TY - JOUR
T1 - Temporal changes in prevalence of molecular markers mediating antimalarial drug resistance in a high malaria transmission setting in Uganda
AU - Mbogo, George W.
AU - Nankoberanyi, Sheila
AU - Tukwasibwe, Stephen
AU - Baliraine, Frederick N.
AU - Nsobya, Samuel L.
AU - Conrad, Melissa D.
AU - Arinaitwe, Emmanuel
AU - Kamya, Moses
AU - Tappero, Jordan
AU - Staedke, Sarah
AU - Dorsey, Grant
AU - Greenhouse, Bryan
AU - Rosenthal, Philip J.
PY - 2014/7/1
Y1 - 2014/7/1
N2 - 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 resistancemediating 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.
AB - 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 resistancemediating 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.
U2 - 10.4269/ajtmh.13-0647
DO - 10.4269/ajtmh.13-0647
M3 - Article
VL - 91
SP - 54
EP - 61
JO - The American Journal of Tropical Medicine and Hygiene
JF - The American Journal of Tropical Medicine and Hygiene
IS - 1
ER -
