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

Am J Trop Med Hyg. 1999 Sep;61(3):375-7. doi: 10.4269/ajtmh.1999.61.375.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Distribution
  • Animals
  • Antimalarials / blood
  • Antimalarials / pharmacology
  • Antimalarials / therapeutic use*
  • Child
  • Child, Preschool
  • Cross-Sectional Studies
  • DNA, Protozoan / analysis
  • Drug Resistance / genetics
  • Genes, Protozoan
  • Genotype
  • Humans
  • Infant
  • Malaria, Falciparum / drug therapy
  • Malaria, Falciparum / epidemiology
  • Malaria, Falciparum / parasitology*
  • Nigeria / epidemiology
  • Plasmodium falciparum / drug effects
  • Plasmodium falciparum / enzymology
  • Plasmodium falciparum / genetics*
  • Point Mutation*
  • Polymerase Chain Reaction / methods
  • Prevalence
  • Pyrimethamine / blood
  • Pyrimethamine / pharmacology
  • Pyrimethamine / therapeutic use*
  • Tetrahydrofolate Dehydrogenase / genetics*

Substances

  • Antimalarials
  • DNA, Protozoan
  • Tetrahydrofolate Dehydrogenase
  • Pyrimethamine