Abstract
The ability to block human-to-mosquito and mosquito-to-human transmission of Plasmodium parasites is fundamental to accomplish the ambitious goal of malaria elimination. The WHO currently recommends only primaquine as a transmission-blocking drug but its use is severely restricted by toxicity in some populations. New, safe and clinically effective transmission-blocking drugs therefore need to be discovered. While natural products have been extensively investigated for the development of chemotherapeutic antimalarial agents, their potential use as transmission-blocking drugs is comparatively poorly explored. Here, we provide a comprehensive summary of the activities of natural products (and their derivatives) of plant and microbial origins against sexual stages of Plasmodium parasites and the Anopheles mosquito vector. We identify the prevailing challenges and opportunities and suggest how these can be mitigated and/or exploited in an endeavor to expedite transmission-blocking drug discovery efforts from natural products.
Highlights
Transmission-BlockingIn spite of the many efforts that have been explored to control malaria, the disease still remains a global health threat [1,2,3]
Sexual development relies on gametocytogenesis of a small fraction of the parasites (~1% of the population) and is characterised by the parasite differentiating through five developmental stages in the human host to produce mature gametocytes able to be transmitted by a feeding mosquito
In line with the innovative thought and approach of the MMV Malaria Boxes [133], we propose the assembling of a box consisting of a set of structurally diverse natural compounds with proven antiplasmodial activity, that could be used as interrogative control set
Summary
In spite of the many efforts that have been explored to control malaria, the disease still remains a global health threat [1,2,3]. As global malaria programs shift from control to elimination and eradication [13], emphasis has been placed on discovery of additional activities associated with new antimalarial candidates Should such candidates be able to kill asexual parasites and be useful therapeutically, but they should have transmission-blocking activity, targeting either sexual stages of Plasmodium parasites (classified by the Medicines for Malaria Venture as target candidate profile 5, TCP-5, [10,14,15]) or the Anopheles mosquito vector (endectocides, TCP-6, [10,16]). The plant species investigated were drawn from 17 different plant families with Asteraceae, Meliaceae and Combretaceae being the most represented (Figure 1b)
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