Effects of water quality, sanitation, handwashing and nutritional interventions on enteric pathogen seroconversion in rural Bangladesh: a cluster randomised trial
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Background
Improvements to water quality, sanitation, handwashing (WASH) and nutrition may prevent enteric pathogen infection during the first two years of life. Few randomised controlled trials have measured pathogen-specific effects of WASH and nutritional interventions.
Methods
Within a 2×2 factorial cluster-randomized trial of WASH and nutritional interventions in Bangladesh, we tested dried blood spot specimens with multiplex assay for IgG responses to 12 enteric pathogens: Norovirus , Campylobacter , LT-producing enterotoxigenic E. coli (LT-ETEC), Shigella , non-typhoidal and typhoidal Salmonella enterica , Vibrio cholerae , Cryptosporidium , Giardia , Entamoeba histolytica , Taenia solium , and Strongyloides stercoralis . Primary analysis included children with IgG measurements at ∼24 months, and secondary analysis assessed early effects in a sub-study at ∼14 months. We estimated age-specific seroprevalence and marginal seroprevalence differences for WASH and nutrition effects. Trial is registered with ClinicalTrials.gov ( NCT01590095 ).
Findings
Across the four arms (450 clusters), 4817 samples were tested for IgG responses, 2453 samples at the primary endpoint. Seroprevalence increased with age, consistent with intense early-life transmission. For highest transmission pathogens, >94% of children had seroconverted to norovirus , LT-ETEC and Campylobacter by 12-18 months. WASH effects were modest and pathogen-specific but generally protective. At 24 months, children that received WASH interventions had less antibody against Shigella (–4.5%, 95% CI –7.6% to –1.5%), non-typhoidal S. enterica (–4.0%, 95% CI –6.5% to –1.5%), and Giardia (–3.4%, 95% CI –6.7% to –0.2%), although not after multiple-testing correction. Nutrition had limited effects on most enteric pathogens, but reduced non-typhoidal S. enterica at 14 months (–6.4%, 95% CI: –9.8% to –3.0%).
Interpretation
Multiplex serology provided evidence that WASH may modestly reduce cumulative exposure to selected enteric pathogens, but household-level interventions were insufficient to substantially disrupt transmission in this high-exposure setting.
Funding
National Institutes of Health (R01AI166671, R01AI106878, R01AI134814). The original WASH Benefits trial was funded by Gates Foundation (OPPGD759).
