Repurposing isoxazoline veterinary drugs for control of vector-borne human diseases

Isoxazolines are oral insecticidal drugs currently licensed fo ectoparasite control in companion animals. Here we propose thei use in humans for the reduction of vector-borne disease incidence Fluralaner and afoxolaner rapidly killed Anopheles, Aedes, an Culex mosquitoes and Phlebotomus sand flies after feeding on drug-supplemented blood meal, with IC50 values ranging from 33 to 575 nM, and were fully active against strains with preexist ing resistance to common insecticides. Based on allometric scalin of preclinical pharmacokinetics data, we predict that a single hu man median dose of 260 mg (IQR, 177–407 mg) for afoxolaner, o 410 mg (IQR, 278–648 mg) for fluralaner, could provide an insecti cidal effect lasting 50–90 days against mosquitoes and Phleboto mus sand flies. Computational modeling showed that seasona mass drug administration of such a single dose to a fraction of regional population would dramatically reduce clinical cases o Zika and malaria in endemic settings. Isoxazolines therefore rep resent a promising new component of drug-based vector control