Insecticidal efficacy against Phlebotomus perniciosus in dogs treated orally with fluralaner in two different parallel-group, negative-control, random and masked trials.

BACKGROUND: Dogs are the reservoir host of Leishmania infantum, the agent of zoonotic visceral leishmaniasis (VL), which is transmitted by the bite of phlebotomine sand flies. The sand fly Phlebotomus perniciosus is the main vector of zoonotic VL in the western Mediterranean region. Fluralaner has been shown to effectively kill this vector. The aim of this study was to evaluate the insecticidal efficacy of oral fluralaner in dogs bitten by P. perniciosus. METHODS: Two parallel-group, negative-controlled, randomized, masked laboratory trials with equivalent designs were performed in two different locations using two different pathogen-free laboratory-bred P. perniciosus strains for the challenge. In each trial, 12 purpose-bred beagles, initially ranked on natural attractiveness to sand flies, were randomly allocated to two groups (6 animals/group). Dogs in one group received fluralaner orally at the approved dose on day 0, and dogs in the control group were not treated. Each dog was subsequently exposed to an average of 70 unfed live sand fly females on days 1, 28, 56 and 84. Viability of blood-fed females was then evaluated for up to 96 h after exposure, and insecticidal efficacy was measured as the survival rate of flies fed on the fluralaner-treated dogs versus that of dogs in the control group. Significance was calculated for the proportion of live fed sand fly counts from treated versus control group dogs. RESULTS: Comparison of the survival proportions between treated and control groups showed that fluralaner insecticidal efficacy was highly significant in both trials (P < 0.001 or P < 0.01 in different assessments) through to day 56. In the first trial, efficacy reached 100% on days 1 and 28, and 99.1% on day 56; in the second trial, the insecticidal efficacy was 98.5, 100 and 85.9%, respectively on the same days. On day 84, efficacy was in the range of 53-57% (P < 0.05) in the first trial and 0% in the second trial. CONCLUSION: A single oral fluralaner administration to dogs under laboratory conditions results in strong and reproducible insecticidal efficacy against P. perniciosus for at least 8 weeks.

Efficacy of orally administered combination of moxidectin, sarolaner and pyrantel (Simparica Trio™) for the prevention of experimental Angiostrongylus vasorum infection in dogs.

BACKGROUND: Infection with Angiostrongylus vasorum may cause severe clinical disease, even death in dogs, however, due to the often non-specific clinical signs, diagnosis is not always straightforward. Regular prophylactic treatment may offer a safe means to protect dogs against infection. The efficacy of a novel oral endectocide containing moxidectin, sarolaner and pyrantel was investigated for the prevention of angiostrongylosis in dogs in three placebo-controlled, randomized, masked studies. The initial study (Study 1) determined the efficacious dosage of moxidectin in the combination product by evaluating three different dose levels, and two follow-up studies (Studies 2 and 3) confirmed the efficacy of the selected moxidectin dose. METHODS: Animals were infected orally with 200 infective third-stage larvae (L3) of A. vasorum and were treated 28 days later with the combination product or with placebo. Timing of dosing relative to infection allowed for efficacy to be evaluated against the immature adult (L5) stage. Dogs in Study 1 received treatments with oral tablets to deliver 3, 12 or 24 µg/kg moxidectin in combination with 2 mg/kg sarolaner and 5.0 mg/kg pyrantel (as pamoate salt) or placebo. In Studies 2 and 3, Simparica Trio™ tablets were administered to provide minimum dosages of 1.2 mg/kg sarolaner, 24 µg/kg moxidectin and 5.0 mg/kg pyrantel (as pamoate salt). Efficacy of the combination product was calculated as the percent reduction in adult worm counts at necropsy relative to placebo. RESULTS: In Study 1, the 3, 12 and 24 µg/kg moxidectin dosage in the combination product provided 7.2%, 54.5% and 94.7% efficacy against the immature adult stages of A. vasorum, respectively. Studies 2 and 3 confirmed that the efficacy of 24 µg/kg moxidectin combined with 1.2 mg/kg sarolaner and 5 mg/kg pyrantel in Simparica Trio™ was ≥ 92.9%. All three studies established that a single oral administration of 24 µg/kg moxidectin in the combination product provided effective prophylactic treatment for angiostrongylosis, reduced L1 production and fecal excretion and minimized the tissue damage to the lungs. CONCLUSIONS: A single oral treatment of dogs with Simparica Trio™ providing moxidectin at a minimum dose of 24 µg/kg was efficacious in the prevention of angiostrongylosis.

Efficacy of a novel oral formulation of sarolaner (Simparica™) against four common tick species infesting dogs in Europe.

The efficacy of single oral treatment of sarolaner (Simparica™, Zoetis), a novel isoxazoline compound, was evaluated against four tick species known to commonly infest dogs in Europe. Eight laboratory studies were conducted using adult purpose-bred Beagle dogs. In each study, 16 animals were randomly allocated to one of two treatment groups based on pre-treatment host-suitability tick counts. Dogs were infested with 50 unfed adult Dermacentor reticulatus (two studies), Ixodes hexagonus (three studies), Ixodes ricinus (two studies) or Rhipicephalus sanguineus (one study) ticks on Days -2, 5, 12, 19, 26 and 33. On Day 0, dogs were treated orally with placebo or sarolaner tablets providing the minimum dose of 2.0mg/kg bodyweight and tick counts were conducted 48h after treatment and after each subsequent weekly re-infestation. There were no treatment-related adverse reactions in any of the studies. Dogs in the placebo-treated group maintained tick infestations throughout the studies. Geometric mean live tick counts were significantly (P≤0.0001) lower in the sarolaner-treated group compared to the tick counts in the placebo group at all time-points. A single oral administration of sarolaner resulted in 100% efficacy against existing infestations of all tick species except R. sanguineus, for which the efficacy was 99.7%, within 48h. Efficacy against weekly re-infestations was ≥97.5% for all tick species for 35 days. Thus, a single dose of sarolaner administered orally at the minimum dosage of 2 mg/kg, resulted in ≥99.7% efficacy within 48h against existing tick infestations, and in ≥97.5% efficacy against weekly re-infestations, for at least 35 days after treatment. These studies confirmed that administration of the minimum dose of sarolaner will provide treatment of existing infestations and give at least one month of control against re-infestation by the common tick species affecting dogs in Europe.