Polymorphisms in the Pfcrt, Pfmdr1, and Pfk13 genes of Plasmodium falciparum isolates from southern Brazzaville, Republic of Congo

Sci Rep. 2024 Nov 14;14(1):27988. doi: 10.1038/s41598-024-78670-2.

Abstract

This study aimed to analyze polymorphisms in Pfcrt, Pfmdr1, and Pfk13 genes' markers of resistance to Artemisinin-based combination therapy (ACT), in Plasmodium falciparum isolates from southern Brazzaville, 15 years after the adoption of ACT in the Republic of Congo. A total of 369 microscopy-confirmed malaria-infected individuals were enrolled from March to October 2021 in the community and in health facilities during a cross-sectional study. The K76T mutation in the Pfcrt gene, N86Y and Y184F mutations in the Pfmdr1 gene were investigated using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) while the codons region (1005-1300) of the Pfmdr1gene, and Pfk13 gene were sequenced. The prevalences of K76T, N86Y, Y184F mutations were 26.0%, 6.8%, and 27.7%, respectively. However, no mutations were detected in codons 1034, 1042, and 1246 of the Pfmdr1 gene. None of the mutations previously associated with artemisinin-based resistance were detected in the Pfk13 gene. The results reveal a significant decrease in the prevalence of K76T, N86Y, Y184F mutations, in Plasmodium falciparum isolates following the change of therapeutic policy. As artemisinin resistance is emerging throughout Africa, continued surveillance for early detection of these mutations and relevant partner markers of drug resistance are recommended in the Republic of Congo.

Keywords: Pfcrt; Pfk13; Pfmdr1; Plasmodium falciparum; Polymorphism; Republic of Congo.

MeSH terms

  • Adolescent
  • Adult
  • Antimalarials* / pharmacology
  • Antimalarials* / therapeutic use
  • Artemisinins* / pharmacology
  • Artemisinins* / therapeutic use
  • Child
  • Child, Preschool
  • Congo / epidemiology
  • Cross-Sectional Studies
  • Drug Resistance* / genetics
  • Female
  • Humans
  • Malaria, Falciparum* / drug therapy
  • Malaria, Falciparum* / epidemiology
  • Malaria, Falciparum* / parasitology
  • Male
  • Membrane Transport Proteins* / genetics
  • Middle Aged
  • Multidrug Resistance-Associated Proteins* / genetics
  • Mutation
  • Plasmodium falciparum* / drug effects
  • Plasmodium falciparum* / genetics
  • Plasmodium falciparum* / isolation & purification
  • Polymorphism, Genetic
  • Protozoan Proteins* / genetics
  • Young Adult

Substances

  • Protozoan Proteins
  • Multidrug Resistance-Associated Proteins
  • Membrane Transport Proteins
  • Mdr1 protein, Plasmodium falciparum
  • Antimalarials
  • PfCRT protein, Plasmodium falciparum
  • Artemisinins
  • artemisinin