title: Plasmodium vivax: prevalence of mutations associated with sulfadoxine-pyrimethamine resistance in Plasmodium vivax clinical isolates from Pakistan.
abstract: The main aim of the present study was to investigate the frequency of SNPs-haplotypes of dhfr and dhps genes associated to sulfadoxine-pyrimethamine (SP) resistance in Plasmodium vivax clinical isolates circulating in a malaria endemic area, Pakistan. All 164 collected isolates were analyzed for SNPs-haplotypes at positions 13, 33, 57, 58, 61, 117 and 173 of pvdhfr and 383 and 553 of pvdhps genes using PCR-RFLP methods. All examined isolates were found to carry wild-type amino acids at positions 13, 33, 57, 61 and 173, while 58R and 117N mutations were detected among 15.2% and 53.6% of isolates, respectively. Based on the size polymorphism of pvdhfr genes at repeat region, type B (79.3%) was the most prevalent variant. The combination of pvdhfr and pvdhps haplotypes demonstrated nine distinct haplotypes. The three most prevalent haplotypes were I(13)P(33)F(57)S(58)T(61)S(117)I(173)/A(383)A(553) (43.9%), I(13)P(33)F(57)S(58)T(61)N(117)I(173)/A(383)A(553) (33.6%) and I(13)P(33)F(57)R(58)T(61)N(117)I(173)/A(383)A(553) (12.2%). The presence of mutant haplotypes is worrying and indicates the emergence of drug tolerant/resistant P. vivax isolates in Pakistan in near future.
authors.affiliation: Malaria and Vector Research Group, Biotechnology Research Center, Pasteur Institute of Iran, Pasteur Avenue, PO Box 1316943551, Tehran, Iran. zakeris@yahoo.com
authors.forename: Sedigheh
authors.initials: S
authors.lastname: Zakeri
authors.forename: Mandana
authors.initials: M
authors.lastname: Afsharpad
authors.forename: Faezeh
authors.initials: F
authors.lastname: Ghasemi
authors.forename: Ahmad
authors.initials: A
authors.lastname: Raeisi
authors.forename: Qutbuddin
authors.initials: Q
authors.lastname: Kakar
authors.forename: Hoda
authors.initials: H
authors.lastname: Atta
authors.forename: Navid Dinparast
authors.initials: ND
authors.lastname: Djadid
mesh_terms: D000293:Adolescent; D000328:Adult; D000962:Antimalarials / Q000494:pharmacology*; D002648:Child; D002675:Child, Preschool; D004094:Dihydropteroate Synthase / Q000235:genetics; D004338:Drug Combinations; D004351:Drug Resistance / Q000235:genetics*; D005260:Female; D006239:Haplotypes; D006801:Humans; D007223:Infant; D016780:Malaria, Vivax / Q000188:drug therapy / Q000453:epidemiology / Q000469:parasitology*; D008297:Male; D009154:Mutation; D010154:Pakistan / Q000453:epidemiology; D010966:Plasmodium vivax / Q000187:drug effects / Q000235:genetics*; D015995:Prevalence; D011739:Pyrimethamine / Q000494:pharmacology*; D013413:Sulfadoxine / Q000494:pharmacology*; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics
chemical_list: D000962:Antimalarials; D004338:Drug Combinations; C001205:fanasil, pyrimethamine drug combination; D013413:Sulfadoxine; D013762:Tetrahydrofolate Dehydrogenase; D004094:Dihydropteroate Synthase; D011739:Pyrimethamine