Abstract

Artemisinin-based combination therapies have remained the cornerstone of global malaria treatment for over two 
decades, achieving remarkable reductions in morbidity and mortality. However, the emergence and spread of 
artemisinin-resistant Plasmodium falciparum strains in Southeast Asia threatens to undermine these gains and poses 
substantial challenges to malaria elimination efforts worldwide. This review examined the molecular mechanisms 
underlying artemisinin resistance in Plasmodium falciparum, evaluated current surveillance strategies employed in 
Southeast Asia, and assessed the implications for treatment efficacy and public health responses. A comprehensive 
synthesis of peer-reviewed literature on artemisinin resistance mechanisms, genetic markers, clinical manifestations, 
and epidemiological surveillance approaches was conducted. Mutations in the Kelch propeller domain, particularly 
K13, constituted the primary genetic determinant of artemisinin resistance, mediating delayed parasite clearance 
through enhanced cellular stress responses and altered hemoglobin metabolism. Resistance had spread across the 
Greater Mekong Subregion with distinct geographical clustering patterns. Molecular surveillance utilizing 
polymerase chain reaction-based detection of resistance markers, coupled with therapeutic efficacy studies and in 
vitro susceptibility testing, provided essential data for treatment policy adaptation. The emergence of partner drug 
resistance threatened the efficacy of artemisinin-based combination therapy. Integrated molecular and clinical 
surveillance frameworks were essential for tracking resistance evolution, informing treatment guidelines, and 
supporting malaria elimination strategies in endemic regions.