Prevalence of Plasmodium falciparum parasites resistant to sulfadoxine/pyrimethamine in pregnant women in Yaoundé, Cameroon: emergence of highly resistant pfdhfr/pfdhps alleles

J Antimicrob Chemother. 2015 Sep;70(9):2566-71. doi: 10.1093/jac/dkv160. Epub 2015 Jun 16.

Abstract

Objectives: To determine, 6 years after the adoption of intermittent preventive treatment of pregnant women with sulfadoxine/pyrimethamine (IPTp-SP) in Cameroon, (i) the polymorphism and prevalence of Plasmodium falciparum dihydrofolate reductase (pfdhfr) and dihydropteroate synthase (pfdhps) gene mutations associated with sulfadoxine/pyrimethamine resistance and (ii) the consequences of sulfadoxine/pyrimethamine use in the selection of pfdhfr/pfdhps alleles.

Methods: pfdhfr and pfdhps genes from P. falciparum isolates collected in Yaoundé (Cameroon) from pregnant women with symptomatic malaria before taking IPTp-SP [SP- group (control) (n = 51)] or afterwards [SP+ group (n = 49)] were sequenced.

Results: The pfdhfr N51I, C59R, S108N triple mutant had a prevalence close to 100% (96/100) and no mutations at codons 50 and 164 were detected in either of the groups. The most frequent pfdhps mutation was A437G with a prevalence of 76.5% (39/51) in the SP- group, which was significantly higher in pregnant women who took sulfadoxine/pyrimethamine [95.9% (47/49)] (P = 0.012). Our study confirmed the presence of the pfdhps K540E mutation in Cameroon, but it remained rare. The prevalence of pfdhps A581G and A613S mutations had increased [5.9% (3/51) and 11.8% (6/51) in the control group, respectively] since the last studies in 2005. Surprisingly, the new pfdhps I431V mutation was detected, at a prevalence of 9.8% (5/51), and was found to be associated with other pfdhfr/pfdhps alleles to form an octuple N51I, C59R, S108N/I431V, S436A, A437G, A581G, A613S mutant.

Conclusions: Significant changes were found in pfdhps polymorphism. In particular, we observed several parasites carrying eight mutations in pfdhfr/pfdhps genes, which are very susceptible to having a high level of resistance to sulfadoxine/pyrimethamine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antimalarials / pharmacology*
  • Cameroon / epidemiology
  • Dihydropteroate Synthase / genetics
  • Drug Combinations
  • Drug Resistance*
  • Female
  • Gene Frequency*
  • Humans
  • Malaria, Falciparum / epidemiology
  • Malaria, Falciparum / parasitology*
  • Mutation
  • Plasmodium falciparum / drug effects*
  • Plasmodium falciparum / isolation & purification
  • Polymorphism, Genetic
  • Pregnancy
  • Pregnancy Complications, Infectious / epidemiology
  • Pregnancy Complications, Infectious / parasitology*
  • Prevalence
  • Pyrimethamine / pharmacology*
  • Sequence Analysis, DNA
  • Sulfadoxine / pharmacology*
  • Tetrahydrofolate Dehydrogenase / genetics
  • Young Adult

Substances

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