Authors

Discussion

Artemisinin-based combination therapy (ACT) for malaria has been widely deployed in Africa since 2006. Evidence is starting to accrue that artemether-lumefantrine (AL), the most widely used ACT on the continent, is losing efficacy against Plasmodium falciparum. Published work from the MALACTRES project in Western Kenya and recent papers from Uganda support this view, as does compelling anecdotal data from a clinic in Zambia, which will be presented. AL treatment failure is not associated with the appearance or spread of variant forms of the gene encoding the K13 kelch propeller protein, a key determinant of reduced artemisinin efficacy in Asia. Two other features of reduced artemisinin susceptibility in Asia, slow clearance of parasites measured by exhaustive microscopy over the first 72 hours of treatment in vivo, and parasite growth in vitro after a pulse of 700nM dihydroartemisinin in the ring-stage survival assay (RSA), are not seen in P. falciparum isolates of African-origin. Alternative approaches to studies of ACT efficacy in vivo  and in vitro, developed specifically for Africa, will be presented. Finally, the evidence supporting our current list of candidate markers of reduced susceptibility to artemisinins and ACT partner drugs will be summarised.