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Background: Canine acaricides with rapid onset and sustained activity can reduce pathogen transmission risk and enhance pet owner experience. This randomized, complete block design, investigator-masked study compared the speed of kill of Amblyomma americanum provided by three monthly-use isoxazoline-containing products., Methods: Eight randomized beagles per group were treated (day 0), per label, with sarolaner (combined with moxidectin and pyrantel, Simparica Trio™), afoxolaner (NexGard™), or lotilaner (Credelio™), or remained untreated. Infestations with 50 adult A. americanum were conducted on days - 7, - 2, 21, and 28, and tick counts were performed on day - 5 (for blocking), and at 4, 8, 12, 24, 48, and 72 h following treatment and subsequent infestations. Efficacy calculations were based on geometric mean live tick counts. A linear mixed model was used for between-group comparisons., Results: On day 0, only lotilaner significantly reduced an A. americanum infestation by 12 h (43.3%; P = 0.002). Efficacy of lotilaner and afoxolaner at 24 h post-treatment was 95.3% and 97.6%, respectively, both significantly different from sarolaner (74%) (P = 0.002, P < 0.001, respectively). On day 21, at 12 h postinfestation, lotilaner efficacy (59.6%) was significantly different from sarolaner (0.0%) (P < 0.001) and afoxolaner (6.3%) (P < 0.001). At 24 h, lotilaner efficacy (97.4%) was significantly different (P < 0.001) from sarolaner and afoxolaner (13.6% and 14.9%, respectively). On day 28, at 12 h postinfestation, lotilaner efficacy (47.8%) was significantly different from sarolaner (17.1%) (P = 0.020) and afoxolaner (9.0%) (P = 0.006). At 24 h, lotilaner efficacy (92.3%) was significantly different from sarolaner 4.9% (P < 0.001) and afoxolaner (0.0%) (P < 0.001). Speed of kill for sarolaner and afoxolaner, but not lotilaner, significantly declined over the study period. Following reinfestation on day 28, neither sarolaner nor afoxolaner reached 90% efficacy by 48 h. By 72 h, sarolaner efficacy was 97.4% and afoxolaner efficacy was 86.3%. Only lotilaner achieved ≥ 90% efficacy by 24 h post-treatment and 24 h postinfestation on days 21 and 28. Time to ≥ 90% efficacy following new infestations consistently occurred 24-48 h earlier for lotilaner compared with sarolaner or afoxolaner., Conclusions: Credelio (lotilaner) has a more rapid onset of acaricidal activity against A. americanum than Simparica Trio (sarolaner-moxidectin-pyrantel) and NexGard (afoxolaner). Only lotilaner's speed of tick kill is sustained throughout the dosing period., (© 2024. The Author(s).)

A veterinarian and pet owner survey (Project Jake) examined the use and safety of isoxazoline parasiticides given to dogs. Data were received during August 1-31, 2018 from a total of 2,751 survey responses. Forty-two percent (1,157) reported no flea treatment or adverse events (AE), while 58% (1594) had been treated with some parasiticide for flea control, and of those that received a parasiticide, the majority, or 83% (1,325), received an isooxazoline. When any flea treatment was given, AE were reported for 66.6% of respondents, with no apparent AE noted for 36.1%. Project Jake findings were compared to a retrospective analysis of publicly available Food and Drug Administration (FDA) and European Medicines Agency (EMA) reported AE. The number of total AE reported to FDA and EMA were comparable, although a 7 to 10 times higher occurrence of death and seizures was reported from the EMA or from outside the United States (US). Serious AE responses for death, seizures and neurological effects reported in our survey were higher than the FDA but moderately lower than the EMA reports. These sizable global data sets combined with this pre- and post-parasiticide administration survey indicated that isoxazoline neurotoxicity was not flea- and tick-specific. Post-marketing serious AE were much higher than in Investigational New Drug (IND) submissions. Although the labels have recently been updated, dogs, cats and their caregivers remain impacted by their use. These aggregate data reports support the need for continued cross-species studies and critical review of product labelling by regulatory agencies and manufacturers., (© 2020 The Authors. Veterinary Medicine and Science Published by John Wiley & Sons Ltd.)

