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).

Social Desirability Bias in a Randomized Controlled Trial That Included Breastfeeding Promotion in Western Kenya.

Background: Breastfeeding promotion is associated with improved measures of breastfeeding practice; however, most studies rely on participant-reported outcomes.

Objectives: This study aimed to evaluate the likelihood of bias in self-reported breastfeeding outcomes.

Methods: We used data from the WASH Benefits randomized controlled trial in Kenya (clinicaltrials.

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.

Maternal experience of intimate partner violence, maternal depression, and parental stress are not associated with child telomere length in Bangladesh.

Shorter telomere length (TL) is associated with an increased risk for developing chronic or age-related diseases in adults. The process of telomere shortening is accelerated in response to stress and is well characterized in adult populations from high-income countries. Prior studies suggest the relationship between stress, shorter TL, and disease risk initiates in early life.

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.

Seroprevalence, incidence estimates, and environmental risk factors for dengue, chikungunya, and Zika infection amongst children living in informal urban settlements in Indonesia and Fiji.

Background: The burden of Aedes aegypti-transmitted viruses such as dengue, chikungunya, and Zika are increasing globally, fueled by urbanization and climate change, with some of the highest current rates of transmission in Asia. Local factors in the built environment have the potential to exacerbate or mitigate transmission.

Methods: In 24 informal urban settlements in Makassar, Indonesia and Suva, Fiji, we tested children under 5 years old for evidence of prior infection with dengue, chikungunya, and Zika viruses by IgG serology.

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.

Seroprevalence, incidence estimates, and environmental risk factors for dengue, chikungunya, and Zika infection amongst children living in informal urban settlements in Indonesia and Fiji.

Background: The burden of -transmitted viruses such as dengue, chikungunya, and Zika are increasing globally, fueled by urbanization and climate change, with some of the highest current rates of transmission in Asia. Local factors in the built environment have the potential to exacerbate or mitigate transmission.

Methods: In 24 informal urban settlements in Makassar, Indonesia and Suva, Fiji, we tested children under 5 years old for evidence of prior infection with dengue, chikungunya, and Zika viruses by IgG serology.

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.

Addressing Fecal Contamination in Rural Kenyan Households: The Roles of Environmental Interventions and Animal Ownership.

Combined water, sanitation, and handwashing (WSH) interventions could reduce fecal contamination along more transmission pathways than single interventions alone. We measured levels in 3909 drinking water samples, 2691 child hand rinses, and 2422 toy ball rinses collected from households enrolled in a 2-year cluster-randomized controlled trial evaluating single and combined WSH interventions. Water treatment with chlorine reduced in drinking water.

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.

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.

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.

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.

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.

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.

Geographic pair-matching in large-scale cluster randomized trials.

Custer 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. Pair matched randomization is one strategy with potential to increase trial efficiency, but to our knowledge there have been no empirical evaluations of pair-matching in large-scale, epidemiologic field trials.

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.

Contamination of Fresh Produce with Antibiotic-Resistant Bacteria and Associated Risks to Human Health: A Scoping Review.

Fresh produce, when consumed raw, can be a source of exposure to antimicrobial residues, antimicrobial-resistant bacteria (ARB) and antimicrobial resistance genes (ARGs) of clinical importance. This review aims to determine: (1) the presence and abundance of antimicrobial residues, ARB and ARGs in fresh agricultural products sold in retail markets and consumed raw; (2) associated health risks in humans; and (3) pathways through which fresh produce becomes contaminated with ARB/ARGs. We searched the Ovid Medline, Web of Science and Hinari databases as well as grey literature, and identified 40 articles for inclusion.

Effective Treatment Strategies for the Removal of Antibiotic-Resistant Bacteria, Antibiotic-Resistance Genes, and Antibiotic Residues in the Effluent From Wastewater Treatment Plants Receiving Municipal, Hospital, and Domestic Wastewater: Protocol for a Systematic Review.

Background: The widespread and unrestricted use of antibiotics has led to the emergence and spread of antibiotic-resistant bacteria (ARB), antibiotic-resistance genes (ARGs), and antibiotic residues in the environment. Conventional wastewater treatment plants (WWTPs) are not designed for effective and adequate removal of ARB, ARGs, and antibiotic residues, and therefore, they play an important role in the dissemination of antimicrobial resistance (AMR) in the natural environment.

Objective: We will conduct a systematic review to determine the most effective treatment strategies for the removal of ARB, ARGs, and antibiotic residues from the treated effluent disposed into the environment from WWTPs that receive municipal, hospital, and domestic discharge.

Characteristics that modify the effect of small-quantity lipid-based nutrient supplementation on child anemia and micronutrient status: an individual participant data meta-analysis of randomized controlled trials.

Background: Small-quantity lipid-based nutrient supplements (SQ-LNSs) have been shown to reduce the prevalence of child anemia and iron deficiency, but effects on other micronutrients are less well known. Identifying subgroups who benefit most from SQ-LNSs could support improved program design.

Objectives: We aimed to identify study-level and individual-level modifiers of the effect of SQ-LNSs on child hemoglobin (Hb), anemia, and inflammation-adjusted micronutrient status outcomes.

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.