Short report: High prevalence and imbalanced age distribution of the Plasmodium falciparum dihydrofolate reductase gene Asn(108) mutation in an area of low pyrimethamine usage in Nigeria

Resistance of Plasmodium falciparum to pyrimethamine is associated with a n on-silent point mutation of the parasite dihydrofolate reductase (DHFR) gen e (Ser(108) --> Asn(108)). Wide-scale use of antimalarials is thought to co ntribute to the emergence of drug resistance. In 131 P. falciparum-infected children in rural Nigeria, the frequency of the resistant Asn(108) genotyp e was assessed by enzymatic restriction digestion of polymerase chain react ion-amplified DHFR sequences and compared with residual pyrimethamine blood levels. The prevalence of the Asn(108) variant was 41.2%. In 18.3% of the isolates, both the Asn(108) and the wild-type alleles were present. In cont rast to the high prevalence of resistant genotypes, residual pyrimethamine blood levels were detected in only 4%. Furthermore, age was found to be a d eterminant of the parasite genotype since the proportion of Asn(108) varian ts 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.