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ASSOCIATION OF FAILURES OF SEVEN-DAY COURSES OF ARTESUNATE IN A NON-IMMUNE POPULATION IN BANGUI, CENTRAL AFRICAN REPUBLIC WITH DECREASED SENSITIVITY OF PLASMODIUM FALCIPARUM

We assessed the efficacy and safety of a seven-day course of artesunate for the treatment of uncomplicated Plasmodium falciparum malaria in 55 non-immune patients living in Bangui, Central African Republic. The parasitologic cure rates were 100%, 95%, and 85% on days 14, 28, and 42, respectively. There were no significant differences in parasitemia density, 50% inhibitory concentration of dihydroartemisinin, and frequency of mutant P. falciparum multidrug resistance 1 codon 86 between patients who were cured and those who displayed recrudescence. However, the 90% inhibitory concentration for dihydroartemisinin and the number of genotypes isolated were both higher in the recrudescent patients (five- and two-fold, respectively). We found an association between recrudescence and decreased sensitivity. This suggests that the use of artemisinin compounds alone will select resistant strains. We conclude that artesunate should not be used in monotherapy even in seven-day courses, but only in combination with other anti-malarials to prevent the emergence of resistant P. falciparum.

Received February 4, 2005. Accepted for publication April 19, 2005.

Acknowledgments: We thank the patients for participating in the study.

Financial support: This work was supported by the French Government, via the PAL+ project (French Ministry of Research) and the Fonds de Solidarité Prioritaire, Résistance aux Anti Infectieux project (French Ministry of Foreign Affairs).

Disclaimer: None of the authors has any conflicts of interest.

^* Address correspondence to Didier Menard, Unité du Paludisme, Institut Pasteur de Madagascar, BP 1274 Antananarivo 101, Madagascar. E-mail: dmenard{at}pasteur.mg

Authors’ addresses: Didier Menard, Unité du Paludisme, Institut Pasteur de Madagascar, BP 1274, Antananarivo 101, Madagascar, Telephone: 261-20-22-412-72, Fax: 261-20-22-415-34, E-mail: dmenard{at}pasteur.mg. Marcelle Diane Matsika-Claquin, Djibrine Djalle, Ferdinand Yapou, Alexandre Manirakiza, Virginie Dolmazon, and Antoine Talarmin, Institut Pasteur de Bangui, BP 923, Bangui, Central African Republic. Jacques Sarda, Centre Médico-Social de l’Ambassade de France à Bangui, Bangui, Central African Republic.

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