title: Combined molecular and clinical assessment of Plasmodium falciparum antimalarial drug resistance in the Lao People's Democratic Republic (Laos).
abstract: Molecular markers provide a rapid and relatively inexpensive approach for assessing antimalarial drug susceptibility. We collected 884 Plasmodium falciparum-infected blood samples from 17 Lao provinces. Each sample was genotyped for 11 codons in the chloroquine resistance transporter (pfcrt), dihydrofolate reductase (pfdhfr), and dihydropteroate synthase (pfdhps) genes. The samples included 227 collected from patients recruited to clinical trials. The pfcrt K76T mutation was an excellent predictor of treatment failure for both chloroquine and chloroquine plus sulfadoxine-pyrimethamine, and mutations in both pfdhfr and pfdhps were predictive of sulfadoxine-pyrimethamine treatment failure. In multivariate analysis, the presence of the pfdhfr triple mutation (51 + 59 + 108) was strongly and independently correlated with sulfadoxine-pyrimethamine failure (odds ratio = 9.1, 95% confidence interval = 1.4-60.2, P = 0.017). Considerable geographic heterogeneity in allele frequencies occurred at all three loci with lower frequencies of mutant alleles in southern than in northern Laos. These findings suggest that chloroquine and sulfadoxine-pyrimethamine are no longer viable therapy in this country.
authors.affiliation: Wellcome Trust-Mahosot Hospital-Oxford Tropical Medicine Research Collaboration, Mahosot Hospital, Vientiane, Lao People' Democratic Republic.
authors.forename: Mayfong
authors.initials: M
authors.lastname: Mayxay
authors.forename: Shalini
authors.initials: S
authors.lastname: Nair
authors.forename: Dan
authors.initials: D
authors.lastname: Sudimack
authors.forename: Mallika
authors.initials: M
authors.lastname: Imwong
authors.forename: Naowarat
authors.initials: N
authors.lastname: Tanomsing
authors.forename: Tiengkham
authors.initials: T
authors.lastname: Pongvongsa
authors.forename: Samlane
authors.initials: S
authors.lastname: Phompida
authors.forename: Rattanaxay
authors.initials: R
authors.lastname: Phetsouvanh
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: White
authors.forename: Tim J C
authors.initials: TJ
authors.lastname: Anderson
authors.forename: Paul N
authors.initials: PN
authors.lastname: Newton
mesh_terms: D000293:Adolescent; D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage / Q000627:therapeutic use*; D004338:Drug Combinations; D004351:Drug Resistance / Q000235:genetics*; D005260:Female; D006801:Humans; D007812:Laos / Q000453:epidemiology; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000453:epidemiology / Q000209:etiology / Q000469:parasitology; D008297:Male; D009154:Mutation; D010963:Plasmodium falciparum / Q000235:genetics* / Q000302:isolation & purification; D015800:Protozoan Proteins / Q000235:genetics*; D011739:Pyrimethamine / Q000008:administration & dosage / Q000627:therapeutic use; D013413:Sulfadoxine / Q000008:administration & dosage / Q000627:therapeutic use
chemical_list: D000962:Antimalarials; D004338:Drug Combinations; D015800:Protozoan Proteins; C001205:fanasil, pyrimethamine drug combination; D013413:Sulfadoxine; D011739:Pyrimethamine