Zinc or albendazole attenuates the progression of environmental enteropathy: a randomized controlled trial.
OBJECTIVE
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. Clinicaltrials.gov Number: NCT01440608.
Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri.
Kelsey N
KN
Ryan
Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri.
Kevin B
KB
Stephenson
Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri; Department of Paediatrics and Child Health, University of Malawi College of Medicine, Blantyre, Malawi.
Indi
I
Trehan
Children's Nutrition Research Center, Baylor College of Medicine, Houston, Texas.
Robert J
RJ
Shulman
Department of Community Health, University of Malawi College of Medicine, Blantyre, Malawi.
Chrissie
C
Thakwalakwa
Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri.
Ellen
E
Murray
Department of Community Health, University of Malawi College of Medicine, Blantyre, Malawi.
Kenneth
K
Maleta
Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri; Children's Nutrition Research Center, Baylor College of Medicine, Houston, Texas; Department of Community Health, University of Malawi College of Medicine, Blantyre, Malawi. Electronic address: manary@kids.wustl.edu.
Mark J
MJ
Manary
D015766:Albendazole / Q000008:administration & dosage*; D058070:Asymptomatic Diseases; D002675:Child, Preschool; D018450:Disease Progression; D004311:Double-Blind Method; D018876:Environmental Illness / Q000188:drug therapy* / Q000517:prevention & control*; D005260:Female; D005765:Gastrointestinal Agents / Q000008:administration & dosage*; D006801:Humans; D007223:Infant; D007408:Intestinal Absorption / Q000187:drug effects; D007410:Intestinal Diseases / Q000188:drug therapy* / Q000517:prevention & control*; D007792:Lactulose / Q000032:analysis; D008295:Malawi; D008297:Male; D008353:Mannitol / Q000032:analysis; D010919:Placebos / Q000008:administration & dosage; D016896:Treatment Outcome; D014556:Urine / Q000737:chemistry; D015032:Zinc / Q000008:administration & dosage*
D005765:Gastrointestinal Agents; D010919:Placebos; D008353:Mannitol; D007792:Lactulose; D015766:Albendazole; D015032:Zinc
Helminths; Intestinal Function; Intestinal Integrity; Micronutrients; Stunting