Decreased in vitro susceptibility of Plasmodium falciparum isolates to artesunate, mefloquine, chloroquine, and quinine in Cambodia from 2001 to 2007.
This study describes the results of in vitro antimalarial susceptibility assays and molecular polymorphisms of Plasmodium falciparum isolates from Cambodia. The samples were collected from patients enrolled in therapeutic efficacy studies (TES) conducted by the Cambodian National Malaria Control Program for the routine efficacy monitoring of artemisinin-based combination therapy (ACT) (artesunate-mefloquine and artemether-lumefantrine combinations). The isolates (n = 2,041) were obtained from nine sentinel sites during the years 2001 to 2007. Among these, 1,588 were examined for their in vitro susceptibilities to four antimalarials (artesunate, mefloquine, chloroquine, and quinine), and 851 isolates were genotyped for single nucleotide polymorphisms (SNPs). The geometric means of the 50% inhibitory concentrations (GMIC(50)s) of the four drugs tested were significantly higher for isolates from western Cambodia than for those from eastern Cambodia. GMIC(50)s for isolates from participants who failed artesunate-mefloquine therapy were significantly higher than those for patients who were cured (P, <0.001). In vitro correlation of artesunate with the other drugs was observed. The distributions of the SNPs differed between eastern and western Cambodia, suggesting different genetic backgrounds of the parasite populations in these two parts of the country. The GMIC(50)s of the four drugs tested increased significantly in eastern Cambodia during 2006 to 2007. These results are worrisome, because they may signal deterioration of the efficacy of artesunate-mefloquine beyond the Cambodian-Thai border.
Lim
Pharath
P
Institut Pasteur in Cambodia, Molecular Epidemiology Unit, Phnom Penh, Cambodia. pharathl@yahoo.com
Wongsrichanalai
Chansuda
C
Chim
Pheaktra
P
Khim
Nimol
N
Kim
Saorin
S
Chy
Sophy
S
Sem
Rithy
R
Nhem
Sina
S
Yi
Poravuth
P
Duong
Socheat
S
Bouth
Denis Mey
DM
Genton
Blaise
B
Beck
Hans-Peter
HP
Gobert
Jean Gerard
JG
Rogers
William O
WO
Coppee
Jean-Yves
JY
Fandeur
Thierry
T
Mercereau-Puijalon
Odile
O
Ringwald
Pascal
P
Le Bras
Jacques
J
Ariey
Frederic
F
D000962:Antimalarials / Q000494:pharmacology*; D037621:Artemisinins / Q000494:pharmacology*; D000077332:Artesunate; D002160:Cambodia; D002738:Chloroquine / Q000494:pharmacology; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D040362:Geographic Information Systems; D066298:In Vitro Techniques; D020128:Inhibitory Concentration 50; D016778:Malaria, Falciparum / Q000188:drug therapy*; D015767:Mefloquine / Q000494:pharmacology; D020411:Oligonucleotide Array Sequence Analysis; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics* / Q000254:growth & development; D017354:Point Mutation; D020641:Polymorphism, Single Nucleotide; D011803:Quinine / Q000494:pharmacology
D000962:Antimalarials; D037621:Artemisinins; D000077332:Artesunate; D002738:Chloroquine; D011803:Quinine; D015767:Mefloquine