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Selection of Antifolate-Resistant Plasmodium falciparum by Sulfadoxine-Pyrimethamine Treatment and Infectivity to Anopheles Mosquitoes

Resistance-conferring mutations in dihydrofolate reductase (DHFR) and dihydropteroate synthase (DHPS) in Plasmodium falciparum are selected by treatment with sulfadoxine pyrimethamine (SP). We assessed the association between these mutations and transmission capacity of parasites to Anopheles mosquitoes on the Pacific coast of Colombia. Patients with uncomplicated P. falciparum malaria received SP treatment and were followed-up to compare the prevalence of DHFR and DHPS mutations before and after SP treatment. Membrane feeding assays were used to measure infectivity to mosquitoes of post-treatment gametocytes with and without these mutations. Per-protocol treatment efficacy was 95.0% (132 of 139). Gametocytes carrying resistance-conferring mutations were selected after SP treatment and were infective to mosquitoes. Seven days after treatment, infections with two DHFR mutations had a 10-fold higher probability of infecting mosquitoes than infections with no DHFR mutations (odds ratio = 10.23, P < 0.05). Low-level drug resistance mutations have the potential to enhance transmission of P. falciparum and spread resistant parasites.

Received April 11, 2007. Accepted for publication June 13, 2007.

Financial support: This study was supported in part by a grant AI055687-02 from the National Institutes of Health and the Universidad del Valle, Cali, Colombia.

^* Address correspondence to Fabián Méndez, Escuela de Salud Pública, Universidad del Valle, San Fernando, Calle 4B No. 36-140, Edificio 118, Cali, Colombia. E-mail: famendez{at}univalle.edu.co

Authors’ addresses: Fabián Méndez, Escuela de Salud Pública, Universidad del Valle, San Fernando, Calle 4B No. 36-140, Edificio 118, Cali, Colombia, Fax: 57-2-557 0425, E-mail: famendez{at}univalle.edu.co. Sócrates Herrera, Bermans Murrain, Andrés Gutiérrez, and Luz A. Moreno, Malaria Vaccine and Drug Testing Center, Carrera 35 No. 4A-53, A.A. 25574, Cali, Colombia, Telephone: 57-2-5583937, Fax: 57-2-5560141, E-mail: sherrera{at}inmuno.org. María Manzano, Universidad Nacional de Colombia, Sede Palmira, Colombia. Álvaro Muñoz, Department of Epidemiology. The Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe Street, E-7648, Baltimore, MD 21205, E-mail: jvaldez{at}jhsph.edu. Christopher V. Plowe, Center for Vaccine Development, University of Maryland School of Medicine, 685 West Baltimore Street, HSF 480, Baltimore, MD 21201, E-mail: cplowe{at}medicine.umaryland.edu.