Micronutrient supplementation has limited effects on intestinal infectious disease and mortality in a Zambian population of mixed HIV status: a cluster randomized trial1-3

Background: Diarrheal disease remains a major contributor to morbidity and mortality in Africa, but host defense against intestinal infection is poorly understood and may depend on nutritional status. Objective: To test the hypothesis that defense against intestinal infection depends on micronutrient status, we undertook a randomized controlled trial of multiple micronutrient supplementation in a population where there is borderline micronutrient deficiency. Design: All consenting adults (≥18 y) living in a carefully defined sector of Misisi, Lusaka, Zambia, were included in a cluster-randomized (by household), double-blind, placebo-controlled trial with a midpoint crossover. There were no exclusion criteria. Participants were given a daily tablet containing 15 micronutrients at just above the recommended nutrient intake or placebo. The primary endpoint was the incidence of diarrhea; secondary endpoints were severe episodes of diarrhea, respiratory infection, nutritional status, CD4 count, and mortality. Results: Five hundred participants were recruited and followed up for 3.3 y (10 846 personmonths). The primary endpoint, incidence of diarrhea (1.4 episodes/y per person), did not differ with treatment allocation. However, severe episodes of diarrhea were reduced in the supplementation group (odds ratio: 0.50; 95% CI: 0.26, 0.92; P = 0.017). Mortality was reduced in HIV-positive participants from 12 with placebo to 4 with supplementation (P = 0.029 by log-rank test), but this was not due to changes in CD4 count or nutritional status. Conclusion: Micronutrient supplementation with this formulation resulted in only modest reductions in severe diarrhea and reduced mortality in HIV-positive participants. The trial was registered as ISRCTN31173864. © 2008 American Society for Nutrition 3 Address reprint requests to P Kelly, Tropical Gastroenterology and Nutrition Group, University of Zambia School of Medicine, Nationalist Road, Lusaka, Zambia. [email protected].. The contributions of the authors were as follows—the study was designed by PK, MK, JT, IZ, IRS, and AT; the trial was set up and the data were collected by PK, MK, RB, VY, MF, and FY; the analysis was carried out by PK, MK, EK, IRS, and AT; and the manuscript was written and reviewed by all authors. There were no conflicts of interest and none of the authors had any financial interest in the manufacture or licensing of any micronutrient formulation. 2Supported by The Wellcome Trust. Europe PMC Funders Group Author Manuscript Am J Clin Nutr. Author manuscript; available in PMC 2009 November 16. Published in final edited form as: Am J Clin Nutr. 2008 October ; 88(4): 1010–1017. E uope PM C Fuders A uhor M ancripts E uope PM C Fuders A uhor M ancripts