Molecular insights into artemisinin resistance in Plasmodium falciparum: An updated review

Wihda Aisarul Azmi, Andita Fitri Mutiara Rizki, Yenny Djuardi, I. Made Artika, Josephine Elizabeth Siregar

Research output: Contribution to journalReview articlepeer-review

4 Citations (Scopus)

Abstract

Malaria still poses a major burden on human health around the world, especially in endemic areas. Plasmodium resistance to several antimalarial drugs has been one of the major hindrances in control of malaria. Thus, the World Health Organization recommended artemisinin-based combination therapy (ACT) as a front-line treatment for malaria. The emergence of parasites resistant to artemisinin, along with resistant to ACT partner drugs, has led to ACT treatment failure. The artemisinin resistance is mostly related to the mutations in the propeller domain of the kelch13 (k13) gene that encodes protein Kelch13 (K13). The K13 protein has an important role in parasite reaction to oxidative stress. The most widely spread mutation in K13, with the highest degree of resistance, is a C580Y mutation. Other mutations, which are already identified as markers of artemisinin resistance, are R539T, I543T, and Y493H. The objective of this review is to provide current molecular insights into artemisinin resistance in Plasmodium falciparum. The trending use of artemisinin beyond its antimalarial effect is described. Immediate challenges and future research directions are discussed. Better understanding of the molecular mechanisms underlying artemisinin resistance will accelerate implementation of scientific findings to solve problems with malarial infection.

Original languageEnglish
Article number105460
JournalInfection, Genetics and Evolution
Volume112
DOIs
Publication statusPublished - Aug 2023

Keywords

  • Artemisinin
  • Artemisinin resistance
  • Artemisinin-based combination therapy
  • K13
  • Molecular marker
  • Plasmodium falciparum

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