The potential use of isoxazolines as late-life-acting insecticides against the yellow fever mosquito, Aedes aegypti, and the common malaria mosquito, Anopheles quadrimaculatus

Mosquito-vectored disease remains a public health threat in many tropical regions. The largest barrier to eradication continues to be the evolution of insecticide resistance. One ‘evolution-proof’ method to remove these selective pressures while minimizing disease transmission is to use late-life-acting insecticides (LLAIs) to kill older mosquitos while sparing the younger. LLAIs may be created by lowering the dosages of insecticidal compounds to a degree that is only lethal to older mosquitos which are more susceptible to toxins. In this study, the isoxazolines, an emerging group of Class 30 parasiticides orally used in companion animals, are explored for their potential to act as LLAIs in mosquito-vector control. Topical assays were conducted on laboratory colonies of the yellow fever mosquito, Aedes agypti, and the common malaria mosquito, Anopheles quadrimaculatus, using the four Class 30 compounds fluralaner, broflanilide, fluxametamide, and afoxolaner, as well as the pyrethroid permethrin. The lethal doses for Ae. agypti were compared between pyrethroid resistant and susceptible strains, while the lethality for young (1-4 d old) and old (6-9 d old) mosquitos were compared within each species. Broflanilide and afoxolaner were found to be the most and least toxic isoxazolines, respectively, and all five compounds were more toxic to Ae. aegypti than An. quadrimaculatus. Resistance and age ratios were low to insignificant, suggesting a lack of cross-resistance to pyrethroids and lack of increased susceptibility in older mosquitos. While the isoxazolines may be an effective insecticide in more conventional control programs, they may not be ideal for use in LLAI applications.