Discussion

As we near the end of a second decade of widespread artemisinin combination therapy (ACT) use for treating human malaria, there are signs of waning efficacy in some African settings. Evidence to date suggests the parasite factors linked to ACT treatment failure in Asia, such as K13 variants and markers of piperaquine drug failure, have not themselves spread to Africa. Rather, a suite of variant Plasmodium falciparum loci, experimentally linked to reduced artemisinin susceptibility in vitro, are under scrutiny in African parasite populations. These include not only pfk13 variants, but also variant alleles of pfcoronin, pfk10, pfubp1 and pfap2mu. I will present recent molecular, epidemiological and in vitro data and attempt to provide some mechanistic insights that could help us understand the emerging complexity of the genetic polymorphisms underlying reduced artemisinin susceptibility. Finally, the importance of such variant loci in resistance surveillance will be considered.