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.
Highlights
Sustainable control and elimination of malaria mainly relies on effective treatment, as well as on the ability to eliminate the dormant forms responsible for the relapses of the widely distributed Plasmodium vivax (Mazier et al, 2009)
Exposure of P. falciparum rings to infusions from either plant for 72 h inhibited their growth in a dose-dependent manner (Fig 1A), with that of A. annua active at slightly lower doses
The investigations of the in vitro anti-malarial efficacy of Artemisia infusions have been essentially conducted with the species A. annua or A. afra, and this exclusively on the erythrocytic stages of P. falciparum parasites (Silva et al, 2012; Suberu et al, 2013; Elfawal et al, 2015)
Summary
Sustainable control and elimination of malaria mainly relies on effective treatment, as well as on the ability to eliminate the dormant forms (hypnozoites) responsible for the relapses of the widely distributed Plasmodium vivax (Mazier et al, 2009). Decoctions of Artemisia-dried leaves have been controversially advocated as cheaper traditional plant-based treatments for malaria Such selfadministered and unregulated treatments are strongly discouraged because of variable and potentially sub-optimal artemisinin content not least as they would promote the emergence of drug resistance (WHO, 2019a). This claim is supported by the purported anti-malarial traditional herbal teas based on the African wormwood Artemisia afra, a species devoid of artemisinin (du Toit & van der Kooy, 2019).
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