Child wasting and concurrent stunting in low- and middle-income countries.

Sustainable Development Goal 2.2-to end malnutrition by 2030-includes the elimination of child wasting, defined as a weight-for-length z-score that is more than two standard deviations below the median of the World Health Organization standards for child growth1. Prevailing methods to measure wasting rely on cross-sectional surveys that cannot measure onset, recovery and persistence-key features that inform preventive interventions and estimates of disease burden. Here we analyse 21 longitudinal cohorts and show that wasting is a highly dynamic process of onset and recovery, with incidence peaking between birth and 3 months. Many more children experience an episode of wasting at some point during their first 24 months than prevalent cases at a single point in time suggest. For example, at the age of 24 months, 5.6% of children were wasted, but by the same age (24 months), 29.2% of children had experienced at least one wasting episode and 10.0% had experienced two or more episodes. Children who were wasted before the age of 6 months had a faster recovery and shorter episodes than did children who were wasted at older ages; however, early wasting increased the risk of later growth faltering, including concurrent wasting and stunting (low length-for-age z-score), and thus increased the risk of mortality. In diverse populations with high seasonal rainfall, the population average weight-for-length z-score varied substantially (more than 0.5 z in some cohorts), with the lowest mean z-scores occurring during the rainiest months; this indicates that seasonally targeted interventions could be considered. Our results show the importance of establishing interventions to prevent wasting from birth to the age of 6 months, probably through improved maternal nutrition, to complement current programmes that focus on children aged 6-59 months.

Early-childhood linear growth faltering in low- and middle-income countries.

Globally, 149 million children under 5 years of age are estimated to be stunted (length more than 2 standard deviations below international growth standards)1,2. Stunting, a form of linear growth faltering, increases the risk of illness, impaired cognitive development and mortality. Global stunting estimates rely on cross-sectional surveys, which cannot provide direct information about the timing of onset or persistence of growth faltering-a key consideration for defining critical windows to deliver preventive interventions. Here we completed a pooled analysis of longitudinal studies in low- and middle-income countries (n = 32 cohorts, 52,640 children, ages 0-24 months), allowing us to identify the typical age of onset of linear growth faltering and to investigate recurrent faltering in early life. The highest incidence of stunting onset occurred from birth to the age of 3 months, with substantially higher stunting at birth in South Asia. From 0 to 15 months, stunting reversal was rare; children who reversed their stunting status frequently relapsed, and relapse rates were substantially higher among children born stunted. Early onset and low reversal rates suggest that improving children's linear growth will require life course interventions for women of childbearing age and a greater emphasis on interventions for children under 6 months of age.

Causes and consequences of child growth faltering in low-resource settings.

Growth faltering in children (low length for age or low weight for length) during the first 1,000 days of life (from conception to 2 years of age) influences short-term and long-term health and survival1,2. Interventions such as nutritional supplementation during pregnancy and the postnatal period could help prevent growth faltering, but programmatic action has been insufficient to eliminate the high burden of stunting and wasting in low- and middle-income countries. Identification of age windows and population subgroups on which to focus will benefit future preventive efforts. Here we use a population intervention effects analysis of 33 longitudinal cohorts (83,671 children, 662,763 measurements) and 30 separate exposures to show that improving maternal anthropometry and child condition at birth accounted for population increases in length-for-age z-scores of up to 0.40 and weight-for-length z-scores of up to 0.15 by 24 months of age. Boys had consistently higher risk of all forms of growth faltering than girls. Early postnatal growth faltering predisposed children to subsequent and persistent growth faltering. Children with multiple growth deficits exhibited higher mortality rates from birth to 2 years of age than children without growth deficits (hazard ratios 1.9 to 8.7). The importance of prenatal causes and severe consequences for children who experienced early growth faltering support a focus on pre-conception and pregnancy as a key opportunity for new preventive interventions.

Estimating community-wide indirect effects of influenza vaccination: triangulation using mathematical models and bias analysis.

