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We assessed whether mutations in the Plasmodium falciparum multidrug-resistance gene 1 (pfmdr1) (C1034S, D1042N, and Y1246D) would predict treatment outcome during a 28-day in vivo treatment trial in the Peruvian Amazon. Mefloquine (MQ) was compared with mefloquine-artesunate (MQ-AS) in a randomized, multi-clinic protocol for the first time in the Americas. Of 115 patients enrolled in the in vivo arm, 97 patients were eligible for molecular analysis. All 97 patients remained parasite-free during 28 days of follow-up (MQ, n = 46; MQ-AS, n = 51), indicating 100% clinical efficacy of the MQ and MQ-AS treatment regimens. The reported MQ-sensitive alleles (C1034, D1042, and Y1246) were present in 48.5% (n = 47) of the cases, whereas 49 isolates (50.5%) contained the D1246 mutation reported to confer MQ resistance in vitro. However, neither this mutation nor a double mutation (S1034, D1246; n = 16) was predictive of MQ treatment outcome.
Received May 4, 2002. Accepted for publication August 15, 2002.
Acknowledgments: We are indebted to the Peruvian Ministerio de Salud and Instituto Nacional de Salud for facilitating all stages of this study. Expert technical assistance was provided by Nancy Arróspide, Sonia Gutierrez, Carmen Lucas, and Carola Salas (Instituto Nacional de Salud and Naval Medical Research Center Detachment), as well as Kathleen Zhong (University of Toronto).
Financial support: This study was supported in part by a Canadian International Development Agency award from the Canadian Bureau for International Education (Dylan R. Pillai), the Canadian Institutes of Health Research (grant MT-13721 to Keven C. Kain), a Career Scientist Award from the Ontario Ministry of Health (Kevin C. Kain), and a Canada Research Chair from the Canadian Institutes of Health (Kevin C. Kain).
Authors’ addresses: Dylan R. Pillai, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305. Gisely Hijar, Ysabel Montoya, and Wilmer Marquiño, Departments of Molecular Biology and Parasitology, Instituto Nacional de Salud, Lima, Peru. Trenton K. Ruebush II, Center for Disease Control and Prevention, Atlanta, GA. Chansuda Wongsrichanalai, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand. Kevin C. Kain, Tropical Disease Unit, Toronto General Hospital, 200 Elizabeth Street, EN G-224, Toronto, Ontario, Canada, M5G 2C4, Telephone: 416-340-3535, Fax: 416-595-5826, E-mail: kevin.kain{at}uhn.on.ca
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