Evaluation of the efficacy of Simparica Trio® in the prevention of the transmission of Babesia canis by infected Dermacentor reticulatus to dogs.

BACKGROUND: Babesia canis is a clinically relevant vector-borne pathogen in dogs, and its presence is expanding. The efficacy of Simparica Trio® (Zoetis) in the prevention of B. canis transmission was evaluated at the minimum recommended label dose of 1.2 mg/kg sarolaner, 24 µg/kg moxidectin and 5 mg/kg pyrantel per kg bodyweight. METHODS: Twenty-four (24) dogs were randomly allocated to either a placebo-treated group or one of two treatment groups with Simparica Trio. Dogs were infested with B. canis-infected Dermacentor reticulatus ticks 21 or 28 days after treatment administration. Blood samples for antibody and DNA detection were collected from each dog prior to tick infestation until 28 days after infestation. A dog was defined as being B. canis positive if it tested positive by both an indirect immunofluorescence assay (IFA) and PCR at any time during the study. RESULTS: No treatment-related adverse reactions were recorded during the study. All placebo-treated animals displayed clinical signs due to babesiosis and tested positive on both IFA and PCR. None of the Simparica Trio-treated animals displayed any clinical symptoms or tested positive, resulting in a 100% efficacy in the prevention of canine babesiosis (P < 0.0001). CONCLUSIONS: A single treatment with Simparica Trio at the minimum recommended label dose of 1.2 mg/kg sarolaner, 24 µg/kg moxidectin and 5 mg/kg pyrantel per kg bodyweight prevents the transmission of B. canis by infected D. reticulatus to dogs for at least 28 days.

Efficacy of a chewable tablet containing sarolaner, moxidectin, and pyrantel (Simparica Trio®) in the treatment of sarcoptic mange caused by Sarcoptes scabiei mite infestations in dogs.

BACKGROUND: Infestation with Sarcoptes scabiei in dogs is a debilitating disease if left untreated and is transmissible to humans. Two field studies were conducted to confirm the efficacy of orally administered sarolaner in combination with moxidectin and pyrantel (Simparica Trio®) in the treatment of sarcoptic mange in dogs. METHODS: Client-owned dogs with S. scabiei infestation were enrolled and received 2 monthly treatments. In the first, small-scale study, 12 dogs each were allocated randomly to treatment with either placebo or Simparica Trio®. Skin scrapings to detect live mites and assessment of clinical signs of sarcoptic mange were conducted on Days 0, 14, 30, 44, and 60. Efficacy was calculated based on the percent reduction in arithmetic mean live mite counts relative to placebo. In the second, large-scale study, 75 dogs were allocated randomly to treatment with Simparica Trio® and 37 to treatment with afoxolaner + milbemycin oxime (NexGard Spectra®). Skin scrapings to detect live mites and assessment of clinical signs of sarcoptic mange were conducted on Days 0, 14, 30, and 60. The parasitological cure rate (percentage of dogs without live mites) was determined and non-inferiority of Simparica Trio® to the control product was assessed. RESULTS: In the small-scale study, 2 monthly doses of Simparica Trio® resulted in a significant reduction (P ≤ 0.0050) in live S. scabiei mite numbers and provided a 99.2% reduction relative to placebo by Day 60. Clinical signs of sarcoptic mange improved throughout the study in Simparica Trio®-treated dogs. In the large-scale study, the parasitological cure rate on Days 30 and 60 was 97.3% and 100% in the Simparica Trio® group and 91.9% and 100% in the afoxolaner + milbemycin oxime group, respectively. The parasitological cure rate for Simparica Trio® was non-inferior to afoxolaner + milbemycin oxime at both time points. Clinical signs of sarcoptic mange improved throughout the study in both groups. CONCLUSIONS: Two-monthly doses of Simparica Trio® reduced S. scabiei mite counts by 99.2% relative to placebo in one study and eliminated S. scabiei mites in 100% of dogs in the second study, thus confirming that Simparica Trio® is highly effective in the treatment of sarcoptic mange in dogs caused by S. scabiei var. canis.

Efficacy Studies against PCV-2 of a New Trivalent Vaccine including PCV-2a and PCV-2b Genotypes and Mycoplasma hyopneumoniae When Administered at 3 Weeks of Age.