Background: The Australian paralysis tick, Ixodes holocyclus, causes tick paralysis in dogs and cats in the eastern coastal regions of Australia. Prevention is the best option to protect dogs against this potentially fatal disease and sarolaner provides rapid and sustained efficacy against I. holocyclus. In this laboratory study, the efficacy of two combination endectocides containing sarolaner + moxidectin + pyrantel (Simparica Trio™) and afoxolaner + milbemycin (NexGard Spectra ® ) was evaluated against an artificial infestation of I. holocyclus., Methods: Twenty-four (n =24) foxhounds were randomly allocated to three treatment groups and artificially infested with 30 adult female viable ticks on Days - 1, 7, 14, 21, 28 and 35. On Day 0, dogs in each treatment group were treated with either Drontal ® (control group), Simparica Trio™ at the label dose to provide minimum doses of sarolaner (1.2 mg/kg), moxidectin (24 µg/kg) and pyrantel (5 mg/kg) or NexGard Spectra ® to provide minimum doses of afoxolaner (2.5 mg/kg) and milbemycin (0.5 mg/kg). Live tick counts were performed at 48 and 72 hours after treatment and after each re-infestation on Days 7, 14, 21, 28 and 35. Efficacy was determined at each time point relative to counts for control dogs based on geometric means., Results: Against an existing infestation, efficacy of both Simparica Trio™ and NexGard Spectra ® was 99.6% and 100% at 48 and 72 h time points, respectively (P = 1.000). Against subsequent weekly infestations, treatment with Simparica Trio™ and NexGard Spectra ® resulted in efficacy of ≥ 97.7% and ≥ 95.5% (P ≥ 0.0911), respectively at the 48 h time point and at the 72 h time point, Simparica Trio™ and NexGard Spectra ® resulted in efficacy of ≥ 99.0% and ≥ 98.4% (P ≥ 0.0511), respectively. There were no treatment-related adverse events in the study., Conclusions: Single doses of Simparica Trio™ and NexGard Spectra ® were highly efficacious and provided comparable efficacy against the Australian paralysis tick, I. holocyclus for up to 35 days.

Background: A novel chewable oral tablet containing sarolaner, moxidectin and pyrantel (Simparica Trio™) has recently been developed to provide persistent protection against flea and tick infections for a month, treatment of hookworm and roundworm infections and prevention of heartworm and lungworm disease in dogs. Two field studies were conducted to evaluate the safety and efficacy of Simparica Trio™ against natural flea and tick infestations on dogs in Europe., Methods: Dogs with natural flea or tick infestations were allocated randomly to treatment on Day 0 with either Simparica Trio™ tablets (flea study: n = 297; tick study: n = 189) to provide 1.2-2.4 mg/kg sarolaner, 24-48 µg/kg moxidectin and 5-10 mg/kg pyrantel (as pamoate salt) or with NexGard® Spectra (afoxolaner + milbemycin oxime) according to the label instructions (flea study: n = 164; tick study: n = 91). Efficacy was calculated based on the mean percent reduction in live parasite counts compared to the respective pre-treatment counts on Days 14 and 30 in the flea study and on Days 7, 14, 21 and 30 in the tick study. To count the fleas, the dog's entire coat was systematically combed using an extra fine-tooth flea comb until all fleas were removed. For the tick counts, the dog's entire coat was searched manually. Resolution of the clinical signs of flea allergy dermatitis (FAD) was assessed in flea allergic dogs in the flea study. Palatability was assessed in both studies., Results: Simparica Trio™ was well tolerated in both studies. Efficacy against fleas was ≥ 97.9% in the Simparica Trio™ group and ≥ 96.1% in the NexGard® Spectra group. Efficacy against ticks was ≥ 94.8% in the Simparica Trio™ group and ≥ 94.4% in the NexGard® Spectra group. Clinical signs of flea allergy dermatitis improved following treatment with Simparica Trio™. Simparica Trio™ tablets were voluntarily and fully consumed on ≥ 78% of the 485 occasions they were offered., Conclusions: A single oral dose of Simparica Trio™ was safe and highly efficacious against naturally occurring flea and tick infestations for 1 month on dogs. Clinical signs of FAD improved following treatment. Simparica Trio™ was voluntarily and readily consumed by most dogs.

