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Artemisinin tolerance (resistance) and threat of multidrug resistant malaria in Africa

Warning signs emerging of evolution of major malaria parasite

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.

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