title: Frequency distribution of antimalarial drug-resistant alleles among isolates of Plasmodium falciparum in Purworejo district, Central Java Province, Indonesia.
abstract: Treatment failures to the first- and second-lines antimalarial drugs chloroquine and sulfadoxine-pyrimethamine have increased in the Purworejo district on the island of Java, Indonesia. A molecular epidemiologic study was conducted to determine the frequency distribution of mutant alleles of the genes associated with the resistance among the isolates of Plasmodium falciparum from the area. Analyses using a polymerase chain reaction and restriction fragment length polymorphism showed that nearly all of the 111 samples carried mutant alleles in genes associated with chloroquine resistance: P. falciparum multi-drug resistance 1 (pfmdrl) 86Y (92%), 1042D (4.5%), and P. falciparum chloroquine resistance transporter (pfcrt) 76T (99.1%). Mutant alleles of the in the dihydrofolate reductase (dhfr) gene were also high (84.7%), either as 108N and 108T or paired with 59R, and 16V, respectively. Mutant alleles in the dihydropteroate synthase gene were the least common, either as a single 437G mutation (35.3%) or paired with 540E (26.5%). These results are consistent with the antimalarial drug resistance situation in the area and emphasize the need for a proper treatment strategy.
authors.affiliation: Eijkman Institute for Molecular Biology, Jakarta, Indonesia. din@eijkman.go.id
authors.forename: D
authors.initials: D
authors.lastname: Syafruddin
authors.forename: Puji B S
authors.initials: PB
authors.lastname: Asih
authors.forename: Sona L
authors.initials: SL
authors.lastname: Aggarwal
authors.forename: Anuraj H
authors.initials: AH
authors.lastname: Shankar
mesh_terms: D000483:Alleles; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology* / Q000627:therapeutic use; D004094:Dihydropteroate Synthase / Q000235:genetics; D018432:Drug Resistance, Multiple / Q000235:genetics*; D006801:Humans; D007214:Indonesia / Q000453:epidemiology; D016778:Malaria, Falciparum / Q000097:blood / Q000188:drug therapy* / Q000453:epidemiology; D009154:Mutation; D010963:Plasmodium falciparum / Q000187:drug effects / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics
chemical_list: D000962:Antimalarials; D013762:Tetrahydrofolate Dehydrogenase; D004094:Dihydropteroate Synthase