Influence of hydrometeorological risk factors on child diarrhea and enteropathogens in rural Bangladesh.

BACKGROUND: A number of studies have detected relationships between weather and diarrhea. Few have investigated associations with specific enteric pathogens. Understanding pathogen-specific relationships with weather is crucial to inform public health in low-resource settings that are especially vulnerable to climate change. OBJECTIVES: Our objectives were to identify weather and environmental risk factors associated with diarrhea and enteropathogen prevalence in young children in rural Bangladesh, a population with high diarrheal disease burden and vulnerability to weather shifts under climate change. METHODS: We matched temperature, precipitation, surface water, and humidity data to observational longitudinal data from a cluster-randomized trial that measured diarrhea and enteropathogen prevalence in children 6 months-5.5 years from 2012-2016. We fit generalized additive mixed models with cubic regression splines and restricted maximum likelihood estimation for smoothing parameters. RESULTS: Comparing weeks with 30°C versus 15°C average temperature, prevalence was 3.5% higher for diarrhea, 7.3% higher for Shiga toxin-producing Escherichia coli (STEC), 17.3% higher for enterotoxigenic E. coli (ETEC), and 8.0% higher for Cryptosporidium. Above-median weekly precipitation (median: 13mm; range: 0-396mm) was associated with 29% higher diarrhea (adjusted prevalence ratio 1.29, 95% CI 1.07, 1.55); higher Cryptosporidium, ETEC, STEC, Shigella, Campylobacter, Aeromonas, and adenovirus 40/41; and lower Giardia, sapovirus, and norovirus prevalence. Other associations were weak or null. DISCUSSION: Higher temperatures and precipitation were associated with higher prevalence of diarrhea and multiple enteropathogens; higher precipitation was associated with lower prevalence of some enteric viruses. Our findings emphasize the heterogeneity of the relationships between hydrometeorological variables and specific enteropathogens, which can be masked when looking at composite measures like all-cause diarrhea. Our results suggest that preventive interventions targeted to reduce enteropathogens just before and during the rainy season may more effectively reduce child diarrhea and enteric pathogen carriage in rural Bangladesh and in settings with similar meteorological characteristics, infrastructure, and enteropathogen transmission.

Influence of Temperature and Precipitation on the Effectiveness of Water, Sanitation, and Handwashing Interventions against Childhood Diarrheal Disease in Rural Bangladesh: A Reanalysis of the WASH Benefits Bangladesh Trial.

BACKGROUND: Diarrheal disease is a leading cause of childhood morbidity and mortality globally. Household water, sanitation, and handwashing (WASH) interventions can reduce exposure to diarrhea-causing pathogens, but meteorological factors may impact their effectiveness. Information about effect heterogeneity under different weather conditions is critical to refining these targeted interventions. OBJECTIVES: We aimed to determine whether temperature and precipitation modified the effect of low-cost, point-of-use WASH interventions on child diarrhea. METHODS: We analyzed data from a trial in rural Bangladesh that compared child diarrhea prevalence between clusters (N=720) that were randomized to different WASH interventions between 2012 and 2016 (NCT01590095). We matched temperature and precipitation measurements to diarrhea outcomes (N=12,440 measurements, 6,921 children) by geographic coordinates and date. We estimated prevalence ratios (PRs) using generative additive models and targeted maximum likelihood estimation to assess the effectiveness of each WASH intervention under different weather conditions. RESULTS: Generally, WASH interventions most effectively prevented diarrhea during monsoon season, particularly following weeks with heavy rain or high temperatures. The PR for diarrhea in the WASH interventions group compared with the control group was 0.49 (95% CI: 0.35, 0.68) after 1 d of heavy rainfall, with a less-protective effect [PR=0.87 (95% CI: 0.60, 1.25)] when there were no days with heavy rainfall. Similarly, the PR for diarrhea in the WASH intervention group compared with the control group was 0.60 (95% CI: 0.48, 0.75) following above-median temperatures vs. 0.91 (95% CI: 0.61, 1.35) following below-median temperatures. The influence of precipitation and temperature varied by intervention type; for precipitation, the largest differences in effectiveness were for the sanitation and combined WASH interventions. DISCUSSION: WASH intervention effectiveness was strongly influenced by precipitation and temperature, and nearly all protective effects were observed during the rainy season. Future implementation of these interventions should consider local environmental conditions to maximize effectiveness, including targeted efforts to maintain latrines and promote community adoption ahead of monsoon seasons. https://doi.org/10.1289/EHP13807.

A cluster-randomized trial of water, sanitation, handwashing and nutritional interventions on stress and epigenetic programming.

