London School of Hygiene & Tropical Medicine

Warning signs are emerging of evolution of the major malaria parasite, Plasmodium falciparum towards resistance to Artemisinin, a potent component of Artemisinin Combination Therapies (ACTs) with long-lasting partner drugs [piperaquine (PPQ), amodiaquine (AQ), lumefantrine (LUM) and mefloquine (MQ)]. The report published in the New England Journal of Medicine in September 2021 was from a longitudinal study of responses to intravenous artesunate in 240 malaria patients. The study identified ~6% of patients with increased parasite clearance half-life (>5 hours) and mutations in the Kelch13 gene (https://www.nejm.org/doi/full/10.1056/NEJMoa2101746).

This adds to a previous report of indigenous emergence of artemisinin associated mutations in the Kelch13 gene in P. falciparum isolates in Rwanda (https://www.nature.com/articles/s41591-020-1005-2). Genetic markers associated with resistance to most partner drugs in ACTs are highly prevalent, sparking fears of multidrug resistant malaria in Africa. Africa bears about 94% of the world’s malaria burden, 70% occurring in children under 5 years of age. Resistance to current drugs will spell doom for malaria elimination plans across the continent.