Plant extracts for developing mosquito larvicides: From laboratory to the field, with insights on the modes of action.

In the last decades, major research efforts have been done to investigate the insecticidal activity of plant-based products against mosquitoes. This is a modern and timely challenge in parasitology, aimed to reduce the frequent overuse of synthetic pesticides boosting resistance development in mosquitoes and causing serious threats to human health and environment. This review covers the huge amount of literature available on plant extracts tested as mosquito larvicides, particularly aqueous and alcoholic ones, due to their easy formulation in water without using surfactants. We analysed results obtained on more than 400 plant species, outlining that 29 of them have outstanding larvicidal activity (i.e., LC50 values below 10 ppm) against major vectors belonging to the genera Anopheles, Aedes and Culex, among others. Furthermore, synergistic and antagonistic effects between plant extracts and conventional pesticides, as well as among selected plant extracts are discussed. The efficacy of pure compounds isolated from the most effective plant extracts and - when available - their mechanism of action, as well as the impact on non-target species, is also covered. These belong to the following class of secondary metabolites: alkaloids, alkamides, sesquiterpenes, triterpenes, sterols, flavonoids, coumarins, anthraquinones, xanthones, acetogenonins and aliphatics. Their mode of action on mosquito larvae ranges from neurotoxic effects to inhibition of detoxificant enzymes and larval development and/or midugut damages. In the final section, current drawbacks as well as key challenges for future research, including technologies to synergize efficacy and improve stability - thus field performances - of the selected plant extracts, are outlined. Unfortunately, despite the huge amount of laboratory evidences about their efficacy, only a limited number of studies was aimed to validate their efficacy in the field, nor the epidemiological impact potentially arising from these vector control operations has been assessed. This strongly limits the development of commercial mosquito larvicides of botanical origin, at variance with plant-borne products developed in the latest decades to kill or repel other key arthropod species of medical and veterinary importance (e.g., ticks and lice), as well as mosquito adults. Further research on these issues is urgently needed.