Mapping the prevalence of molecular markers of Plasmodium falciparum artemisinin partial resistance in Africa: a systematic review and spatiotemporal modelling study.

Plasmodium falciparum kelch13(k13) mutations in Africa signal emerging artemisinin partial resistance (ART-R), endangering malaria control by undermining artemisinin-based combination therapies (ACTs). Sparse surveillance obscures whether rising k13 ART-R prevalence reflects local emergence or geographical expansion. We aimed to model and infer high-resolution spatiotemporal prevalence of k13 ART-R mutations, as well as mdr1 and crt mutations (markers of reduced susceptibility to ACT partner drugs), to inform public health policy.

Malaria is a severe mosquito-borne disease caused predominantly in Africa by the parasite Plasmodium falciparum. For years, the main line of defense against malaria has been Artemisinin-based Combination Therapies (ACTs). ACTs combine a fast-acting artemisinin derivative with a longer-lasting partner drug. However, malaria parasites have developed mutations in a gene called kelch13 (k13), which give them partial resistance to artemisinin—allowing them to linger longer and sometimes survive treatment, leading to disease recurrence and continued transmission. Led by the Bailey Lab with co-first authors PhD students Neeva Young and Cecile Meier Scherling, along with investigators at the University of North Carolina and Imperial College London, this study collected all current data on kelch13 mutations and used advanced modeling techniques to build high-resolution maps to track their emergence and spread. This revealed multiple k13 mutations and independent emergence events, all of which showed rapid outward spread from their origins.  This reinforces the grave concern that artemisinin is becoming compromised across large portions of Africa and heightens fears that additional mutations for artemisinin or partner-drug resistance could significantly undermine treatments and threaten millions of lives.

Full publication located at:  https://pubmed.ncbi.nlm.nih.gov/42413528/