Molecular epidemiology of Plasmodium falciparum resistance to antimalarial drugs in Indonesia

Syafruddin, D; Asih, PBS; Casey, GJ; Maguire, J; Baird, JK; Nagesha, HS; Cowman, AF; Reeder, JC

Author(s): Syafruddin, D; Asih, PBS; Casey, GJ; Maguire, J; Baird, JK; Nagesha, HS; Cowman, AF; Reeder, JC;
Details: Publication Year 2005-02-01,Volume 72,Issue #2,Page 174-181
Journal Title: AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
Publication Type: Journal Article
Abstract: The extent of gene polymorphisms associated with resistance to chloroquine and sulfadoxine-pyrimethamine was examined in field isolates of Plasmodium falciparum from Indonesia. Eight malaria-endemic areas, representing a broad region of the western and eastern Indonesian Archipelago were surveyed. Blood from 20-50 patients was collected at each site, DNA was isolated, and the sequences of four different genes (dihydrofolate reductase [dhfr], dihydropteroate synthase [dhps], P. falciparum multidrug resistance 1 [pfmdr1], and P. fialciparum chloroquine resistance transporter [pfcrt]) were analyzed using polymerase chain reaction and restriction fragment length polymorphisms to detect polymorphisms previously shown to be associated with resistance. This analysis identified polymorphisms in dhfr at 108-Asn/Thr, 16-Val, and 59-Arg. Polymorphisms in dhps were found less frequently, either 437-Gly alone or paired with 540-Glu. The pfcrt 76-Thr polymorphism was fixed in all parasite populations and pfmdr1 86-Tyr polymorphisms in all populations except in the most eastern regions. The pfmdr1 1042-Asp polymorphism occurred less frequently. These findings indicate that polymorphisms in genes associated with drug resistance in P. falciparum are found across a broad region of Indonesia.
Publisher: AMER SOC TROP MED & HYGIENE
Keywords: PAPUA-NEW-GUINEA; DIHYDROPTEROATE-SYNTHETASE GENES; THYMIDYLATE SYNTHASE GENE; TRANSPORTER PFCRT GENE; DIHYDROFOLATE-REDUCTASE; CHLOROQUINE-RESISTANCE; SULFADOXINE-PYRIMETHAMINE; IRIAN-JAYA; THERAPEUTIC-EFFICACY; CENTRAL JAVA
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Creation Date: 2005-02-01 12:00:00