Background: Tick infestations can cause direct deleterious effects to dogs as a result of tick blood-feeding, and indirectly ticks can transmit disease agents that can be detrimental to the health of both dogs and humans. Six laboratory studies were conducted to support dosage selection and efficacy confirmation of a novel combination of sarolaner, moxidectin and pyrantel against four tick species that commonly infest dogs in Europe., Methods: Two studies were conducted against Dermacentor reticulatus (one of which was a dose determination study), two against Ixodes ricinus, and one each against Ixodes hexagonus and Rhipicephalus sanguineus (sensu lato). In each study, eight purpose-bred Beagle or mix-breed dogs were randomly allocated to each treatment group and infested with 50 unfed adult ticks on Days-2, 5, 12, 19, 26 and 33. On Day 0 dogs were treated orally with placebo or the combination product. In the dose determination study, dogs received sarolaner at point dosages of 0.6 mg/kg, 1.2 mg/kg or 2.4 mg/kg in combination with moxidectin and pyrantel, and in all other studies dogs received Simparica Trio™ to provide minimum dosages of 1.2 mg/kg sarolaner, 24 µg/kg moxidectin and 5 mg/kg pyrantel (as pamoate salt). Efficacy was assessed based on live tick counts conducted 48 hours after treatment and each weekly infestation., Results: There were no treatment-related adverse events in any study. In the dose determination study, 1.2 mg/kg sarolaner was the lowest dosage evaluated that provided > 90% efficacy for at least 28 days and therefore was selected as the dosage to provide tick control for at least one month following a single oral treatment. In the dose confirmation studies, a single oral dose of Simparica Trio™ provided ≥ 99.2% efficacy against existing infestations of all tick species, and against re-infestations efficacy was ≥ 97.2% against D. reticulatus for 28 days and against all other species for 35 days., Conclusions: These studies support the sarolaner dose selected and confirm the efficacy of a single oral dose of Simparica Trio™ against existing infestations and re-infestations of the common tick species infesting dogs in Europe for at least one month.

Background: The efficacy of a novel oral combination product, Simparica Trio™, containing sarolaner, moxidectin and pyrantel was evaluated against five tick species that commonly infest dogs in the USA, Amblyomma americanum, Amblyomma maculatum, Dermacentor variabilis, Ixodes scapularis and Rhipicephalus sanguineus., Methods: Laboratory studies were conducted against two different strains of each tick species. In each study, 10 purpose-bred Beagle or mixed-breed dogs were randomly allocated to one of two treatment groups based on pre-treatment host-suitability tick counts. Dogs were infested with approximately 50 (45-55) unfed adult ticks on Days -2, 5, 12, 19, 26 and 33. On Day 0, dogs received either a single oral dose of 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) or placebo. Tick counts were conducted at 48 h post-treatment and after each subsequent weekly re-infestation for A. maculatum, D. variabilis, I. scapularis and R. sanguineus studies and at 48 hours or at 72 h post-treatment and after weekly re-infestation in the first and second A. americanum studies, respectively., Results: No treatment-related adverse reactions occurred in any study. In all studies, placebo-treated dogs maintained infestations throughout the entire study duration, and dogs treated with Simparica Trio™ had significantly lower (P ≤ 0.0010) mean live tick counts than placebo-treated dogs at all time-points. Against A. maculatum, D. variabilis, I. scapularis and R. sanguineus, a single oral dose of Simparica Trio™ evaluated at 48 h post-treatment provided ≥ 98.9% efficacy against existing infestations, and within 48 h of re-infestation efficacy was ≥ 90.4% through at least Day 28 (except for R. sanguineus on Day 14 in a single study with an efficacy of 89.7%). Against A. americanum, Simparica Trio™ provided ≥ 99.4% efficacy at ≤ 72 h after treatment of existing infestations and maintained ≥ 98.4% efficacy at ≤ 72 h after re-infestation through at least Day 35., Conclusions: A single dose of Simparica Trio™ administered orally at the minimum label dosage of 1.2 mg/kg sarolaner, 24 µg/kg moxidectin and 5 mg/kg pyrantel provided treatment and control of the common tick species infesting dogs in the USA for at least one month.