Understanding whether influenza vaccine promotion strategies produce community-wide indirect effects is important for establishing vaccine coverage targets and optimizing vaccine delivery. Empirical epidemiologic studies and mathematical models have been used to estimate indirect effects of vaccines but rarely for the same estimand in the same dataset. Using these approaches together could be a powerful tool for triangulation in infectious disease epidemiology because each approach is subject to distinct sources of bias. We triangulated evidence about indirect effects from a school-located influenza vaccination program using two approaches: a difference-in-difference (DID) analysis, and an age-structured, deterministic, compartmental model. The estimated indirect effect was substantially lower in the mathematical model than in the DID analysis (2.1% (95% Bayesian credible intervals 0.4 - 4.4%) vs. 22.3% (95% CI 7.6% - 37.1%)). To explore reasons for differing estimates, we used sensitivity analyses and probabilistic bias analyses. When we constrained model parameters such that projections matched the DID analysis, results only aligned with the DID analysis with substantially lower pre-existing immunity among school-age children and older adults. Conversely, DID estimates corrected for potential bias only aligned with mathematical model estimates under differential outcome misclassification. We discuss how triangulation using empirical and mathematical modelling approaches could strengthen future studies.

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.

A Review of the Ring Trial Design for Evaluating Ring Interventions for Infectious Diseases.

In trials of infectious disease interventions, rare outcomes and unpredictable spatiotemporal variation can introduce bias, reduce statistical power, and prevent conclusive inferences. Spillover effects can complicate inference if individual randomization is used to gain efficiency. Ring trials are a type of cluster-randomized trial that may increase efficiency and minimize bias, particularly in emergency and elimination settings with strong clustering of infection. They can be used to evaluate ring interventions, which are delivered to individuals in proximity to or contact with index cases. We conducted a systematic review of ring trials, compare them with other trial designs for evaluating ring interventions, and describe strengths and weaknesses of each design. Of 849 articles and 322 protocols screened, we identified 26 ring trials, 15 cluster-randomized trials, 5 trials that randomized households or individuals within rings, and 1 individually randomized trial. The most common interventions were postexposure prophylaxis (n = 23) and focal mass drug administration and screening and treatment (n = 7). Ring trials require robust surveillance systems and contact tracing for directly transmitted diseases. For rare diseases with strong spatiotemporal clustering, they may have higher efficiency and internal validity than cluster-randomized designs, in part because they ensure that no clusters are excluded from analysis due to zero cluster incidence. Though more research is needed to compare them with other types of trials, ring trials hold promise as a design that can increase trial speed and efficiency while reducing bias.

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.

Evaluating the robustness of targeted maximum likelihood estimators via realistic simulations in nutrition intervention trials.

Several recently developed methods have the potential to harness machine learning in the pursuit of target quantities inspired by causal inference, including inverse weighting, doubly robust estimating equations and substitution estimators like targeted maximum likelihood estimation. There are even more recent augmentations of these procedures that can increase robustness, by adding a layer of cross-validation (cross-validated targeted maximum likelihood estimation and double machine learning, as applied to substitution and estimating equation approaches, respectively). While these methods have been evaluated individually on simulated and experimental data sets, a comprehensive analysis of their performance across real data based simulations have yet to be conducted. In this work, we benchmark multiple widely used methods for estimation of the average treatment effect using ten different nutrition intervention studies data. A nonparametric regression method, undersmoothed highly adaptive lasso, is used to generate the simulated distribution which preserves important features from the observed data and reproduces a set of true target parameters. For each simulated data, we apply the methods above to estimate the average treatment effects as well as their standard errors and resulting confidence intervals. Based on the analytic results, a general recommendation is put forth for use of the cross-validated variants of both substitution and estimating equation estimators. We conclude that the additional layer of cross-validation helps in avoiding unintentional over-fitting of nuisance parameter functionals and leads to more robust inferences.

Longitudinal Effects of a Sanitation Intervention on Environmental Fecal Contamination in a Cluster-Randomized Controlled Trial in Rural Bangladesh.

