Biomarkers of environmental enteric dysfunction and neurodevelopmental outcomes among children in rural Bangladesh and Kenya: a prospective cohort study.

Background: Environmental enteric dysfunction (EED) may worsen undernutrition, with potential adverse effects on the developmental trajectories of millions of children in low-resource settings.

Objectives: This study aimed to assess associations between EED biomarkers and subsequent child development.

Methods: In a prospective cohort of 2646 children nested within 2 randomized trials in rural Bangladesh (n = 1374) and Kenya (n = 1272), EED was measured by markers of intestinal permeability (fecal alpha-1 antitrypsin; urinary lactulose and mannitol assessed through the dual sugar absorption test), inflammation (fecal myeloperoxidase and neopterin), and repair (fecal regenerating gene 1β).

Pathways through which water, sanitation, hygiene, and nutrition interventions reduce antibiotic use in young children: a mediation analysis of a cohort nested within a cluster-randomized trial.

Background: Low-cost, household-level water, sanitation, and hygiene (WASH) and nutrition interventions can reduce pediatric antibiotic use, but the mechanism through which interventions reduce antibiotic use has not been investigated.

Methods: We conducted a causal mediation analysis using data collected between September 2013 and October 2015 from a cohort nested within the WASH Benefits Bangladesh cluster-randomized trial (NCT01590095). Among a subsample of children within the WASH, nutrition, nutrition + WASH, and control arms (N = 1409 children; 267 clusters), we recorded caregiver-reported antibiotic use at ages 14 and 28 months and collected stool at age 14 months.

Treatment heterogeneity of water, sanitation, hygiene, and nutrition interventions on child growth by environmental enteric dysfunction and pathogen status for young children in Bangladesh.

Background: Water, sanitation, hygiene (WSH), nutrition (N), and combined (N+WSH) interventions are often implemented by global health organizations, but WSH interventions may insufficiently reduce pathogen exposure, and nutrition interventions may be modified by environmental enteric dysfunction (EED), a condition of increased intestinal permeability and inflammation. This study investigated the heterogeneity of these treatments' effects based on individual pathogen and EED biomarker status with respect to child linear growth.

Methods: We applied cross-validated targeted maximum likelihood estimation and super learner ensemble machine learning to assess the conditional treatment effects in subgroups defined by biomarker and pathogen status.

Associations between weather extremes and faecal contamination along pathogen transmission pathways in rural Bangladeshi households: a prospective observational study.

Background: Weather extremes are predicted to influence pathogen exposure but their effects on specific faecal-oral transmission pathways are not well investigated. We evaluated associations between extreme rain and temperature during different antecedent periods (0-14 days) and Escherichia coli along eight faecal-oral pathways in rural Bangladeshi households.

Methods: We used data from the WASH Benefits Bangladesh cluster-randomised controlled trial (NCT01590095).

Water, sanitation, handwashing, and nutritional interventions can reduce child antibiotic use: evidence from Bangladesh and Kenya.

Antibiotics can trigger antimicrobial resistance and microbiome alterations. Reducing pathogen exposure and undernutrition can reduce infections and antibiotic use. We assess effects of water, sanitation, handwashing (WSH) and nutrition interventions on caregiver-reported antibiotic use in Bangladesh and Kenya, longitudinally measured at three timepoints among birth cohorts (ages 3-28 months) in a cluster-randomized trial.

Pathways through which water, sanitation, hygiene, and nutrition interventions reduce antibiotic use in young children: a mediation analysis of a cluster-randomized trial.

Background: Low-cost, household-level water, sanitation, and hygiene (WASH) and nutrition interventions can reduce pediatric antibiotic use, but the mechanism through which interventions reduce antibiotic use has not been investigated.

Methods: We conducted a causal mediation analysis using data from the WASH Benefits Bangladesh cluster-randomized trial (NCT01590095). Among a subsample of children within the WSH, nutrition, nutrition+WSH, and controls arms (N=1,409), we recorded caregiver-reported antibiotic use at ages 14 and 28 months and collected stool at age 14 months.

Treatment Heterogeneity of Water, Sanitation, Hygiene, and Nutrition Interventions on Child Growth by Environmental Enteric Dysfunction and Pathogen Status for Young Children in Bangladesh.

Background: Water, sanitation, hygiene (WSH), nutrition (N), and combined (N+WSH) interventions are often implemented by global health organizations, but WSH interventions may insufficiently reduce pathogen exposure, and nutrition interventions may be modified by environmental enteric dysfunction (EED), a condition of increased intestinal permeability and inflammation. This study investigated the heterogeneity of these treatments' effects based on individual pathogen and EED biomarker status with respect to child linear growth.

Methods: We applied cross-validated targeted maximum likelihood estimation and super learner ensemble machine learning to assess the conditional treatment effects in subgroups defined by biomarker and pathogen status.

Is detection of enteropathogens and human or animal faecal markers in the environment associated with subsequent child enteric infections and growth: an individual participant data meta-analysis.

Background: Quantifying contributions of environmental faecal contamination to child diarrhoea and growth faltering can illuminate causal mechanisms behind modest health benefits in recent water, sanitation, and hygiene (WASH) trials. We aimed to assess associations between environmental detection of enteropathogens and human or animal microbial source tracking markers (MSTM) and subsequent child health outcomes.

