the article DOI: 10.1371/journal.pone.0244214.].

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.

Prevalence of Soil-Transmitted Helminths at Baseline and after Albendazole Treatment in the School-Age Children of Forcibly Displaced Myanmar Nationals in Bangladesh.

The forcibly displaced Myanmar nationals (FDMNs) known as Rohingya refugees are the largest group of stateless individuals globally. According to the emergencies humanitarian actors at the United Nations Office for the Coordination of Humanitarian Affairs, the worldwide refugee crisis involving FDMNs is intensifying at the fastest rate in history. Growing public health demands are being exacerbated by current difficulties in addressing poor access to health services, severe food shortages, and a lack of adequate housing. Infectious diseases constitute a major public health emergency in this vulnerable population. A study was carried out in FDMN children to investigate common soil-transmitted helminth (STH) infection at the time of enrollment and prospectively followed-up to 12 months after 2 doses albendazole treatment. At baseline, the prevalence of STH infection with at least one species was found to be 91.7% and 87.3% for Kato-Katz (KK) and quantitative polymerase chain reaction (qPCR) methods, respectively. Similarly, for follow-up children, the overall infection rate was 95.3% and 91.5%, respectively. Trichuris trichiura was the most predominant STH infection by both KK (baseline 87%, follow-up 89.1%) and qPCR (baseline 77.5%, follow-up 82.9%). The overall prevalence of stunting in the children was 37.8% at baseline and rose to 51.3% at 12 months. Alpha-1 antitrypsin (r = 0.13, P = 0.01) and myeloperoxidase (r = 0.12, P = 0.01) levels showed a positive correlation with Aascaris lumbricoides egg count per gram at baseline. An in-depth investigation is urgently needed to identify the underlying protective measures and the root cause of STH infections to improve the health of FDMN children.

Effectiveness, safety and economic viability of daycare versus usual hospital care management of severe pneumonia with or without malnutrition in children using the existing health system of Bangladesh: a cluster randomised controlled trial.

Background: We aimed to define clinical and cost-effectiveness of a Day Care Approach (DCA) alternative to Usual Care (UC, comparison group) within the Bangladesh health system to manage severe childhood pneumonia. Methods: This was a cluster randomised controlled trial in urban Dhaka and rural Bangladesh between November 1, 2015 and March 23, 2019. Children aged 2-59 months with severe pneumonia with or without malnutrition received DCA or UC. The DCA treatment settings comprised of urban primary health care clinics run by NGO under Dhaka South City Corporation and in rural Union health and family welfare centres under the Ministry of Health and Family welfare Services. The UC treatment settings were hospitals in these respective areas. Primary outcome was treatment failure (persistence of pneumonia symptoms, referral or death). We performed both intention-to-treat and per-protocol analysis for treatment failure. Registered at www.ClinicalTrials.gov, NCT02669654. Findings: In total 3211 children were enrolled, 1739 in DCA and 1472 in UC; primary outcome data were available in 1682 and 1357 in DCA and UC, respectively. Treatment failure rate was 9.6% among children in DCA (167 of 1739) and 13.5% in the UC (198 of 1472) (group difference, -3.9 percentage point; 95% confidence interval (CI), -4.8 to -1.5, p = 0.165). Treatment success within the health care systems [DCA plus referral vs. UC plus referral, 1587/1739 (91.3%) vs. 1283/1472 (87.2%), group difference 4.1 percentage point, 95% CI, 3.7 to 4.1, p = 0.160)] was better in DCA. One child each in UC of both urban and rural sites died within day 6 after admission. Average cost of treatment per child was US$94.2 (95% CI, 92.2 to 96.3) and US$184.8 (95% CI, 178.6 to 190.9) for DCA and UC, respectively. Interpretation: In our population of children with severe pneumonia with or without malnutrition, >90% were successfully treated at Day care Clinics at 50% lower cost. A modest investment to upgrade Day care facilities may provide a cost-effective, accessible alternative to hospital management. Funding: UNICEF, Botnar Foundation, UBS Optimus Foundation, and EAGLE Foundation, Switzerland.

Symptomatic and Asymptomatic Campylobacter Infections and Child Growth in South Asia: Analyzing Data from the Global Enteric Multicenter Study.