Household latrine access generally is not associated with reduced fecal contamination in the environment, but its long-term effectiveness has not been measured. We conducted an environmental assessment nested within the WASH Benefits Bangladesh randomized controlled trial (NCT01590095). We quantified E. coli and fecal coliforms in samples of stored drinking water, child hands, mother hands, soil, and food among a random sample of households from the sanitation and control arms of the trial. Samples were collected during eight quarterly visits approximately 1-3.5 years after intervention initiation. Overall, there were no substantial differences in environmental fecal contamination between households enrolled in the sanitation and control arms. Statistically significant reductions were found in stored water and child hands after pooling across sampling rounds, but the effects were small and not consistent across rounds. In addition, we assessed potential effect modification of intervention effects by follow-up time, season, wealth, community-level latrine density and coverage, population density, and domestic animal ownership. While the intervention had statistically significant effects within some subgroups, there were no consistent patterns of effect modification. Our findings support a growing consensus that on-site latrines are insufficient to prevent fecal contamination in the rural household environment.

Effect of water, sanitation, handwashing and nutrition interventions on enteropathogens in children 14 months old: a cluster-randomized controlled trial in rural Bangladesh.

BACKGROUND: We evaluated the impact of low-cost water, sanitation, handwashing (WSH) and child nutrition interventions on enteropathogen carriage in the WASH Benefits cluster-randomized controlled trial in rural Bangladesh. METHODS: We analyzed 1411 routine fecal samples from children 14±2 months old in the WSH (n = 369), nutrition counseling plus lipid-based nutrient supplement (n = 353), nutrition plus WSH (n = 360), and control (n = 329) arms for 34 enteropathogens using quantitative PCR. Outcomes included the number of co-occurring pathogens; cumulative quantity of four stunting-associated pathogens; and prevalence and quantity of individual pathogens. Masked analysis was by intention-to-treat. RESULTS: 326 (99.1%) control children had one or more enteropathogens detected (mean 3.8±1.8). Children receiving WSH interventions had lower prevalence and quantity of individual viruses than controls (prevalence difference for norovirus: -11% [95% confidence interval [CI], -5 to -17%]; sapovirus: -9% [95%CI, -3 to -15%]; and adenovirus 40/41: -9% [95%CI, -2 to - 15%]). There was no difference in bacteria, parasites, or cumulative quantity of stunting-associated pathogens between controls and any intervention arm. CONCLUSIONS: WSH interventions were associated with fewer enteric viruses in children aged 14 months. Different strategies are needed to reduce enteric bacteria and parasites at this critical young age.

Effects of Water, Sanitation, Handwashing, and Nutritional Interventions on Environmental Enteric Dysfunction in Young Children: A Cluster-randomized, Controlled Trial in Rural Bangladesh.

BACKGROUND: We hypothesized that drinking water, sanitation, handwashing (WSH), and nutritional interventions would improve environmental enteric dysfunction (EED), a potential contributor to stunting. METHODS: Within a subsample of a cluster-randomized, controlled trial in rural Bangladesh, we enrolled pregnant women in 4 arms: control, WSH, child nutrition counseling plus lipid-based nutrient supplements (N), and nutrition plus WSH (N+WSH). Among the birth cohort, we measured biomarkers of gut inflammation (myeloperoxidase, neopterin), permeability (alpha-1-antitrypsin, lactulose, mannitol), and repair (regenerating gene 1ß) at median ages 3, 14, and 28 months. Analysis was intention-to-treat. RESULTS: We assessed 1512 children. At age 3 months, compared to controls, neopterin was reduced by nutrition (-0.21 log nmol/L; 95% confidence interval [CI], -.37, -.05) and N+WSH (-0.20 log nmol/L; 95% CI, -.34, -.06) interventions; similar reductions were observed at 14 months. At 3 months, all interventions reduced lactulose and mannitol (-0.60 to -0.69 log mmol/L). At 28 months, myeloperoxidase was elevated in the WSH and nutrition arms (0.23-0.27 log ng/mL) and lactulose was higher in the WSH arm (0.30 log mmol/L; 95% CI, .07, .53). CONCLUSIONS: Reductions in permeability and inflammation at ages 3 and 14 months suggest that the interventions promoted healthy intestinal maturation; however, by 28 months, the WSH and nutrition arms showed elevated EED biomarkers. These results underscore the importance of developing a better understanding of EED pathophysiology and targeting interventions early in childhood, when they are likely to have the largest benefit to intestinal health. CLINICAL TRIALS REGISTRATION: NCT01590095.