A regulated stress response is essential for healthy child growth and development trajectories. We conducted a cluster-randomized trial in rural Bangladesh (funded by the Bill & Melinda Gates Foundation, ClinicalTrials.gov NCT01590095) to assess the effects of an integrated nutritional, water, sanitation, and handwashing intervention on child health. We previously reported on the primary outcomes of the trial, linear growth and caregiver-reported diarrhea. Here, we assessed additional prespecified outcomes: physiological stress response, oxidative stress, and DNA methylation (N = 759, ages 1-2 years). Eight neighboring pregnant women were grouped into a study cluster. Eight geographically adjacent clusters were block-randomized into the control or the combined nutrition, water, sanitation, and handwashing (N + WSH) intervention group (receiving nutritional counseling and lipid-based nutrient supplements, chlorinated drinking water, upgraded sanitation, and handwashing with soap). Participants and data collectors were not masked, but analyses were masked. There were 358 children (68 clusters) in the control group and 401 children (63 clusters) in the intervention group. We measured four F2-isoprostanes isomers (iPF(2α)-III; 2,3-dinor-iPF(2α)-III; iPF(2α)-VI; 8,12-iso-iPF(2α)-VI), salivary alpha-amylase and cortisol, and methylation of the glucocorticoid receptor (NR3C1) exon 1F promoter including the NGFI-A binding site. Compared with control, the N + WSH group had lower concentrations of F2-isoprostanes isomers (differences ranging from -0.16 to -0.19 log ng/mg of creatinine, P < 0.01), elevated post-stressor cortisol (0.24 log µg/dl; P < 0.01), higher cortisol residualized gain scores (0.06 µg/dl; P = 0.023), and decreased methylation of the NGFI-A binding site (-0.04; P = 0.037). The N + WSH intervention enhanced adaptive responses of the physiological stress system in early childhood.

Improved Child Feces Management Mediates Reductions in Childhood Diarrhea from an On-Site Sanitation Intervention: Causal Mediation Analysis of a Cluster-Randomized Trial in Rural Bangladesh.

BACKGROUND: The WASH benefits Bangladesh trial multi-component sanitation intervention reduced diarrheal disease among children < 5 years. Intervention components included latrine upgrades, child feces management tools, and behavioral promotion. It remains unclear which components most impacted diarrhea. METHODS: We conducted mediation analysis within a subset of households (n = 720) from the sanitation and control arms. Potential mediators were categorized into indicators of latrine quality, latrine use practices, and feces management practices. We estimated average causal mediation effects (ACME) as prevalence differences (PD), defined as the intervention's effect on diarrhea through its effect on the mediator. RESULTS: The intervention improved all indicators compared to controls. We found significant mediation through multiple latrine use and feces management practice indicators. The strongest mediators during monsoon seasons were reduced open defecation among children aged < 3 and 3-8 years, and increased disposal of child feces into latrines. The strongest mediators during dry seasons were access to a flush/pour-flush latrine, reduced open defecation among children aged 3-8 years, and increased disposal of child feces into latrines. Individual mediation effects were small (PD = 0.5-2 percentage points) compared to the overall intervention effect but collectively describe significant mediation pathways. DISCUSSION: The effect of the WASH Benefits Bangladesh sanitation intervention on diarrheal disease was mediated through improved child feces management and reduced child open defecation. Although the intervention significantly improved latrine quality, relatively high latrine quality at baseline may have limited benefits from additional improvements. Targeting safe child feces management may increase the health benefits of rural sanitation interventions.

Stress biomarkers and child development in young children in Bangladesh.

BACKGROUND: Hundreds of millions of children in low- and middle-income countries are exposed to chronic stressors, such as poverty, poor sanitation and hygiene, and sub-optimal nutrition. These stressors can have physiological consequences for children and may ultimately have detrimental effects on child development. This study explores associations between biological measures of chronic stress in early life and developmental outcomes in a large cohort of young children living in rural Bangladesh. METHODS: We assessed physiologic measures of stress in the first two years of life using measures of the hypothalamic-pituitary-adrenal (HPA) axis (salivary cortisol and glucocorticoid receptor gene methylation), the sympathetic-adrenal-medullary (SAM) system (salivary alpha-amylase, heart rate, and blood pressure), and oxidative status (F2-isoprostanes). We assessed child development in the first two years of life with the MacArthur-Bates Communicative Development Inventories (CDI), the WHO gross motor milestones, and the Extended Ages and Stages Questionnaire (EASQ). We compared development outcomes of children at the 75th and 25th percentiles of stress biomarker distributions while adjusting for potential confounders using generalized additive models, which are statistical models where the outcome is predicted by a potentially non-linear function of predictor variables. RESULTS: We analyzed data from 684 children (49% female) at both 14 and 28 months of age; we included an additional 765 children at 28 months of age. We detected a significant relationship between HPA axis activity and child development, where increased HPA axis activity was associated with poor development outcomes. Specifically, we found that cortisol reactivity (coefficient -0.15, 95% CI (-0.29, -0.01)) and post-stressor levels (coefficient -0.12, 95% CI (-0.24, -0.01)) were associated with CDI comprehension score, post-stressor cortisol was associated with combined EASQ score (coefficient -0.22, 95% CI (-0.41, -0.04), and overall glucocorticoid receptor methylation was associated with CDI expression score (coefficient -0.09, 95% CI (-0.17, -0.01)). We did not detect a significant relationship between SAM activity or oxidative status and child development. CONCLUSIONS: Our observations reveal associations between the physiological evidence of stress in the HPA axis with developmental status in early childhood. These findings add to the existing evidence exploring the developmental consequences of early life stress.

Stress Biomarkers and Child Development in Young Children in Bangladesh.