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.

Background: Haemaphysalis longicornis is the major tick affecting dogs in most of the East Asia/Pacific region and has recently been detected in a number of areas of the USA. This tick is a vector for a number of pathogens of dogs, other mammals and humans. In this study, the efficacy of a single oral administration of sarolaner (Simparica ® , Zoetis) at the minimum label dosage (2 mg/kg) was evaluated against an existing infestation of H. longicornis and subsequent weekly reinfestations for 5 weeks after treatment., Methods: Sixteen dogs were ranked on pretreatment tick counts and randomly allocated to treatment on Day 0 with sarolaner at 2 mg/kg or a placebo. The dogs were infested with H. longicornis nymphs on Days - 2, 5, 12, 19, 26 and 33. Efficacy was determined at 48 hours after treatment and subsequent re-infestations based on live tick counts relative to placebo-treated dogs., Results: There were no adverse reactions to treatment. A single dose of sarolaner provided 100% efficacy on Days 2, 7, 14 and 21; and ≥ 97.4% efficacy on Days 28 and 35. Considering only attached, live ticks, efficacy was 100% for the entire 35 days of the study. Geometric mean live tick counts for sarolaner were significantly lower than those for placebo on all days (11.62 ≤ t (df)  ≤ 59.99, where 13.0 ≤ df ≤ 14.1, P < 0.0001)., Conclusions: In this study, a single oral administration of sarolaner at 2 mg/kg provided 100% efficacy against an existing infestation of H. longicornis nymphs and ≥ 97.4% efficacy (100% against attached ticks) against weekly reinfestation for at least 35 days after treatment.

Cytauxzoonosis, caused by infection with Cytauxzoon felis, is the most severe tick-borne disease of cats. The purpose of our study was to determine the efficacy of selamectin (6.0 mg/kg) plus sarolaner (1.0 mg/kg) formulated in combination (Revolution® Plus / Stronghold ® Plus, Zoetis) applied topically once a month on cats for three months against induced infestations of Amblyomma americanum adults and to evaluate the effectiveness of the product in preventing the transmission of C. felis. This study was conducted in two phases. Sixteen cats were dosed with selamectin/sarolaner or a placebo (vehicle control) on Days 0, 28, and 56. In phase 1, each cat was infested with 50 (±5) unfed adult A. americanum on Day 4 and tick counts were conducted on Day 6 (48 h post infestation) and Day 7 (72 h post infestation) to evaluate acaricidal efficacy. In phase 2, to confirm acaricidal efficacy and evaluate prevention of C. felis transmission, each cat was infested on Day 60 with 50 (±5) adult A. americanum acquisition fed as nymphs on two C. felis-infected donor cats. Tick counts were conducted on Day 62 (48 h post infestation) and Day 63 (72 h post infestation). Blood samples were collected on Days -9, 60, 70, 76, and 90 and tested for infection with C. felis. Placebo cats were adequately infested on all count days, with least squares (geometric) mean live tick counts ranging from 34.0 (28.8) to 46.1 (46.0). Treatment reduced the least squares (geometric) mean counts compared to placebo by 27.1 (32.1)% and 90.4 (96.8)% on Days 6 and 7, respectively. The corresponding percent reductions were 56.4 (60.6)% and 94.7 (97.3)% on Days 62 and 63, respectively. Least squares mean counts were significantly lower in the treated group compared with the placebo group on all count days (P ≤ 0.0286). All cats were negative for C. felis by PCR prior to study start. In phase 2, seven cats in the control group and no cats in the selamectin/sarolaner group became infected with C. felis (P = 0.0017). Topical treatment with selamectin/sarolaner was >90% effective in reducing A. americanum tick counts 72 h after infestation and prevented the transmission of C. felis from infected ticks following the third of three monthly treatments. Revolution ® Plus / Stronghold ® Plus offers an option for the control of A. americanum infestations on cats and for preventing the transmission of C. felis to cats., (Copyright © 2019 Zoetis Services LLC. Published by Elsevier B.V. All rights reserved.)

