Abstract

Artemisinin and its derivatives are the cornerstone of global malaria treatment, primarily through artemisinin
based combination therapies (ACTs). These drugs have significantly reduced malaria morbidity and mortality due 
to their rapid parasite clearance and broad efficacy. However, the emergence of artemisinin resistance, first 
detected in Southeast Asia, now poses a critical threat to malaria elimination efforts. Resistance is characterized 
clinically by delayed parasite clearance and is strongly associated with mutations in the Plasmodium falciparum 
kelch13 (PfK13) gene. Beyond PfK13, multiple genetic loci, biochemical adaptations, and physiological 
mechanisms contribute to parasite survival under drug pressure. This review synthesizes current knowledge of 
resistance mechanisms, geographical spread, clinical implications, and strategies to mitigate the threat. Effective 
containment will require continued molecular surveillance, novel therapeutic development, and integrated malaria 
control strategies.