Dynamics of malaria drug resistance patterns in the amazon basin region following changes in peruvian national treatment policy for uncomplicated malaria

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

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)2042-2051
Number of pages10
JournalAntimicrobial Agents and Chemotherapy
Volume53
Issue number5
DOIs
StatePublished - May 2009

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Drug Resistance
Malaria
Genotype
MDR Genes
Tetrahydrofolate Dehydrogenase
Plasmodium falciparum
Chloroquine
Genes
Haplotypes
Microsatellite Repeats
Dihydropteroate Synthase
Mefloquine
Peru
Calcium-Transporting ATPases
South America
Pharmaceutical Preparations
Clinical Trials
Mutation

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology
  • Infectious Diseases

Cite this

Dynamics of malaria drug resistance patterns in the amazon basin region following changes in peruvian national treatment policy for uncomplicated malaria. / Bacon, David J.; McCollum, Andrea M.; Griffing, Sean M.; Salas, Carola; Soberon, Valeria; Santolalla, Meddly; Haley, Ryan; Tsukayama, Pablo; Lucas, Carmen; Escalante, Ananias A.; Udhayakumar, Venkatachalam.

In: Antimicrobial Agents and Chemotherapy, Vol. 53, No. 5, 05.2009, p. 2042-2051.

Research output: Contribution to journalArticle

Bacon, DJ, McCollum, AM, Griffing, SM, Salas, C, Soberon, V, Santolalla, M, Haley, R, Tsukayama, P, Lucas, C, Escalante, AA & Udhayakumar, V 2009, 'Dynamics of malaria drug resistance patterns in the amazon basin region following changes in peruvian national treatment policy for uncomplicated malaria', Antimicrobial Agents and Chemotherapy, vol. 53, no. 5, pp. 2042-2051. https://doi.org/10.1128/AAC.01677-08
Bacon, David J. ; McCollum, Andrea M. ; Griffing, Sean M. ; Salas, Carola ; Soberon, Valeria ; Santolalla, Meddly ; Haley, Ryan ; Tsukayama, Pablo ; Lucas, Carmen ; Escalante, Ananias A. ; Udhayakumar, Venkatachalam. / Dynamics of malaria drug resistance patterns in the amazon basin region following changes in peruvian national treatment policy for uncomplicated malaria. In: Antimicrobial Agents and Chemotherapy. 2009 ; Vol. 53, No. 5. pp. 2042-2051.
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