In vitro antimalarial drug susceptibility and pfcrt mutation among fresh Plasmodium falciparum isolates from the Lao PDR (Laos).
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.
Mayxay
Mayfong
M
Wellcome Trust-Mahosot Hospital-Oxford Tropical Medicine Research Collaboration, Mahosot Hospital, Vientiane, Lao PDR. mmayxay@yahoo.com
Barends
Marion
M
Brockman
Alan
A
Jaidee
Anchalee
A
Nair
Shalini
S
Sudimack
Dan
D
Pongvongsa
Tiengkham
T
Phompida
Samlane
S
Phetsouvanh
Rattanaxay
R
Anderson
Tim
T
White
Nicholas J
NJ
Newton
Paul N
PN
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
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