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SULFADOXINE–PYRIMETHAMINE EFFICACY AND SELECTION OF PLASMODIUM FALCIPARUM DHFR MUTATIONS IN BURKINA FASO BEFORE ITS INTRODUCTION AS INTERMITTENT PREVENTIVE TREATMENT FOR PREGNANT WOMEN

Sulfadoxine-pyrimethamine efficacy was determined with a 28-day follow-up in 97 children between 6 months and 15 years of age. The polymerase chain reaction (PCR)-corrected treatment failure was 8.2% and the uncorrected was 21.6%. The presence of the dihydrofolate reductase (DHFR) and dihydropteroate synthetase (DHPS) mutations linked to sulfadoxine-pyrimethamine resistance before and after treatment was determined by PCR-restriction fragment length polymorphism (RFLP) and by a fluorogenic PCR assay. Before treatment, the prevalence of the triple DHFR mutations was higher among the patients having had a recurrent parasitemia (either recrudescence or new infection; 28.6% versus 9.3%), although the difference was not significant (P = 0.1). The double mutation Ala-436/Gly-437 was observed in 67% of samples, whereas no Glu-540 mutation was found. After treatment, the triple DHFR mutation was found in 76.2% of patients with recurrent parasitemia, recrudescence, and new infection alike. Such high prevalence of mutant parasites indicates that sulfadoxine-pyrimethamine should not be used as monotherapy.

Received July 20, 2005. Accepted for publication March 13, 2006.

Acknowledgments: The authors thank the parents of the children included in this study for participation. We also thank the health staff of Nanoro for collaboration. Many thanks to Saskia Decuypere for her suggestions and MR4 for providing the controls.

Financial support: We thank the International Atomic Energy Agency (IAEA) for its financial support for the field study and the Belgium cooperation for supporting the laboratory work through a training grant for Halidou Tinto. The FRET assay was supported by the Fonds voor Wetenschappelijk Onderzoek-Vlaanderen (FWO).

^* Address correspondence to Umberto D’Alessandro, Institute of Tropical Medicine, Nationalestraat 155, B-2000 Antwerp, Belgium. E-mail: udalessandro{at}itg.be (cc: tintohalidou{at}yahoo.fr)

Authors’ addresses: Halidou Tinto, Chantal Van Overmeir, and Umberto D’Alessandro, Institut of Tropical Medicine, Nationalestraat 155 Antwerp B-2000, Belgium, E-mail: udalessandro{at}itg.be. Halidou Tinto, Issaka Zongo, Jean-Bosco Ouédraogo, and Tinga Robert Guiguemdé, Centre Muraz/Institut de Recherche en Sciences de la Santé, BP 153 Bobo Dioulasso, Burkina Faso, E-mail: tintohalidou{at}yahoo.fr. Halidou Tinto and Eric Van Marck, University of Antwerp, Faculty of Medicine, Universiteitsplein 1, B-2610 Antwerp, Belgium, E-mail: Eric.Van.Marck{at}uza.be.

Reprint requests: Umberto D’Alessandro, Institute of Tropical Medicine, Nationalestraat 155, Antwerp B-2000, Belgium. E-mail: udalessandro{at}itg.be (cc to tintohalidou{at}yahoo.fr).