Pathogens and childhood undernutrition: physiologic mechanisms mediating stunting and wasting

The National Institute of Allergy and Infectious Diseases awarded Rhode Island Hospital $195,475 on September 1, 2026, under the Allergy and Infectious Diseases Research program (CFDA 93.855) to advance understanding of the physiological mechanisms by which infections contribute to stunting and wasting in young children and to support career development of the principal investigator.

The research leverages well-characterized samples and clinical data from a completed NIH-funded randomized, controlled Phase II trial of praziquantel treatment in 354 children under age four with Schistosoma mansoni infection in the Lake Albert region of Uganda. The project investigates the mechanistic role of intestinal schistosomiasis in the pathogenesis of undernutrition, with focus on environmental enteric dysfunction, malabsorption, and systemic immune activation as drivers of schistosomiasis-related morbidities including undernutrition, anemia of inflammation, and linear growth stunting. Understanding these mechanisms will identify early intervention opportunities to reduce infection-related morbidities in young children in low- and middle-income countries.

Rhode Island Hospital, a division of Lifespan Corporation and an affiliate of Brown University, serves as the recipient. Place of performance is Providence, Rhode Island. The period of performance runs from September 1, 2026, through August 31, 2031. This is a Project Grant, classified as assistance funding.

Abstract

The overall goals of this proposal are to advance our understanding of the physiological mechanisms by which infections contribute to stunting and wasting in young children and to advance the career development of the candidate. In low- and middle-income countries (lmics), the overlapping burdens of infection and undernutrition have significant health consequences for infants and children, including stunting and wasting. Stunting affects a third of children living in lmics and can lead to life-long impacts on educational outcomes, economic productivity, and birth outcomes for women. Child wasting is the life-threatening result of poor nutrient intake and/or recurrent illnesses and is associated with weakened immunity, long-term developmental delays, and an increased risk of death. In children, schistosomiasis is known to cause undernutrition, however, the physiological mechanisms are not well understood. Understanding the mechanistic role of intestinal schistosomiasis in the pathogenesis of undernutrition will offer opportunities for early intervention to reduce these infection-related morbidities in young children. The proposed research will leverage the well- characterized samples and clinical data from a completed NIH-funded randomized, controlled phase II trial (R01 HD095562) of praziquantel (PZQ) treatment in n=354 children under age four with schistosoma mansoni infection in the lake albert region of uganda. The parent trial hypothesized that key morbidities related to schistosomiasis (undernutrition, anemia of inflammation, and linear growth stunting) are in part driven by environmental enteric dysfunction (EED) with consequent malabsorption and systemic immune activation. In this cohort, 19% of participants were stunted at baseline and preliminary findings reveal an indirect association between higher parasite burden, increased systemic inflammation, and an increased risk for stunting. The proposed research will add measurements of malaria, enteric infections, and endocrine growth hormones in samples collected from the parent trial to examine mechanisms through which infection, EED, and inflammation disrupt endocrine function and impair growth. The proposed research aims to 1) elucidate the mechanistic pathways by which schistosomiasis and other CO-infections contribute to stunting and wasting in young children using baseline data and samples collected from the parent trial and 2) determine how PZQ treatment for schistosomiasis and natural reinfection impact child growth trajectories over 12 months using longitudinal data and samples from the same cohort. This work will address innovative hypotheses regarding the mechanistic role of intestinal schistosomiasis in the pathophysiology of stunting and wasting in children and offer opportunities for early intervention for children living in regions with overlapping burdens of infection and undernutrition. The career development goals of this proposal are to gain expertise in the physiology of impaired child growth specific to infection, expand on laboratory techniques and statistical methodology, and strengthen scientific career skills specific to communication, mentoring, and clinical research design.