title: In vitro antimalarial drug susceptibility and pfcrt mutation among fresh Plasmodium falciparum isolates from the Lao PDR (Laos).
abstract: Recent drug trials in Laos have shown high levels of Plasmodium falciparum resistance to chloroquine, but there are no published data on in vitro antimalarial drug susceptibility. We used the double-site enzyme-linked pLDH immunodetection (DELI) assay to estimate the in vitro antimalarial drug susceptibility of 108 fresh P. falciparum isolates from southern Laos. The geometric mean (95% confidence interval) 50% inhibitory concentration values (nmol/L) were 152.4 (123.8-187.6) for chloroquine, 679.8 (533.8-863.0) for quinine, 45.9 (37.9-55.7) for mefloquine, 5.0 (4.4-6.4) for artesunate, 6.3 (4.5-8.9) for dihydroartemisinin, and 59.1 (46.4-75.3) for lumefantrine. The proportion of isolates defined as resistant were 65%, 40%, and 8% for chloroquine, quinine, and mefloquine, respectively. Of 53 isolates genotyped for the pfcrt T76K chloroquine-resistance mutation, 48 (91%) were mutants. P. falciparum in Laos is multi-drug resistant; antimalarial immunity resulting from the use of ineffective chloroquine before 2005 probably contributes significantly to the therapeutic responses in clinical trials.
authors.affiliation: Wellcome Trust-Mahosot Hospital-Oxford Tropical Medicine Research Collaboration, Mahosot Hospital, Vientiane, Lao PDR. mmayxay@yahoo.com
authors.forename: Mayfong
authors.initials: M
authors.lastname: Mayxay
authors.forename: Marion
authors.initials: M
authors.lastname: Barends
authors.forename: Alan
authors.initials: A
authors.lastname: Brockman
authors.forename: Anchalee
authors.initials: A
authors.lastname: Jaidee
authors.forename: Shalini
authors.initials: S
authors.lastname: Nair
authors.forename: Dan
authors.initials: D
authors.lastname: Sudimack
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: Tim
authors.initials: T
authors.lastname: Anderson
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: White
authors.forename: Paul N
authors.initials: PN
authors.lastname: Newton
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D037621:Artemisinins / Q000494:pharmacology; D000077332:Artesunate; D002648:Child; D002675:Child, Preschool; D002738:Chloroquine / Q000494:pharmacology; D016054:DNA, Protozoan / Q000737:chemistry / Q000235:genetics; D004351:Drug Resistance; D004983:Ethanolamines / Q000494:pharmacology; D005260:Female; D005449:Fluorenes / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D007812:Laos; D000078102:Lumefantrine; D016778:Malaria, Falciparum / Q000469:parasitology*; D008297:Male; D015767:Mefloquine / Q000494:pharmacology; D026901:Membrane Transport Proteins / Q000737:chemistry / Q000235:genetics*; D008875:Middle Aged; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics* / Q000254:growth & development / Q000302:isolation & purification; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics*; D012717:Sesquiterpenes / Q000494:pharmacology
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D016054:DNA, Protozoan; D004983:Ethanolamines; D005449:Fluorenes; D026901:Membrane Transport Proteins; C416369:PfCRT protein, Plasmodium falciparum; D015800:Protozoan Proteins; D012717:Sesquiterpenes; D000077332:Artesunate; C039060:artenimol; D002738:Chloroquine; D000078102:Lumefantrine; D015767:Mefloquine