Molecular epidemiology of malaria in Cameroon. XXVI. Twelve-year in vitro and molecular surveillance of pyrimethamine resistance and experimental studies to modulate pyrimethamine resistance.
In vitro pyrimethamine response of Plasmodium falciparum isolates and dihydrofolate reductase (dhfr) gene sequences were analyzed in 2004-2005 and compared with our previous data. Most isolates (n = 103, all dhfr mutants) had 50% inhibitory concentrations (IC(50)s) > or = 119 nM, and six isolates had low IC(50)s (five wild-type or mixed dhfr, 0.04-1.37 nM; one triple mutant, 6.4 nM). Of 194 isolates, only 7 had the wild-type dhfr and 187 were mutants. The results of the two methods were highly concordant and indicated a significant increase (P < 0.05) in the prevalence of mutant, pyrimethamine-resistant P. falciparum between 1994 and 2005. The addition of probenecid or sulfinpyrazone to pyrimethamine resulted in a slight-to-moderate decrease in the level of in vitro pyrimethamine resistance without rendering the parasites susceptible to pyrimethamine. Analysis of molecular markers may be useful for the long-term surveillance of antifolate-resistant malaria.
Tahar
Rachida
R
Unité de Recherche 77 Paludologie Afro-Tropicale, Institut de Recherche pour le Développement, Organisation de Coordination pour la lutte contre les Endémies en Afrique Centrale, Yaoundé, Cameroon. rachidatahar@yahoo.fr
Basco
Leonardo K
LK
D000293:Adolescent; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D002163:Cameroon / Q000453:epidemiology; D016054:DNA, Protozoan / Q000737:chemistry / Q000235:genetics; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D006801:Humans; D016778:Malaria, Falciparum / Q000097:blood / Q000188:drug therapy / Q000453:epidemiology / Q000469:parasitology*; D017720:Molecular Epidemiology; D009154:Mutation; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics / Q000302:isolation & purification; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011339:Probenecid / Q000494:pharmacology; D011739:Pyrimethamine / Q000494:pharmacology*; D017422:Sequence Analysis, DNA; D013442:Sulfinpyrazone / Q000494:pharmacology; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics / Q000378:metabolism
D000962:Antimalarials; D016054:DNA, Protozoan; D013762:Tetrahydrofolate Dehydrogenase; D011339:Probenecid; D013442:Sulfinpyrazone; D011739:Pyrimethamine