Abstract
ABSTRACTAvermectins are powerful endectocides with an established potential to reduce the incidence of vector-borne diseases. Here, we show that several avermectins inhibit the hepatic stage of Plasmodium infection in vitro. Notably, ivermectin potently inhibits liver infection in vivo by impairing parasite development inside hepatocytes. This impairment has a clear impact on the ensuing blood stage parasitemia, reducing disease severity and enhancing host survival. Ivermectin has been proposed as a tool to control malaria transmission because of its effects on the mosquito vector. Our study extends the effect of ivermectin to the early stages of mammalian host infection and supports the inclusion of this multipurpose drug in malaria control strategies.
Highlights
Avermectins are powerful endectocides with an established potential to reduce the incidence of vector-borne diseases
These results provide further support for the potential of ivermectin, a drug that is already employed in mass drug administration (MDA) in regions where malaria is endemic and has an established impact on malaria transmission, as a multipurpose, multistage tool for malaria control
Our results show that the impairment of liver parasite development caused by ivermectin treatment affects the onset of blood parasitemia (Fig. 3D) and, most importantly, has a clear impact on host survival, with 80% of the treated mice surviving for 10 days, compared with all of the control mice dying with symptoms of experimental cerebral malaria (ECM) within the same period (Fig. 3E)
Summary
Avermectins are powerful endectocides with an established potential to reduce the incidence of vector-borne diseases. Avermectins are a family of macrocyclic lactones that includes compounds presenting a best-in-class antiparasitic activity and a strong insecticidal effect [3] Their impact on vector populations led to the suggestion of a potential role for avermectins in reducing the incidence of vector-borne disease [4]. Ivermectin has emerged as a potential tool for malaria control [4, 8,9,10], given its insecticidal effect [11,12,13,14,15,16], its ability to inhibit Plasmodium falciparum sporogony [17], its inhibitory effect on the blood stages of Plasmodium berghei (in vivo) and P. falciparum (in vitro) [18], and its ability to disrupt parasite transmission [19,20,21]. These results provide further support for the potential of ivermectin, a drug that is already employed in mass drug administration (MDA) in regions where malaria is endemic and has an established impact on malaria transmission, as a multipurpose, multistage tool for malaria control
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