Inhibition of Plasmodium sporogonic stages by ivermectin and other avermectins

Background 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. However, it remains unclear whether ivermectin also exerts a direct action on the parasite’s blood and transmission stages. Methods We 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. Results Our 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. Conclusions Our 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.