title: Short report: high prevalence and imbalanced age distribution of the Plasmodium falciparum dihydrofolate reductase gene Asn108 mutation in an area of low pyrimethamine usage in Nigeria.
abstract: Resistance of Plasmodium falciparum to pyrimethamine is associated with a non-silent point mutation of the parasite dihydrofolate reductase (DHFR) gene (Ser108 --> Asn108). Wide-scale use of antimalarials is thought to contribute to the emergence of drug resistance. In 131 P. falciparum-infected children in rural Nigeria, the frequency of the resistant Asn108 genotype was assessed by enzymatic restriction digestion of polymerase chain reaction-amplified DHFR sequences and compared with residual pyrimethamine blood levels. The prevalence of the Asn108 variant was 41.2%. In 18.3% of the isolates, both the Asn108 and the wild-type alleles were present. In contrast to the high prevalence of resistant genotypes, residual pyrimethamine blood levels were detected in only 4%. Furthermore, age was found to be a determinant of the parasite genotype since the proportion of Asn108 variants decreased with age (P < 0.05). These findings indicate that additional, unidentified factors, rather than selection by residual drug levels alone, might be responsible for the emergence of pyrimethamine-resistant parasite genotypes.
authors.affiliation: Institute for Tropical Medicine, Medical Faculty Charité, Humboldt-University Berlin, Germany.
authors.forename: F P
authors.initials: FP
authors.lastname: Mockenhaupt
authors.forename: J
authors.initials: J
authors.lastname: May
authors.forename: T A
authors.initials: TA
authors.lastname: Eggelte
authors.forename: F L
authors.initials: FL
authors.lastname: Thies
authors.forename: O G
authors.initials: OG
authors.lastname: Ademowo
authors.forename: U
authors.initials: U
authors.lastname: Bienzle
authors.forename: C G
authors.initials: CG
authors.lastname: Meyer
mesh_terms: D017677:Age Distribution; D000818:Animals; D000962:Antimalarials / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D016054:DNA, Protozoan / Q000032:analysis; D004351:Drug Resistance / Q000235:genetics; D017125:Genes, Protozoan; D005838:Genotype; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000453:epidemiology / Q000469:parasitology*; D009549:Nigeria / Q000453:epidemiology; D010963:Plasmodium falciparum / Q000187:drug effects / Q000201:enzymology / Q000235:genetics*; D017354:Point Mutation; D016133:Polymerase Chain Reaction / Q000379:methods; D015995:Prevalence; D011739:Pyrimethamine / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics*
chemical_list: D000962:Antimalarials; D016054:DNA, Protozoan; D013762:Tetrahydrofolate Dehydrogenase; D011739:Pyrimethamine