Evaluation of the speed of kill of a novel orally administered combination product containing sarolaner, moxidectin and pyrantel (Simparica Trio™) against induced infestations of Ixodes scapularis on dogs

Abstract

Background: The black-legged (or deer) tick, Ixodes scapularis, commonly infests dogs in the USA and is the vector of important zoonotic pathogens, including Borrelia burgdorferi, the causative agent of Lyme disease. Rapid onset of activity is important in reducing the feeding activity of ticks, thereby reducing the possibility of transmission of infections. The speed of kill of a novel oral combination product, Simparica Trio ™ containing sarolaner, moxidectin and pyrantel was evaluated in a well-controlled laboratory study against an existing infestation and subsequent weekly induced infestations of I. scapularis ticks on dogs. Methods: Dogs were allocated randomly based on host suitability tick counts to treatment with a single dose of either placebo or Simparica Trio ™ at the minimum label dose of 1.2 mg/kg sarolaner, 24 µg/kg moxidectin and 5 mg/ kg pyrantel (as pamoate salt). All dogs were infested with approximately 50 unfed adult I. scapularis ticks at a 1:1 sex ratio on Days −2, 7, 14, 21, 28 and 35. Tick counts were conducted at 8, 12 and 24 h after treatment on Day 0 and after each subsequent infestation. Results: No treatment-related adverse events occurred during the study. Dogs in the placebo-treated group maintained adequate tick infestations for the duration of the study. Day 0 tick counts at 8 h after treatment with Simparica Trio ™ were reduced relative to placebo against an existing infestation with efficacy of 67.5%, demonstrating that Simparica Trio ™ started killing ticks soon after treatment. Efficacy was 98.4 % at 12 h and 99.4% at 24 h. Rapid speed of kill was maintained throughout the month, with efficacy of ≥ 94.2% at 24 h after re-infestation through Day 28. Conclusions: A single dose of Simparica Trio ™ administered orally to dogs at the minimum label dose of 1.2 mg/kg sarolaner, 24 µg/kg moxidectin and 5 mg/kg pyrantel (as pamoate salt) was safe and began to kill existing I. scapularis ticks within 8 h after treatment and resulted in ≥ 94.2% efficacy within 24 h against re-infestations for a month.

Comparison of the initial and residual speed of Ixodes scapularis kill on dogs treated with a single dose of Bravecto® Chew (25 mg/kg fluralaner) or Simparica TRIO® (1.2 mg/kg sarolaner, 24 µg/kg moxidectin, 5 mg/kg pyrantel)

“…In this study, the initial 24-h efficacy of Bravecto ® (100%) was similar to that of Simparica TRIO ® (99.5%) (Table 2 ). The Simparica TRIO ® results are similar to those of a previous study that demonstrated 99.4% efficacy against I. scapularis at 24 h post-treatment [ 24 ].…”

“…The efficacy of Simparica TRIO ® at 8 and 12 h on Day 28 was only 0% and 27.7%, respectively. Similar to a previous study, a slower residual speed of tick kill efficacy was observed for Simparica TRIO ® -treated dogs, where the efficacy of Simparica TRIO ® against I. scapularis at 8 and 12 h post-infestation on 28 days post-treatment was 3.1%, and 52.2%, respectively [ 24 ].…”

Efficacy of a novel orally administered combination product containing sarolaner, moxidectin and pyrantel (Simparica Trio™) against induced infestations of five common tick species infesting dogs in the USA

“…The first few days after host attachment is a critical time in tick biology and provides a window of opportunity for intervention. Simparica Trio ™ administered to dogs has shown rapid efficacy against I. scapularis, beginning to kill ticks within 8 hours of administration against an existing infestation and providing ≥ 94.2% effectiveness against re-infestations within 24 hours for 28 days [28]. While the studies reported here did not focus on speed of Table 5 Arithmetic mean tick counts and percent efficacy relative to placebo for dogs following one oral treatment with Simparica Trio ™ with existing Rhipicephalus sanguineus infestations and after subsequent weekly re-infestations kill, it is important to note that the efficacy of Simparica Trio ™ was ≥ 98.9% at the first post-treatment evaluations for all five tick species.…”

Human and Veterinary Vaccines for Lyme Disease

“…Furthermore, it is recommended that B. burgdorferi antibody positive dogs be tested for proteinuria due to concerns about the development of potentially fatal kidney disease (Lyme nephritis). Acaricides, including fluralaner and afoxolaner (isooxazoline family), are widely used on dogs and have good efficacy and safety profiles (Allen et al, 2020;Holzmer et al, 2020;Kryda et al, 2020;Petersen et al, 2020). While varying with the product, acaricides can be delivered orally as chewables, topically (so called "spot on" application) or through the use of treated collars.…”