Plasmodium falciparum malaria in Laos: chloroquine treatment outcome and predictive value of molecular markers.
A 28-day treatment trial was undertaken, to determine the efficacy of chloroquine in Laos and to assess the predictive value of molecular markers (cg2, pfmdr1, and pfcrt) that were previously linked to chloroquine resistance. In total, 522 febrile patients were screened for falciparum malaria by rapid diagnostic assays. Of 81 patients (15.5% prevalence) who were positive by the assays and microscopy, 48 were eligible to participate in the 28-day trial. Nine patients defaulted. Chloroquine cured 54% (95% confidence interval, 45.8-61.8) of falciparum-infected patients. Of 18 (46%) patients with treatment failure, 13 (72%) experienced high-grade resistance. Polymorphisms in cg2 and the N86Y mutation in PfMDR1 were not predictive of treatment outcome. A mutation in PfCRT (K76T) was perfectly associated with in vivo chloroquine resistance. However, K76T was also present in in vivo-sensitive isolates, which suggests that the presence of this mutation was necessary, but not sufficient, to predict in vivo outcome in this cohort.
Pillai
D R
DR
Centre for Travel and Tropical Medicine, Division of Infectious Diseases, Department of Medicine, Toronto General Hospital and University of Toronto, Toronto, Canada, M5G 2C4.
Labbé
A C
AC
Vanisaveth
V
V
Hongvangthong
B
B
Pomphida
S
S
Inkathone
S
S
Zhong
K
K
Kain
K C
KC
D000293:Adolescent; D000328:Adult; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D002738:Chloroquine / Q000494:pharmacology / Q000627:therapeutic use*; D015331:Cohort Studies; D004352:Drug Resistance, Microbial / Q000235:genetics; D005260:Female; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D007812:Laos; D016778:Malaria, Falciparum / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D015995:Prevalence; D016896:Treatment Outcome
D000962:Antimalarials; D005819:Genetic Markers; D002738:Chloroquine