Insights into the factors contributing to artemisinin resistance in Plasmodium falciparum

Artemisinin (ART)-based combination therapies are instrumental in reducing the burden of malaria worldwide. However, the emergence of ART resistance (ARTR) threatens the elimination of malaria. Understanding the mechanisms regulating ARTR is essential for developing effective strategies to prevent malaria. While various mutations in the Plasmodium falciparum Kelch13 gene, particularly in the propeller domain, are linked to ARTR, data from in vitro and field-based studies indicate that additional genetic determinants and pathways, including reduced haemoglobin endocytosis, increased phosphatidylinositol-3-kinase levels, activation of unfolded protein response and polymorphism in various other genes, also contribute to the development of resistance. This narrative provides an overview of the molecular mechanisms related to ARTR.