Background: Hundreds of millions of children in low- and middle-income countries are exposed to chronic stressors, such as poverty, poor sanitation and hygiene, and sub-optimal nutrition. These stressors can have physiological consequences for children and may ultimately have detrimental effects on child development. This study explores associations between biological measures of chronic stress in early life and developmental outcomes in a large cohort of young children living in rural Bangladesh. Methods: We assessed physiologic measures of stress in the first two years of life using measures of the hypothalamic-pituitary-adrenal (HPA) axis (salivary cortisol and glucocorticoid receptor gene methylation), the sympathetic-adrenal-medullary (SAM) system (salivary alpha-amylase, heart rate, and blood pressure), and oxidative status (F2-isoprostanes). We assessed child development in the first two years of life with the MacArthur-Bates Communicative Development Inventories (CDI), the WHO gross motor milestones, and the Extended Ages and Stages Questionnaire (EASQ). We compared development outcomes of children at the 75th and 25th percentiles of stress biomarker distributions while adjusting for potential confounders (hereafter referred to as contrasts) using generalized additive models, which are statistical models where the outcome is predicted by a potentially non-linear function of predictor variables. Results: We analyzed data from 684 children (49% female) at both 14 and 28 months of age; we included an additional 765 children at 28 months of age. We observed 135 primary contrasts of the differences in child development outcomes at the 75th and 25th percentiles of stress biomarkers, where we detected significant relationships in 5 out of 30 contrasts (17%) of HPA axis activity, 1 out of 30 contrasts (3%) of SAM activity, and 3 out of 75 contrasts (4%) of oxidative status. These findings revealed that measures of HPA axis activity were associated with poor development outcomes. We did not find consistent evidence that markers of SAM system activity or oxidative status were associated with developmental status. Conclusions: Our observations reveal associations between the physiological evidence of stress in the HPA axis with developmental status in early childhood. These findings add to the existing evidence exploring the developmental consequences of early life stress.

Micronutrient status during pregnancy is associated with child immune status in rural Bangladesh.

Background: Poor immune function increases children's risk of infection and mortality. Several maternal factors during pregnancy may affect infant immune function during the postnatal period. Objectives: We aimed to evaluate whether maternal micronutrients, stress, estriol, and immune status during the first or second trimester of pregnancy were associated with child immune status in the first two years after birth. Methods: We conducted observational analyses within the water, sanitation, and hygiene (WASH) Benefits Bangladesh randomized controlled trial. We measured biomarkers in 575 pregnant women and postnatally in their children. Maternal biomarkers measured during the first and second trimester of pregnancy included nutrition status via vitamin D (25-hydroxy-D [25(OH)D]), ferritin, soluble transferrin receptor (sTfR), and retinol-binding protein (RBP); cortisol; estriol. Immune markers were assessed in pregnant women at enrollment and their children at ages 14 and 28 mo, including C-reactive protein (CRP), alpha-1-acid glycoprotein (AGP), and 13 cytokines (including IFN-γ). We generated a standardized sum score of log-transformed cytokines. We analyzed IFN-γ individually because it is a critical immunoregulatory cytokine. All outcomes were prespecified. We used generalized additive models and reported the mean difference and 95% confidence intervals at the 25th and 75th percentiles of exposure distribution. Results: At child age 14 mo, concentrations of maternal RBP were inversely associated with the cytokine sum score in children (-0.34 adjusted difference between the 25th and 75th percentile [95% confidence interval -0.61, -0.07]), and maternal vitamin A deficiency was positively associated with the cytokine sum score in children (1.02 [0.13, 1.91]). At child age of 28 mo, maternal RBP was positively associated with IFN-γ in children (0.07 [0.01, 0.14]), whereas maternal vitamin A deficiency was negatively associated with child AGP (-0.07 [-0.13, -0.02]). Maternal iron deficiency was associated with higher AGP concentrations in children at age 14 mo (0.13 [0.04, 0.23]), and maternal sTfR concentrations were positively associated with child CRP concentrations at age 28 mo (0.18 [0, 0.36]). Conclusion: Maternal deficiencies in vitamin A or iron during the first 2 trimesters of pregnancy may shape the trajectory of a child's immune status.

Assessing sustained uptake of latrine and child feces management interventions: Extended follow-up of a cluster-randomized controlled trial in rural Bangladesh 1-3.5 years after intervention initiation.

