Mutations in the antifolate-resistance-associated genes dihydrofolate reductase and dihydropteroate synthase in Plasmodium vivax isolates from malaria-endemic countries.
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| Abstract |
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.
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| Authors | Feng Lu, Chae Seung Lim, Deok Hwa Nam, Kwonkee Kim, Khin Lin, Tong-Soo Kim, Hyeong-Woo Lee, Jun-Hu Chen, Yue Wang, Jetsumon Sattabongkot, Eun-Taek Han |
| Journal | The American journal of tropical medicine and hygiene (Am J Trop Med Hyg) Vol. 83 Issue 3 Pg. 474-9 (Sep 2010) ISSN: 1476-1645 [Electronic] United States |
| PMID | 20810806 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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