Ivermectin Impairs the Development of Sexual and Asexual Stages of Plasmodium falciparum In Vitro.

ABSTRACT

Ivermectin is the drug of choice for many parasitic infections, with more than one billion doses being distributed in onchocerciasis programs. The drug has been put into focus recently by the malaria community because of its potential to kill blood-sucking mosquitoes, thereby reducing malaria transmission. However, the activity of ivermectin against the malaria parasite itself has been only partly investigated. This study aimed to investigate the in vitro activity of ivermectin against asexual and sexual stages of Plasmodium falciparum Both asexual and late-stage gametocytes were incubated with ivermectin and control drugs in vitro The growth-inhibiting effects were assessed for asexual stages of different Plasmodium falciparum laboratory strains and culture-adapted clinical isolates using the histidine-rich protein 2 enzyme-linked immunosorbent assay technique. The effect against stage IV/V gametocytes was evaluated based on ATP quantification. Ivermectin showed activities at nanomolar concentrations against asexual stages (50% inhibitory concentration of ∼100 nM) and stage IV/V gametocytes (500 nM) of P. falciparum Stage-specific assays suggested that ivermectin arrests the parasite cycle at the trophozoite stage. Ivermectin might add a feature to its "wonder drug" properties with activity against asexual stages of the malaria parasite Plasmodium falciparum The observed activities might be difficult to reach with current regimens but will be more relevant with future high-dose regimens under investigation. Further studies should be performed to confirm these results in vitro and in vivo.