BACKGROUND: Sanitation interventions typically result in modest increases in latrine access, and any gains in latrine access and use are often not sustained over time. Sanitation programs also rarely include child-focused interventions such as potties. We aimed to assess the sustained effect of a multi-component sanitation intervention on access to and use of latrines and child feces management tools in rural Bangladesh. METHODS: We conducted a longitudinal substudy nested within the WASH Benefits randomized controlled trial. The trial provided latrine upgrades, child potties and sani-scoops for feces removal, along with behavior change promotion to encourage use of the delivered hardware. Promotion visits to intervention recipients were frequent during the first 2 years after intervention initiation, decreased in frequency between years 2-3, and ceased after 3 years. We enrolled a random subset of 720 households from the sanitation and control arms of the trial in a substudy and visited them quarterly between 1 and 3.5 years after intervention initiation. At each visit, field staff recorded sanitation-related behaviors through spot-check observations and structured questionnaires. We assessed intervention effects on observed indicators of hygienic latrine access, potty use and sani-scoop use and investigated whether these effects were modified by duration of follow-up, ongoing behavior change promotion and household characteristics. RESULTS: The intervention increased hygienic latrine access from 37% among controls to 94% in the sanitation arm (p < 0.001). Access among intervention recipients remained high 3.5 years after intervention initiation, including periods with no active promotion. Gains in access were higher among households with less education, less wealth and larger number of residents. The intervention increased availability of child potties from 29% among controls to 98% in the sanitation arm (p < 0.001). However, fewer than 25% of intervention households reported exclusive child defecation in a potty or had observed indicators of potty and sani-scoop use, and gains in potty use declined over the follow-up period, even with ongoing promotion. CONCLUSION: Our findings from an intervention that provided free products and intensive initial behavior change promotion suggest a sustained increase in hygienic latrine access up to 3.5 years after intervention initiation but infrequent use of child feces management tools. Studies should investigate strategies to ensure sustained adoption of safe child feces management practices.

Exploring customers' perceptions of food adulteration at bazaars and supermarkets in Dhaka, Bangladesh; a qualitative exploration.

BACKGROUND: Food adulteration is an increasingly recognized global public health problem. In low- and middle-income countries like Bangladesh, adulteration is difficult to detect and respond to. We explored customers' perceptions on food adulteration, perception of risk and connections between information, participant characteristics and patterns of adulterated food concerns that impact risk perception in urban Bangladesh. METHODS: A formative study was conducted in Dhaka, between June and August 2015 at a supermarket and a wet market. We explored community awareness and response to chemical contaminants (adulterants) among participants from a range of socio-economic backgrounds. The team conducted 38 in-depth interviews with 12 customers and 4 staff from a supermarket, and 12 customers and 10 vendors from a wet market. Participants were selected purposively. Audio recorded data were coded based on thematic content and analyzed manually. RESULTS: We asked participants how common foods were likely adulterated, and most gave figures of 70% or more. They reported that foods were adulterated with chemicals or artificial colors, especially fish, milk, and vegetables. The supermarket more commonly sold packaged foods with nutritional and expiry information on the label; and offered convenience in terms of building size, layout, and cleanliness. All customers from the wet market thought that foods were cheaper and fresher than from supermarkets. Supermarket customers expressed greater concern about adulterated foods than wet market customers. Most participants from both markets reported that food adulteration is invisible, adulterated foods cannot be avoided, and have long-term negative health impacts including cancer, diabetes, paralysis, heart attack, and others. Nearly half of customers from both markets were concerned about the poor nutritional value of adulterated food. Participants from both settings expressed the need for access to credible information about adulteration to help choose safe foods. The majority expressed the need for government action against those who are responsible for adulteration. CONCLUSIONS: Food adulteration was considered a major health threat. The government could act on food adulteration prevention if provided credible population-based data on disease burden, a model food sampling and testing protocol, a model for inspections, organizational strengthening and training, example social and behavioral change communications with estimated costs.

Gender and urban-rural influences on antibiotic purchasing and prescription use in retail drug shops: a one health study.

INTRODUCTION: Few studies have reported antibiotic purchases from retail drug shops in relation to gender in low and middle-income countries (LMICs). Using a One Health approach, we aimed to examine gender dimensions of antibiotic purchases for humans and animals and use of prescriptions in retail drug shops in Bangladesh. METHODS: We conducted customer observations in 20 drug shops in one rural and one urban area. Customer gender, antibiotic purchases, and prescription use were recorded during a four-hour observation (2 sessions of 2 hours) in each shop. We included drug shops selling human medicine (n = 15); animal medicine (n = 3), and shops selling both human and animal medicine (n = 2). RESULTS: Of 582 observations, 31.6% of drug shop customers were women. Women comprised almost half of customers (47.1%) in urban drug shops but only 17.2% of customers in rural drug shops (p < 0.001). Antibiotic purchases were more common in urban than rural shops (21.6% versus 12.2% of all transactions, p = 0.003). Only a quarter (26.0%) of customers who purchased antibiotics used a prescription. Prescription use for antibiotics was more likely among women than men (odds ratio (OR) = 4.04, 95% CI 1.55, 10.55) and more likely among urban compared to rural customers (OR = 4.31 95% CI 1.34, 13.84). After adjusting for urban-rural locality, women remained more likely to use a prescription than men (adjusted OR = 3.38, 95% CI 1.26, 9.09) but this was in part due to antibiotics bought by men for animals without prescription. Customers in drug shops selling animal medicine had the lowest use of prescriptions for antibiotics (4.8% of antibiotic purchases). CONCLUSION: This study found that nearly three-quarters of all antibiotics sold were without prescription, including antibiotics on the list of critically important antimicrobials for human medicine. Men attending drug shops were more likely to purchase antibiotics without a prescription compared to women, while women customers were underrepresented in rural drug shops. Antibiotic stewardship initiatives in the community need to consider gender and urban-rural dimensions of drug shop uptake and prescription use for antibiotics in both human and animal medicine. Such initiatives could strengthen National Action Plans.

