Artemisinin-independent inhibitory activity of Artemisia sp. infusions against different Plasmodium stages including relapse-causing hypnozoites

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 A. afra (lacking artemisinin) has been controversially advocated. Such unregulated plant-based...

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Published inbioRxiv
Main Authors Kutub Ashraf, Tajeri, Shahin, Christophe-Sébastien Arnold, Amanzougaghene, Nadia, Jean-François Franetich, Vantaux, Amélie, Soulard, Valérie, Bordessoulles, Mallaury, Cazals, Guillaume, Bousema, Teun, Geert-Jan Van Gemert, Roger Le Grand, Dereuddre-Bosquet, Nathalie, Barale, Jean-Christophe, Witkowski, Benoit, Snounou, Georges, Duval, Romain, Botté, Cyrille, Mazier, Dominique
Format Paper
LanguageEnglish
Published Cold Spring Harbor Cold Spring Harbor Laboratory Press 11.08.2021
Subjects
Antimalarial agents
Antiprotozoal agents
Artemisia afra
Artemisia annua
Artemisinin
Drug resistance
Erythrocytes
Malaria
Parasites
Plasmodium falciparum
Sporozoites
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Summary: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 A. 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 P. 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 P. 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. Competing Interest Statement The authors have declared no competing interest.
DOI:10.1101/2021.08.10.455849