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Antimicrobial Agents and Chemotherapy, November 2008, p. 4089-4097, Vol. 52, No. 11
0066-4804/08/$08.00+0     doi:10.1128/AAC.00623-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Hitchhiking and Selective Sweeps of Plasmodium falciparum Sulfadoxine and Pyrimethamine Resistance Alleles in a Population from Central Africa{triangledown} ,{dagger}

Andrea M. McCollum,1,2,3 Leonardo K. Basco,4 Rachida Tahar,4 Venkatachalam Udhayakumar,2 and Ananias A. Escalante5*

Emory University, Program in Population Biology, Ecology, and Evolution, Atlanta, Georgia,1 Malaria Branch, Division of Parasitic Diseases, National Center for Zoonotic, Vectorborne and Enteric Diseases, Coordinating Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia,2 Atlanta Research and Education Foundation, Atlanta, Georgia,3 Unité de Recherche Paludologie Afro-tropicale, Institut de Recherche pour le Développement (IRD), and Laboratoire de Recherche sur le Paludisme, Organisation de Coordination pour la lutte contre les Endémies en Afrique Centrale (OCEAC), Yaoundé, Cameroon,4 Arizona State University, School of Life Sciences, Tempe, Arizona5

Received 12 May 2008/ Returned for modification 3 August 2008/ Accepted 20 August 2008

Sulfadoxine-pyrimethamine (SP) resistance in Plasmodium falciparum is encoded by a number of mutations in the dihydrofolate reductase (dhfr) and dihydropteroate synthetase (dhps) genes. Here, we have characterized point mutations in dhfr and dhps and microsatellite loci around dhfr on chromosome 4 and dhps on chromosome 8 as well as neutral markers on chromosomes 2 and 3 in 332 samples from Yaoundé, Cameroon. The triple mutant dhfr haplotype that originated in Southeast Asia is the most predominant in this sample set, but we also find additional independent haplotypes at low frequency and an incipient process of genetic differentiation among alleles of Southeast Asian origin. As reported for other African populations, we find evidence of a selective sweep for resistant dhfr mutants in this Cameroonian population due to drug selection. Although we find evidence for a selective sweep in dhps mutants associated with SP resistance, the dynamics of dhps mutants appear different than those observed for dhfr mutants. Overall, our results yield support for the use of microsatellite markers to track resistant parasites; however, the detection of resistant dhfr alleles in low frequency, the evidence of divergence among dhfr alleles that share a common evolutionary origin, and the distinct dynamics of resistant dhps alleles emphasize the importance of comprehensive, population-based investigations to evaluate the effects of drug selection on parasite populations.

* Corresponding author. Mailing address: School of Life Sciences, Arizona State University, P.O. Box 874501, Tempe, AZ 85287-4501. Phone: (480) 965-3739. Fax: (480) 965-6899. E-mail: Ananias.Escalante{at}asu.edu

{triangledown} Published ahead of print on 2 September 2008.

{dagger} Supplemental material for this article may be found at http://aac.asm.org/.

Antimicrobial Agents and Chemotherapy, November 2008, p. 4089-4097, Vol. 52, No. 11
0066-4804/08/$08.00+0     doi:10.1128/AAC.00623-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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