Artemisinin-independent inhibitory activity ofArtemisiasp. infusions against differentPlasmodiumstages including relapse-causing hypnozoites

AbstractArtemisinin-based combination therapies (ACT) are the frontline treatments against malaria worldwide. Recently the use of traditional infusions fromArtemisia annua(from which artemisinin is obtained) orA. afra(lacking artemisinin) has been controversially advocated. Such unregulated plant-based remedies are strongly discouraged as they might constitute sub-optimal therapies and promote drug resistance. Here, we conducted the first comparative study of the anti-malarial effects of both plant infusionsin vitroagainst the asexual erythrocytic stages ofP. falciparumand the pre-erythrocytic (i. e., liver) stages of variousPlasmodiumspecies. Low concentrations of either infusion accounted for significant inhibitory activities across every parasite species and stage studied. We show that these antiplasmodial effects were essentially artemisinin-independent and were additionally monitored by observations of the parasite apicoplast and mitochondrion. In particular, the infusions significantly incapacitated sporozoites, and forP. vivaxandP. cynomolgi,disrupted the hypnozoites. This provides the first indication that compounds other than 8-aminoquinolines could be effective antimalarials against relapsing parasites. These observations advocate for further screening to uncover urgently needed novel antimalarial lead compounds.