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Community and International Nutrition

Plasma Zinc Concentrations Are Depressed during the Acute Phase Response in Children with Falciparum Malaria¹

Christopher Duggan^*,, William B. MacLeod^**, Nancy F. Krebs, Jamie L. Westcott, Wafaie W. Fawzi, Zul G. Premji, Victor Mwanakasale, Jonathon L. Simon^**, Kojo Yeboah-Antwi^**,¶, Davidson H. Hamer^**,,2 and the Zinc Against Plasmodium Study Group³

^* Division of Gastroenterology and Nutrition, Children’s Hospital, Boston, MA; Department of Nutrition, Harvard School of Public Health, Boston, MA; ^** Center for International Health and Development, Boston University School of Public Health, Boston, MA; Section of Nutrition, Department of Pediatrics, University of Colorado Health Sciences Center, Denver, CO; Muhimbili University College of Health Sciences, Dar es Salaam, Tanzania; Tropical Diseases Research Centre, Ndola, Zambia; ^¶ Malaria Consortium, Accra, Ghana; and Gerald J. and Dorothy R. Friedman School of Nutrition Science and Policy, Tufts University, Medford, MA

²To whom correspondence should be addressed. E-mail: dhamer{at}bu.edu.

Plasma concentrations of some micronutrients are altered in the setting of acute infectious or inflammatory stress. Previous studies have provided conflicting evidence concerning the extent and direction of changes in plasma zinc concentrations during the acute phase response. We carried out an observational cohort study in 689 children enrolled in a randomized trial of zinc supplementation during acute falciparum malaria in order to evaluate the relation between plasma zinc concentration and the acute phase response. Plasma zinc was measured by atomic absorption spectrophotometry. On admission, 70% of all subjects had low plasma zinc (<9.2 µmol/L). Multivariate analysis of predictors of admission plasma zinc showed that admission C-reactive protein (CRP), parasite density, and study site were the most important predictors. Predictors of changes in plasma zinc from admission to 72 h included baseline CRP, change in CRP, treatment group, study site, and baseline zinc concentration. In children with acute malaria infection, baseline plasma zinc concentrations were very low and were inversely correlated with CRP (r = –0.24, P < 0.0001) and the degree of parasitemia (r = –0.19, P < 0.0001). Even when CRP and time were taken into account, zinc supplementation increased plasma zinc concentration from admission to 72 h. When available, plasma zinc concentrations should be interpreted with concurrent measures of the acute phase response such as CRP. In children whose age, diet, and/or nutritional status place them at risk of zinc deficiency, those with low plasma zinc levels should be supplemented with oral zinc and followed for clinical and/or biochemical response.

KEY WORDS: • malaria • zinc • Plasmodium falciparum • child • acute phase response • C-reactive protein

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