Prevalence of Plasmodium falciparum Pfcrt and Pfmdr1 alleles in settings with different levels of Plasmodium vivax co-endemicity in Ethiopia

Int J Parasitol Drugs Drug Resist. 2019 Dec:11:8-12. doi: 10.1016/j.ijpddr.2019.09.002. Epub 2019 Sep 9.

Abstract

Plasmodium falciparum and P. vivax co-exist at different endemicity levels across Ethiopia. For over two decades Artemether-Lumefantrine (AL) is the first line treatment for uncomplicated P. falciparum, while chloroquine (CQ) is still used to treat P. vivax. It is currently unclear whether a shift from CQ to AL for P. falciparum treatment has implications for AL efficacy and results in a reversal of mutations in genes associated to CQ resistance, given the high co-endemicity of the two species and the continued availability of CQ for the treatment of P. vivax. This study thus assessed the prevalence of Pfcrt-K76T and Pfmdr1-N86Y point mutations in P. falciparum. 18S RNA gene based nested PCR confirmed P. falciparum samples (N = 183) collected through community and health facility targeted cross-sectional surveys from settings with varying P. vivax and P. falciparum endemicity were used. The proportion of Plasmodium infections that were P. vivax was 62.2% in Adama, 41.4% in Babile, 30.0% in Benishangul-Gumuz to 6.9% in Gambella. The Pfcrt-76T mutant haplotype was observed more from samples with higher endemicity of P. vivax as being 98.4% (61/62), 100% (31/31), 65.2% (15/23) and 41.5% (22/53) in samples from Adama, Babile, Benishangul-Gumuz and Gambella, respectively. However, a relatively higher proportion of Pfmdr1-N86 allele (77.3-100%) were maintained in all sites. The observed high level of the mutant Pfcrt-76T allele in P. vivax co-endemic sites might require that utilization of CQ needs to be re-evaluated in settings co-endemic for the two species. A country-wide assessment is recommended to clarify the implication of the observed level of variation in drug resistance markers on the efficacy of AL-based treatment against uncomplicated P. falciparum malaria.

Keywords: Artemether-Lumefantrine; Artemisinin resistance; Drug resistance; Ethiopia; Pfcrt; Pfmdr.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Alleles
  • Antimalarials / pharmacology
  • Antimalarials / therapeutic use
  • Artemether, Lumefantrine Drug Combination / pharmacology
  • Artemether, Lumefantrine Drug Combination / therapeutic use
  • Child
  • Chloroquine / pharmacology
  • Chloroquine / therapeutic use
  • Drug Resistance
  • Endemic Diseases
  • Ethiopia / epidemiology
  • Female
  • Haplotypes
  • Humans
  • Malaria, Falciparum / complications
  • Malaria, Falciparum / drug therapy
  • Malaria, Falciparum / epidemiology
  • Malaria, Falciparum / parasitology
  • Malaria, Vivax / complications
  • Malaria, Vivax / drug therapy
  • Malaria, Vivax / epidemiology
  • Malaria, Vivax / parasitology
  • Male
  • Membrane Transport Proteins / genetics*
  • Multidrug Resistance-Associated Proteins / genetics*
  • Plasmodium falciparum / classification
  • Plasmodium falciparum / genetics*
  • Plasmodium falciparum / physiology
  • Plasmodium vivax / classification
  • Plasmodium vivax / genetics*
  • Plasmodium vivax / physiology
  • Point Mutation
  • Polymorphism, Genetic
  • Prevalence
  • Protozoan Proteins / genetics*
  • Young Adult

Substances

  • Antimalarials
  • Artemether, Lumefantrine Drug Combination
  • Mdr1 protein, Plasmodium falciparum
  • Membrane Transport Proteins
  • Multidrug Resistance-Associated Proteins
  • PfCRT protein, Plasmodium falciparum
  • Protozoan Proteins
  • Chloroquine