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Global Health

Pathways through which water, sanitation, hygiene, and nutrition interventions reduce antibiotic use in young children: a mediation analysis of a cluster-randomized trial Anna Nguyen* Anna Nguyen Gabby Barratt Heitmann Andrew Mertens Sania Ashraf Md Ziaur Rahman Shahjahan Ali Mahbubur Rahman Benjamin F. Arnold Jessica A. Grembi Audrie Lin Ayse Ercumen Jade Benjamin-Chung

Background: Low-cost 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. Mediators included caregiver-reported child diarrhea, acute respiratory infection (ARI), and fever; and enteric pathogen carriage in stool measured by qPCR. Models controlled for mediator-outcome confounders.

Results: The receipt of any WASH or nutrition intervention reduced antibiotic use through all pathways in the past month by 5.5 percentage points (95% CI 1.2, 9.9), from 49.5% (95% CI 45.9%, 53.0%) in the control group to 45.0% (95% CI 42.7%, 47.2%) in the pooled intervention group. When separating this effect into different pathways, we found that interventions reduced antibiotic use by 0.6 percentage points (95% CI 0.1, 1.3) through reduced diarrhea, 0.7 percentage points (95% CI 0.1, 1.5) through reduced ARI with fever, and 1.5 percentage points (95% CI 0.4, 3.0) through reduced prevalence of enteric viruses. Interventions reduced antibiotic use through any of these measured mediators (diarrhea, fever, ARI, or enteric viruses) by 2.1 percentage points (95% CI -0.3, 4.5).

Conclusion: WASH and nutrition interventions reduced pediatric antibiotic use through the prevention of enteric and respiratory infections in a rural, low-resource population. Given that many of these infections are caused by viruses or parasites, WASH and nutrition interventions may help reduce inappropriate antibiotic use in similar settings.