The efficacy of a single application of a new topical formulation containing selamectin plus sarolaner (Revolution ® Plus / Stronghold ® Plus, Zoetis) was evaluated against fleas and ticks infesting cats enrolled as veterinary patients in two field studies conducted in Japan and against Haemaphysalis longicornis ticks on cats in a laboratory study. In the laboratory study, sixteen cats were ranked based on pre-treatment tick counts and allocated randomly to treatment on Day 0 with either selamectin plus sarolaner or placebo. Cats were infested with adult H. longicornis on Days -2, 5, 12, 19, 26 and 33. Efficacy relative to placebo was based on live attached tick counts conducted 48 h after treatment and subsequent re-infestations. Selamectin plus sarolaner reduced live, attached H. longicornis counts by 96.4% within 48 h of treatment, and by ≥91.7% within 48 h of weekly re-infestation for 35 days, based on arithmetic means. In the field studies, 67 client-owned cats harboring six or more live fleas and 63 cats harboring four or more live attached ticks were enrolled to evaluate selamectin plus sarolaner for efficacy and safety compared with a registered product. Cats were allocated randomly to treatment with selamectin plus sarolaner or fipronil plus (S)-methoprene based on order of presentation. Treatment was administered once on Day 0 and efficacy was assessed by parasite counts conducted on Days 14 and 30 compared to the pre-treatment count. In the flea field study, live flea counts on Days 14 and 30 were reduced by 99.5% and 99.9% in the selamectin plus sarolaner group, and by 97.6% and 98.6% in the fipronil plus (S)-methoprene group, based on least squares mean percentage reductions. Clinical signs typically associated with flea allergy dermatitis improved following treatment. In the tick field study, live tick counts on Days 14 and 30 were reduced by 97.5% and 97.7% in the selamectin plus sarolaner group, and by 91.5% and 93.4% in the fipronil plus (S)-methoprene group, based on least squares mean percentage reductions. Selamectin plus sarolaner was determined to be non-inferior to fipronil plus (S)-methoprene in both field studies. There were no treatment-related adverse events in any study. A single topical dose of Revolution ® Plus / Stronghold ® Plus providing a minimum dosage of 6.0 mg/kg selamectin and 1.0 mg/kg sarolaner was confirmed to be effective against H. longicornis ticks on cats for one month and safe and effective in the treatment of fleas and ticks on cats enrolled as veterinary patients in Japan., (Copyright © 2019 Zoetis Services LLC. Published by Elsevier B.V. All rights reserved.)

