Prevalence of Plasmodium falciparum parasites resistant to sulfadoxine/pyrimethamine in the Democratic Republic of the Congo: emergence of highly resistant pfdhfr/pfdhps alleles

J Antimicrob Chemother. 2018 Oct 1;73(10):2704-2715. doi: 10.1093/jac/dky258.

Abstract

Background: In 2005, the Democratic Republic of the Congo (DRC) switched to artesunate/amodiaquine as the first-line antimalarial in response to increasing sulfadoxine/pyrimethamine resistance and adopted intermittent preventive treatment using sulfadoxine/pyrimethamine in pregnancy.

Objectives: To determine the prevalence of molecular markers of sulfadoxine/pyrimethamine resistance in southwestern DRC 10 years after the new policy was instituted.

Methods: From March 2014 to December 2015, blood samples were collected from symptomatic patients presenting to outpatient centres in urban and rural areas. A total of 2030 confirmed Plasmodium falciparum isolates were genotyped at codons associated with sulfadoxine/pyrimethamine resistance.

Results: The prevalence of pfdhfr-N51I, C59R and S108N and pfdhps-A437G mutations was consistently high; the prevalence of the pfdhps-K540E mutation was low but increased since its first report in 2008 in the same region, reaching 17.6% by 2015. The pfdhps-A581G mutation increased from ∼4.5% in 2014 to ∼14.0% in 2015 at urban sites while in rural areas it remained low (∼4.0%). The mutations pfdhfr-I164L and pfdhps-A613S were detected for the first time in DRC. Also, 11 (0.8%) isolates revealed the presence of the newly described pfdhps-I431V mutation. Combining pfdhfr and pfdhps alleles, quintuple and sextuple mutations were observed, with the emergence of septuple (IRNI/IAGEGA)- and octuple (IRNI/VAGKGS)-mutant genotypes.

Conclusions: Intermittent preventive treatment using sulfadoxine/pyrimethamine during pregnancy remains warranted in southwestern DRC. However, the expansion of pfdhps-K540E mutation and emergence of mutants that cause higher levels of sulfadoxine/pyrimethamine resistance is concerning and may present a challenge for future preventive interventions in the country.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Alleles
  • Ambulatory Care Facilities / statistics & numerical data
  • Antimalarials / pharmacology*
  • Child
  • Child, Preschool
  • Democratic Republic of the Congo
  • Drug Resistance, Multiple / genetics*
  • Female
  • Genotype
  • Humans
  • Malaria, Falciparum / blood
  • Malaria, Falciparum / drug therapy
  • Male
  • Mutation
  • Plasmodium falciparum / drug effects*
  • Polymorphism, Genetic
  • Prevalence
  • Protozoan Proteins / genetics*
  • Pyrimethamine / pharmacology*
  • Sulfadoxine / pharmacology*
  • Tetrahydrofolate Dehydrogenase / genetics*
  • Young Adult

Substances

  • Antimalarials
  • Protozoan Proteins
  • Sulfadoxine
  • DHFR protein, Plasmodium falciparum
  • Tetrahydrofolate Dehydrogenase
  • Pyrimethamine