Influence of community-level sanitation coverage and population density on environmental fecal contamination and child health in a longitudinal cohort in rural Bangladesh.

BACKGROUND: Household-level sanitation interventions have had limited effects on child health or environmental contamination, potentially due to low community coverage. Higher community-level coverage with safely managed sanitation can reduce opportunities for disease transmission. METHODS: We estimated associations between community sanitation coverage, environmental fecal contamination, and child health among 360 compounds in the control arm of the WASH Benefits trial in rural Bangladesh (NCT01590095). In each compound, we enumerated E. coli in environmental samples and recorded the 7-day prevalence of caregiver-reported diarrheal disease and acute respiratory infections (ARI) in children under five. We observed indicators of latrine access and quality among all neighboring compounds within 100 m of study compounds. We defined community coverage as the proportion of neighboring compounds with (1) at least one latrine, and (2) exclusively hygienic latrines (improved facility observed to safely contain feces), within both 50 m and 100 m of study compounds. We assessed effect modification by population density and season. RESULTS: Adjusted for confounders, study compounds surrounded by 100% coverage of at least one latrine per compound within 50 m had slightly lower log10E. coli counts in stored water (Δlog = -0.13, 95% CI -0.26, -0.01), child hand rinses (Δlog = -0.13, 95% CI -0.24, -0.02), and caregiver hand rinses (Δlog = -0.16, 95% CI -0.29, -0.03) and marginally lower prevalence of diarrheal disease (prevalence ratio [PR] = 0.82, 95% CI 0.64, 1.04) and ARI (PR = 0.84, 95% CI 0.69, 1.03) compared to compounds surrounded by <100% coverage. Effects were similar but less pronounced at 100 m. At higher population densities, community latrine coverage was associated with larger reductions in E. coli on child and caregiver hands and prevalence of diarrheal disease. Coverage with exclusively hygienic latrines was not associated with any outcome. CONCLUSION: Higher community sanitation coverage was associated with reduced fecal contamination and improved child health, with stronger effects at highly local scales (50m) and at high population densities. Our findings indicate that the relationship between community sanitation coverage, environmental contamination, and child health varies by definition of coverage, distance, and population density. This work highlights significant uncertainty around how to best measure sanitation coverage and the expected health effects of increasing sanitation coverage using a specific metric. Better understanding of community-level sanitation access is needed to inform policy for implementing sanitation systems that effectively protect community health.

The effect of a large-scale water, sanitation and hygiene intervention in Bangladesh on knowledge, behaviour and health: Findings from an endline programme evaluation.

OBJECTIVES: The Sanitation, Hygiene Education and Water Supply in Bangladesh Programme (SHEWA-B) was a 5-year intervention aiming to improve water, sanitation and hygiene (WASH) practices among 20 million rural residents through community hygiene promoters. This analysis evaluates the impact of SHEWA-B on knowledge, behaviour and childhood diarrhoea outcomes. METHODS: The evaluation included repeated cross-sectional surveys and health surveillance in matched cohorts in intervention and control clusters. Cross-sectional surveys and structured observations at baseline, midline, and endline assessed the availability of WASH technology, caregiver knowledge and behaviour. Fieldworkers collected monthly health data in a subset of control and intervention households to determine the prevalence of diarrhoea. RESULTS: Of 5091 households surveyed, participants residing in intervention clusters showed minimal improvements in knowledge, reported behaviour, or use of WASH technology compared to the control clusters. During structured observations, intervention households increased more than control households at handwashing before preparing food and after cleaning a baby's anus when comparing endline to baseline, but these changes were not seen when comparing endline to the midline. The prevalence of childhood diarrhoea remained similar in both groups before (10.2% in intervention, 10.0% in control) and after (8.8% in intervention, 11.7% in control) midline changes were made to improve the intervention. Intervention clusters showed no improvement in diarrhoea over time compared to control clusters. CONCLUSIONS: SHEWA-B's community-based WASH promotion did not yield the intended impact on knowledge, behaviour or health. Greater priority should be given to approaches that have demonstrated effectiveness. Including rigorous evaluations would broaden the evidence base to support and improve large-scale programmes.

Evaluation of an on-site sanitation intervention against childhood diarrhea and acute respiratory infection 1 to 3.5 years after implementation: Extended follow-up of a cluster-randomized controlled trial in rural Bangladesh.

