Abstract
Pyrethroid-impregnated nets have contributed significantly to halving the burden of malaria but resistance threatens their future efficacy and the pipeline of new insecticides is short. Here we report that an invertebrate automated phenotyping platform (INVAPP), combined with the algorithm Paragon, provides a robust system for measuring larval motility in Anopheles gambiae (and An. coluzzi) as well as Aedes aegypti with the capacity for high-throughput screening for new larvicides. By this means, we reliably quantified both time- and concentration-dependent actions of chemical insecticides faster than using the WHO standard larval assay. We illustrate the effectiveness of the system using an established larvicide (temephos) and demonstrate its capacity for library-scale chemical screening using the Medicines for Malaria Venture (MMV) Pathogen Box library. As a proof-of-principle, this library screen identified a compound, subsequently confirmed to be tolfenpyrad, as an effective larvicide. We have also used the INVAPP / Paragon system to compare responses in larvae derived from WHO classified deltamethrin resistant and sensitive mosquitoes. We show how this approach to monitoring larval response to insecticides can be adapted for use with a smartphone camera application and therefore has potential for further development as a simple portable field-assay with associated real-time, geo-located information to identify hotspots.
Highlights
Mosquito-borne pathogens kill more than one million people every year, while severely debilitating diseases including malaria, dengue, Zika, West Nile virus, chikungunya, yellow fever and Japanese encephalitis, transmitted by these vectors cause suffering for hundreds of millions
Using the invertebrate automated phenotyping platform (INVAPP) system to study the actions of the larvicide temephos on larvae of Aedes aegypti
The INVAPP / Paragon system enables robust, automated detection of larval motility and the severe motility impairment resulting from exposure to the larvicide temephos
Summary
Mosquito-borne pathogens kill more than one million people every year, while severely debilitating diseases including malaria, dengue, Zika, West Nile virus, chikungunya, yellow fever and Japanese encephalitis, transmitted by these vectors cause suffering for hundreds of millions. The ineffectiveness of ITNs against Aedes and the absence of drugs or vaccines for most vector-borne viruses means that a mainstay of viral disease control has been larval source management (LSM) [5]. This integrated approach targets aquatic egg-laying sites with the aim of reducing the number of immature forms, leading in turn to fewer biting adults. LSM can incorporate community environmental measures to limit temporary aquatic breeding sites in and around homes, as well as the application of larvicidal agents, such as temephos, to important, permanent water sources These traditional LSM methods are effective where the breeding sites that produce the majority of adults can be readily identified and treated [6]. The most important breeding sites are targeted [7]
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