Campylobacter is a major cause of food-borne gastrointestinal illnesses worldwide, predominantly affecting children under 5 years of age. This study examined potential associations of symptomatic (with diarrhea) and asymptomatic (without diarrhea) Campylobacter infections with child growth among children under 5 years of age in South Asia. The Global Enteric Multicenter Study was conducted from 2007 to 2011 with a case-control design. Children were followed for 60 days after enrollment. Stool culture was performed to isolate Campylobacter spp. Among the 22,567 enrolled children, 9,439 were symptomatic, with 786 (8.28%) testing positive for Campylobacter. Conversely, 13,128 asymptomatic healthy controls were included, with 1,057 (8.05%) testing positive for Campylobacter. Growth faltering was observed in the symptomatic group, particularly among children aged 0-11 months (-0.19 height-for-age z score [HAZ]; 95% CI: -0.36, -0.03; P = 0.018) and 24-59 months (-0.16 HAZ; 95% CI: -0.28, -0.04; P = 0.010). However, in the asymptomatic group, growth faltering was observed only in the 24- to 59-month age group, in terms of HAZ (-0.15 HAZ; 95% CI: -0.24, -0.05; P = 0.002) and weight-for-height z score (-0.16; 95% CI: -0.26, -0.06; P = 0.001). These findings underscore the importance of immediate and enhanced introduction of preventive modalities to reduce the burden of Campylobacter infections and reduce their long-term sequelae.

Efficacy of dopamine, epinephrine and blood transfusion for treatment of fluid refractory shock in children with severe acute malnutrition or severe underweight and cholera or other dehydrating diarrhoeas: protocol for a randomised controlled clinical trial.

INTRODUCTION: Diarrhoea is one of the leading causes of under-5 childhood mortality and accounts for 8% of 5.4 million global under-5 deaths. In severely malnourished children, diarrhoea progresses to shock, where the risk of mortality is even higher. At icddr,b Dhaka Hospital, the fatality rate is as high as 69% in children with severe malnutrition and fluid refractory septic shock. To date, no study has evaluated systematically the effects of inotrope or vasopressor or blood transfusion in children with dehydrating diarrhoea (eg, in cholera) and severe acute malnutrition (SAM) or severe underweight who are in shock and unresponsive to WHO-recommended fluid therapy. To reduce the mortality of severely malnourished children presenting with diarrhoea and fluid refractory shock, we aim to compare the efficacy of blood transfusion, dopamine and epinephrine in fluid refractory shock in children who do not respond to WHO-recommended fluid resuscitation. METHODS AND ANALYSIS: In this randomised, three-arm, controlled, non-masked clinical trial in children 1-59 months old with SAM or severe underweight and fluid refractory shock, we will compare the efficacy of dopamine or epinephrine administration versus blood transfusion in children who failed to respond to WHO-recommended fluid resuscitation. The primary outcome variable is the case fatality rate. The effect of the intervention will be assessed by performing an intention-to-treat analysis. Recruitment and data collection began in July 2021 and are now ongoing. Results are expected by May 2023. ETHICS AND DISSEMINATION: This study has been approved by the icddr,b Institutional Review Board. We adhere to the 'Declaration of Helsinki' (2000), guidelines for Good Clinical Practice. Before enrolment, we collect signed informed consent from the parents or caregivers of the children. We will publish the results in a peer-reviewed journal and will arrange a dissemination seminar. TRIAL REGISTRATION NUMBER: NCT04750070.

Site-Specific Incidence Rate of Blastocystis hominis and Its Association with Childhood Malnutrition: Findings from a Multi-Country Birth Cohort Study.

In this study, we investigated the potential association between the burden of asymptomatic Blastocystis spp. (Blastocystis hominis) infection and nutritional status among children under 2 years of age using the data collected from 1,715 children from eight distinct geographic locations, including Bangladesh, Brazil, India, Peru, Tanzania, Pakistan, Nepal, and South Africa. Childhood stunting, wasting, and underweight were the outcome variables, and B. hominis infection was the exposure variable of this present study. The presence of B. hominis in nondiarrheal stools was evaluated by TaqMan Array Cards. Site-specific incidence rates were estimated using Poisson regression, and multiple generalized estimating equation was used to assess the association between the B. hominis infection and nutritional status. The site-specific incidence rates of asymptomatic B. hominis infections per 100 child-months were higher in Tanzania, Peru, and South Africa when compared with the other study sites. Moreover, in terms of site-specific association, childhood stunting was significantly associated with asymptomatic B. hominis infection in Bangladesh (odds ratio [OR]: 1.62; 95% CI: 1.26-2.08), India (OR: 1.78; 95% CI: 1.46-2.16), Nepal (OR: 2.26; 95% CI: 1.60-3.21), Peru (OR: 1.47; 95% CI: 1.26-1.71), South Africa (OR: 1.57; 95% CI: 1.35-1.83), and Tanzania (OR: 2.46; 95% CI: 2.18-2.79) sites. Wasting was associated with B. hominis in the Brazil site only (OR: 3.19; 95% CI: 1.31-7.77). On the other hand, underweight was associated in the Bangladesh (OR: 1.89; 95% CI: 1.48-2.42), Brazil (OR: 4.41; 95% CI: 1.57-12.4), Nepal (OR: 2.25; 95% CI: 1.52-3.35), and Tanzania (OR: 1.68; 95% CI: 1.42-1.99) sites. Our analysis further reveals that the presence of additional pathogens may play a pathogenic role in children who have B. hominis infection.

