Artemisinin and its derivatives (ART) are crucial first-line antimalarial drugs that rapidly clear parasitemia, but recrudescences of the infection frequently follow ART monotherapy. For this reason, ART must be used in combination with one or more partner drugs that ensure complete cure. The ability of malaria parasites to survive ART monotherapy may relate to an innate growth bistability phenomenon whereby a fraction of the drug-exposed population enters into metabolic quiescence (dormancy) as persister forms. Characterization of the events that underlie entry and waking from persistence may lead to lasting breakthroughs in malaria chemotherapy that can prevent recrudescences and protect the future of ART-based combination therapies.
Keywords: Plasmodium falciparum K13 propeller; artemisinin-based combination therapy (ACT); dormancy; growth bistability; persisters; recrudescence.
Published by Elsevier Ltd.