TY - JOUR
T1 - Mutations in the antifolate-resistance-associated genes dihydrofolate reductase and dihydropteroate synthase in Plasmodium vivax isolates from malaria-endemic countries
AU - Lu, Feng
AU - Lim, Chae Seung
AU - Nam, Deok Hwa
AU - Kim, Kwonkee
AU - Lin, Khin
AU - Kim, Tong Soo
AU - Lee, Hyeong Woo
AU - Chen, Jun Hu
AU - Wang, Yue
AU - Sattabongkot, Jetsumon
AU - Han, Eun Taek
PY - 2010/9
Y1 - 2010/9
N2 - Parasite dihydrofolate reductase (DHFR) and dihydropteroate synthase (DHPS) are known target enzymes of antifolate drugs used for the treatment and prophylaxis of persons with malaria. We sequenced the Plasmodium vivax dihydrofolate reductase ( pvdhfr ) and dihydropteroate synthase ( pvdhps ) genes to examine the prevalence and extent of point mutations in isolates from malaria-endemic countries. Double mutations (S58R and S117N) or quadruple mutations (F57L/I, S58R, T61M, and S117T) in the pvdhfr gene were found in isolates from Thailand (96.4%) and Myanmar (71.4%), but in only one isolate (1.0%) from Korea, where sulfadoxine-pyrimethamine has never been used. The pvdhfr point mutations correlated strongly with the pvdhps point mutations and ranged from single to triple mutations (S382A, A383G, and A553G), among isolates from Thailand, Myanmar, and Korea. These findings suggests that the prevalence of mutations in pvdhfr and pvdhps in P. vivax isolates from different malaria-endemic countries is associated with selection pressure imposed by sulfadoxine-pyrimethamine.
AB - Parasite dihydrofolate reductase (DHFR) and dihydropteroate synthase (DHPS) are known target enzymes of antifolate drugs used for the treatment and prophylaxis of persons with malaria. We sequenced the Plasmodium vivax dihydrofolate reductase ( pvdhfr ) and dihydropteroate synthase ( pvdhps ) genes to examine the prevalence and extent of point mutations in isolates from malaria-endemic countries. Double mutations (S58R and S117N) or quadruple mutations (F57L/I, S58R, T61M, and S117T) in the pvdhfr gene were found in isolates from Thailand (96.4%) and Myanmar (71.4%), but in only one isolate (1.0%) from Korea, where sulfadoxine-pyrimethamine has never been used. The pvdhfr point mutations correlated strongly with the pvdhps point mutations and ranged from single to triple mutations (S382A, A383G, and A553G), among isolates from Thailand, Myanmar, and Korea. These findings suggests that the prevalence of mutations in pvdhfr and pvdhps in P. vivax isolates from different malaria-endemic countries is associated with selection pressure imposed by sulfadoxine-pyrimethamine.
UR - http://www.scopus.com/inward/record.url?scp=77957062531&partnerID=8YFLogxK
U2 - 10.4269/ajtmh.2010.10-0004
DO - 10.4269/ajtmh.2010.10-0004
M3 - Article
C2 - 20810806
AN - SCOPUS:77957062531
SN - 0002-9637
VL - 83
SP - 474
EP - 479
JO - American Journal of Tropical Medicine and Hygiene
JF - American Journal of Tropical Medicine and Hygiene
IS - 3
ER -