Integrating genomics, epidemiology, and evolutionary dynamics in the study of artemisinin resistance

Background: Artemisinin resistance in Plasmodium falciparum jeopardizes global malaria elimination, particularly with recent emergence in Africa. Objectives: This narrative review synthesizes current evidence on artemisinin resistance to link molecular mechanisms with epidemiological spread, informing public health strategy. Methods: A narrative literature review was conducted using PubMed, Web of Science, Google Scholar, and African Journals Online (AJOL). Peer-reviewed articles published between 2008 and 2025 were included. The review integrated molecular, genomic, and epidemiological studies focusing on kelch13 (k13) mutations, genomic surveillance data, and spatiotemporal models of resistance emergence across malaria-endemic regions. Results: Artemisinin resistance is primarily mediated by kelch13 gene mutations, which increase phosphatidylinositol-3-phosphate (PI3P) levels and enhance ring-stage survival. It has arisen via multiple independent mutations (a soft selective sweep), with distinct regional patterns: established in Southeast Asia and recently independent emergence in Africa. Notably, k13 mutations such as C469Y, A675V, and R561H are increasing in prevalence in Uganda, Rwanda, and neighboring regions. Integrated genomic surveillance improves resistance tracking. Conclusion: Preserving artemisinin efficacy requires coordinated global action, strengthened surveillance, optimized treatment, and robust stewardship. Early genomic signals in Africa provide a critical window for intervention.