Effects of drinking water, sanitation, handwashing, and nutritional interventions on immune status in young children: a cluster-randomized controlled trial in rural Bangladesh

While studies have speculated that immune function may play a role in how water, sanitation, hygiene, and nutritional (N+WSH) interventions may individually impact child growth and development, the combined effects of these interventions on immune system development are unknown. Here, we report on a trial in rural Bangladesh, where we cluster-randomized pregnant women into control and N+WSH arms. Among the birth cohort, we quantified plasma IL-1{beta}, IL-6, TNF-, IL-2, IL-12p70, IFN-{gamma}, IL-4, IL-5, IL-13, IL-17A, IL-21, IL-10, and GM-CSF at ages 14 and 28 months. Cytokine ratios were included as prespecified outcomes to examine the net inflammatory environment. We assessed 704 children. After one year, TNF-/IL-10, IL-12/IL-10, and IL-17A/IL-10 ratios were lower in the intervention group compared to the control group (mean difference: -0.12 to -0.19, p<0.05), indicating the intervention promoted IL-10 driven immunoregulation. Similar reductions in ratios of pro-inflammatory cytokines to IL-10 were sustained in the intervention group after two years. After one year, IL-12/IL-4, IL-12/IL-5, IFN-{gamma}/IL-5, and IL-12/IL-13 ratios were lower in the intervention group (-0.18 to -0.27, p<0.05), suggesting a shift towards a Th2 cytokine response. These findings suggest that the N+WSH intervention enhanced the immunoprotective and immunoregulatory responses, and suppressed/counteracted the inflammatory/immunopathological response, of the immune triad.