Document Detail

Dynamics of malaria drug resistance patterns in the Amazon basin region following changes in Peruvian national treatment policy for uncomplicated malaria.
MedLine Citation:
PMID:  19258269     Owner:  NLM     Status:  MEDLINE    
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 Ca(2+) 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.
David J Bacon; Andrea M McCollum; Sean M Griffing; Carola Salas; Valeria Soberon; Meddly Santolalla; Ryan Haley; Pablo Tsukayama; Carmen Lucas; Ananias A Escalante; Venkatachalam Udhayakumar
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.     Date:  2009-03-02
Journal Detail:
Title:  Antimicrobial agents and chemotherapy     Volume:  53     ISSN:  1098-6596     ISO Abbreviation:  Antimicrob. Agents Chemother.     Publication Date:  2009 May 
Date Detail:
Created Date:  2009-04-27     Completed Date:  2009-06-24     Revised Date:  2014-05-05    
Medline Journal Info:
Nlm Unique ID:  0315061     Medline TA:  Antimicrob Agents Chemother     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2042-51     Citation Subset:  IM    
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MeSH Terms
Antimalarials* / pharmacology,  therapeutic use
Drug Resistance / genetics*
Health Policy*
Malaria, Falciparum* / drug therapy,  epidemiology,  parasitology
Microsatellite Repeats / genetics
Parasitic Sensitivity Tests
Peru / epidemiology
Plasmodium falciparum / drug effects*,  genetics,  isolation & purification
Protozoan Proteins / genetics*
Grant Support
Reg. No./Substance:
0/Antimalarials; 0/Protozoan Proteins
Comment In:
Antimicrob Agents Chemother. 2010 May;54(5):2280; author reply 2280-1   [PMID:  20404129 ]
Erratum In:
Antimicrob Agents Chemother. 2010 May;54(5):2282

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