Analysis of pfcrt, pfmdr1, dhfr, and dhps mutations and drug sensitivities in Plasmodium falciparum isolates from patients in Vietnam before and after treatment with artemisinin.
We have analyzed artemisinin sensitivity in Plasmodium falciparum isolates obtained from patients in South Vietnam and show that artemisinin sensitivity does not differ before and after drug treatment. There was an increase in the level of mefloquine resistance in the isolates after drug treatment that was concomitant with a decrease in chloroquine resistance, suggesting that treatment with artemisinin has selected for increased mefloquine resistance. Mutations in the pfmdr1 gene, previously shown to be associated with sensitivity to mefloquine, were selected against. All isolates resistant to chloroquine encoded Thr-76 in the pfcrt gene consistent with an essential role in the mechanism of chloroquine resistance. Mutations in pfmdr1 also were linked to chloroquine resistance. High levels of mutation in dhfr and dhps genes, which have previously been associated with Fansidar resistance, also were found, suggesting that this drug would not be useful for malaria control in this part of Vietnam.
Ngo
Thanh
T
Walter and Eliza Hall Institute of Medical Research, PO Royal Melbourne Hospital, Victoria, Melbourne, Australia.
Duraisingh
Manoj
M
Reed
Michael
M
Hipgrave
David
D
Biggs
Beverley
B
Cowman
Alan F
AF
D018528:ATP-Binding Cassette Transporters; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology / Q000627:therapeutic use*; D037621:Artemisinins / Q000494:pharmacology / Q000627:therapeutic use*; D004094:Dihydropteroate Synthase / Q000235:genetics*; D004351:Drug Resistance / Q000235:genetics; D005838:Genotype; D016778:Malaria, Falciparum / Q000188:drug therapy*; D008565:Membrane Proteins / Q000235:genetics*; D026901:Membrane Transport Proteins; D009154:Mutation; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics; D015800:Protozoan Proteins / Q000235:genetics*; D012717:Sesquiterpenes / Q000494:pharmacology / Q000627:therapeutic use*; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics*; D014744:Vietnam
D018528:ATP-Binding Cassette Transporters; D000962:Antimalarials; D037621:Artemisinins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C416369:PfCRT protein, Plasmodium falciparum; D015800:Protozoan Proteins; D012717:Sesquiterpenes; C059987:mdr gene protein, Plasmodium; C031327:artemisinin; D013762:Tetrahydrofolate Dehydrogenase; D004094:Dihydropteroate Synthase