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. We analyzed treatment (N+WSH, WSH, N, or control) randomly assigned in-utero, child pathogen and EED data at 14 months of age, and child LAZ at 28 months of age. We estimated the difference in mean child length for age Z-score (LAZ) under the treatment rule and the difference in stratified treatment effect (treatment effect difference) comparing children with high versus low pathogen/biomarker status while controlling for baseline covariates. Results: We analyzed data from 1,522 children, who had median LAZ of -1.56. We found that myeloperoxidase (N+WSH treatment effect difference 0.0007 LAZ, WSH treatment effect difference 0.1032 LAZ, N treatment effect difference 0.0037 LAZ) and Campylobacter infection (N+WSH treatment effect difference 0.0011 LAZ, WSH difference 0.0119 LAZ, N difference 0.0255 LAZ) were associated with greater effect of all interventions on growth. In other words, children with high myeloperoxidase or Campylobacter infection experienced a greater impact of the interventions on growth. We found that a treatment rule that assigned the N+WSH (LAZ difference 0.23, 95% CI (0.05, 0.41)) and WSH (LAZ difference 0.17, 95% CI (0.04, 0.30)) interventions based on EED biomarkers and pathogens increased predicted child growth compared to the randomly allocated intervention. Conclusions: These findings indicate that EED biomarker and pathogen status, particularly Campylobacter and myeloperoxidase (a measure of gut inflammation), may be related to impact of N+WSH, WSH, and N interventions on child linear growth.

Bioaccessibility and speciation of arsenic in children's diets and health risk assessment of an endemic area in Bangladesh.

This study determines the bioaccessibility of toxic and carcinogenic arsenic (As) in composite food samples and evaluates potential exposure from food intake in Bangladesh children. Total As (tAs), inorganic As (iAs) and bioaccessible As (BAs) in food composite samples consumed by children were compared between an exposed and a control group (based on As in drinking water). Total As concentrations in composite food samples of children exposed to mean As level of 331 µg/l in drinking and cooking water ranged from 586 to 1975 µg/kg, dry weight over 76-90 µg/kg in the unexposed group. Average iAs in food composites was 73.9% (range: 49.3-90.8%). The fraction of BAs using gastric and gastrointestinal phases was 91 ± 13% and 98 ± 11%, respectively. Daily intake of iAs in the exposed group ranged from 0.41 to 6.38 µg per kg body weight (BW), which was much higher than the unexposed group (0.08-0.15 µg per kg BW). High iAs content and BAs in composite food samples indicated the elevated risk to exposed children. Further research should include both adults and children using larger sample size to determine overall As exposure from food intake in Bangladesh, attention must be given to lowering of As in food.

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.

Speciation of arsenic metabolite intermediates in human urine by ion-exchange chromatography and flow injection hydride generation atomic absorption spectrometry.

Biomethylation is considered as the principal metabolic and detoxification pathway for inorganic arsenic in human. The end products of methylation are less toxic and more readily excreted through urine. Therefore, speciation of metabolites in urine is essential to a better understanding of arsenic metabolism, health effects and detoxification ability of individuals exposed to arsenic through drinking water, food and environmental materials. Speciation of inorganic and methylated arsenic in urine is an analytical challenge and often requires expensive instrumentation. We have applied a relatively inexpensive technique for the separation and analysis of various arsenic species, such as, arsenite, arsenate, monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA) in human urine. The technique is based on ion exchange chromatographic separation followed by flow injection hydride generation atomic absorption spectroscopy (FI-HG-AAS). The detection limit varies from 1.0 to 2.0 microg/L for various species. The technique has been successfully applied to speciation of arsenic metabolite intermediates in urine samples collected from patients in Hajiganj, a serious arsenic affected area in Bangladesh. Arsenite (AsIII) was found to be the major component in the urine from these patients. Our findings from patients in Hajiganj, Bangladesh are presented in this paper. The technique permits us to carry out arsenic speciation in urine, essential for toxicological studies and possible nutritional intervention in combating arsenic poisoning in Bangladesh.