Updates on k13 mutant alleles for artemisinin resistance in Plasmodium falciparum

J Microbiol Immunol Infect. 2018 Apr;51(2):159-165. doi: 10.1016/j.jmii.2017.06.009. Epub 2017 Jun 29.

Abstract

Background: In the fight against malaria caused by Plasmodium falciparum, the successes achieved by artemisinin were endangered by resistance of the parasites to the drug. Whole genome sequencing approach on artemisinin resistant parasite line discovered k13 gene associated with drug resistance. In vitro and in vivo studies indicated mutations in the k13 gene were linked to the artemisinin resistance.

Methodology: The literatures published after April, 2015 up to December, 2016 on k13 mutant alleles for artemisinin resistance in Plasmodium falciparum and relevant literatures were comprehensively reviewed.

Results: To date, 13 non-synonymous mutations of k13 gene have been observed to have slow parasite clearance. Worldwide mapping of k13 mutant alleles have shown mutants associated with artemisinin resistance were confined to southeast Asia and China and did not invade to African countries. Although in vitro ring stage survival assay of 0-3 h was a recently developed assay, it was useful for rapid detection of artemisinin resistance associated k13 allelic marker in the parasite. Recently, dissemination of k13 mutant alleles was recommended to be investigated by identity of haplotypes. Significant characteristics of well described alleles in the reports were mentioned in this review for the benefit of future studies.

Conclusion: According to the updates in the review, it can be concluded artemisinin resistance does not disseminate to India and African countries within short period whereas regular tracking of these mutants is necessary.

Keywords: Artemisinin resistance; Plasmodium falciparum; Ring stage survival assay; k13 mutant alleles.

Publication types

  • Review

MeSH terms

  • Africa / epidemiology
  • Alleles
  • Antimalarials / pharmacology*
  • Artemisinins / pharmacology*
  • Asia, Southeastern / epidemiology
  • Base Sequence
  • China / epidemiology
  • Drug Resistance / genetics*
  • Genome, Protozoan / genetics
  • Humans
  • India / epidemiology
  • Malaria, Falciparum / drug therapy*
  • Malaria, Falciparum / epidemiology*
  • Malaria, Falciparum / parasitology
  • Plasmodium falciparum / drug effects*
  • Plasmodium falciparum / genetics
  • Plasmodium falciparum / isolation & purification*
  • Polymorphism, Single Nucleotide / genetics
  • Protozoan Proteins / genetics*
  • Sequence Analysis, DNA

Substances

  • Antimalarials
  • Artemisinins
  • Protozoan Proteins