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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.

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

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.

Many diarrhea-causing pathogens are climate-sensitive, and populations with the lowest socioeconomic position (SEP) are often most vulnerable to climate-related transmission. Household Water, Sanitation, and Handwashing (WASH) interventions constitute one potential effective strategy to reduce child diarrhea, especially among low-income households. Capitalizing on a cluster randomized trial population (360 clusters, 4941 children with 8440 measurements) in rural Bangladesh, one of the worlds most climate-sensitive regions, we show that improved WASH substantially reduces diarrhea risk with largest benefits among children with lowest SEP and during the monsoon season. We extrapolated trial results to rural Bangladesh regions using high-resolution geospatial layers to identify areas most likely to benefit. Scaling up a similar intervention could prevent an estimated 734 (95% CI 385, 1085) cases per 1000 children per month during the seasonal monsoon, with marked regional heterogeneities. Here, we show how to extend large-scale trials to inform WASH strategies among climate-sensitive and low-income populations.

Cluster randomized trials are often used to study large-scale public health interventions. In large trials, even small improvements in statistical efficiency can have profound impacts on the required sample size and cost. Location integrates many socio-demographic and environmental characteristics into a single, readily available feature. Here we show that pair matching by geographic location leads to substantial gains in statistical efficiency for 14 child health outcomes that span growth, development, and infectious disease through a re-analysis of two large-scale trials of nutritional and environmental interventions in Bangladesh and Kenya. Relative efficiencies from pair matching are ≥1.1 for all outcomes and regularly exceed 2.0, meaning an unmatched trial would need to enroll at least twice as many clusters to achieve the same level of precision as the geographically pair matched design. We also show that geographically pair matched designs enable estimation of fine-scale, spatially varying effect heterogeneity under minimal assumptions. Our results demonstrate broad, substantial benefits of geographic pair matching in large-scale, cluster randomized trials.

Abstract: In addition to diet, drinking water can be an important contributor to the total body burden of salts. Water salinity (defined as the amount of dissolved salts in a body of water) has been associated with adverse health effects. We mapped the current research on drinking water salinity and its effects on blood pressure (BP). We aimed to identify knowledge gaps in the methodology and tools used in the epidemiological literature to address water salinity effects on BP. We performed a scoping review of epidemiological studies by searching PubMed and Web of Science databases from 1980 to 2022. Reviews, study comparisons, meta-analyses, commentaries, viewpoints, correspondence, protocols, studies in clinical settings, animal or in vitro studies, or not in English, were excluded. Epidemiologic studies including systolic/diastolic BP and/or the risk of hypertension as the main health outcome and drinking water salts (sodium, potassium, calcium, magnesium, including electrical conductivity and total dissolved solids) as the main exposures were included. After screening 246 articles, 29 articles were retained. Most studies were conducted in Bangladesh and USA (n = 9 and n = 9, respectively). The majority of studies were cross-sectional (n = 18; 62%). The study populations were adults (55%) or children (35%) or both (10%). Only eight (28%) studies did not collect urine samples and only three studies (10%) did not record participant BP. About half of the studies (n = 15, 52%) reported a positive significant (p < 0.05) association between salts in drinking water and higher BP and/or risk of hypertension; while 24% and 24% reported non-significant (p > 0.05) and significant (p < 0.05) negative associations (with lower BP mainly attributed to higher Mg, Ca, and K (rather than Na) levels in drinking water). More longitudinal studies are warranted to investigate the impact of drinking water salinization on cardiovascular health and risk of hypertension. Under a changing climate, this may be particularly important for coastal populations, as sea level rise in combination with the overexploitation of groundwater would differentially perturb the salinity of their drinking water supplies.

BACKGROUND: Poor immune function increases childrens 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 childs immune status.

Human noroviruses pose grave threats to public health and economy. In this study, we genetically engineered yeast (Saccharomyces cerevisiae EBY100) to display specific norovirus-binding nanobodies (Nano-26 and Nano-85) on cell surface to facilitate the concentration of noroviruses for improved detection. Binding of norovirus virus-like particles (VLPs) to these nanobody-displaying yeasts was confirmed and characterized using confocal microscopy and flow cytometry. The ability of our engineered yeasts to capture norovirus VLPs can reach up to 91.3%. Furthermore, this approach was applied to concentrate and detect norovirus VLPs in a real food matrix. A wide linear detection range (1-104 pg/g) was observed, and the detection limit on spiked spinach was calculated as low as 0.071 pg/g. Overall, our engineered yeasts could be a promising approach to concentrate and purify noroviruses in food samples for easy detection, which allows us to prevent the spread of food-borne virus in the food supply chain.

