Transmission blocking activity of Azadirachta indica and Guiera senegalensis extracts on the sporogonic development of Plasmodium falciparum field isolates in Anopheles coluzzii mosquitoes

Abstract

BackgroundTargeting the stages of the malaria parasites responsible for transmission from the human host to the mosquito vector is a key pharmacological strategy for malaria control. Research efforts to identify compounds that are active against these stages have significantly increased in recent years. However, at present, only two drugs are available, namely primaquine and artesunate, which reportedly act on late stage gametocytes.MethodsIn this study, we assessed the antiplasmodial effects of 5 extracts obtained from the neem tree Azadirachta indica and Guiera senegalensis against the early vector stages of Plasmodium falciparum, using field isolates. In an ex vivo assay gametocytaemic blood was supplemented with the plant extracts and offered to Anopheles coluzzii females by membrane feeding. Transmission blocking activity was evaluated by assessing oocyst prevalence and density on the mosquito midguts.ResultsInitial screening of the 5 plant extracts at 250 ppm revealed transmission blocking activity in two neem preparations. Up to a concentration of 70 ppm the commercial extract NeemAzal® completely blocked transmission and at 60 ppm mosquitoes of 4 out of 5 replicate groups remained uninfected. Mosquitoes fed on the ethyl acetate phase of neem leaves at 250 ppm showed a reduction in oocyst prevalence of 59.0% (CI95 12.0 - 79.0; p < 10-4) and in oocyst density of 90.5% (CI95 86.0 - 93.5; p < 10-4 ), while the ethanol extract from the same plant part did not exhibit any activity. No evidence of transmission blocking activity was found using G. senegalensis ethyl acetate extract from stem galls.ConclusionsThe results of this study highlight the potential of antimalarial plants for the discovery of novel transmission blocking molecules, and open up the potential of developing standardized transmission blocking herbal formulations as malaria control tools to complement currently used antimalarial drugs and combination treatments.

In vitro inhibition of Plasmodium falciparum early and late stage gametocyte viability by extracts from eight traditionally used South African plant species

“…V. amygdalina gametocytocidal activity was demonstrated in vivo with the active principles identified as the sesquiterpene lactones vernadalol and vernolide . G. senegalensis did not have any transmission blocking properties (Yerbanga et al, 2014).…”

“…that are structurally similar to those known to be gametocytocidal either in vitro, in vivo or ex vivo Adjalley et al, 2011;D'Alessandro et al, 2013;Duffy and Avery, 2013;Jones et al, 1994;Lucantoni et al, 2013Lucantoni et al, , 2010Saenz et al, 2013;Sun et al, 2013;Yerbanga et al, 2014). Using these two parallel selection strategies, the ethnobotanical set was narrowed down to a hundred plant species from which eight were collected and screened in the current study.…”

“…By contrast, less effort has been channeled towards examining extracts of plants for their activity against the sexual stages of the parasite. Currently, only three plant species have been directly screened for their malaria transmission blocking capacity: Azadirachta indica (Meliaceae) (Dhar et al, 1998;Jones et al, 1994;Lucantoni et al, 2010;Udeinya et al, 2006Udeinya et al, , 2008Yerbanga et al, 2014), Vernonia amygdalina (Asteraceae) and Guiera senegalensis (Combretaceae) (Yerbanga et al, 2014). A. indica has been comprehensively studied and…”

“…shown to have good gametocytocidal activity in vitro (Dhar et al, 1998;Jones et al, 1994;Udeinya et al, 2008Udeinya et al, , 2006, in vivo (Lucantoni et al, 2010) and ex vivo (Yerbanga et al, 2014). The active components are a diverse range of limonoid compounds (Jones et al, 1994;Lucantoni et al, 2010;Yerbanga et al, 2014).…”

“…The active components are a diverse range of limonoid compounds (Jones et al, 1994;Lucantoni et al, 2010;Yerbanga et al, 2014). V. amygdalina gametocytocidal activity was demonstrated in vivo with the active principles identified as the sesquiterpene lactones vernadalol and vernolide .…”