Frequency of chloroquine-resistant haplotype of Plasmodium falciparum (CVIET) in Ibadan, Southwest Nigeria 17 years post-chloroquine withdrawal

Acta Trop. 2024 Dec:260:107435. doi: 10.1016/j.actatropica.2024.107435. Epub 2024 Oct 15.

Abstract

The replacement of chloroquine with artemisinin-based combination therapies (ACTs) for over a decade has had varying impacts on the ability of the malaria parasite to sustain its chloroquine resistance prowess in different malaria-endemic regions. We evaluated the frequency of Plasmodium falciparum chloroquine resistance transporter (PfCRT) mutations in Ibadan, Nigeria 17 years after the replacement of chloroquine with ACTs for malaria treatment. Fragments of PfCRT gene from genomic DNA of microscopically confirmed P. falciparum-infected patients were amplified and sequenced. There were 19% CVIET mutant and 81% CVMNK wild-type haplotypes on residues 72-76. A220S change were found in 16.7% of samples occurring concurrently with the CVIET haplotype, while a Q271E mutation occurred in a PfCRT wild-type isolate. The reduced prevalence of the PfCRT mutant alleles in this study compared to previous reports suggests a gradual disappearance of chloroquine-resistant malaria parasites following reduced drug pressure. It may also be a result of fitness demand on the parasites in attempts to evolve resistance against the current first-line regimen. However, evaluating the prevalence of other chloroquine resistance markers such as Plasmodium falciparum multidrug resistance 1 gene mutations in this population, and a more robust sample size will help to consolidate these findings.

Keywords: Allele frequency; Chloroquine resistance; Mutations; Plasmodium falciparum.

MeSH terms

  • Adolescent
  • Adult
  • Antimalarials* / pharmacology
  • Antimalarials* / therapeutic use
  • Child
  • Chloroquine* / pharmacology
  • Chloroquine* / therapeutic use
  • DNA, Protozoan / genetics
  • Drug Resistance* / genetics
  • Female
  • Haplotypes*
  • Humans
  • Malaria, Falciparum* / drug therapy
  • Malaria, Falciparum* / epidemiology
  • Malaria, Falciparum* / parasitology
  • Male
  • Membrane Transport Proteins* / genetics
  • Nigeria / epidemiology
  • Plasmodium falciparum* / drug effects
  • Plasmodium falciparum* / genetics
  • Protozoan Proteins* / genetics
  • Sequence Analysis, DNA

Substances

  • Chloroquine
  • Membrane Transport Proteins
  • PfCRT protein, Plasmodium falciparum
  • Protozoan Proteins
  • Antimalarials
  • DNA, Protozoan