The F423Y mutation in the pfmdr2 gene and mutations N51I, C59R, and S108N in the pfdhfr gene are independently associated with pyrimethamine resistance in Plasmodium falciparum isolates.
Screening for in vitro susceptibility to pyrimethamine and sequencing of the pfmdr2 and pfdhfr genes were performed in 140 Plasmodium falciparum isolates. The risk of in vitro resistance to pyrimethamine was analyzed with a logistic regression model. The mutation F423Y in pfmdr2 (odds ratio [OR] = 2.12 [confidence interval {CI}, 1.02 to 4.59]; P = 0.0489) and the mutation N51I, C59R, or S108N in pfdhfr (OR = 42.34 [CI, 5.52 to 324.61]; P = 0.0003) were independently associated with in vitro resistance to pyrimethamine.
Unité de Recherche en Biologie et Epidémiologie Parasitaires, Institut de Recherche Biomédicale des Armées—Antenne de Marseille, Marseille, France.
Sébastien
S
Briolant
Hervé
H
Bogreau
Marine
M
Gil
Housem
H
Bouchiba
Eric
E
Baret
Rémy
R
Amalvict
Christophe
C
Rogier
Bruno
B
Pradines
D000962:Antimalarials / Q000494:pharmacology; D004351:Drug Resistance / Q000235:genetics*; D005493:Folic Acid Antagonists / Q000494:pharmacology*; D017125:Genes, Protozoan; D006801:Humans; D016015:Logistic Models; D016778:Malaria, Falciparum / Q000469:parasitology; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics*; D015999:Multivariate Analysis; D009154:Mutation; D010963:Plasmodium falciparum / Q000235:genetics* / Q000302:isolation & purification; D016133:Polymerase Chain Reaction; D011739:Pyrimethamine / Q000494:pharmacology*; D017422:Sequence Analysis, DNA; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics*
D000962:Antimalarials; D005493:Folic Acid Antagonists; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D011739:Pyrimethamine; D013762:Tetrahydrofolate Dehydrogenase; C513499:Mdr2 protein, Plasmodium falciparum