Genetically Determined Response to Artemisinin Treatment in Western Kenyan Plasmodium falciparum Parasites

PLoS One. 2016 Sep 9;11(9):e0162524. doi: 10.1371/journal.pone.0162524. eCollection 2016.

Abstract

Genetically determined artemisinin resistance in Plasmodium falciparum has been described in Southeast Asia. The relevance of recently described Kelch 13-propeller mutations for artemisinin resistance in Sub-Saharan Africa parasites is still unknown. Southeast Asia parasites have low genetic diversity compared to Sub-Saharan Africa, where parasites are highly genetically diverse. This study attempted to elucidate whether genetics provides a basis for discovering molecular markers in response to artemisinin drug treatment in P. falciparum in Kenya. The genetic diversity of parasites collected pre- and post- introduction of artemisinin combination therapy (ACT) in western Kenya was determined. A panel of 12 microsatellites and 91 single nucleotide polymorphisms (SNPs) distributed across the P. falciparum genome were genotyped. Parasite clearance rates were obtained for the post-ACT parasites. The 12 microsatellites were highly polymorphic with post-ACT parasites being significantly more diverse compared to pre-ACT (p < 0.0001). The median clearance half-life was 2.55 hours for the post-ACT parasites. Based on SNP analysis, 15 of 90 post-ACT parasites were single-clone infections. Analysis revealed 3 SNPs that might have some causal association with parasite clearance rates. Further, genetic analysis using Bayesian tree revealed parasites with similar clearance phenotypes were more closely genetically related. With further studies, SNPs described here and genetically determined response to artemisinin treatment might be useful in tracking artemisinin resistance in Kenya.

MeSH terms

  • Antimalarials / pharmacology*
  • Artemisinins / pharmacology*
  • Bayes Theorem
  • Genetic Variation / genetics
  • Genotype
  • Humans
  • Kenya
  • Microsatellite Repeats / genetics
  • Phylogeny
  • Plasmodium falciparum / classification
  • Plasmodium falciparum / drug effects
  • Plasmodium falciparum / genetics*
  • Polymorphism, Single Nucleotide / genetics
  • Protozoan Proteins / genetics
  • Protozoan Proteins / metabolism

Substances

  • Antimalarials
  • Artemisinins
  • Protozoan Proteins

Grants and funding

This work was supported by the Armed Forces Health Surveillance Center, Division of Global Emerging Infections Surveillance and Response System Operations. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.