K-13 propeller gene polymorphisms isolated between 2014 and 2017 from Cameroonian Plasmodium falciparum malaria patients

PLoS One. 2019 Sep 3;14(9):e0221895. doi: 10.1371/journal.pone.0221895. eCollection 2019.

Abstract

The emergence of artemisinin-resistant parasites since the late 2000s at the border of Cambodia and Thailand poses serious threats to malaria control globally, particularly in Africa which bears the highest malaria transmission burden. This study aimed to obtain reliable data on the current state of the kelch13 molecular marker for artemisinin resistance in Plasmodium falciparum in Cameroon. DNA was extracted from the dried blood spots collected from epidemiologically distinct endemic areas in the Center, Littoral and North regions of Cameroon. Nested PCR products from the Kelch13-propeller gene were sequenced and analyzed on an ABI 3730XL automatic sequencer. Of 219 dried blood spots, 175 were sequenced successfully. We identified six K13 mutations in 2.9% (5/175) of samples, including 2 non-synonymous, the V589I allele had been reported in Africa already and one new allele E612K had not been reported yet. These two non-synonymous mutations were uniquely found in parasites from the Littoral region. One sample showed two synonymous mutations within the kelch13 gene. We also observed two infected samples with mixed K13 mutant and K13 wild-type infection. Taken together, our data suggested the circulation of the non-synonymous K13 mutations in Cameroon. Albeit no mutations known to be associated with parasite clearance delays in the study population, there is need for continuous surveillance for earlier detection of resistance as long as ACTs are used and scaled up in the community.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Antimalarials / pharmacology
  • Artemisinins / pharmacology
  • Cameroon / epidemiology
  • Child
  • Child, Preschool
  • Drug Resistance / genetics
  • Female
  • Genes, Protozoan
  • Humans
  • Kelch Repeat
  • Malaria, Falciparum / epidemiology
  • Malaria, Falciparum / parasitology*
  • Male
  • Mutation
  • Plasmodium falciparum / drug effects
  • Plasmodium falciparum / genetics*
  • Polymorphism, Genetic
  • Prospective Studies
  • Protozoan Proteins / genetics*

Substances

  • Antimalarials
  • Artemisinins
  • Protozoan Proteins
  • artemisinin

Associated data

  • Dryad/10.5061/dryad.1rk753f

Grants and funding

This work was supported by: CEEM, grant awarded PRODESO (Programme Franco-Camerounais pour un Développement Solidaire) fund from the Cameroonian Ministry of Foreign Affairs and the French Ministry of Interior, Overseas France, Territorial Communities and Immigration. FH: sponsor from Natural Science Foundation of Shanghai from China (18ZR1443400) for extracting DNA and sequencing K13.