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THE ADDITION OF ARTESUNATE TO CHLOROQUINE FOR TREATMENT OF PLASMODIUM FALCIPARUM MALARIA IN GAMBIAN CHILDREN DELAYS, BUT DOES NOT PREVENT TREATMENT FAILURE

In a randomized controlled trial, chloroquine monotherapy was compared with the combination of artesunate and chloroquine for treating uncomplicated Plasmodium falciparum malaria in 536 Gambian children. Chloroquine-treated children exhibited a 28-day clinical failure rate of 15% (95% confidence interval [CI] = 9.2–22%) compared with 11% (7.8–15%) among children receiving the combination (P = 0.08, by Wilcoxon test). Seventy-three percent of chloroquine-treated children exhibited parasitemia during follow-up compared with 49% of children receiving the combination (relative risk = 1.5, 95% CI = 1.3–1.7; ² = 21.18, P < 0.001). A significant reduction in clinical and parasitologic treatment failure in the combination group occurred in the first two weeks following treatment, but this was eroded over weeks three and four of follow-up. The impact of combination therapy on the transmission of chloroquine-resistant parasites is discussed. Chloroquine plus artesunate is not sufficiently efficacious to justify its introduction as a replacement for chloroquine monotherapy in The Gambia.

Received January 25, 2003. Accepted for publication April 2, 2003.

Acknowledgments: We thank Professor Keith McAdam for his support, and Dr. Neal Alexander for helpful discussions. We acknowledge the crucial contributions of the field and laboratory staff of the Farafenni Field Station and of the nursing staff of the Gambian Government Hospital in Farafenni. We particularly thank the children and parents from Farafenni who participated in the study.

Financial support: This study was supported by Wellcome Trust Project no. 061910 (awarded to Colin J. Sutherland) and by the Medical Research Council Laboratories, The Gambia (project no. 838).

Authors’ addresses: Colin J. Sutherland and Geoffrey A.T. Targett, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, United Kingdom, Telephone: 44-020-7927-2338, Fax: 44-20-7636-8739, E-mail: colin.sutherland{at}lshtm.ac.uk. Christopher J. Drakeley, Joint Malaria Programme, PO Box 2228, Moshi, Tanzania. Uche Obisike, Rosalind Coleman, Musa Jawara, and Gijs Walraven, Farafenni Field Station, Farafenni, The Gambia. Paul Milligan Margaret Pinder, Fajara Medical Research Council Laboratories, PO Box 273, Banjul, The Gambia.

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