title: Comparative speed of kill of sarolaner (Simparica®) and afoxolaner (NexGard®) against induced infestations of Ixodes holocyclus on dogs.
abstract: The Australian paralysis tick, Ixodes holocyclus, causes paralysis predominantly in dogs and cats in the Eastern coastal regions of Australia. Rapid onset of effect of a parasiticide is critical to minimize the deleterious effects of these tick infestations, especially tick paralysis caused by the salivary neurotoxin. The speed of kill of a novel orally administered isoxazoline parasiticide, sarolaner chewable tablets (Simparica®), against I. holocyclus on dogs was evaluated and compared with afoxolaner (NexGard®) for 5 weeks after a single oral dose.
  
  
  
  Twenty-four (24) dogs were randomly allocated to treatment with either placebo, sarolaner (label dose of 2 to 4 mg/kg as per dosing table), or afoxolaner (label dose of 2.7 to 6.9 mg/kg) based on pre-treatment body weights. Following artificial infestation on Day -1, dogs were examined and live ticks counted at 8, 12, 24 and 48 h after treatment on Day 0, and at 12, 24 and 48 h after subsequent re-infestations on Days 7, 14, 21, 28 and 35. Efficacy was determined at each time point relative to counts for placebo dogs based on geometric means.
  
  
  
  At 8 and 12 h time points on Day 0, sarolaner-treated dogs had significantly lower geometric mean tick counts compared to the dogs treated with afoxolaner (P ≤ 0.0303). Efficacy of sarolaner against an existing infestation was 86.2 and 96.9% compared with that of afoxolaner which had efficacy of 21.3 and 85.0% at 8 and 12 h time points, respectively. Against subsequent weekly re-infestations at 12 h time points, treatment with sarolaner resulted in significantly lower geometric mean tick counts than afoxolaner-treated dogs on all days (P ≤ 0.0077) with the efficacy ranging from 60.2 to 92.2%, compared to 5.8 to 61.0% in the afoxolaner-treated dogs. Against subsequent weekly re-infestations at the 24 h time points on Days 22 and 36, efficacy of sarolaner was significantly higher at 99.2 and 97.9%, respectively, compared with afoxolaner which had efficacy of 92.4 and 91.9% (P ≤ 0.0356). At the 48 h time points following each of the five weekly re-infestations, the mean efficacy results of sarolaner and afoxolaner treated dogs were similar on most occasions. There were no adverse reactions to treatments.
  
  
  
  In this controlled laboratory evaluation, a single dose of sarolaner had a significantly faster speed of kill against an existing infestation of I. holocyclus, than afoxolaner at 8 and 12 h post-treatment. The rapid and consistent kill of ticks provided by sarolaner within 24 h after a single oral dose and following weekly re-infestations over 35 days suggests this treatment will provide highly effective, rapid and reliable control of ticks over the entire treatment interval, thereby minimizing the risk of tick paralysis in dogs.
authors.affiliation: Zoetis Australia Research and Manufacturing Pty Ltd, Veterinary Medicine Research and Development, Level 6, 5 Rider Boulevard, Rhodes, NSW, 2138, Australia. raj.packianathan@zoetis.com.
authors.forename: Raj
authors.initials: R
authors.lastname: Packianathan
authors.affiliation: Zoetis Australia Research and Manufacturing Pty Ltd, Veterinary Medicine Research and Development, Level 6, 5 Rider Boulevard, Rhodes, NSW, 2138, Australia.
authors.forename: Andrew
authors.initials: A
authors.lastname: Hodge
authors.affiliation: Zoetis Australia Research and Manufacturing Pty Ltd, Veterinary Medicine Research and Development, Level 6, 5 Rider Boulevard, Rhodes, NSW, 2138, Australia.
authors.forename: Natalie
authors.initials: N
authors.lastname: Bruellke
authors.affiliation: Zoetis Australia Research and Manufacturing Pty Ltd, Veterinary Medicine Research and Development, Level 6, 5 Rider Boulevard, Rhodes, NSW, 2138, Australia.
authors.forename: Kylie
authors.initials: K
authors.lastname: Davis
authors.affiliation: Zoetis, Veterinary Medicine Research and Development, 333 Portage St, Kalamazoo, MI, 49007, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Maeder
mesh_terms: D000818:Animals; D001315:Australia; D001384:Azetidines / Q000008:administration & dosage / Q000494:pharmacology*; D004283:Dog Diseases / Q000188:drug therapy*; D004285:Dogs; D007555:Isoxazoles / Q000008:administration & dosage / Q000494:pharmacology*; D018884:Ixodes / Q000187:drug effects* / Q000502:physiology; D009281:Naphthalenes / Q000008:administration & dosage / Q000494:pharmacology*; D059208:Parasite Load; D010919:Placebos / Q000008:administration & dosage; D011897:Random Allocation; D013141:Spiro Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D016019:Survival Analysis; D013984:Tick Infestations / Q000188:drug therapy / Q000662:veterinary*; D013997:Time Factors
chemical_list: D001384:Azetidines; D007555:Isoxazoles; D009281:Naphthalenes; D010919:Placebos; D013141:Spiro Compounds; C000623191:sarolaner; C000589002:afoxolaner
keywords: Afoxolaner; Dog; Isoxazoline; Ixodes holocyclus; NexGard®; Oral; Sarolaner; Simparica®; Speed of kill; Tick