An overview of artemisinin-resistant malaria and associated Pfk13 gene mutations in Central Africa

Malaria caused by Plasmodium falciparum is one of the deadliest and most common tropical infectious diseases. However, the emergence of artemisinin drug resistance associated with the parasite’s Pfk13 gene, threatens the public health of individual countries as well as current efforts to reduce malaria burdens globally. It is of concern that artemisinin-resistant parasites may be selected or have already emerged in Africa. This narrative review aims to evaluate the published evidence concerning validated, candidate, and novel Pfk13 polymorphisms in ten Central African countries. Results show that six validated non-synonymous polymorphisms (M476I, R539T, P553L, R561H, P574L and C580Y), therefore directly associated with a delayed therapy response, have been reported in the region. Also, three Pfk13 polymorphisms associated to artemisinin resistance but not validated (C469F, P527H and N537D) have been reported. Furthermore, several non-validated mutations have been observed in Central Africa, and one allele A578S, is commonly found in different countries, although additional molecular and biochemical studies are needed to investigate whether those mutations alter artemisinin effects. This information is discussed in the context of biochemical and genetic aspects of Pfk13, and related to the regional malaria epidemiology of Central African countries.