ResultsĪrtemisinin resistance evolved very rapidly up to extreme, near-lethal doses of artesunate (240 mg/kg), an increase of > 3000-fold in the effective in vivo dose, far above resistance levels reported from the field. The parasite’s response to artemisinins and other available anti-malarial compounds was characterized in vivo and in vitro. falciparum-infected humanized NOD/SCID IL-2Rγ −/−immunocompromised mice, with progressive dose increments as parasites recovered. Intravenous artesunate was administered, using either single flash-doses or a 2-day regimen, to P. falciparum was subjected to discontinuous in vivo artemisinin drug pressure by capitalizing on a novel model that allows for long-lasting, high-parasite loads. Therefore, we must know how fast, and by how much, artemisinin-resistance can strengthen. A Plasmodium falciparum phenotype with delayed parasite clearance during artemisinin-based combination therapy has established in Southeast Asia, and is emerging elsewhere. Humanity has become largely dependent on artemisinin derivatives for both the treatment and control of malaria, with few alternatives available.
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