title: Efficacy of milbemycin oxime in combination with spinosad in the treatment of larval and immature adult stages of Ancylostoma caninum and Toxocara canis in experimentally infected dogs.
abstract: Ancylostoma caninum and Toxocara canis are two important zoonotic parasites of dogs. The primary objective of these studies were to confirm the oral effectiveness of milbemycin oxime (MO) and spinosad in dogs experimentally infected with immature (L4 and immature adult) stages of T. canis or A. caninum. Both trials were conducted as randomized, blinded, placebo-controlled dose confirmation studies. Treatments using the intended European commercial tablet formulation of Trifexis were administered in a timeframe relative to inoculation so that effectiveness could be assessed against specific immature stages of A. caninum or T. canis. In each study on Day 0, each of 32, 3-4 month old dogs were inoculated with 250 infective eggs of T. canis or 300 infective L3 of the hookworm, A. caninum. All dogs were weighed before their scheduled treatment, randomized to 1 of the 4 treatment groups in each study (8 dogs/group). All dogs were fed just prior to dosing. For T. canis, dogs were treated orally with an MO/spinosad tablet on Day 14 or Day 24. For A. caninum, dogs were treated orally with an MO/spinosad tablet on Day 7 or Day 11. Corresponding control groups in each study received a placebo tablet. Dogs were necropsied 5 or 6 days after their respective treatments. The digestive tract was removed and processed to recover, count, and identify all stages. The GM worm count for the MO/spinosad tablet on Day 14 (L4 T. canis) was 0.0, with efficacy calculated as 100%; however, only 3 of 8 control dogs had adequate infections. The GM worm count for the MO/spinosad tablet on Day 24 (immature adult stage) was 0.30; efficacy calculated at 96.15%. This is based on 5 of the 8 control dogs with adequate infections. In the two A. caninum studies, GM worm counts for the MO/spinosad tablets on Day 7 (L4 efficacy) was 2.37 and 0.8 with efficacy calculated as 98.92% and 99.25%, respectively. The GM count for the group treated with the MO/spinosad combination on Day 11 (immature adult) was 6.19 and 1.4; efficacy calculated at 97.77% and 98.58%, respectively. A minimum MO oral dose of 0.75 mg/kg was highly effective for the treatment of immature stages of T. canis and A. caninum infections in dogs. The ability to kill immature stages of these two parasites before they become patent will benefit dogs, their owners and family members due to reduced exposure to these potentially zoonotic parasites.
authors.affiliation: College of Veterinary Medicine, Cornell University, Ithaca, NY, USA.
authors.forename: Dwight D
authors.initials: DD
authors.lastname: Bowman
authors.affiliation: East Tennessee Clinical Research Inc., Rockwood, TN, USA.
authors.forename: Craig R
authors.initials: CR
authors.lastname: Reinemeyer
authors.affiliation: Elanco Animal Health, Eli Lilly and Company Limited, Basingstoke, Hampshire, United Kingdom.
authors.forename: Scott
authors.initials: S
authors.lastname: Wiseman
authors.affiliation: Elanco Animal Health Research and Development, a Division of Eli Lilly and Company, 2500 Innovation Way, Greenfield, IN, USA. Electronic address: snyder_daniel_e@elanco.com.
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Snyder
mesh_terms: D000722:Ancylostoma; D000724:Ancylostomiasis / Q000188:drug therapy / Q000662:veterinary*; D000818:Animals; D004283:Dog Diseases / Q000188:drug therapy / Q000469:parasitology*; D004285:Dogs; D004338:Drug Combinations; D007814:Larva / Q000187:drug effects; D018942:Macrolides / Q000008:administration & dosage / Q000627:therapeutic use*; D017166:Toxocara canis; D014120:Toxocariasis / Q000188:drug therapy*; D015047:Zoonoses
chemical_list: D004338:Drug Combinations; D018942:Macrolides; C078973:milbemycin oxime; C415329:spinosad
keywords: Ancylostoma caninum; Chemoprophylaxis; Larval; Milbemycin oxime; Spinosad; Toxocara canis