Current status of 4-aminoquinoline resistance markers 18 years after cessation of chloroquine use for the treatment of uncomplicated falciparum malaria in the littoral coastline region of Cameroon

Pathog Glob Health. 2022 Dec;116(8):509-514. doi: 10.1080/20477724.2022.2056674. Epub 2022 Mar 31.

Abstract

The onset and rapid spread of chloroquine resistance and the introduction of amodiaquine for the treatment of uncomplicated malaria in Cameroon have influenced the proportion of Plasmodium falciparum sensitive and resistant alleles related to 4-aminoquinoline drugs. This study was undertaken to determine the prevalence of resistance markers to antimalarial 4-aminoquinolines in Douala in the Littoral Region, and Buea in the South West Region in June 2020. Dry blood spots were prepared from malaria microscopy positive cases and used for parasite DNA extraction by chelex-100 method. Plasmodium species identification was carried out by PCR amplification/agarose gel electrophoresis of 18srRNA. The Pfcrt and Pfmdr1 genes were amplified by PCR followed by restriction digestion. The prevalence of single nucleotide polymorphisms (SNPs) was compared between study sites and with previous studies carried out between 2003-2005 and 2009-2011 using the Chi square test. The results showed that Plasmodium falciparum was the dominant species occurring as mono-infections (84.6%). The wild type K76 allele of the Pfcrt gene was found in 74.9% of isolates while the wild N86, Y184 and D1246 alleles of the Pfmdr1 gene were found respectively in 87.2%, 89.6% and 100% of field isolates. The results showed a significant reduction in the mutant alleles compared to results obtained in 2003-2005 and 2009-2013. The KNYD haplotype was observed to be the most prevalent. The results indicated that there is a gradual erosion of the mutant Pfcrt and Pfmdr1 genotype and a gradual return to the sensitive P. falciparum genotype in Cameroon.

Keywords: 4-aminoquinoline; Plasmodium falciparum; alleles; buea; drug resistance; pfcrt; pfmdr1.

MeSH terms

  • Antimalarials* / pharmacology
  • Antimalarials* / therapeutic use
  • Cameroon / epidemiology
  • Chloroquine / pharmacology
  • Chloroquine / therapeutic use
  • Drug Resistance / genetics
  • Humans
  • Malaria, Falciparum* / drug therapy
  • Malaria, Falciparum* / epidemiology
  • Malaria, Falciparum* / parasitology
  • Membrane Transport Proteins / genetics
  • Multidrug Resistance-Associated Proteins / genetics
  • Plasmodium falciparum
  • Protozoan Proteins / genetics

Substances

  • 4-aminoquinoline
  • Antimalarials
  • Chloroquine
  • Membrane Transport Proteins
  • Multidrug Resistance-Associated Proteins
  • Protozoan Proteins