Methods: In this individual participant data meta-analysis we searched we searched PubMed, Embase, CAB Direct Global Health, Agricultural and Environmental Science Database, Web of Science, and Scopus for WASH intervention studies with a prospective design and concurrent control that measured enteropathogens or MSTM in environmental samples, or both, and subsequently measured enteric infections, diarrhoea, or height-for-age Z-scores (HAZ) in children younger than 5 years.

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.

Profiling the human intestinal environment under physiological conditions.

The spatiotemporal structure of the human microbiome, proteome and metabolome reflects and determines regional intestinal physiology and may have implications for disease. Yet, little is known about the distribution of microorganisms, their environment and their biochemical activity in the gut because of reliance on stool samples and limited access to only some regions of the gut using endoscopy in fasting or sedated individuals. To address these deficiencies, we developed an ingestible device that collects samples from multiple regions of the human intestinal tract during normal digestion.

Effects of water, sanitation, and hygiene interventions on detection of enteropathogens and host-specific faecal markers in the environment: a systematic review and individual participant data meta-analysis.

Background: Water, 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.

Introducing riskCommunicator: An R package to obtain interpretable effect estimates for public health.

Common statistical modeling methods do not necessarily produce the most relevant or interpretable effect estimates to communicate risk. Overreliance on the odds ratio and relative effect measures limit the potential impact of epidemiologic and public health research. We created a straightforward R package, called riskCommunicator, to facilitate the presentation of a variety of effect measures, including risk differences and ratios, number needed to treat, incidence rate differences and ratios, and mean differences.

High-throughput low-cost nl-qPCR for enteropathogen detection: A proof-of-concept among hospitalized patients in Bangladesh.

Background: Diarrheal disease is a leading cause of morbidity and mortality globally, especially in low- and middle-income countries. High-throughput and low-cost approaches to identify etiologic agents are needed to guide public health mitigation. Nanoliter-qPCR (nl-qPCR) is an attractive alternative to more expensive methods yet is nascent in application and without a proof-of-concept among hospitalized patients.

Advantageous microbial community development and improved performance of pilot-scale field systems treating high-risk acid mine drainage with crab shell.

Microbial communities are crucial to the effectiveness and stability of bioremediation systems treating acid mine drainage (AMD); however, little research has addressed how they correlate to system performance under changing environmental conditions. In this study, 16S rRNA gene sequencing and quantitative PCR (qPCR) were used to characterize microbial communities within different substrate combinations of crab shell (CS) and spent mushroom compost (SMC) and their association with chemical performance in pilot-scale vertical flow ponds (VFPs) treating high risk AMD in central Pennsylvania over 643 days of operation. As compared to a control containing SMC, VFPs containing CS sustained higher alkalinity, higher sulfate-reducing rates, and more thorough metals removal (>90% for Fe and Al, >50% for Mn and Zn).

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.

High-Throughput Multiparallel Enteropathogen Detection via Nano-Liter qPCR.

Quantitative molecular diagnostic methods can effectively detect pathogen-specific nucleic acid sequences, but costs associated with multi-pathogen panels hinder their widespread use in research trials. Nano-liter qPCR (nL-qPCR) is a miniaturized tool for quantification of multiple targets in large numbers of samples based on assay parallelization on a single chip, with potentially significant cost-savings due to rapid throughput and reduced reagent volumes. We evaluated a suite of novel and published assays to detect 17 enteric pathogens using a commercially available nL-qPCR technology.

Author Correction: Gut microbiota plasticity is correlated with sustained weight loss on a low-carb or low-fat dietary intervention.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Shared bacterial communities between soil, stored drinking water, and hands in rural Bangladeshi households.

Understanding household-level transmission pathways of fecal pathogens can provide insight for developing effective strategies to reduce diarrheal illness in low- and middle-income countries. We applied whole bacterial community analysis to investigate pathways of bacterial transmission in 50 rural Bangladeshi households. SourceTracker was used to quantify the shared microbial community in household reservoirs (stored drinking water, soil, and hands) and estimate the percentage of fecal-associated bacteria from child and mothers' feces in these reservoirs.

Gut microbiota plasticity is correlated with sustained weight loss on a low-carb or low-fat dietary intervention.

While low-carbohydrate and low-fat diets can both lead to weight-loss, a substantial variability in achieved long-term outcomes exists among obese but otherwise healthy adults. We examined the hypothesis that structural differences in the gut microbiota explain a portion of variability in weight-loss using two cohorts of obese adults enrolled in the Diet Intervention Examining The Factors Interacting with Treatment Success (DIETFITS) study. A total of 161 pre-diet fecal samples were sequenced from a discovery cohort (n = 66) and 106 from a validation cohort (n = 56).

Identification of Widespread Antibiotic Exposure in Patients With Cholera Correlates With Clinically Relevant Microbiota Changes.

Background: A first step to combating antimicrobial resistance in enteric pathogens is to establish an objective assessment of antibiotic exposure. Our goal was to develop and evaluate a liquid chromatography-ion trap mass spectrometry (LC/MS) method to determine antibiotic exposure in patients with cholera.

Methods: A priority list for targeted LC/MS was generated from medication-vendor surveys in Bangladesh.

Effects of lipid-based nutrient supplements and infant and young child feeding counseling with or without improved water, sanitation, and hygiene (WASH) on anemia and micronutrient status: results from 2 cluster-randomized trials in Kenya and Bangladesh.

Background: Anemia in young children is a global health problem. Risk factors include poor nutrient intake and poor water quality, sanitation, or hygiene.

Objective: We evaluated the effects of water quality, sanitation, handwashing, and nutrition interventions on micronutrient status and anemia among children in rural Kenya and Bangladesh.