Prevalence of the Pfdhfr and Pfdhps mutations among asymptomatic pregnant women in Southeast Nigeria

Parasitol Res. 2018 Mar;117(3):801-807. doi: 10.1007/s00436-018-5754-5. Epub 2018 Jan 13.

Abstract

Sulfadoxine-pyrimethamine (SP) is the recommended drug for intermittent preventive treatment of malaria in pregnancy in most of sub-Saharan Africa. Resistance to SP is related to mutations in the dhfr and dhps gene of Plasmodium falciparum. This study determined the prevalence of Pfdhfr and Pfdhps polymorphisms found in asymptomatic pregnant women attending antenatal care in Calabar, Nigeria. From October 2013 to November 2014, asymptomatic pregnant women attending antenatal care clinics were enrolled after obtaining informed consent. Malaria diagnosis testing was done using thick and thin smears. Dried blood spot filter papers were collected. Parasite DNA was extracted from the filter papers using a chelex extraction. Extraction was followed by nested PCR and restriction enzyme digestion. P. falciparum infection was detected by microscopy in 7% (32/459) participants. Twenty-eight P. falciparum isolates were successfully genotyped. In the Pfdhfr gene, the triple mutation was almost fixed; S108N mutation was (100%), N51I (93%) and C59R mutations (93%), whereas the I164L mutation was absent. The prevalence of Pfdhps S436A, A437G, A581G and A613S mutations was 82.1% (23/28), 96.4% (27/28), 71.4% (20/28) and 71.4% (20/28) respectively. The K540E mutation was absent. The prevalence of the Pfdhfr triple mutation IRNI was 92.9% (26/28). The efficacy of SP as IPTp in Southeast Nigeria may be severely threatened. The continuous monitoring of SP molecular markers of resistance is required to assess thresholds. The evaluation of alternative preventive treatment strategies and drug options for preventing malaria in pregnancy may be necessary.

Keywords: Antenatal clinic; Malaria; Molecular markers; SP resistance.

MeSH terms

  • Adult
  • Antimalarials / administration & dosage
  • Drug Combinations
  • Female
  • Genotype
  • Humans
  • Malaria, Falciparum / parasitology*
  • Mutation Rate
  • Mutation*
  • Nigeria
  • Plasmodium falciparum / enzymology
  • Plasmodium falciparum / genetics*
  • Plasmodium falciparum / isolation & purification
  • Polymerase Chain Reaction
  • Polymorphism, Genetic
  • Pregnancy
  • Pregnancy Complications, Parasitic / parasitology*
  • Protozoan Proteins / genetics*
  • Pyrimethamine / administration & dosage
  • Sulfadoxine / administration & dosage
  • Tetrahydrofolate Dehydrogenase / genetics*

Substances

  • Antimalarials
  • Drug Combinations
  • Protozoan Proteins
  • fanasil, pyrimethamine drug combination
  • Sulfadoxine
  • DHFR protein, Plasmodium falciparum
  • Tetrahydrofolate Dehydrogenase
  • Pyrimethamine