title: Molecular epidemiology of malaria in Cameroon. XXVI. Twelve-year in vitro and molecular surveillance of pyrimethamine resistance and experimental studies to modulate pyrimethamine resistance.
abstract: 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.
authors: 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
authors: Rachida
authors: R
authors: Tahar
authors: Leonardo K
authors: LK
authors: Basco
mesh_terms: 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
chemical_list: D000962:Antimalarials; D016054:DNA, Protozoan; D013762:Tetrahydrofolate Dehydrogenase; D011339:Probenecid; D013442:Sulfinpyrazone; D011739:Pyrimethamine