Site-Specific Analysis of the Incidence Rate of Enterotoxigenic Escherichia coli Infection Elucidates an Association with Childhood Stunting, Wasting, and Being Underweight: A Secondary Analysis of the MAL-ED Birth Cohort.

Asymptomatic infection by fecal enteropathogens is a major contributor to childhood malnutrition. Here, we investigated the incidence rate of asymptomatic infection by enterotoxigenic Escherichia coli (ETEC) and assessed its association with childhood stunting, wasting, and being underweight among children under 2 years of age. The Malnutrition and Enteric Disease birth cohort study included 1,715 children who were followed from birth to 24 months of age from eight distinct geographic locations including Bangladesh, Brazil, India, Peru, Tanzania, Pakistan, Nepal, and South Africa. The TaqMan array card assay was used to determine the presence of ETEC in the nondiarrheal stool samples collected from these children. Poisson regression was used to estimate the incidence rate, and multiple generalized estimating equations with binomial family, logit link function, and exchangeable correlation were used to analyze the association between asymptomatic ETEC infection and anthropometric indicators such as stunting, wasting, and being underweight. The site-specific incidence rates of asymptomatic ETEC infections per 100 child-months were also higher at the study locations in Tanzania (54.81 [95% CI: 52.64, 57.07]) and Bangladesh (46.75 [95% CI: 44.75, 48.83]). In the Bangladesh, India, and Tanzania sites, the composite indicator of anthropometric failure was significantly associated with asymptomatic ETEC infection. Furthermore, a significant association between asymptomatic heat-stable toxin ETEC infections and childhood stunting, wasting, and being underweight was found in only the Bangladesh and Tanzania sites.

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.

Is Fibersol-2 efficacious in reducing duration of watery diarrhea and stool output in children 1-3 years old? A randomized, parallel, double-blinded, placebo-controlled, two arm clinical trial.

BACKGROUND: Fibersol-2 has innumerable beneficial effects on human health. It is a fermentable, non-viscous, water-soluble, indigestible dextrin containing 90% dietary fiber produced from corn starch. We aimed to evaluate whether additional intake of Fibersol-2 along with oral rehydration solution treatment can reduce the duration of watery diarrhea and daily stool output in children 1-3 years as well as recovery of such children within 72 hours, compared to placebo. METHODS: This placebo-controlled double-blinded, randomized parallel two arm trial conducted in Kumudini Women's Medical College Hospital in rural Bangladesh between March and October, 2018 used 5 gm of either Fibersol-2 or placebo dissolved in 50-ml drinking water which was given orally to ninety-two children with watery diarrhea on enrollment twice daily for a period of 7 days. Randomization was done using a randomization table. We randomly allocated 45 (49%) and 47 (51%) children in Fibersol-2 and placebo groups, respectively. Outcome measures were duration of resolution of watery diarrhea, daily stool output and the proportion of children recovered within 72 hours. Primary and safety analyses were by intention to treat. This trial was registered at ClinicalTrials.gov, number NCT03565393. RESULTS: There was no significant difference observed in terms of duration of resolution of diarrhea (adjusted mean difference 8.20, 95% CI -2.74 to 19.15, p = 0.14, adjusted effect size 0.03); the daily stool output (adjusted mean difference 73.57, 95% CI -94.17 to 241.32, p = 0.38, adjusted effect size 0.33) and the proportion of children recovered within 72 hours (adjusted odds ratio 0.49, 95% CI = 0.12 to 1.96, p = 0.31, adjusted risk difference -0.06 (95% CI -0.19 to -0.06), after regression analysis between Fibersol-2 and placebo. CONCLUSION: No beneficial role of Fibersol-2 was observed in diarrheal children aged 1-3 years. TRIAL REGISTRATION: This trial is registered at ClinicalTrials.gov, number NCT03565393. The authors confirmed that all ongoing and related trials for this drug/intervention are registered. https://clinicaltrials.gov/ct2/show/NCT03565393.

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.

Digestive tolerability and acceptability of Fibersol-2 in healthy and diarrheal children 1-3 years old at a rural facility, Bangladesh: Results from a four arm exploratory study.

