title: Mutations in the antifolate-resistance-associated genes dihydrofolate reductase and dihydropteroate synthase in Plasmodium vivax isolates from malaria-endemic countries.
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.
authors.affiliation: Department of Parasitology, Kangwon National University College of Medicine, Chuncheon, Republic of Korea. lufeng981@hotmail.com
authors.forename: Feng
authors.initials: F
authors.lastname: Lu
authors.forename: Chae Seung
authors.initials: CS
authors.lastname: Lim
authors.forename: Deok Hwa
authors.initials: DH
authors.lastname: Nam
authors.forename: Kwonkee
authors.initials: K
authors.lastname: Kim
authors.forename: Khin
authors.initials: K
authors.lastname: Lin
authors.forename: Tong-Soo
authors.initials: TS
authors.lastname: Kim
authors.forename: Hyeong-Woo
authors.initials: HW
authors.lastname: Lee
authors.forename: Jun-Hu
authors.initials: JH
authors.lastname: Chen
authors.forename: Yue
authors.initials: Y
authors.lastname: Wang
authors.forename: Jetsumon
authors.initials: J
authors.lastname: Sattabongkot
authors.forename: Eun-Taek
authors.initials: ET
authors.lastname: Han
mesh_terms: D000483:Alleles; D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D004094:Dihydropteroate Synthase / Q000235:genetics*; D004351:Drug Resistance / Q000235:genetics*; D019353:Endemic Diseases; D005493:Folic Acid Antagonists / Q000494:pharmacology*; D006801:Humans; D016780:Malaria, Vivax / Q000453:epidemiology*; D009154:Mutation; D010966:Plasmodium vivax / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D016133:Polymerase Chain Reaction; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics*
chemical_list: D017931:DNA Primers; D005493:Folic Acid Antagonists; D013762:Tetrahydrofolate Dehydrogenase; D004094:Dihydropteroate Synthase
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