title: Fluralaner activity against life stages of ticks using Rhipicephalus sanguineus and Ornithodoros moubata IN in vitro contact and feeding assays.
abstract: BACKGROUND
  Fluralaner is a novel isoxazoline eliciting both acaricidal and insecticidal activity through potent blockage of GABA- and glutamate-gated chloride channels. The aim of the study was to investigate the susceptibility of juvenile stages of common tick species exposed to fluralaner through either contact (Rhipicephalus sanguineus) or contact and feeding routes (Ornithodoros moubata).
  
  
  METHODS
  Fluralaner acaricidal activity through both contact and feeding exposure was measured in vitro using two separate testing protocols. Acaricidal contact activity against Rhipicephalus sanguineus life stages was assessed using three minute immersion in fluralaner concentrations between 50 and 0.05 μg/mL (larvae) or between 1000 and 0.2 μg/mL (nymphs and adults). Contact and feeding activity against Ornithodoros moubata nymphs was assessed using fluralaner concentrations between 1000 to 10(-4) μg/mL (contact test) and 0.1 to 10(-10) μg/mL (feeding test). Activity was assessed 48 hours after exposure and all tests included vehicle and untreated negative control groups.
  
  
  RESULTS
  Fluralaner lethal concentrations (LC₅₀, LC₉₀/₉₅) were defined as concentrations with either 50%, 90% or 95% killing effect in the tested sample population. After contact exposure of R. sanguineus life stages lethal concentrations were (μg/mL): larvae - LC₅₀ 0.7, LC₉₀ 2.4; nymphs - LC₅₀ 1.4, LC₉₀ 2.6; and adults - LC₅₀ 278, LC₉₀ 1973. After exposure of O. moubata nymphs to fluralaner lethal concentrations were (μg/mL): contact exposure - LC₅₀ 720, LC₉₅ 1133; and feeding exposure- LC₅₀ 0.00007, LC₉₅ 0.09.
  
  
  CONCLUSIONS
  Fluralaner demonstrates potent in vitro acaricidal activity against all life stages of the brown dog tick, R.sanguineus. The testing of fluralaner contact and feeding routes using O. moubata nymphs demonstrates a high acaricidal activity in both exposure routes.
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.affiliation: MSD Animal Health Innovation GmbH, Research Antiparasitics, Zur Propstei, 55270, Schwabenheim, Germany. hartmut.zoller@msd.de.
authors.forename: Hartmut
authors.initials: H
authors.lastname: Zoller
authors.affiliation: MSD Animal Health Innovation GmbH, Research Antiparasitics, Zur Propstei, 55270, Schwabenheim, Germany. rainer.roepke@msd.de.
authors.forename: Rainer K A
authors.initials: RK
authors.lastname: Roepke
authors.affiliation: MSD Animal Health Innovation GmbH, Research Antiparasitics, Zur Propstei, 55270, Schwabenheim, Germany. eva.zschiesche@msd.de.
authors.forename: Eva
authors.initials: E
authors.lastname: Zschiesche
authors.affiliation: MSD Animal Health Innovation GmbH, Research Antiparasitics, Zur Propstei, 55270, Schwabenheim, Germany. anja.heckeroth@msd.de.
authors.forename: Anja R
authors.initials: AR
authors.lastname: Heckeroth
mesh_terms: D056810:Acaricides / Q000633:toxicity*; D000818:Animals; D004283:Dog Diseases / Q000469:parasitology*; D004285:Dogs; D005247:Feeding Behavior / Q000187:drug effects; D005260:Female; D007555:Isoxazoles / Q000633:toxicity*; D008297:Male; D026861:Ornithodoros / Q000187:drug effects* / Q000254:growth & development / Q000502:physiology; D048508:Rhipicephalus sanguineus / Q000187:drug effects* / Q000254:growth & development* / Q000502:physiology; D013984:Tick Infestations / Q000469:parasitology / Q000662:veterinary*
chemical_list: C000591860:A1443 compound; D056810:Acaricides; D007555:Isoxazoles