Evaluation of a city-wide school-located influenza vaccination program in Oakland, California, with respect to vaccination coverage, school absences, and laboratory-confirmed influenza: A matched cohort study.

BACKGROUND: It is estimated that vaccinating 50%-70% of school-aged children for influenza can produce population-wide indirect effects. We evaluated a city-wide school-located influenza vaccination (SLIV) intervention that aimed to increase influenza vaccination coverage. The intervention was implemented in ≥95 preschools and elementary schools in northern California from 2014 to 2018. Using a matched cohort design, we estimated intervention impacts on student influenza vaccination coverage, school absenteeism, and community-wide indirect effects on laboratory-confirmed influenza hospitalizations. METHODS AND FINDINGS: We used a multivariate matching algorithm to identify a nearby comparison school district with pre-intervention characteristics similar to those of the intervention school district and matched schools in each district. To measure student influenza vaccination, we conducted cross-sectional surveys of student caregivers in 22 school pairs (2017 survey, N = 6,070; 2018 survey, N = 6,507). We estimated the incidence of laboratory-confirmed influenza hospitalization from 2011 to 2018 using surveillance data from school district zip codes. We analyzed student absenteeism data from 2011 to 2018 from each district (N = 42,487,816 student-days). To account for pre-intervention differences between districts, we estimated difference-in-differences (DID) in influenza hospitalization incidence and absenteeism rates using generalized linear and log-linear models with a population offset for incidence outcomes. Prior to the SLIV intervention, the median household income was $51,849 in the intervention site and $61,596 in the comparison site. The population in each site was predominately white (41% in the intervention site, 48% in the comparison site) and/or of Hispanic or Latino ethnicity (26% in the intervention site, 33% in the comparison site). The number of students vaccinated by the SLIV intervention ranged from 7,502 to 10,106 (22%-28% of eligible students) each year. During the intervention, influenza vaccination coverage among elementary students was 53%-66% in the comparison district. Coverage was similar between the intervention and comparison districts in influenza seasons 2014-2015 and 2015-2016 and was significantly higher in the intervention site in seasons 2016-2017 (7%; 95% CI 4, 11; p < 0.001) and 2017-2018 (11%; 95% CI 7, 15; p < 0.001). During seasons when vaccination coverage was higher among intervention schools and the vaccine was moderately effective, there was evidence of statistically significant indirect effects: The DID in the incidence of influenza hospitalization per 100,000 in the intervention versus comparison site was -17 (95% CI -30, -4; p = 0.008) in 2016-2017 and -37 (95% CI -54, -19; p < 0.001) in 2017-2018 among non-elementary-school-aged individuals and -73 (95% CI -147, 1; p = 0.054) in 2016-2017 and -160 (95% CI -267, -53; p = 0.004) in 2017-2018 among adults 65 years or older. The DID in illness-related school absences per 100 school days during the influenza season was -0.63 (95% CI -1.14, -0.13; p = 0.014) in 2016-2017 and -0.80 (95% CI -1.28, -0.31; p = 0.001) in 2017-2018. Limitations of this study include the use of an observational design, which may be subject to unmeasured confounding, and caregiver-reported vaccination status, which is subject to poor recall and low response rates. CONCLUSIONS: A city-wide SLIV intervention in a large, diverse urban population was associated with a decrease in the incidence of laboratory-confirmed influenza hospitalization in all age groups and a decrease in illness-specific school absence rate among students in 2016-2017 and 2017-2018, seasons when the vaccine was moderately effective, suggesting that the intervention produced indirect effects. Our findings suggest that in populations with moderately high background levels of influenza vaccination coverage, SLIV programs are associated with further increases in coverage and reduced influenza across the community.