BACKGROUND: Diarrhea and acute respiratory infection (ARI) are leading causes of death in children. The WASH Benefits Bangladesh trial implemented a multicomponent sanitation intervention that led to a 39% reduction in the prevalence of diarrhea among children and a 25% reduction for ARI, measured 1 to 2 years after intervention implementation. We measured longer-term intervention effects on these outcomes between 1 to 3.5 years after intervention implementation, including periods with differing intensity of behavioral promotion. METHODS AND FINDINGS: WASH Benefits Bangladesh was a cluster-randomized controlled trial of water, sanitation, hygiene, and nutrition interventions (NCT01590095). The sanitation intervention included provision of or upgrades to improved latrines, sani-scoops for feces removal, children's potties, and in-person behavioral promotion. Promotion was intensive up to 2 years after intervention initiation, decreased in intensity between years 2 to 3, and stopped after 3 years. Access to and reported use of latrines was high in both arms, and latrine quality was significantly improved by the intervention, while use of child feces management tools was low. We enrolled a random subset of households from the sanitation and control arms into a longitudinal substudy, which measured child health with quarterly visits between 1 to 3.5 years after intervention implementation. The study period therefore included approximately 1 year of high-intensity promotion, 1 year of low-intensity promotion, and 6 months with no promotion. We assessed intervention effects on diarrhea and ARI prevalence among children <5 years through intention-to-treat analysis using generalized linear models with robust standard errors. Masking was not possible during data collection, but data analysis was masked. We enrolled 720 households (360 per arm) from the parent trial and made 9,800 child observations between June 2014 and December 2016. Over the entire study period, diarrheal prevalence was lower among children in the sanitation arm (11.9%) compared to the control arm (14.5%) (prevalence ratio [PR] = 0.81, 95% CI 0.66, 1.00, p = 0.05; prevalence difference [PD] = -0.027, 95% CI -0.053, 0, p = 0.05). ARI prevalence did not differ between sanitation (21.3%) and control (22.7%) arms (PR = 0.93, 95% CI 0.82, 1.05, p = 0.23; PD = -0.016, 95% CI -0.043, 0.010, p = 0.23). There were no significant differences in intervention effects between periods with high-intensity versus low-intensity/no promotion. Study limitations include use of caregiver-reported symptoms to define health outcomes and limited data collected after promotion ceased. CONCLUSIONS: The observed effect of the WASH Benefits Bangladesh sanitation intervention on diarrhea in children appeared to be sustained for at least 3.5 years after implementation, including 1.5 years after heavy promotion ceased. Existing latrine access was high in the study setting, suggesting that improving on-site latrine quality can deliver health benefits when latrine use practices are in place. Further work is needed to understand how latrine adoption can be achieved and sustained in settings with low existing access and how sanitation programs can adopt transformative approaches of excreta management, including safe disposal of child and animal feces, to generate a hygienic home environment. TRIAL REGISTRATION: ClinicalTrials.gov; NCT01590095; https://clinicaltrials.gov/ct2/show/NCT01590095.

Evaluation of a menstrual hygiene intervention in urban and rural schools in Bangladesh: a pilot study.

Girls' menstrual experiences impact their social and educational participation, physical and psychological health. We conducted a pilot study to assess the acceptability and feasibility of a multi-component intervention intended to support menstruating girls; improve menstrual care knowledge, practices, and comfort; and increase school attendance.We conducted a pre/post evaluation of a 6-month pilot intervention in four schools (2 urban, 2 rural) in Dhaka, Bangladesh. We selected 527 schoolgirls (grades 5 to 10; aged 10 to 17 years) for a baseline survey and 528 girls at endline. The intervention included: 1) Menstrual Hygiene Management (MHM) packs- reusable cloth pads, underwear, carry bags and menstrual cycle tracking calendars, 2) education curriculum- pictorial flipcharts, puberty related-booklets, and teachers' training to deliver puberty and MHM sessions, 3) maintenance- improvements to school sanitation, provision of disposable pads in the school office, provision of chute disposal systems for disposable pads, and gender committees to promote a gender-friendly school environment and maintenance of intervention facilities. We estimated intervention uptake and intervention effect by calculating prevalence differences and 95% confidence intervals using fixed-effects logistic regression.The intervention uptake was more than 85% for most indicators; 100% reported receiving puberty education, 85% received MHM packs, and 92% received booklets. Reusable cloth pads uptake was 34% by endline compared with 0% at baseline. Knowledge about menstrual physiology and knowledge of recommended menstrual management practices significantly improved from baseline to endline. Reported improvements included more frequent changing of menstrual materials (4.2 times/day at endline vs. 3.4 times/day at baseline), increased use of recommended disposal methods (prevalence difference (PD): 8%; 95% Confidence Interval: 1, 14), and fewer staining incidents (PD: - 12%; 95% CI: - 22, - 1). More girls reported being satisfied with their menstrual materials (59% at endline vs. 46% at baseline, p < 0.005) and thought school facilities were adequate for menstrual management at endline compared to baseline (54% vs. 8%, p < 0.001). At endline, 64% girls disagreed/strongly disagreed that they felt anxious at school due to menstruation, compared to 33% at baseline (p < 0.001). Sixty-five percent girls disagreed/strongly disagreed about feeling distracted or trouble concentrating in class at endline, compared to 41% at baseline (p < 0.001). Self-reported absences decreased slightly (PD: - 8%; 95% CI: - 14, - 2).Uptake of cloth pads, improved maintenance and disposal of menstrual materials, and reduced anxiety at school suggest acceptability and feasibility of the intervention aiming to create a supportive school environment.

Higher helminth ova counts and incomplete decomposition in sand-enveloped latrine pits in a coastal sub-district of Bangladesh.

