Mutations in the antifolate-resistance-associated genes dihydrofolate reductase and dihydropteroate synthase in Plasmodium vivax isolates from malaria-endemic countries

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

Research output: Contribution to journalArticle

32 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)474-479
Number of pages6
JournalAmerican Journal of Tropical Medicine and Hygiene
Volume83
Issue number3
DOIs
Publication statusPublished - 2010 Sep 1

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Dihydropteroate Synthase
Vivax Malaria
Folic Acid Antagonists
Plasmodium vivax
Tetrahydrofolate Dehydrogenase
Mutation
Point Mutation
Myanmar
Malaria
Genes
Thailand
Korea
Parasites
Pressure
Enzymes
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Parasitology
  • Infectious Diseases
  • Virology
  • Medicine(all)

Cite this

Mutations in the antifolate-resistance-associated genes dihydrofolate reductase and dihydropteroate synthase in Plasmodium vivax isolates from malaria-endemic countries. / Lu, Feng; Lim, Chae Seung; Nam, Deok Hwa; Kim, Kwonkee; Lin, Khin; Kim, Tong Soo; Lee, Hyeong Woo; Chen, Jun Hu; Wang, Yue; Sattabongkot, Jetsumon; Han, Eun Taek.

In: American Journal of Tropical Medicine and Hygiene, Vol. 83, No. 3, 01.09.2010, p. 474-479.

Research output: Contribution to journalArticle

Lu, Feng ; Lim, Chae Seung ; Nam, Deok Hwa ; Kim, Kwonkee ; Lin, Khin ; Kim, Tong Soo ; Lee, Hyeong Woo ; Chen, Jun Hu ; Wang, Yue ; Sattabongkot, Jetsumon ; Han, Eun Taek. / Mutations in the antifolate-resistance-associated genes dihydrofolate reductase and dihydropteroate synthase in Plasmodium vivax isolates from malaria-endemic countries. In: American Journal of Tropical Medicine and Hygiene. 2010 ; Vol. 83, No. 3. pp. 474-479.
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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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