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Title: Zinc or albendazole attenuates the progression of environmental enteropathy a randomized controlled trial

Author
item RYAN, KELSEY - Washington University School Of Medicine
item STEPHENSON, KEVIN - Washington University School Of Medicine
item TREHAN, INDI - Washington University School Of Medicine
item SHULMAN, ROBERT - Children'S Nutrition Research Center (CNRC)
item THAKWALAKWA, CHRISSIE - University Of Malawi
item MURRAY, ELLEN - Washington University School Of Medicine
item MALETA, KENNETH - University Of Malawi
item MANARY, MARK - Children'S Nutrition Research Center (CNRC)

Submitted to: Clinical Gastroenterology and Hepatology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/1/2014
Publication Date: 9/1/2014
Citation: Ryan, K.N., Stephenson, K.B., Trehan, I., Shulman, R.J., Thakwalakwa, C., Murray, E., Maleta, K., Manary, M.J. 2014. Zinc or albendazole attenuates the progression of environmental enteropathy a randomized controlled trial. Clinical Gastroenterology and Hepatology. 12:1507-1513.

Interpretive Summary: Many children in the developing world suffer from poor growth. This often is related to inflammation in the intestine, the cause of which is unclear. In this study we treated children with zinc or a medicine to treat parasites. We showed that both can improve the health of the intestine and prevent a condition that causes intestinal inflammation. By preventing inflammation, children are able to absorb nutrients better and grow normally. Environmental enteropathy, which is a subclinical condition among children in the developing world, leads to macronutrient and micronutrient malabsorption and stunting, with a resultant increased risk for infection and reduced cognitive development.

Technical Abstract: Environmental enteropathy (EE) is a subclinical condition among children in the developing world, characterized by T-cell infiltration of the small-bowel mucosa and diffuse villous atrophy. EE leads to macronutrient and micronutrient malabsorption and stunting, with a resultant increased risk for infection and reduced cognitive development. We tested the hypothesis that zinc and albendazole treatments would reduce the severity of EE in rural African children. In a randomized, double-blind, placebo-controlled trial in rural southern Malawi, asymptomatic children, 1 to 3 years old and at high risk for EE, received either a single dose of albendazole, a 14-day course of 20 mg zinc sulfate, or a placebo. Subjects were given the dual-sugar absorption test, and the ratio of lactulose to mannitol (L:M) in urine was used to determine the severity of EE at baseline and 34 days after completion of the assigned regimen. The primary outcome was the change in the L:M. A complete set of urine samples was obtained from 222 of 234 children enrolled and analyzed. The mean baseline L:M was 0.32 +/- 0.18 among all children and did not differ among groups (normal L:M range, 0.12). At the end of the study, the L:M ratio had increased more in the placebo group (0.12 +/- 0.31) than in the zinc group (0.03 +/- 0.20; P=.03) or the albendazole group (0.04 +/- 0.22; P=.04). Treatment with zinc or albendazole protects against a significant increase in the L:M ratio, a biomarker for EE, in asymptomatic rural Malawian children. These findings could provide insight into the etiology and pathogenesis of EE.