This study aimed to evaluate the efficacy of a new trivalent vaccine containing inactivated Porcine Circovirus 1-2a and 1-2b chimeras and a Mycoplasma hyopneumoniae bacterin administered to pigs around 3 weeks of age. This trivalent vaccine has already been proved as efficacious in a split-dose regimen but has not been tested in a single-dose scenario. For this purpose, a total of four studies including two pre-clinical and two clinical studies were performed. Globally, a significant reduction in PCV-2 viraemia and faecal excretion was detected in vaccinated pigs compared to non-vaccinated animals, as well as lower histopathological lymphoid lesion plus PCV-2 immunohistochemistry scorings, and incidence of PCV-2-subclinical infection. Moreover, in field trial B, a significant increase in body weight and in average daily weight gain were detected in vaccinated animals compared to the non-vaccinated ones. Circulation of PCV-2b in field trial A and PCV-2a plus PCV-2d in field trial B was confirmed by virus sequencing. Hence, the efficacy of this new trivalent vaccine against a natural PCV-2a, PCV-2b or PCV-2d challenge was demonstrated in terms of reduction of histopathological lymphoid lesions and PCV-2 detection in tissues, serum and faeces, as well as improvement of production parameters.

Efficacy of a formulation of sarolaner/moxidectin/pyrantel (Simparica Trio®) for the prevention of Thelazia callipaeda canine eyeworm infection.

BACKGROUND: For a long time known as the oriental eyeworm, Thelazia callipaeda is a zoonotic nematode that infects the eyes of a wide range of vertebrate hosts including dogs, cats, wildlife carnivores, lagomorphs, and humans. The high occurrence of this infection in Europe and the first cases in the United States have increased scientific interest in the parasite, as it also represents a risk for people living in endemic areas. Therefore, treatment and prevention of thelaziosis in canine population are advocated to reduce the risk of human infection as well. Here, we assessed the efficacy of a formulation containing sarolaner/moxidectin/pyrantel (Simparica Trio®) administered orally at monthly intervals, for the prevention of establishment of infection with T. callipaeda in naturally infected dogs. In this formulation, moxidectin is expected to have efficacy against eyeworms, whereas sarolaner and pyrantel are not. METHODS: The study was conducted in eyeworm endemic areas of Italy and France, where dogs (n = 125) were assigned into two groups consisting of a negative control group (G1; n = 62), in which animals were treated monthly with a control product (sarolaner; Simparica®), and a treatment group (G2; n = 63) in which animals were treated monthly with Simparica Trio (sarolaner/moxidectin/pyrantel) from day 0 to day 150. In total, nine animals were withdrawn from the study (two animals became positive at day 30, and seven for reasons unrelated to eyeworm infection), resulting in 116 animals (n = 58 for G1; n = 58 for G2). RESULTS: In G1, 16 out of 58 animals (27.6%) were observed with eyeworms during the study, and none of the animals from G2 were ever observed with eyeworms, resulting in 100% efficacy (P < 0.0001) in the prevention of establishment of T. callipaeda infection. Adult nematodes and fourth-instar (L4)-stage larvae were recovered from the eyes of positive animals, counted, and morphologically identified as T. callipaeda. In addition, specimens from Italy were molecularly confirmed as belonging to the haplotype 1 (i.e., the only one circulating in Europe so far). CONCLUSIONS: Data presented herein demonstrated 100% efficacy of Simparica Trio for the prevention of T. callipaeda eyeworm infection in dogs from highly endemic areas of France and Italy. The use of this formulation is advantageous, as it is a licensed product in Europe with a wide efficacy spectrum against other nematodes, multiple tick species, and fleas. In addition, preventing the development of infection in dogs could also be a prophylaxis measure for zoonotic T. callipaeda infection in humans inhabiting endemic areas.

Efficacy Studies of a Trivalent Vaccine Containing PCV-2a, PCV-2b Genotypes and Mycoplasma hyopneumoniae When Administered at 3 Days of Age and 3 Weeks Later against Porcine Circovirus 2 (PCV-2) Infection.

Four studies under preclinical and clinical conditions were performed to evaluate the efficacy of a new trivalent vaccine against Porcine circovirus 2 (PCV-2) infection. The product contained inactivated PCV-1/PCV-2a (cPCV-2a) and PCV-1/PCV-2b (cPCV-2b) chimeras, plus M. hyopneumoniae inactivated cell-free antigens, which was administered to piglets in a two-dose regime at 3 days of age and 3 weeks later. The overall results of preclinical and clinical studies show a significant reduction in PCV-2 viraemia and faecal excretion, and lower histopathological lymphoid lesions and PCV-2 immunohistochemistry scores in vaccinated pigs when compared to non-vaccinated ones. Furthermore, in field trial A, a statistically significant reduction in the incidence of PCV-2-subclinical infection, an increase in body weight from 16 weeks of age to slaughterhouse and an average daily weight gain over the whole period (from 3 days of age to slaughterhouse) was detected in the vaccinated group when compared to the non-vaccinated one. Circulation of PCV-2a in field trial A, and PCV-2b plus PCV-2d in field trial B was confirmed by virus sequencing. In conclusion, a double immunization with a cPCV-2a/cPCV-2b/M. hyopneumoniae vaccine was efficacious against PCV-2 infection by reducing the number of histopathological lymphoid lesions and PCV-2 detection in tissues, serum, and faeces, as well as reducing losses in productive parameters.

