The role of environmental enteric dysfunction in the pathogenesis of Schistosoma mansoni-associated morbidity in school-aged children

Abstract

BackgroundStudies have implicated schistosomiasis as a cause of intestinal barrier disruption, a salient feature of environmental enteric dysfunction (EED), as eggs translocate from the sterile bloodstream through the gut wall. We examined the longitudinal impact of praziquantel (PZQ) treatment on a) EED biomarkers and b) Insulin growth factor I (IGF-1), a key driver of childhood linear growth, since EED has been implicated in linear growth stunting.Methodology290 children infected withS.mansoniin Brazil were treated with PZQ at baseline. EED biomarkers lipopolysaccharide (LPS) and intestinal fatty acid binding-protein (I-FABP) were measured, as well as IGF-1 at baseline, 6 and 12-months. Multivariate regression analysis was applied to assess associations betweenS.mansoniintensity and plasma biomarkers (LPS, I-FABP, and IGF-1), controlling for potential confounding variables.Principal findingsAt baseline,S.mansoniinfection intensities were 27.2% light, 46.9% moderate, and 25.9% heavy. LPS concentrations were significantly reduced at the 12-month visit compared to baseline (p = 0.0002). No longitudinal changes were observed for I-FABP or IGF-1 in the 6- or 12-month periods following baseline treatment. After 6-months, I-FABP concentration was significantly higher in high vs low intensity (p = 0.0017). IGF-1 concentrations were significantly lower among children with high and moderate vs low intensity infections at each study visit.Conclusions/significanceWe report thatS.mansoniinfection impacts LPS, I-FABP and IGF-1. These findings suggest a mechanistic role for EED in schistosomiasis-related morbidities, particularly linear growth.