BackgroundIn South Asia, roughly half of women attend at least four antenatal care visits with skilled health personnel, the minimum number recommended by the World Health Organization for optimal birth outcomes. A much greater proportion of women attend at least one antenatal care visit, suggesting that a key challenge is ensuring that women initiate antenatal care early in pregnancy and continue to attend after their first visit. One critical barrier to antenatal care attendance may be that women do not have sufficient power in their relationships, households, or communities to attend antenatal care when they want to. The main goals of this paper were to 1) understand the potential effects of intervening on direct measures of women's empowerment-including household decision making, freedom of movement, and control over assets-on antenatal care attendance in a rural population of women in Bangladesh, and 2) examine whether differential associations exist across strata of socioeconomic status.MethodsWe analyzed data on 1609 mothers with children under 24 months old in rural Bangladesh and employed targeted maximum likelihood estimation with ensemble machine learning to estimate population average treatment effects.ResultsGreater women's empowerment was associated with an increased number of antenatal care visits. Specifically, among women who attended at least one antenatal care visit, having high empowerment was associated with a greater probability of ≥ 4 antenatal care visits, both in comparison to low empowerment (15.2 pp, 95% CI: 6.0, 24.4) and medium empowerment (9.1 pp, 95% CI: 2.5, 15.7). The subscales of women's empowerment driving the associations were women's decision-making power and control over assets. We found that greater women's empowerment is associated with more antenatal care visits regardless of socioeconomic status.ConclusionsEmpowerment-based interventions, particularly those targeting women's involvement in household decisions and/or facilitating greater control over assets, may be a valuable strategy for increasing antenatal care attendance.Trial registrationClinicalTrials.gov Identifier: NCT04111016, Date First Registered: 01/10/2019.

BackgroundSanitation 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.MethodsWe 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.ResultsThe intervention increased hygienic latrine access from 37% among controls to 94% in the sanitation arm (p

BackgroundWater, sanitation, and hygiene (WASH) improvements are promoted to reduce diarrhoea in low-income countries. However, trials from the past 5 years have found mixed effects of household-level and community-level WASH interventions on child health. Measuring pathogens and host-specific faecal markers in the environment can help investigate causal pathways between WASH and health by quantifying whether and by how much interventions reduce environmental exposure to enteric pathogens and faecal contamination from human and different animal sources. We aimed to assess the effects of WASH interventions on enteropathogens and microbial source tracking (MST) markers in environmental samples.MethodsWe did a systematic review and individual participant data meta-analysis, which included searches from Jan 1, 2000, to Jan 5, 2023, from PubMed, Embase, CAB Direct Global Health, Agricultural and Environmental Science Database, Web of Science, and Scopus, of prospective studies with water, sanitation, or hygiene interventions and concurrent control group that measured pathogens or MST markers in environmental samples and measured child anthropometry, diarrhoea, or pathogen-specific infections. We used covariate-adjusted regression models with robust standard errors to estimate study-specific intervention effects and pooled effect estimates across studies using random-effects models.FindingsFew trials have measured the effect of sanitation interventions on pathogens and MST markers in the environment and they mostly focused on onsite sanitation. We extracted individual participant data on nine environmental assessments from five eligible trials. Environmental sampling included drinking water, hand rinses, soil, and flies. Interventions were consistently associated with reduced pathogen detection in the environment but effect estimates in most individual studies could not be distinguished from chance. Pooled across studies, we found a small reduction in the prevalence of any pathogen in any sample type (pooled prevalence ratio [PR] 0·94 [95% CI 0·90-0·99]). Interventions had no effect on the prevalence of MST markers from humans (pooled PR 1·00 [95% CI 0·88-1·13]) or animals (pooled PR 1·00 [95% CI 0·97-1·03]).InterpretationThe small effect of these sanitation interventions on pathogen detection and absence of effects on human or animal faecal markers are consistent with the small or null health effects previously reported in these trials. Our findings suggest that the basic sanitation interventions implemented in these studies did not contain human waste and did not adequately reduce exposure to enteropathogens in the environment.FundingBill and Melinda Gates Foundation and the UK Foreign and Commonwealth Development Office.

BackgroundReliable and valid measurement of early child development are necessary for the design of effective interventions, programs, and policies to improve early child outcomes. One widely used measure in low- and middle-income countries (LMICs) is the Bayley Scales of Infant and Toddler Development III (Bayley-III). Alternatively, the Bangladeshi-adapted Ages and Stages Questionnaire Inventory (ASQ:I) can be administered more quickly, inexpensively, and with less training than the Bayley-III. We aimed to assess the concurrent validity of the Bangladeshi-adapted ASQ:I with the Bayley-III in children 4-27 months old in rural Bangladesh.MethodsThe sample was a sub-sample (n = 244) of endline participants from an evaluation of an early child development intervention (July-August 2018). We assessed concurrent validity between internally age-standardized domain-specific and total scores using Pearson correlations both overall and stratified by age and intervention status. We also assessed correlations between scores and variables theoretically related to child development including maternal education and stimulation in the home.ResultsThe overall correlation between ASQ:I and Bayley-III total scores was moderate (r = 0.42 95% CI: 0.30-0.53), with no systematic differences by intervention status. Overall, concurrent validity was highest for the gross motor domain (r = 0.51, 0.40-0.60), and lowest for the fine motor domain (r = 0.20, 0.04-0.33). Total ASQ:I and Bayley-III scores were positively correlated with child stimulation and maternal education.ConclusionThe Bangladeshi-adapted ASQ:I is a low-cost tool that can be feasibly administered in rural Bangladesh, is moderately correlated with the Bayley-III, and can be used to measure child development when human, time, or financial resources are constrained.

BackgroundHousehold-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.MethodsWe 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.ResultsAdjusted 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

BackgroundDiarrhea 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 findingsWASH 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