Abstract
BackgroundThe transmissible forms of Plasmodium parasites result from a process of sporogony that takes place inside their obligatory mosquito vector and culminates in the formation of mammalian-infective parasite forms. Ivermectin is a member of the avermectin family of endectocides, which has been proposed to inhibit malaria transmission due its insecticidal effect. However, it remains unclear whether ivermectin also exerts a direct action on the parasite’s blood and transmission stages.MethodsWe employed a rodent model of infection to assess the impact of ivermectin treatment on P. berghei asexual and sexual blood forms in vivo. We then made use of a newly established luminescence-based methodology to evaluate the activity of ivermectin and other avermectins against the sporogonic stages of P. berghei parasites in vitro independent of their role on mosquito physiology.ResultsOur results show that whereas ivermectin does not affect the parasite’s parasitemia, gametocytemia or exflagellation in the mammalian host, several members of the avermectin family of compounds exert a strong inhibitory effect on the generation and development of P. berghei oocysts.ConclusionsOur results shed light on the action of avermectins against Plasmodium transmission stages and highlight the potential of these compounds to help prevent the spread of malaria.
Highlights
The transmissible forms of Plasmodium parasites result from a process of sporogony that takes place inside their obligatory mosquito vector and culminates in the formation of mammalian-infective parasite forms
In vitro activity of avermectins against P. berghei sporogonic development We sought to clarify whether the proposed transmission-reducing activity of ivermectin would include a direct action of the drug on the parasite’s transmission stages in the mosquito or if it would result solely from its effect on the mosquito
Our results suggest that the impact of ivermectin on Plasmodium transmission does not result from an inhibition of Plasmodium spp. transmissible forms in the mammalian host, and stems solely from its effect during the mosquito stage of infection
Summary
The transmissible forms of Plasmodium parasites result from a process of sporogony that takes place inside their obligatory mosquito vector and culminates in the formation of mammalian-infective parasite forms. Ivermectin is a member of the avermectin family of endectocides, which has been proposed to inhibit malaria transmission due its insecticidal effect. It remains unclear whether ivermectin exerts a direct action on the parasite’s blood and transmission stages. Malaria is a parasitic disease caused by Plasmodium parasites that are transmitted to their mammalian hosts by the bites of infected female Anopheles mosquitoes. Plasmodium sporozoites are injected by infected Anopheles mosquitoes into a mammalian host, homing to the liver, where they replicate into thousands of bloodinfective merozoites [2].While most merozoites cyclically. The identification of new compounds that have a broad spectrum of action, long half-life and strong inhibitory activity remains a priority in the fight against malaria
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