Artemisininbased

Artemisinin-based combination therapies (ACTs) are the standard treatment for uncomplicated malaria caused by Plasmodium falciparum in many endemic countries. An ACT combines an artemisinin derivative (such as artesunate, artemether, or dihydroartemisinin) with a longer-acting partner drug (for example lumefantrine, mefloquine, amodiaquine, piperaquine). Artemisinin derivatives are fast-acting antimalarials that rapidly reduce parasite biomass, while the partner drug completes parasite clearance and helps prevent the emergence of resistance.

Artemisinin compounds are sesquiterpene lactones containing an endoperoxide. Activation of the endoperoxide by iron yields reactive radicals that damage parasite proteins and membranes. The artemisinin component has a short half-life, hence the necessity of the longer-acting partner to maintain therapeutic levels.

ACTs are the recommended first-line therapy for uncomplicated P. falciparum malaria by WHO and many national programs. They are increasingly used for mixed infections and severe malaria (in conjunction with parenteral artesunate for severe cases).

Resistance concerns: reduced parasite clearance times linked to mutations in the Plasmodium falciparum K13 propeller gene have emerged in parts of Southeast Asia, raising monitoring concerns though ACTs remain effective in many areas. Ongoing surveillance and stewardship are emphasized.

Safety: ACTs are generally well tolerated with common side effects including nausea, dizziness, and transient anemia. Safety in pregnancy is supported for several ACT regimens, but local guidelines should guide use in the first trimester.

History: The artemisinin class was discovered from Artemisia annua by Chinese scientist Tu Youyou in the 1970s; the discovery led to the development of ACTs and earned a Nobel Prize in Physiology or Medicine in 2015.