Effect of an onsite shared sanitation intervention on markers of environmental enteric dysfunction in children living in Maputo, Mozambique

The relationship between enteric pathogen exposure and long-term health effects like stunting and cognitive deficiencies may be mediated, in part, by environmental enteric dysfunction (EED). We aimed to assess whether access to a shared sanitation intervention affected the concentration of biomarkers of intestinal inflammation and permeability in the stool of young children living in Maputo, Mozambique. The Maputo Sanitation trial was a controlled before-and-after study of a shared onsite sanitation intervention in low-income, unplanned urban neighborhoods of Maputo, Mozambique. We collected data and stool specimens at baseline (pre-intervention) and 12- and 24-months post-intervention and measured the concentration of four biomarkers of EED: alpha-1-antitrypsin, neopterin, myeloperoxidase, and calprotectin. We assessed the effect of the intervention at 12- and 24-months post-intervention among all children, as well as among sub-groups of children with longitudinal data and children who were born into study sites post-intervention. After 12-months, the concentration of neopterin was higher among intervention children compared with controls (mean difference 0.39 log nmol/L, 95% CI: 0.15 - 0.62). Concentrations of calprotectin (mean difference 0.43 log ng/mL, 95% CI: 0.041 - 0.82) and neopterin (mean difference 0.38 nmol/L, 95% CI: 0.0079, 0.76), both measures of intestinal inflammation, were also higher among children born into intervention sites by the 24-month follow-up visit. The intervention did not a have statistically significant effect on the concentration of alpha-1-antitrypsin, the only marker of intestinal permeability.The intervention did not reduce the concentration of EED biomarkers after 12- and 24-months of exposure. The etiology and pathophysiologic mechanisms underlying EED have not been fully described, complicating its measurement. The lack of a formal case definition and of representative healthy reference concentrations for common EED biomarkers makes interpretation of effect estimates, including their potential clinical significance, complex. Our results highlight the importance of filling these evidence gaps so we may begin designing and implementing sanitation interventions that prevent, or at least delay, the onset of EED.