AJTMH Transactions of the Royal Society of Tropical Medicine and Hygiene
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Am. J. Trop. Med. Hyg., 73(1), 2005, pp. 166-170
Copyright © 2005 by The American Society of Tropical Medicine and Hygiene

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REDUCTION OF THE EFFICACY OF ANTIFOLATE ANTIMALARIAL THERAPY BY FOLIC ACID SUPPLEMENTATION

JANE Y. CARTER*, MORES P. LOOLPAPIT, ORGENES E. LEMA, JULIUS L. TOME, NICO J. D. NAGELKERKE, AND WILLIAM M. WATKINS
African Medical and Research Foundation, Nairobi, Kenya; Department of Medical Statistics, Leiden University Medical Centre, Leiden, The Netherlands; Department of Pharmacology and Therapeutics, University of Liverpool, Liverpool, United Kingdom

Malaria and anemia are common conditions in patients presenting to outpatient clinics in Kenya. Anemia is usually due to malaria infection with underlying micronutrient deficiency. Iron therapy has been shown to enhance recovery from anemia in children with malaria, without affecting malaria treatment. Iron and folic acid are often prescribed together for anemic individuals. Until recently in Kenya, the drug of first choice for non-severe malaria was sulfadoxine-pyrimethamine (SP), an antifolate antimalarial drug. In this study, 303 patients of all ages with anemia and uncomplicated Plasmodium falciparum malaria attending an outpatient clinic in an area of seasonal malaria were treated with SP and iron, and were randomized to receive folic acid. Parasite clearance rates were measured using a survival analysis plot for both parasitologic and clinical failure. There was a significant reduction in the efficacy of SP in patients taking standard therapeutic doses of folic acid using the survival curve for parasitologic failure (P < 0.0001), but no difference for clinical failure (P = 0.7008). Folic acid supplementation did not enhance recovery from anemia.


Received June 24, 2004. Accepted for publication August 6, 2004.

Acknowledgments: We thank the staff of the Entasopia Health Centre for the use of their facilities and support in carrying out this study. We also thank Professor Bob Snow and the Kenya Medical Research Institute/Wellcome Trust Programme for their assistance with data entry and analysis.

Financial support: This work was supported by a grant from the European Union Cofinancing Scheme through the African Medical and Research Foundation (Germany). W. M. Watkins is a Wellcome Trust resettlement fellow (grant #056305).

Disclosure: William M. Watkins is a member of the LapdapTM product development team, but he receives no renumeration other than travel costs and per diems for this work. This statement is made in the interest of full disclosure, and not because the author considers this to be a conflict of interest.

* Address correspondence to Jane Y. Carter, Clinical Department, African Medical and Research Foundation, PO Box 30125, 001001 GPO, Nairobi, Kenya. E-mail: janec{at}amrefke.org

Authors’ addresses: Jane Y. Carter, Orgenes E. Lema, and Julius L. Tome, Clinical Department, African Medical and Research Foundation, PO Box 30125, 001001 GPO, Nairobi, Kenya. Mores P. Loolpapit, African Medical and Research Foundation Headquarters, PO Box 00506, 27691 Nyayo Stadium, Nairobi, Kenya. Nico J. D. Nagelkerke, Department of Medical Statistics, Leiden University Medical Centre, PO Box 9604, 2300 RC Leiden, The Netherlands. William M. Watkins, Department of Pharmacology and Therapeutics, University of Liverpool, Liverpool L69 3BX, United Kingdom.

Reprint requests: Jane Y. Carter, Clinical Services, African Medical and Research Foundation, PO Box 30125, 00100 GPO, Nairobi, Kenya, Telephone: 254 20 602493. E-mail: janec{at}amrefke.org.




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