Pit latrines are the most common latrine technology in rural Bangladesh, and untreated effluent from pits can directly contaminate surrounding aquifers. Sand barriers installed around the latrine pit can help reduce contamination but can also alter the decomposition of the fecal sludge and accelerate pit fill-up, which can counteract their benefits. We aimed to evaluate whether there was a difference in decomposition of fecal sludge and survival of soil-transmitted helminth (STH) ova among latrines where a 50-cm sand barrier was installed surrounding and at the bottom of the pit, compared to latrines without a sand barrier, in coastal Bangladesh. We assessed decomposition in latrine pits by measuring the carbon-nitrogen (C/N) ratio of fecal sludge. We enumerated Ascaris lumbricoides and Trichuris trichiura ova in the pit following 18 and 24 months of latrine use. We compared these outcomes between latrines with and without sand barriers using generalized linear models with robust standard errors to adjust for clustering at the village level. The C/N ratio in latrines with and without a sand barrier was 13.47 vs. 22.64 (mean difference: 9.16, 95% CI: 0.15, 18.18). Pits with sand barriers filled more quickly and were reportedly emptied three times more frequently than pits without; 27/34 latrines with sand barriers vs. 9/34 latrines without barriers were emptied in the previous six months. Most reported disposal methods were unsafe. Compared to latrines without sand barriers, latrines with sand barriers had significantly higher log10 mean counts of non-larvated A. lumbricoides ova (log10 mean difference: 0.35, 95% CI: 0.12, 0.58) and T. trichiura ova (log10 mean difference: 0.47, 95% CI: 0.20, 0.73). Larvated ova counts were similar for the two types of latrines for both A. lumbricoides and T. trichiura. Our findings suggest that sand barriers help contain helminth ova within the pits but pits with barriers fill up more quickly, leading to more frequent emptying of insufficiently decomposed fecal sludge. Further research is required on latrine technologies that can both isolate pathogens from the environment and achieve rapid decomposition.

Spatiotemporal distribution of antimicrobial resistant organisms in different water environments in urban and rural settings of Bangladesh.

The spatial distribution of clinically important antibiotic resistant bacteria (ARB) and associated genes is important to identify the environmental distribution of contamination and 'hotspots' of antimicrobial resistance (AMR). We conducted an integrated survey of AMR in drinking water, wastewater and surface water (rivers and ponds) in three settings in Bangladesh: rural households, rural poultry farms, and urban food markets. Spatial mapping was conducted via geographic information system (GIS) using ArcGIS software. Samples (n = 397) were analyzed for the presence of extended-spectrum ß-lactamase-producing Escherichia coli (ESBL-Ec), carbapenem-resistant E. coli (CR-Ec) and resistance genes (blaCTX-M-1,blaNDM-1). In rural households, 5% of drinking water supply samples tested positive for ESBL-Ec, and a high proportion of wastewater, pond and river water samples were positive for ESBL-Ec (90%, 76%, and 85%, respectively). In poultry farms, 10% of drinking water samples tested positive for ESBL-Ec compared to a high prevalence in wastewater, pond and river water (90%, 68%, and 85%, respectively). CR-Ec prevalence in household wastewater and pond water was relatively low (8% and 5%, respectively) compared to river water (33%). In urban areas, 38% of drinking water samples and 98% of wastewater samples from food markets tested positive for ESBL-Ec while 30% of wastewater samples tested positive for CR-Ec. Wastewaters had the highest concentrations of ESBL-Ec, CR-Ec, blaCTXM-1 and blaNDM-1 and these were significantly higher in urban compared to rural samples (p < 0.05). ESBL-Ec is ubiquitous in drinking water, wastewater and surface water bodies in both rural and urban areas of Bangladesh. CR-Ec is less widespread but found at a high prevalence in wastewater discharged from urban food markets and in rural river samples. Surveillance and monitoring of antibiotic resistant organisms and genes in waterbodies is an important first step in addressing environmental dimensions of AMR.

Field Trial of an Automated Batch Chlorinator System at Two Shared Shallow Tubewells among Camps for Forcibly Displaced Myanmar Nationals (FDMN) in Cox's Bazar, Bangladesh.

Chlorination of shallow tubewell water is challenging due to various iron concentrations. A mixed-method, small-scale before-and-after field trial assessed the accuracy and consistency of an automated chlorinator, Zimba, in Rohingya camp housing, Cox's Bazar. From August-September 2018, two shallow tubewells (iron concentration = 6.5 mg/L and 1.5 mg/L) were selected and 20 households were randomly enrolled to participate in household surveys and water testing. The field-team tested pre-and post-treated tubewell and household stored water for iron, free and total chlorine, and E. coli. A sub-set of households (n = 10) also received safe storage containers (5 L jerry cans). Overall mean iron concentrations were 5.8 mg/L in Zimba water, 1.9 mg/L in household storage containers, and 2.8 mg/L in the project-provided safe storage containers. At baseline, 0% samples at source and 60% samples stored in household vessels were contaminated with E. coli (mean log10 = 0.62 MPN/100 mL). After treatment, all water samples collected from source and project-provided safe storage containers were free from E. coli, but 41% of post-treated water stored in the household was contaminated with E. coli. E. coli concentrations were significantly lower in the project-provided safe storage containers (log10 mean difference = 0.92 MPN, 95% CI = 0.59-1.14) compared with baseline and post-treated water stored in household vessels (difference = 0.57 MPN, 95% CI = 0.32-0.83). Zimba is a potential water treatment technology for groundwater extracted through tubewells with different iron concentrations in humanitarian settings.

