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.
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.
Mockenhaupt
F P
FP
Institute for Tropical Medicine, Medical Faculty Charité, Humboldt-University Berlin, Germany.
May
J
J
Eggelte
T A
TA
Thies
F L
FL
Ademowo
O G
OG
Bienzle
U
U
Meyer
C G
CG
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*
D000962:Antimalarials; D016054:DNA, Protozoan; D013762:Tetrahydrofolate Dehydrogenase; D011739:Pyrimethamine