The efficacy of three consecutive monthly treatments with a novel topical product (Revolution ® Plus/Stronghold ® Plus, Zoetis) containing selamectin in combination with the isoxazoline, sarolaner, was compared with that of another topical isoxazoline, fluralaner [Bravecto ® (fluralaner topical solution) for Cats, Merck] against Ixodes scapularis ticks on cats. Twenty-four cats were ranked by pre-treatment tick counts to form groups of three and were randomly allocated to be treated with placebo, the minimum label dosage of Revolution ® Plus (6 mg/kg selamectin plus 1 mg/kg sarolaner) or the minimum label dosage of Bravecto ® for Cats (40 mg/kg fluralaner) within the groups. On Days 0, 30, and 60, each cat in the placebo and Revolution ® Plus-treated groups was treated topically, whereas cats in the Bravecto ® for Cats-treated group were treated topically once on Day 0 with fluralaner and, subsequently, these animals were treated with the placebo on Days 30 and 60 to maintain masking. Doses were calculated based on weight to provide the minimum label dosage for each product; the calculated volume of product to be administered was rounded off to the nearest 0.1 mL. The selamectin plus sarolaner-treated cats received effective dosages of 5.29-7.12 mg/kg selamectin and 0.88-1.19 mg/kg sarolaner, while the fluralaner cats received dosages of 35.21-43.16 mg/kg fluralaner. Cats were infested with approximately 50 unfed viable adult I. scapularis ticks on Days 5, 12, 26, 40, 54, 68, 82, and 88. Efficacy was assessed at 48 h after each infestation. There were no adverse reactions to any treatment during the study. The placebo-treated cats maintained adequate tick infestations throughout the study. Three monthly treatments with selamectin plus sarolaner (Revolution ® Plus) resulted in high and consistent efficacy against I. scapularis for up to 30 days after each treatment. Based on geometric means, efficacy was ≥99.1% at all time points assessed. Treatment with fluralaner (Bravecto ® for Cats) provided high and consistent efficacy of ≥99.3% up to Day 70. On Day 84, efficacy was 90.1%; however, cats from which ticks were recovered on Day 84 had received approximately 4%-12% less than the minimum dosage of 40 mg/kg fluralaner. Three consecutive monthly treatments with Revolution ® Plus or a single treatment with Bravecto ® for Cats provided >90% control of I. scapularis ticks over a 12-week time period., (Copyright © 2019 Zoetis Services LLC. Published by Elsevier B.V. All rights reserved.)

The efficacy of a single topical application of a combination product containing selamectin and sarolaner (selamectin/sarolaner; Revolution ® Plus/Stronghold ® Plus) was evaluated in seven laboratory studies against Ixodes scapularis (three studies), Dermacentor variabilis (two studies), or Amblyomma maculatum (two studies). In each study, cats were randomly allocated to treatment groups based on pre-treatment host-suitability tick counts. On Days -2, 5, 12, 19, 26 and 33, the cats were infested with unfed adult ticks. On Day 0, cats were treated with either a placebo (vehicle control) or with the spot-on solution at the minimum dose of 6.0 mg selamectin and 1.0 mg sarolaner/kg bodyweight. In one study with I. scapularis and one with D. variabilis an additional group of cats was treated with selamectin alone (Revolution ® , Zoetis) at 6.0 mg/kg bodyweight. Tick counts were conducted after treatment and after each weekly re-infestation and efficacy determined relative to placebo-treated animals. There were no treatment-related adverse reactions in any of the studies. Geometric mean live tick counts were significantly (P < 0.05) lower in the selamectin/sarolaner-treated groups compared to the geometric mean tick counts in the placebo-treated groups at all time-points in all studies. For all species, a single topical administration of the selamectin/sarolaner combination resulted in>90% efficacy against existing infestations based on geometric means. Efficacy against weekly re-infestations was >90% based on geometric means for at least 5 weeks for I. scapularis and D. variabilis, and for at least 4 weeks against A. maculatum. Selamectin alone had no efficacy against I. scapularis, where counts on selamectin-treated cats were not significantly different from placebo at all time points (P > 0.05), and for D. variabilis, counts were not significantly different from placebo at 2, 3 and 5 weeks after treatment (P > 0.05) and efficacy was never greater than 85%. Thus, the activity of the sarolaner against three common tick species found on cats in the US is complementary to the existing broad-spectrum parasite control of selamectin. The inclusion of sarolaner with selamectin in a combination product (Revolution ® Plus/Stronghold ® Plus) provides for the treatment of existing tick infestations and gives at least one month of control against re-infestation following a single topical application., (Copyright © 2019 Zoetis Services LLC. Published by Elsevier B.V. All rights reserved.)

