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Publication Detail
Automated phenotyping of mosquito larvae enables high-throughput screening for novel larvicides and smartphone-based detection of larval insecticide resistance
  • Publication Type:
    Working discussion paper
  • Authors:
    Buckingham SD, Partridge FA, Poulton BC, Miller B, McKendry RA, Lycett GJ, Sattelle DB
  • Publisher:
    Cold Spring Harbor Laboratory
  • Publication date:
  • Series:
AbstractPyrethroid-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 (MFP) 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 enable detection of resistance to deltamethrin. We show how this approach to monitoring larval susceptibility 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 for insecticide resistance with associated real-time, geo-located information to identify hotspots.Author summaryWe have developed an automated platform for recording the motility of mosquito larvae and applied it to larvae of a mosquito vector of malaria and a mosquito vector of dengue, Zika, yellow fever and other human diseases. The platform facilitates high-throughput, chemical screening for new compounds to control mosquito larvae and also allows detection of larval resistance to the pyrethroid insecticide deltamethrin. Pyrethroid-impregnated bednets have helped to halve the deaths from malaria in recent years but pyrethroid resistance is an important threat to this progress. Our approach assays insecticide actions faster than the current WHO standard test and we show that it can be adapted for use with a smartphone, which offers the prospect of a future field assay for resistance with the added benefit of precise satellite-based location.
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