Effects of Water, Sanitation, Handwashing, and Nutritional Interventions on Child Enteric Protozoan Infections in Rural Bangladesh: A Cluster-Randomized Controlled Trial.

Background: We evaluated effects of individual and combined water, sanitation, handwashing (WSH), and nutritional interventions on protozoan infections in children. Methods: We randomized geographical clusters of pregnant women in rural Bangladesh into chlorinated drinking water, hygienic sanitation, handwashing, nutrition, combined WSH, nutrition plus WSH (N+WSH), or control arms. Participants were not masked. After approximately 2.5 years of intervention, we measured Giardia, Cryptosporidium, and Entamoeba histolytica prevalence and infection intensity by multiplex real-time polymerase chain reaction of child stool. Analysis was intention-to-treat. Results: Between May 2012 and July 2013, we randomized 5551 pregnant women. At follow-up, among 4102 available women, we enrolled 6694 children into the protozoan assessment. We analyzed stool from 5933 children (aged ~31 months) for protozoan infections. Compared with 35.5% prevalence among controls, Giardia infection prevalence was lower in the sanitation (26.5%; prevalence ratio [PR], 0.75 [95% confidence interval {CI}, .64-.88]), handwashing (28.2%; PR, 0.80 [95% CI, .66-.96]), WSH (29.7%; PR, 0.83 [95% CI, .72-.96]), and N+WSH (26.7%; PR, 0.75 [95% CI, .64-.88]) arms. Water and nutrition interventions had no effect. Low prevalence of E. histolytica and Cryptosporidium (<2%) resulted in imprecise effect estimates. Conclusions: Individual handwashing and hygienic sanitation interventions significantly reduced childhood Giardia infections, and there were no effects of chlorinated drinking water and nutrition improvements in this context. Combined WSH interventions provided no additional benefit. To reduce Giardia infection, individual WSH interventions may be more feasible and cost-effective than combined interventions in similar rural, low-income settings. Clinical Trials Registration: NCT01590095.

A Randomized Controlled Trial to Measure Spillover Effects of a Combined Water, Sanitation, and Handwashing Intervention in Rural Bangladesh.

Water, sanitation, and handwashing interventions may confer spillover effects on intervention recipients' neighbors by interrupting pathogen transmission. We measured geographically local spillovers in the Water Quality, Sanitation, and Handwashing (WASH) Benefits Study, a cluster-randomized trial in rural Bangladesh, by comparing outcomes among neighbors of intervention versus those of control participants. Geographically defined clusters were randomly allocated to a compound-level intervention (i.e., chlorinated drinking water, upgraded sanitation, and handwashing promotion) or control arm. From January 2015 to August 2015, in 180 clusters, we enrolled 1,799 neighboring children who were age matched to trial participants who would have been eligible for the study had they been conceived slightly earlier or later. After 28 months of intervention, we quantified fecal indicator bacteria in toy rinse and drinking water samples and measured soil-transmitted helminth infections and caregiver-reported diarrhea and respiratory illness. Neighbors' characteristics were balanced across arms. Detectable Escherichia coli prevalence in tubewell samples was lower for intervention participants' neighbors than control participants' (prevalence ratio = 0.83; 95% confidence interval: 0.73, 0.95). Fecal indicator bacteria prevalence did not differ between arms for other environmental samples. Prevalence was similar in neighbors of intervention participants versus those of control participants for soil-transmitted helminth infection, diarrhea, and respiratory illness. A compound-level water, sanitation, and handwashing intervention reduced neighbors' tubewell water contamination but did not affect neighboring children's health.

Do Sanitation Improvements Reduce Fecal Contamination of Water, Hands, Food, Soil, and Flies? Evidence from a Cluster-Randomized Controlled Trial in Rural Bangladesh.