The speed of kill of a novel, topical product containing selamectin in combination with sarolaner (selamectin/sarolaner; Revolution ® Plus/Stronghold ® Plus) was evaluated against Ixodes scapularis ticks on cats. Sixteen cats were randomly allocated to a treatment group and treated topically on Day 0 with either placebo (vehicle control) or 6 mg/kg selamectin plus 1 mg/kg sarolaner. Cats were infested with approximately 50 unfed viable adult I. scapularis ticks on Days -2, 7, 14, 21, 28 and 35. Efficacy was assessed at 4, 8, 12, 24, 48 and 72 h after treatment on Day 0 and at 4, 8, 12 and 24 h after post-treatment re-infestations. There were no adverse reactions to the topical treatment with selamectin/sarolaner. Placebo-treated cats maintained tick infestations throughout the study. Treatment with selamectin/sarolaner significantly reduced tick counts within 12 h (P < 0.0001) and resulted in 100% efficacy by 24 h. For subsequent re-infestations, live tick counts were significantly reduced by 12 h after infestation on Day 7 (P = 0.0120) and by 24 h for Days 14-35 (P < 0.0001). At 24 h after the post-treatment re-infestations, efficacy based on geometric (arithmetic) means was ≥96.1% (94.5%) through Day 21, 75.3% (67.7%) on Day 28 and 66.4% (56.4%) on Day 35. Thus, a single topical dose of Revolution ® Plus/Stronghold ® Plus at the recommended minimum dose started killing ticks within 12-24 hours after treatment and re-infestations for up to 5 weeks. High acaricidal efficacy (≥90% reduction in tick burden) was achieved within 24 h after treatment and subsequent re-infestations for at least three weeks., (Copyright © 2019 Zoetis Services LLC. Published by Elsevier B.V. All rights reserved.)

Background: Canine babesiosis is a clinically significant emerging vector-borne disease caused among others by the protozoan Babesia canis. The efficacy of sarolaner (Simparica®; Zoetis; at the minimum recommended label dose of 2.0 mg per kg bodyweight) in the prevention of babesiosis was evaluated in twenty-four dogs randomly allocated to either a placebo-treated group or one of two sarolaner-treated groups. At 21 or 28 days after treatment administration, dogs were infested with 50 ± 4 Dermacentor reticulatus ticks of which 25% were confirmed to be infected with Babesia canis. Blood samples were collected from each dog prior to tick infestation and weekly thereafter until 49 days after infestation. The blood was assayed for B. canis antibodies using an indirect immunofluorescence test (IFAT) and for B. canis DNA by PCR assay. A dog was a priori defined as B. canis-positive if it tested positive by both IFAT 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 IFAT and PCR. None of the sarolaner-treated animals displayed any clinical symptoms or tested positive on both IFAT and PCR, resulting in a 100% efficacy in the prevention of canine babesiosis (P = 0.0002)., Conclusion: When given 21 or 28 days before tick infestation, a single treatment with sarolaner at the minimum recommended label dose of 2.0 mg per kg body weight prevented the transmission of B. canis by D. reticulatus to dogs.

Background: Amblyomma cajennense is the main vector of Rickettsia rickettsii which causes Brazilian spotted fever. This adult tick preferably infests horses and capybaras, but has low host specificity during its immature stages, thus posing a threat to humans and dogs. In this study, the efficacy of sarolaner (Simparic™/Simparica®, Zoetis) when administered once orally to dogs at 2 mg/kg was evaluated against induced infestations of A. cajennense nymphs for up to 35 days after treatment., Methods: Based on pretreatment tick counts, 20 dogs were randomly allocated to treatment with sarolaner (Simparic™) dosed at 2 mg/kg of body weight or a placebo on Day 0 of the study. Artificial infestations were performed using laboratory raised A. cajennense nymphs on study days -2, 5, 12, 19, 26 and 33. Efficacy was determined at 48 h post-treatment or post-infestation at each time point relative to the counts for dogs that received placebo., Results: There were no adverse reactions to treatment. A single dose of sarolaner (Simparic™) provided 100% efficacy on study days 2, 7 and 14; and ≥ 99.6% on days 21, 28 and 35. Geometric mean live tick counts for sarolaner were significantly lower than those for placebo on all days (P < 0.0001)., Conclusions: Under the conditions of the present study, sarolaner (Simparic™) administered once orally at 2 mg/kg provided 100% efficacy against existing infestations and ≥ 99.6% efficacy within 48 h against weekly challenges of A. cajennense for at least 35 days after treatment.

Background: 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., Methods: 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., Results: 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., Conclusions: 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.