Pilot of a Low-Cost Elementary School Handwashing Intervention in Bangladesh: Acceptability, Feasibility, and Potential for Sustainability.

Schoolchildren frequently transmit respiratory and gastrointestinal infections because of dense person-to-person contact in schools. We piloted a low-cost handwashing intervention among elementary schoolchildren in Bangladesh. We trained teachers to lead behavior change communication sessions using flipcharts to encourage students' handwashing before eating, after defecating, and after cleaning school toilets; provided handwashing stations (reservoirs with taps and stool + basin + soapy water solution [mix of 30 gm detergent with 1.5 L water] + pump top bottle with steel holder); and formed hygiene committees for maintenance and covering the recurrent cost of detergent. We evaluated intervention acceptability, feasibility, and potential for sustainability at 1 and 14 months after the intervention. At baseline, of 300 before eating events, no one washed hands with soap, and 99.7% (299) did not wash hands at all as soap was unavailable. Out of 269 after toileting events, 0.7% (2) washed hands with soap, and 88% (237) did not wash hands. After 4 weeks of the intervention, 45% (87/195 before eating events), 83% (155/186 after toileting events), and 100% (15/15 after cleaning toilet events) washed both hands with soapy water as children found it accessible, low cost, and child friendly. After 14 months, 9.4% (55/586 before eating events) and 37% (172/465 after toileting events) washed both hands with soapy water for health benefits. The intervention was acceptable and feasible; it overcame limited access to soap and water and was affordable as schools covered the recurrent costs of detergent. Further research should explore long-term habit adoption and impact on health and attendance.

Barriers and facilitators to adherence to national drug policies on antibiotic prescribing and dispensing in Bangladesh.

BACKGROUND: The National Drug Policy in Bangladesh prohibits the sale and distribution of antibiotics without prescription from a registered physician. Compliance with this policy is poor; prescribing antibiotics by unqualified practitioners is common and over-the-counter dispensing widespread. In Bangladesh, unqualified practitioners such as drug shop operators are a major source of healthcare for the poor and disadvantaged. This paper reports on policy awareness among drug shop operators and their customers and identifies current dispensing practices, barriers and facilitators to policy adherence. METHODS: We conducted a qualitative study in rural and urban Bangladesh from June 2019 to August 2020. This included co-design workshops (n = 4) and in-depth interviews (n = 24) with drug shop operators and customers/household members, key informant interviews (n = 12) with key personnel involved in aspects of the antibiotic supply chain including pharmaceutical company representatives, and model drug shop operators; and a group discussion with stakeholders representing key actors in informal market systems namely: representatives from the government, private sector, not-for-profit sector and membership organizations. RESULTS: Barriers to policy compliance among drug shop operators included limited knowledge of government drug policies, or the government-led Bangladesh Pharmacy Model Initiative (BPMI), a national guideline piloted to regulate drug sales. Drug shop operators had no clear knowledge of different antibiotic generations, how and for what diseases antibiotics work contributing to inappropriate antibiotic dispensing. Nonetheless, drug shop operators wanted the right to prescribe antibiotics based on having completed related training. Drug shop customers cited poor healthcare facilities and inadequate numbers of attending physician as a barrier to obtaining prescriptions and they described difficulties differentiating between qualified and unqualified providers. CONCLUSION: Awareness of the National Drug Policy and the BPMI was limited among urban and rural drug shop operators. Poor antibiotic prescribing practice is additionally hampered by a shortage of qualified physicians; cultural and economic barriers to accessing qualified physicians, and poor implementation of regulations. Increasing qualified physician access and increasing training and certification of drug shop operators could improve the alignment of practices with national policy.

Telomere length is associated with growth in children in rural Bangladesh.

Background: Previously, we demonstrated that a water, sanitation, handwashing, and nutritional intervention improved linear growth and was unexpectedly associated with shortened childhood telomere length (TL) (Lin et al., 2017). Here, we assessed the association between TL and growth. Methods: We measured relative TL in whole blood from 713 children. We reported differences between the 10th percentile and 90th percentile of TL or change in TL distribution using generalized additive models, adjusted for potential confounders. Results: In cross-sectional analyses, long TL was associated with a higher length-for-age Z score at age 1 year (0.23 SD adjusted difference in length-for-age Z score [95% CI 0.05, 0.42; FDR-corrected p-value = 0.01]). TL was not associated with other outcomes. Conclusions: Consistent with the metabolic telomere attrition hypothesis, our previous trial findings support an adaptive role for telomere attrition, whereby active TL regulation is employed as a strategy to address 'emergency states' with increased energy requirements such as rapid growth during the first year of life. Although short periods of active telomere attrition may be essential to promote growth, this study suggests that a longer overall initial TL setting in the first 2 years of life could signal increased resilience against future telomere erosion events and healthy growth trajectories. Funding: Funded by the Bill and Melinda Gates Foundation. Clinical trial number: NCT01590095.