Abstract

Malaria remains a major public health challenge, disproportionately affecting low- and middle-income countries, 
particularly in sub-Saharan Africa. Although significant progress has been achieved through vector control 
strategies and artemisinin-based combination therapies (ACTs), the spread of drug-resistant Plasmodium strains 
threatens malaria control and elimination efforts. Resistance to chloroquine, sulfadoxine-pyrimethamine, and, 
more recently, artemisinin and its partner drugs has been documented across endemic regions, driven by genetic 
mutations, drug pressure, and inadequate dosing. The emergence of artemisinin resistance, associated with 
mutations in the kelch13 (K13) propeller domain, is of particular concern given the reliance on ACTs as first-line 
therapy. This review synthesizes evidence on the history, mechanisms, and epidemiology of antimalarial drug 
resistance. It also discusses factors contributing to resistance, current therapeutic strategies, and the urgent need 
for surveillance, novel antimalarials, and integrated approaches to sustain malaria control and move toward 
elimination.