Prevalence of the dhfr and dhps Mutations among Pregnant Women in Rural Burkina Faso Five Years after the Introduction of Intermittent Preventive Treatment with Sulfadoxine-Pyrimethamine

PLoS One. 2015 Sep 14;10(9):e0137440. doi: 10.1371/journal.pone.0137440. eCollection 2015.

Abstract

Background: The emergence and spread of drug resistance represents one of the biggest challenges for malaria control in endemic regions. Sulfadoxine-pyrimethamine (SP) is currently deployed as intermittent preventive treatment in pregnancy (IPTp) to prevent the adverse effects of malaria on the mother and her offspring. Nevertheless, its efficacy is threatened by SP resistance which can be estimated by the prevalence of dihydropteroate synthase (dhps) and dihydrofolate reductase (dhfr) mutations. This was measured among pregnant women in the health district of Nanoro, Burkina Faso.

Methods: From June to December 2010, two hundred and fifty six pregnant women in the second and third trimester, attending antenatal care with microscopically confirmed malaria infection were invited to participate, regardless of malaria symptoms. A blood sample was collected on filter paper and analyzed by PCR-RFLP for the alleles 51, 59, 108, 164 in the pfdhfr gene and 437, 540 in the pfdhps gene.

Results: The genes were successfully genotyped in all but one sample (99.6%; 255/256) for dhfr and in 90.2% (231/256) for dhps. The dhfr C59R and S108N mutations were the most common, with a prevalence of 61.2% (156/255) and 55.7% (142/255), respectively; 12.2% (31/255) samples had also the dhfr N51I mutation while the I164L mutation was absent. The dhps A437G mutation was found in 34.2% (79/231) isolates, but none of them carried the codon K540E. The prevalence of the dhfr double mutations NRNI and the triple mutations IRNI was 35.7% (91/255) and 11.4% (29/255), respectively.

Conclusion: Though the mutations in the pfdhfr and pfdhps genes were relatively common, the prevalence of the triple pfdhfr mutation was very low, indicating that SP as IPTp is still efficacious in Burkina Faso.

MeSH terms

  • Adult
  • Antimalarials / pharmacology
  • Antimalarials / therapeutic use
  • Burkina Faso
  • Dihydropteroate Synthase / genetics*
  • Drug Combinations
  • Drug Resistance
  • Female
  • Humans
  • Malaria, Falciparum / parasitology*
  • Malaria, Falciparum / prevention & control
  • Mutation*
  • Plasmodium falciparum / drug effects
  • Plasmodium falciparum / genetics*
  • Pregnancy
  • Pregnancy Trimester, Second
  • Pregnancy Trimester, Third
  • Prevalence
  • Protozoan Proteins / genetics*
  • Pyrimethamine / pharmacology
  • Pyrimethamine / therapeutic use
  • Sulfadoxine / pharmacology
  • Sulfadoxine / therapeutic use
  • Tetrahydrofolate Dehydrogenase / genetics*
  • Young Adult

Substances

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

Grants and funding

The authors received no specific funding for this work.