title: Comparative speed of kill of sarolaner (Simparica) and afoxolaner (NexGard) against induced infestations of Rhipicephalus sanguineus s.l. on dogs.
abstract: BACKGROUND
  The brown dog tick, Rhipicephalus sanguineus sensu lato, commonly infests dogs globally, is the major vector of the pathogen that causes canine monocytic ehrlichiosis and also transmits Babesia vogeli. A rapid speed of kill of a parasiticide is essential to reduce the direct deleterious effects of tick infestation and the risk of tick-borne pathogen transmission. The speed of kill of a novel orally administered isoxazoline parasiticide, sarolaner (Simparica), against R. sanguineus sensu lato on dogs was evaluated and compared with afoxolaner (NexGard) for 5 weeks after a single oral dose.
  
  
  METHODS
  Based on pretreatment tick counts, 24 dogs were randomly allocated to oral treatment with either placebo, or label doses of sarolaner (2-4 mg/kg) or afoxolaner (2.5-6.8 mg/kg). Dogs were examined and live ticks counted at 8, 12, and 24 h after treatment and subsequent re-infestations on Days 7, 14, 21, 28, and 35. Efficacy was determined at each time point relative to counts for placebo dogs.
  
  
  RESULTS
  There were no adverse reactions to treatment. Based on geometric means, sarolaner provided >94 % efficacy within 8 h of treatment, and >99 % after 12 and 24 h. Against subsequent weekly re-infestations of ticks, sarolaner achieved ≥91.7 % efficacy (based on geometric means) to Day 35 at 24 h. Sarolaner significantly reduced tick counts versus placebo on Days 0 and 28 at 8 h (P ≤ 0.0390), on Days 0 to 14 and 28 at 12 h (P ≤ 0.0142), and on all days at 24 h (P < 0.0001). By comparison, tick counts for afoxolaner were significantly lower than placebo at 8 h on Days 0 and 28 (P ≤ 0.0117), at 12 h on Day 0 only (P < 0.0001), and on all days at 24 h (P ≤ 0.0078). Significantly more live ticks were recovered from afoxolaner-treated dogs than from sarolaner-treated dogs at 8 and 12 h after treatment (P ≤ 0.0286), at 12 h after re-infestation on Days 7 and 28 (P ≤ 0.04630), and at 24 h after re-infestations from Day 7 to Day 35 (P ≤ 0.0119). At 24 h, efficacy (based on geometric mean counts) of afoxolaner was less than 90 % from Day 7 onwards, and declined to less than 45 % by Day 35, while efficacy for sarolaner was >90 % for 35 days.
  
  
  CONCLUSIONS
  In this controlled laboratory evaluation, sarolaner had a faster speed of kill against R. sanguineus sensu lato than afoxolaner. The rapid and consistent kill of ticks within 24 h after a single oral dose of sarolaner over 35 days indicates that this treatment will provide highly effective and reliable control of ticks over the entire treatment interval and should reduce the risk of tick-borne pathogen transmission.
authors.affiliation: Zoetis, Veterinary Medicine Research and Development, 333 Portage St., Kalamazoo, MI, 49007, USA. robert.six@zoetis.com.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Six
authors.affiliation: YVRS, 7243 East Ave, Turlock, CA, 95380, USA. youngdvm@yvrs.com.
authors.forename: David R
authors.initials: DR
authors.lastname: Young
authors.affiliation: Zoetis, Veterinary Medicine Research and Development, 333 Portage St., Kalamazoo, MI, 49007, USA. susan.holzmer@zoetis.com.
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Holzmer
authors.affiliation: Zoetis, Veterinary Medicine Research and Development, 333 Portage St., Kalamazoo, MI, 49007, USA. sean.mahabir@zoetis.com.
authors.forename: Sean P
authors.initials: SP
authors.lastname: Mahabir
mesh_terms: D056810:Acaricides / Q000008:administration & dosage*; D000284:Administration, Oral; D000818:Animals; D004283:Dog Diseases / Q000188:drug therapy* / Q000469:parasitology; D004285:Dogs; D007555:Isoxazoles / Q000008:administration & dosage*; D059208:Parasite Load; D010919:Placebos / Q000008:administration & dosage; D048508:Rhipicephalus sanguineus / Q000187:drug effects* / Q000502:physiology*; D016019:Survival Analysis; D013984:Tick Infestations / Q000188:drug therapy / Q000662:veterinary*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D056810:Acaricides; D007555:Isoxazoles; D010919:Placebos