Mechanisms of Emergence and Spread of Artemisinin and MultiDrug Resistance (AMRED) Malaria Parasites in West Africa

The recent emergence and spread of artemisinin resistant Plasmodium falciparum parasites in Africa pose grave threats to control/elimination programs utilising artemisinin combination therapies (ACTs), the last stronghold for malaria treatments. Over 10 mutations in the parasite’s Kelch 13 gene, K13, have been associated with artemisinin resistance in Africa; particularly, West African parasites harbouring K13 resistant markers also show reduced ex vivo susceptibility to artemisinin. The typical high parasite transmission/recombination rates in West African parasites could rapidly expand these resistant markers on diverse genetic backgrounds, associated with multidrug resistance to partner drugs, and the former first-line treatments, chloroquine and sulphadoxine-pyrimethamine. We are not well equipped, and lack critical knowledge in the evolutionary mechanisms underlying the emergence/spread of these resistant markers, to forestall containment measures in West Africa; how do artemisinin- and multidrug resistant (AMRED) marker combinations influence heterogenous susceptibilities to ACTs in contemporary infections? This study aims to investigate these questions in Ghana, a low-high transmission setting, with ideal parasite populations that harbour resistance markers to most antimalarials. It will innovate genetic tools and approaches to unravel the complexity in resistance evolution and build local capacity in functional genetics studies to detect, track and stop artemisinin resistance.