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We evaluated associations between key polymorphisms in target genes and responses to treatment with sulfadoxine-pyrimethamine (SP) or amodiaquine (AQ) for uncomplicated Plasmodium falciparum malaria in Bobo-Dioulasso, Burkina Faso. Presence of the dihydrofolate reductase (dhfr) 108N or 59R mutations (but not dhfr 51I or dihydropteroate synthetase [dhps] 437G) and P. falciparum chloroquine resistance transporter (pfcrt) 76T or P. falciparum multidrug resistance 1 (pfmdr1) 86Y or 1246Y mutations (but not pfmdr1 184F) predicted recrudescence after treatment with SP and AQ, respectively. Treatment led to significant increases in the prevalence of the same mutations (except 1246Y) in new infections that presented after therapy. The dhfr 164L and dhps 540E mutations were not seen in any isolates. These results clarify the key roles of a small number of mutations in P. falciparum resistance to SP and AQ in west Africa.
Received February 10, 2006. Accepted for publication February 19, 2006.
Acknowledgments: We thank the clinical study teams in the dispensaries of Colsama (Yampa Minata, Ouaro Christine, and Sylvain Zoundi), Sarlafao (Georgette Dabire and Gneme Moumouni), and Ouezzin-Ville (Sanou Yolande, Sontie Korotoumou, and Boly Aïssata), and the laboratory technicians (Hien Patrice, Sankara Adama, Traore Daouda, Coulibaly San, and Minoungou Mahamoudou) for their assistance. We also thank Bryan Greenhouse for assisting with molecular studies at the University of California, San Francisco. Philip J. Rosenthal is a Doris Duke Charitable Foundation Distinguished Clinical Scientist.
Financial support: This work was supported by grant D43 TW01506 from the Fogarty International Center of the National Institutes of Health and by the Doris Duke Charitable Foundation.
* Address correspondence to Philip J. Rosenthal, Box 0811, University of California, San Francisco, CA 94143. E-mail: Philip.Rosenthal{at}ucsf.edu
Authors’ addresses: Christian Dokomajilar, Grant Dorsey, and Philip J. Rosenthal, Box 0811, University of California, San Francisco, CA 94143. Zambende Moise Lankoande, Issaka Zongo, and Jean-Bosco Ouedraogo, Institut de Recherche en Sciences de la Santé, Bobo-Dioulasso, Burkina Faso.
Reprint requests: Philip J. Rosenthal, Box 0811, University of California, San Francisco, CA 94143, Telephone: 415-206-8845, Fax: 415-648-8425, E-mail: Philip.Rosenthal{at}ucsf.edu.
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