High prevalence of sulfadoxine/pyrimethamine-resistant alleles of Plasmodium falciparum isolates in pregnant women at the time of introduction of intermittent preventive treatment with sulfadoxine/pyrimethamine in Gabon

J Antimicrob Chemother. 2010 Mar;65(3):438-41. doi: 10.1093/jac/dkp467. Epub 2010 Jan 6.

Abstract

Objectives: The frequency of dhfr and dhps point mutations was assessed in Plasmodium falciparum isolates from pregnant women in Libreville.

Methods: PCR-restriction fragment length polymorphism of polymorphic codons of the dhfr gene (51, 59 and 108) and the dhps gene (436, 437 and 540) was performed in matched peripheral and placental blood samples.

Results: The proportion of multiple mutations was high (98%), and was not different between women with and without a history of intermittent preventive treatment with sulfadoxine/pyrimethamine (IPTp/SP). The prevalence of triple dhfr mutation was 80%, and that of quadruple and quintuple mutations was 53% and 22%, respectively. The Glu540 mutation was present in two isolates. The concordance of resistant alleles in matched peripheral and placental isolates was >90% for both genes.

Conclusions: These findings underline the need for a regular assessment of the relationship between the presence of resistant isolates and in vitro/in vivo IPTp/SP efficacy, and evaluation of an alternative drug.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Amino Acid Substitution / genetics
  • Animals
  • Antimalarials / pharmacology*
  • Blood / parasitology
  • DNA Restriction Enzymes / metabolism
  • Dihydropteroate Synthase / genetics
  • Drug Combinations
  • Drug Resistance*
  • Female
  • Gabon
  • Genotype
  • Humans
  • Malaria, Falciparum / parasitology*
  • Mutation, Missense
  • Placenta / parasitology
  • Plasmodium falciparum / drug effects
  • Plasmodium falciparum / genetics*
  • Plasmodium falciparum / isolation & purification
  • Polymerase Chain Reaction
  • Pregnancy
  • Pregnancy Complications, Infectious / parasitology*
  • Prevalence
  • Protozoan Proteins / genetics*
  • Pyrimethamine / pharmacology*
  • Sulfadoxine / pharmacology*
  • Tetrahydrofolate Dehydrogenase / genetics

Substances

  • Antimalarials
  • Drug Combinations
  • Protozoan Proteins
  • fanasil, pyrimethamine drug combination
  • Sulfadoxine
  • Tetrahydrofolate Dehydrogenase
  • Dihydropteroate Synthase
  • DNA Restriction Enzymes
  • Pyrimethamine