Sanitation improvements have had limited effectiveness in reducing the spread of fecal pathogens into the environment. We conducted environmental measurements within a randomized controlled trial in Bangladesh that implemented individual and combined water treatment, sanitation, handwashing (WSH) and nutrition interventions (WASH Benefits, NCT01590095). Following approximately 4 months of intervention, we enrolled households in the trial's control, sanitation and combined WSH arms to assess whether sanitation improvements, alone and coupled with water treatment and handwashing, reduce fecal contamination in the domestic environment. We quantified fecal indicator bacteria in samples of drinking and ambient waters, child hands, food given to young children, courtyard soil and flies. In the WSH arm, Escherichia coli prevalence in stored drinking water was reduced by 62% (prevalence ratio = 0.38 (0.32, 0.44)) and E. coli concentration by 1-log (Δlog10 = -0.88 (-1.01, -0.75)). The interventions did not reduce E. coli along other sampled pathways. Ambient contamination remained high among intervention households. Potential reasons include noncommunity-level sanitation coverage, child open defecation, animal fecal sources, or naturalized E. coli in the environment. Future studies should explore potential threshold effects of different levels of community sanitation coverage on environmental contamination.

Effects of Single and Combined Water, Sanitation and Handwashing Interventions on Fecal Contamination in the Domestic Environment: A Cluster-Randomized Controlled Trial in Rural Bangladesh.

Water, sanitation, and hygiene interventions have varying effectiveness in reducing fecal contamination in the domestic environment; delivering them in combination could yield synergies. We conducted environmental assessments within a randomized controlled trial in Bangladesh that implemented single and combined water treatment, sanitation, handwashing (WSH) and nutrition interventions (WASH Benefits, NCT01590095). After one and two years of intervention, we quantified fecal indicator bacteria in samples of drinking water (from source or storage), child hands, children's food and sentinel objects. In households receiving single water treatment interventions, Escherichia coli prevalence in stored drinking water was reduced by 50% and concentration by 1-log. E. coli prevalence in food was reduced by 30% and concentration by 0.5-log in households receiving single water treatment and handwashing interventions. Combined WSH did not reduce fecal contamination more effectively than its components. Interventions did not reduce E. coli in groundwater, on child hands and on objects. These findings suggest that WSH improvements reduced contamination along the direct transmission pathways of stored water and food but not along indirect upstream pathways. Our findings support implementing water treatment and handwashing to reduce fecal exposure through water and food but provide no evidence that combining interventions further reduces exposure.

Acute Illness Among Surfers After Exposure to Seawater in Dry- and Wet-Weather Conditions.

Rainstorms increase levels of fecal indicator bacteria in urban coastal waters, but it is unknown whether exposure to seawater after rainstorms increases rates of acute illness. Our objective was to provide the first estimates of rates of acute illness after seawater exposure during both dry- and wet-weather periods and to determine the relationship between levels of indicator bacteria and illness among surfers, a population with a high potential for exposure after rain. We enrolled 654 surfers in San Diego, California, and followed them longitudinally during the 2013-2014 and 2014-2015 winters (33,377 days of observation, 10,081 surf sessions). We measured daily surf activities and illness symptoms (gastrointestinal illness, sinus infections, ear infections, infected wounds). Compared with no exposure, exposure to seawater during dry weather increased incidence rates of all outcomes (e.g., for earache or infection, adjusted incidence rate ratio (IRR) = 1.86, 95% confidence interval (CI): 1.27, 2.71; for infected wounds, IRR = 3.04, 95% CI: 1.54, 5.98); exposure during wet weather further increased rates (e.g., for earache or infection, IRR = 3.28, 95% CI: 1.95, 5.51; for infected wounds, IRR = 4.96, 95% CI: 2.18, 11.29). Fecal indicator bacteria measured in seawater (Enterococcus species, fecal coliforms, total coliforms) were strongly associated with incident illness only during wet weather. Urban coastal seawater exposure increases the incidence rates of many acute illnesses among surfers, with higher incidence rates after rainstorms.