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Antimicrobial Agents and Chemotherapy, May 2009, p. 2042-2051, Vol. 53, No. 5
0066-4804/09/$08.00+0 doi:10.1128/AAC.01677-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
Dynamics of Malaria Drug Resistance Patterns in the Amazon Basin Region following Changes in Peruvian National Treatment Policy for Uncomplicated Malaria
,
David J. Bacon,1*
Andrea M. McCollum,2,3,5
Sean M. Griffing,2,5
Carola Salas,1
Valeria Soberon,1
Meddly Santolalla,1
Ryan Haley,1
Pablo Tsukayama,1
Carmen Lucas,1
Ananias A. Escalante,4 and
Venkatachalam Udhayakumar3,5
Parasitology Program, Naval Medical Research Center Detachment, Lima, Peru,1 Program in Population Biology, Ecology, and Evolution, Emory University,2 Malaria Branch, Division of Parasitic Diseases, National Center for Zoonotic, Vector-Borne, and Enteric Diseases, Coordinating Center for Infectious Diseases (CCID), Centers for Disease Control and Prevention, Atlanta,5 Atlanta Research and Education Foundation, Decatur, Georgia,3 School of Life Sciences, Arizona State University, Tempe, Arizona4
Received 19 December 2008/ Returned for modification 20 January 2009/ Accepted 13 February 2009
Monitoring changes in the frequencies of drug-resistant and -sensitive genotypes can facilitate in vivo clinical trials to assess the efficacy of drugs before complete failure occurs. Peru changed its national treatment policy for uncomplicated malaria to artesunate (ART)-plus-mefloquine (MQ) combination therapy in the Amazon basin in 2001. We genotyped isolates collected in 1999 and isolates collected in 2006 to 2007 for mutations in the Plasmodium falciparum dihydrofolate reductase (Pfdhfr) and dihydropteroate synthase (Pfdhps) genes, multidrug resistance gene 1 (Pfmdr-1), the chloroquine (CQ) resistance transporter gene (Pfcrt), and the Ca2+ ATPase gene (PfATP6); these have been shown to be involved in resistance to sulfadoxine-pyrimethamine (SP), MQ, CQ, and possibly ART, respectively. Microsatellite haplotypes around the Pfdhfr, Pfdhps, Pfcrt, and Pfmdr-1 loci were also determined. There was a significant decline in the highly SP resistant Pfdhfr and Pfdhps genotypes from 1999 to 2006. In contrast, a CQ-resistant Pfcrt genotype increased in frequency during the same period. Among five different Pfmdr-1 allelic forms noted in 1999, two genotypes increased in frequency while one genotype decreased by 2006. We also noted previously undescribed polymorphisms in the PfATP6 gene as well as an increase in the frequency of a deletion mutant during this period. In addition, microsatellite analysis revealed that the resistant Pfdhfr, Pfdhps, and Pfcrt genotypes have each evolved from a single founder haplotype, while Pfmdr-1 genotypes have evolved from at least two independent haplotypes. Importantly, this study demonstrates that the Peruvian triple mutant Pfdhps genotypes are very similar to those found in other parts of South America.
* Corresponding author. Present address: Laboratory Sciences, Navy Environmental and Preventative Medicine Unit 2, 1887 Powhatan St., Norfolk, VA 23511. Phone: (757) 953-6571. Fax: (757) 953-7212. E-mail: david.bacon{at}med.navy.mil
Published ahead of print on 2 March 2009.
Supplemental material for this article may be found at http://aac.asm.org/.
Antimicrobial Agents and Chemotherapy, May 2009, p. 2042-2051, Vol. 53, No. 5
0066-4804/09/$08.00+0 doi:10.1128/AAC.01677-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
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