Artemisinin-independent inhibitory activity of <i>Artemisia</i> sp. infusions against different <i>Plasmodium</i> stages including relapse-causing hypnozoites
Kutub Ashraf, Shahin Tajeri, Christophe-Sébastien Arnold, Nadia Amanzougaghene, Jean‐François Franetich, Amélie Vantaux, Valérie Soulard, Mallaury Bordessoulles, Guillaume Cazals, Teun Bousema, Geert‐Jan van Gemert, Roger Le Grand, Nathalie Dereuddre‐Bosquet, Jean-Christophe Barale, Benoît Witkowski, Georges Snounou, Romain Duval, Cyrille Y. Botté, Dominique Mazier
Abstract
Artemisinin-based combination therapies (ACT) are the frontline treatments against malaria worldwide. Recently the use of traditional infusions from Artemisia annua (from which artemisinin is obtained) or Artemisia 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 infusions in vitro against the asexual erythrocytic stages of Plasmodium falciparum and the pre-erythrocytic (i.e., liver) stages of various Plasmodium species. 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 for Plasmodium vivax and P. 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.