A blinded, randomized clinical trial evaluating the efficacy and safety of lokivetmab compared to ciclosporin in client-owned dogs with atopic dermatitis.

BACKGROUND: Lokivetmab is an injectable anti-canine-IL-31 monoclonal antibody to treat clinical manifestations of atopic dermatitis (AD) in dogs. HYPOTHESIS/OBJECTIVES: To characterize the efficacy and safety of lokivetmab, and to demonstrate its noninferiority to ciclosporin under field conditions. ANIMALS: Dogs with chronic AD (n = 274) were enrolled from 40 practices in Belgium, The Netherlands, France and Germany. METHODS: Animals were randomized (1:1) to oral ciclosporin (5 mg/kg/once daily) or monthly injectable lokivetmab (1-3.3 mg/kg) for three months. Eighty one animals that successfully completed the comparative phase were enrolled in a continuation phase receiving lokivetmab for an additional six months. Owners assessed pruritus on a Visual Analog Scale, skin lesions were assessed by veterinary investigators with a Canine AD Extent and Severity Index (CADESI-03) scale. RESULTS: Lokivetmab was noninferior to ciclosporin for pruritus reduction on Day 28 (51.90% versus 43.72%). For Day 28 CADESI-03 percentage reduction, noninferiority of lokivetmab (54.17) versus ciclosporin (56.86%) was not achieved. At none of the time points were mean CADESI-03 scores significantly different between groups. Continued efficacy towards pruritus and lesions was demonstrated in the continuation phase where 76.3% of animals (n = 45) were assessed as 'normal' for pruritus at study end. No abnormal health events associated with lokivetmab were observed during the initial three month phase (142 dogs) or during the subsequent six month phase (81 dogs). CONCLUSIONS AND CLINICAL IMPORTANCE: Lokivetmab at a minimum monthly dose of 1 mg/kg provided quick onset (within one day) of a lasting effect in reducing pruritus and skin lesions with a good safety profile.

Comparative efficacy of a new spot-on combination product containing selamectin and sarolaner (Stronghold®Plus) versus fluralaner (Bravecto®) against induced infestations with Ixodes ricinus ticks on cats.

BACKGROUND: Ticks are increasingly reported on cats worldwide, with Ixodes ricinus being a relevant species across Europe and in near by areas of North Africa and the Middle East. Yet there are few acaracidal products with proven efficacy approved for use in cats. The objective of this study was to compare the efficacy of a new spot-on formulation containing selamectin and sarolaner with a topical application of fluralaner (Bravecto®) against Ixodes ricinus ticks on cats. To that end, twenty-four (24) cats were randomly allocated to one of three treatment groups. The cats in the control group remained untreated. Cats in group 2 were treated with selamectin/sarolaner (Stronghold®Plus; Zoetis) at the minimum recommended dose of 1.0 mg/kg sarolaner and 6.0 mg/kg selamectin on Days 0, 30 and 60. The cats in group 3 received a fluralaner treatment (Bravecto®spot-on solution for cats, MSD) at the minimum recommended dose of 40.0 mg/kg on Day 0. Cats were infested with 50 (± 4) viable, adult, unfed I. ricinus ticks on Days 26, 54, 82 and 89 and ticks were removed for counting 48 h (± 2 h) later. RESULTS: Three monthly treatments with selamectin/sarolaner provided high and consistent efficacy against I. ricinus for the entire duration of the study period. In contrast, the efficacy of fluralaner declined in the second month after treatment and was below the efficacy threshold of 90% on Days 56, 84 and 91. The percentage efficacy against I. ricinus was numerically higher in the selemectin/sarolaner treated group than in the fluralaner-treated group on Days 56, 84 and 91. Furthermore, greasiness and spiking of the hair, as well as white deposits were frequently observed in the fluralaner-treated cats. CONCLUSION: The results of the present study confirm the high and consistent efficacy of a new spot-on combination product containing selamectin and sarolaner against I. ricinus in cats, and indicate a decline in fluralaner efficacy during the 91 day period after treatment.