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

Kelsey N. Ryan, Kevin B. Stephenson, Indi Trehan, Robert J. Shulman, Chrissie Thakwalakwa, Ellen Murray, Kenneth Maleta, Mark J. Manary

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31 Scopus citations


Background & Aims: 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. Methods: 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. Results: 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). Conclusions: 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.

Original languageEnglish
Pages (from-to)1507-1513.e1
JournalClinical Gastroenterology and Hepatology
Issue number9
StatePublished - Sep 2014


  • Helminths
  • Intestinal function
  • Intestinal integrity
  • Micronutrients
  • Stunting


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