Genetic Polymorphisms in Plasmodium vivax Dihydrofolate Reductase and Dihydropteroate Synthase in Isolates from the Philippines, Bangladesh, and Nepal.
Genetic polymorphisms of pvdhfr and pvdhps genes of Plasmodium vivax were investigated in 83 blood samples collected from patients in the Philippines, Bangladesh, and Nepal. The SNP-haplotypes of the pvdhfr gene at the amino acid positions 13, 33, 57, 58, 61, 117, and 173, and that of the pvdhps gene at the positions 383 and 553 were analyzed by nested PCR-RFLP. Results suggest diverse polymorphic patterns of pvdhfr alone as well as the combination patterns with pvdhps mutant alleles in P. vivax isolates collected from the 3 endemic countries in Asia. All samples carried mutant combination alleles of pvdhfr and pvdhps. The most prevalent combination alleles found in samples from the Philippines and Bangladesh were triple mutant pvdhfr combined with single mutant pvdhps allele and triple mutant pvdhfr combined with double wild-type pvdhps alleles, respectively. Those collected from Nepal were quadruple mutant pvdhfr combined with double wild-type pvdhps alleles. New alternative antifolate drugs which are effective against sulfadoxine-pyrimethamine (SP)-resistant P. vivax are required.
Graduate Program in Bioclinical Sciences, Chulabhorn International College of Medicine, Thammasat University, Pathumthani, Thailand ; Graduate Program in Biomedical Sciences, Faculty of Allied Health Sciences, Thammasat University, Pathumthani, Thailand.
Pimwan
P
Thongdee
Graduate Program in Biomedical Sciences, Faculty of Allied Health Sciences, Thammasat University, Pathumthani, Thailand.
Jiraporn
J
Kuesap
Malaria Research Program, College of Public Health Sciences, Chulalongkorn University, Bangkok, Thailand.
Kanchana
K
Rungsihirunrat
World Health Organization-Nepal/Epidemiology and Disease Control Division (EDCD), DoHS, Teku Kathmandu, Nepal.
Shyam Prakash
SP
Dumre
Research Institute for Tropical Medicine (RITM), Department of Health (DOH), Muntinlupa, Metro Manila, The Philippines.
Effie
E
Espino
Institute of Specific Prophylaxis and Tropical Medicine, Medical University of Vienna, Vienna, Austria.
Harald
H
Noedl
Graduate Program in Bioclinical Sciences, Chulabhorn International College of Medicine, Thammasat University, Pathumthani, Thailand ; Center of Excellence in Pharmacology and Molecular Biology of Malaria and Cholangiocarcinoma, Thammasat University, Pathumthani, Thailand.
Kesara
K
Na-Bangchang
D000595:Amino Acid Sequence; D001459:Bangladesh; D001483:Base Sequence; D004094:Dihydropteroate Synthase / Q000235:genetics*; D006801:Humans; D016780:Malaria, Vivax / Q000469:parasitology*; D008969:Molecular Sequence Data; D009390:Nepal; D010679:Philippines; D010966:Plasmodium vivax / Q000201:enzymology* / Q000235:genetics* / Q000302:isolation & purification; D011110:Polymorphism, Genetic; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics*
D013762:Tetrahydrofolate Dehydrogenase; D004094:Dihydropteroate Synthase
PCR-RFLP; Plasmodium vivax; Plasmodium vivax dihydrofolate reductase (pvdhfr); Plasmodium vivax dihydropteroate synthase (pvdhps); malaria; sulfadoxine-pyrimethamine (SP)