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FOLIC ACID TREATMENT OF ZAMBIAN CHILDREN WITH MODERATE TO SEVERE MALARIA ANEMIA

Whether administration of folic acid to children with malaria anemia is helpful is controversial. Therefore, we conducted a randomised, placebo-controlled trial of 14 days of treatment with folic acid (1 mg/d) in Zambian children with malaria anemia treated with either sulfadoxine/pyrimethamine (SP) or atovaquone/proguanil (AP). Among children who received SP, the prevalence of parasitemia was higher in children treated with folic acid than among those given placebo at days 3, 7, and 14 after the start of treatment, and the difference at day 3 was statistically significant (P = 0.013). Folic acid treatment had no effect on parasitemia in children treated with AP. Administration of folic acid led to a small increase in packed cell volume over that seen in the placebo group at days 14 and 28 after the start of treatment.

Received December 14, 2005. Accepted for publication February 13, 2006.

Acknowledgments: We thank the patients and families who participated in this study, the staff and management of Macha Mission Hospital for cooperation, and the local chiefs for support. We are grateful to Dr. Emmanuel Kafwembe, Director of Tropical Diseases Research Centre, Ndola, Zambia, for support. The authors thank the staff of the Dunn Nutrition Unit, Cambridge, for the folate measurements and the members of the Data and Safety Monitoring Board (Prof. Winstanley, Prof. Cousens, and Dr. Mukunyandela) for time and advice. We also thank Dr. Kaur for undertaking the HPLC analyses. Malarone and matching placebo were provided by from GlaxoSmithKline, and SP, folic acid, and matching placebos by Cosomos Pharmaceuticals. GSK provided financial support for the field work in Zambia. M.M. received a research-training grant from UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (TDR). The Gates Malaria Partnership supports B.M.G.

^* Address correspondence to Brian Greenwood, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel St., London WC1E 7HT, UK. E-mail: brian.greenwood{at}lshtm.ac.uk

Authors’ addresses: Modest Mulenga and Phidelis Malunga, Tropical Diseases Research Centre, PO Box 71769, 111 Ndola, Zambia. Steve Bennett (deceased), Caroline Shulman, Katherine Fielding, and Brian Greenwood, London School of Hygiene and Tropical Medicine, Keppel St. London WC1E 7HT, UK. Phillip Thuma, Malaria Institute at Macha (MIAM), PO Box 630166, Choma, Zambia, E-mail: brian.greenwood{at}lshtm.ac.uk.