Discordant temporal evolution of Pfcrt and Pfmdr1 genotypes and Plasmodium falciparum in vitro drug susceptibility to 4-aminoquinolines after drug policy change in French Guiana.
Analysis of the evolution of drug target genes under changing drug policy is needed to assist monitoring of Plasmodium falciparum drug resistance in the field. Here we genotype Pfcrt and Pfdmr1 of 700 isolates collected in French Guiana from 2000 (5 years after withdrawal of chloroquine) to 2008, i.e., the period when the artemether-lumefantrine combination was progressively introduced and mefloquine was abandoned. Gene sequencing showed fixation of the 7G8-type Pfcrt SMVNT resistance haplotype and near fixation of the NYCDY Pfdmr1 haplotype. Pfdmr1 gene copy number correlated with 50% inhibitory concentrations of mefloquine and halofantrine (r = 0.64 and 0.47, respectively, n = 547); its temporal changes paralleled changes in in vitro mefloquine susceptibility. However, the molecular parameters studied did not account for the regained in vitro susceptibility to chloroquine and showed a poor correlation with susceptibility to artemether, lumefantrine, or quinine. Identification of novel markers of resistance to these antimalarials is needed in this South American area.
Institut Pasteur de la Guyane, Centre National de Référence sur la Chimiorésistance du Paludisme dans la région Antilles—Guyane, Cayenne, French Guiana. elegrand@pasteur-cayenne.fr
Eric
E
Legrand
Joséphine
J
Yrinesi
Marie-Thérèse
MT
Ekala
Julie
J
Péneau
Béatrice
B
Volney
Franck
F
Berger
Christiane
C
Bouchier
Stéphane
S
Bertani
Lise
L
Musset
Jean-Baptiste
JB
Meynard
Odile
O
Mercereau-Puijalon
D000634:Aminoquinolines / Q000627:therapeutic use*; D000962:Antimalarials / Q000627:therapeutic use*; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins / Q000627:therapeutic use; D002738:Chloroquine / Q000008:administration & dosage / Q000627:therapeutic use; D004338:Drug Combinations; D004351:Drug Resistance / Q000235:genetics*; D004983:Ethanolamines / Q000627:therapeutic use; D019143:Evolution, Molecular; D005449:Fluorenes / Q000627:therapeutic use; D005616:French Guiana / Q000453:epidemiology; D018628:Gene Dosage; D006239:Haplotypes; D006801:Humans; D020128:Inhibitory Concentration 50; D008137:Longitudinal Studies; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000453:epidemiology / Q000469:parasitology; D015767:Mefloquine / Q000627:therapeutic use; D026901:Membrane Transport Proteins / Q000235:genetics*; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics*; D021261:Parasitic Sensitivity Tests; D010616:Phenanthrenes / Q000627:therapeutic use; D010963:Plasmodium falciparum / Q000187:drug effects / Q000235:genetics*; D017410:Practice Guidelines as Topic; D015800:Protozoan Proteins / Q000235:genetics*; D011803:Quinine / Q000008:administration & dosage / Q000627:therapeutic use
D000634:Aminoquinolines; D000962:Antimalarials; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins; D002738:Chloroquine; D004338:Drug Combinations; D004983:Ethanolamines; D005449:Fluorenes; D015767:Mefloquine; D026901:Membrane Transport Proteins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D010616:Phenanthrenes; D015800:Protozoan Proteins; D011803:Quinine; C513498:Mdr1 protein, Plasmodium falciparum; C416369:PfCRT protein, Plasmodium falciparum; C023768:halofantrine