Molecular epidemiology of Plasmodium falciparum resistance to antimalarial drugs in Indonesia.
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. falciparum 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.
Syafruddin
Din
D
Eijkman Institute for Molecular Biology, Jakarta, Indonesia. din@eijkman.go.id
Asih
Puji B S
PB
Casey
Gerard J
GJ
Maguire
Jason
J
Baird
J Kevin
JK
Nagesha
Hadya S
HS
Cowman
Alan F
AF
Reeder
John C
JC
D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage / Q000627:therapeutic use; D016054:DNA, Protozoan / Q000235:genetics; D018432:Drug Resistance, Multiple / Q000235:genetics*; D019450:Genes, MDR / Q000235:genetics*; D006801:Humans; D007214:Indonesia / Q000453:epidemiology; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000453:epidemiology / Q000209:etiology; D010963:Plasmodium falciparum / Q000235:genetics*; D016133:Polymerase Chain Reaction; D015800:Protozoan Proteins / Q000235:genetics
D018528:ATP-Binding Cassette Transporters; D000962:Antimalarials; D016054:DNA, Protozoan; D015800:Protozoan Proteins; C059987:mdr gene protein, Plasmodium