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Am J Trop Med Hyg. 2014 Jul;91(1):54-61. doi: 10.4269/ajtmh.13-0647. Epub 2014 May 5.

Temporal changes in prevalence of molecular markers mediating antimalarial drug resistance in a high malaria transmission setting in Uganda.

Author information

1
Infectious Diseases Research Collaboration, Kampala, Uganda; Le Tourneau University, Longview, Texas; Global AIDS Program, Centers for Disease Control and Prevention, Atlanta, Georgia; London School of Hygiene and Tropical Medicine, United Kingdom; University of California, San Francisco, California.
2
Infectious Diseases Research Collaboration, Kampala, Uganda; Le Tourneau University, Longview, Texas; Global AIDS Program, Centers for Disease Control and Prevention, Atlanta, Georgia; London School of Hygiene and Tropical Medicine, United Kingdom; University of California, San Francisco, California prosenthal@medsfgh.ucsf.edu.

Abstract

Standard therapy for malaria in Uganda changed from chloroquine to chloroquine + sulfadoxine-pyrimethamine in 2000, and artemether-lumefantrine in 2004, although implementation of each change was slow. Plasmodium falciparum genetic polymorphisms are associated with alterations in drug sensitivity. We followed the prevalence of drug resistance-mediating P. falciparum polymorphisms in 982 samples from Tororo, a region of high transmission intensity, collected from three successive treatment trials conducted during 2003-2012, excluding samples with known recent prior treatment. Considering transporter mutations, prevalence of the mutant pfcrt 76T, pfmdr1 86Y, and pfmdr1 1246Y alleles decreased over time. Considering antifolate mutations, the prevalence of pfdhfr 51I, 59R, and 108N, and pfdhps 437G and 540E were consistently high; pfdhfr 164L and pfdhps 581G were uncommon, but most prevalent during 2008-2010. Our data suggest sequential selective pressures as different treatments were implemented, and they highlight the importance of genetic surveillance as treatment policies change over time.

PMID:
24799371
PMCID:
PMC4080569
DOI:
10.4269/ajtmh.13-0647
[Indexed for MEDLINE]
Free PMC Article

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