title: Fluralaner, a novel isoxazoline, prevents flea (Ctenocephalides felis) reproduction in vitro and in a simulated home environment.
abstract: BACKGROUND
  Fluralaner, a novel isoxazoline, has both acaricidal and insecticidal activity through potent blockage of GABA- and L-glutamate-gated chloride channels. This study investigated the in vitro and in vivo effects of fluralaner exposure on flea (Ctenocephalides felis) reproduction.
  
  
  METHODS
  Blood spiked with sub-insecticidal fluralaner concentrations (between 0.09 and 50.0 ng/mL) was fed to fleas for 10 days using a membrane system. Cessation of reproduction in exposed fleas was assessed using flea survival, egg hatchability, and control of oviposition, pupae, and flea emergence. Fluralaner efficacy for in vivo Ctenocephalides (C.) felis control on dogs was assessed using a simulated flea-infested home environment. During a pre-treatment period, dogs were infested twice on days -28 and -21 with 100 adult unfed fleas to establish a thriving population by day 0 of the study. On day 0, one group of dogs was treated with fluralaner (Bravecto™; n=10), while another group served as negative control (n=10). Following treatment, dogs were infested three times with 50 fleas on days 22, 50 and 78 to simulate new infestations. Live flea counts were conducted weekly on all dogs for 12 weeks starting 1 day before treatment.
  
  
  RESULTS
  Fluralaner potently inhibited flea reproduction capacity in vitro. Oviposition ceased completely at concentrations as low as 25.0 ng/mL. While no ovicidal effect was observed, fluralaner exerted a larvicidal effect at exceptionally low concentrations (6.25 ng/mL). In the simulated flea-infested home environment, flea-control efficacy on fluralaner-treated dogs was >99% at every time point measured for 12 weeks. No adverse events were observed in fluralaner-treated dogs.
  
  
  CONCLUSIONS
  Fluralaner completely controls egg laying, larval development and flea reproduction even at sub-insecticidal concentrations. Oral treatment of dogs with fluralaner is highly effective for eliminating fleas in a simulated flea-infested home environment.
authors.affiliation: MSD Animal Health Innovation GmbH, Research Antiparasitics, Zur Propstei, 55270 Schwabenheim, Germany. heike.williams@msd.de.
authors.forename: Heike
authors.initials: H
authors.lastname: Williams
authors.forename: David R
authors.initials: DR
authors.lastname: Young
authors.forename: Tariq
authors.initials: T
authors.lastname: Qureshi
authors.forename: Hartmut
authors.initials: H
authors.lastname: Zoller
authors.forename: Anja R
authors.initials: AR
authors.lastname: Heckeroth
mesh_terms: D000818:Animals; D058251:Ctenocephalides / Q000187:drug effects* / Q000502:physiology; D004283:Dog Diseases / Q000517:prevention & control*; D004285:Dogs; D005260:Female; D058267:Flea Infestations / Q000517:prevention & control / Q000662:veterinary*; D006798:Housing; D007306:Insecticides / Q000494:pharmacology*; D007555:Isoxazoles / Q000494:pharmacology*; D007814:Larva / Q000187:drug effects; D010063:Ovum / Q000187:drug effects; D012098:Reproduction / Q000187:drug effects
chemical_list: C000591860:A1443 compound; D007306:Insecticides; D007555:Isoxazoles