A Countrywide Survey of hrp2/3 Deletions and kelch13 Mutations Co-occurrence in Ethiopia

J Infect Dis. 2024 Dec 16;230(6):e1394-e1401. doi: 10.1093/infdis/jiae373.

Abstract

Malaria elimination relies on detection of Plasmodium falciparum histidine-rich proteins 2/3 (HRP2/3) through rapid diagnostic tests (RDTs) and treatment with artemisinin combination therapies (ACTs). Data from the Horn of Africa suggest increasing hrp2/3 gene deletions and ACT partial resistance kelch13 (k13) mutations. To assess this, 233 samples collected during a national survey from 7 regions of Ethiopia were studied for hrp2/3 deletions with droplet digital polymerase chain reaction (ddPCR) and k13 mutations with DNA sequencing. Approximately 22% of the study population harbored complete hrp2/3 deletions by ddPCR. Thirty-two of 44 of k13 single-nucleotide polymorphisms identified were R622I associated with ACT partial resistance. Both hrp2/3 deletions and k13 mutations associated with ACT partial resistance appear to be co-occurring, especially in Northwest Ethiopia. Ongoing national surveillance relying on accurate laboratory methods are required to elaborate the genetic diversity of P. falciparum.

Keywords: artemisinin; histidine-rich protein 2; kelch13; malaria; rapid diagnostic tests.

MeSH terms

  • Antigens, Protozoan* / genetics
  • Antimalarials / therapeutic use
  • Artemisinins* / therapeutic use
  • Drug Resistance / genetics
  • Ethiopia / epidemiology
  • Female
  • Gene Deletion
  • Humans
  • Malaria, Falciparum* / epidemiology
  • Malaria, Falciparum* / parasitology
  • Male
  • Mutation
  • Plasmodium falciparum* / drug effects
  • Plasmodium falciparum* / genetics
  • Polymorphism, Single Nucleotide
  • Protozoan Proteins* / genetics

Substances

  • Protozoan Proteins
  • HRP-2 antigen, Plasmodium falciparum
  • Antigens, Protozoan
  • HRP3 protein, Plasmodium falciparum
  • Artemisinins
  • Antimalarials
  • artemisinin