BACKGROUND: Fibersol-2 has some beneficial effects on human health. We aimed to evaluate the digestive tolerability and acceptability of Fibersol-2 in healthy and diarrheal children, as well as improvement in stool consistencies in young diarrheal children. METHODS: Sixty children of either sex, aged 1-3 years having four groups (healthy children/low dose, healthy children/high dose, children with diarrhea/low dose and children with diarrhea/high dose) were enrolled into this exploratory study between 1st August to 23rd October 2017. Two presumptive doses, low (2.5g) and high (5g), twice daily with 50 ml drinking water for seven days were the interventions. Outcomes were to observe the development of possible abdominal symptoms, such as pain, distension, rumbling, and bloating during the intervention and post-intervention periods in healthy and diarrheal children as well as improvement in stool consistencies in diarrheal children. RESULTS: Among the diarrheal children, the median (IQR) duration of resolution of diarrhea was 3.9 (2.9, 5.1) days vs. 3.5 (2.0, 8.0) days, p = 0.885; in low dose and high dose groups, respectively. Significant difference was observed in terms of abdominal pain (27% vs. 7%, p = 0.038) and distension (40% vs. 0%, p<0.001) in diarrheal children, compared to healthy children during the pre-intervention period. We also observed significant difference in respect of abdominal distension (23% vs. 0%, p = 0.011), rumbling (27% vs. 0%, p = 0.005) and bloating (43% vs. 3%, p = 0.001) in diarrheal children, compared to healthy children during the intervention period. However, no significant difference was observed in relation to abdominal pain (p = 0.347) and distension (p = 0.165) during the pre-intervention period, compared to the intervention period in diarrheal children. Moreover, no significant difference was observed during the post-intervention period for the diarrheal and healthy children. CONCLUSION: Fibersol-2 was found to be well tolerated in healthy and diarrheal children aged 1-3 years. TRIAL REGISTRATION: This study was registered as part of a randomized trial at ClinicalTrials.gov, number NCT03565393. The authors confirmed that all ongoing and related trials for this drug/intervention were registered.

Does a child's mid-upper arm circumference-for-age z-score represent another nutritional indicator of childhood malnutrition status?

Child wasting is defined as a weight-for-height/length z-score (WLZ/WHZ) < -2, and this indicator of nutritional status is used worldwide. However, a precise measurement is required for the assessment of a child's nutritional status, which may not always be possible due to expensive instruments, especially in poor resource settings. In some instances, mid-upper arm circumference-for-age z-score (MUACZ) is also being used for screening purposes, which is a simple and useful nutritional indicator. The objective of this paper is to identify the optimal cut-off point for the MUACZ to identify wasted children, and also to determine if the same factors are associated with MUACZ and wasting. Data were derived from the Suchana evaluation data. The optimal cut-off value was estimated via receiver operating characteristic (ROC) curve analysis using acute malnutrition as a gold standard with maximum sensitivity and specificity. Multiple logistic regression was used to assess the associated factors with the MUACZ. Using the gold standard indicator of nonwasting (WLZ ≥ -2), a positive outcome, the optimal cut-off point for the MUACZ was -1.27. The area under the ROC curve was 0.88, indicating that the model had a power of 88% to differentiate between the positive and negative classes. It implies that a child's MUACZ was correlated with WLZ, and a MUACZ below -1.27 appeared to accurately identify wasting among children aged 3-23 months. MUACZ < -1.27 might be another useful indicator of childhood wasting than a WLZ < -2.

Prevalence and outcome of anemia among children hospitalized for pneumonia and their risk of mortality in a developing country.

Data are limited on the prevalence and outcome of anemia and its risk on mortality among children under five years of age hospitalized for pneumonia/severe pneumonia. Thus, we conducted a secondary analysis of data extracted from Dhaka Hospital of International Centre for Diarrhoeal Disease Research, Bangladesh to address the evidence gap. Among 3468 children fulfilling the study criteria,1712 (49.4%) had anemia. If children aged ≤ 1.0, > 1.0 to 2.0, > 2.0 to < 6.0, and ≥ 6.0 to 59 months had blood hemoglobin (Hb) value of ≤ 10.7 g/dL, ≤ 9.4 g/dL, ≤ 9.5 g/dL, and ≤ 11 g/dl respectively; we considered them anemic. The trend of prevalence of anemia was found to be inversely related to increasing age (Chi-square for linear trend analysis was done to understand the relation of anemia with increasing age, which was = 6.96; p = 0.008). During hospitalization anemic children more often developed respiratory failure (7.2% vs. 4.4%, p < 0.001) and fatal outcome (7.1.0% vs. 4.2%, p < 0.001) than the children who did not have anemia. After adjusting for potential confounders, such as female sex, lack of immunization, abnormal mental status, severe acute malnutrition, dehydration, hypoxemia, severe sepsis, and bacteremia using multivariable logistic regression analysis, anemia was found to be independently associated with fatal outcome (OR = 1.88, 95% CI 1.23-2.89, p = 0.004). Thus, future interventional studies on the early management of anemia may be warranted to understand whether the intervention reduces the morbidity and deaths in such children.