A cross-sectional survey of Plasmodium falciparum pfcrt mutant haplotypes in the Democratic Republic of Congo

Am J Trop Med Hyg. 2014 Jun;90(6):1094-7. doi: 10.4269/ajtmh.13-0378. Epub 2014 Apr 14.

Abstract

In the Democratic Republic of the Congo (DRC), artesunate-amodiaquine is first-line therapy for falciparum malaria; little is known about the prevalence of molecular markers of parasite drug resistance. Across the DRC, we genotyped 166 parasites in Plasmodium falciparum chloroquine resistance transporter (pfcrt) using polymerase chain reaction (PCR) and sequencing. Of these parasites, 73 (44%) parasites were pure wild-type CVMNK, 55 (31%) parasites were chloroquine-resistant CVIET: , 35 (21.1%) parasites were mixed CVMNK and CVIET: , and 3 parasites were other genotypes. Ninety-two infections (55.4%) harbored the pfcrt K76T: substitution that is highly correlated with chloroquine failure. The amodiaquine-resistant S: VMNT: haplotype was absent. Geographically, pfcrt haplotypes were not clearly clustered. Chloroquine accounted for 19.4% of antimalarial use, and amodiaquine accounted for 15.3% of antimalarial use; there were no associations between drug use and mutant haplotype prevalence. In the DRC, our molecular survey indicates that resistance to chloroquine is substantial but that resistance to amodiaquine is absent. These contrasting findings highlight the need for molecular surveillance of drug resistance to inform malaria control policies.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amodiaquine / pharmacology*
  • Amodiaquine / therapeutic use
  • Animals
  • Antimalarials / pharmacology*
  • Antimalarials / therapeutic use
  • Artemisinins / pharmacology*
  • Artemisinins / therapeutic use
  • Chloroquine / pharmacology*
  • Chloroquine / therapeutic use
  • Cross-Sectional Studies
  • DNA, Protozoan / chemistry
  • DNA, Protozoan / genetics
  • Democratic Republic of the Congo / epidemiology
  • Drug Combinations
  • Drug Resistance
  • Genotype
  • Haplotypes
  • Malaria, Falciparum / drug therapy
  • Malaria, Falciparum / epidemiology*
  • Membrane Transport Proteins / genetics*
  • Mutation
  • Plasmodium falciparum / drug effects
  • Plasmodium falciparum / genetics*
  • Polymerase Chain Reaction
  • Prevalence
  • Protozoan Proteins / genetics*
  • Sequence Analysis, DNA

Substances

  • Antimalarials
  • Artemisinins
  • DNA, Protozoan
  • Drug Combinations
  • Membrane Transport Proteins
  • PfCRT protein, Plasmodium falciparum
  • Protozoan Proteins
  • amodiaquine, artesunate drug combination
  • Amodiaquine
  • Chloroquine