Efficacy of sarolaner (Simparica®) against induced infestations of Haemaphysalis longicornis on dogs.

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.

Efficacy and safety of a new topical formulation containing selamectin and sarolaner in the prevention of heartworm disease and the treatment of roundworm infection in cats presented as veterinary patients in Japan.

The efficacy and safety of a new topical formulation containing selamectin plus sarolaner (Revolution® Plus / Stronghold® Plus, Zoetis) was evaluated for the prevention of heartworm (Dirofilaria immitis) disease and the treatment of roundworm infection in cats enrolled as veterinary patients in two field studies conducted in Japan. In the heartworm field study, 91 cats negative for D. immitis antigen and anti-D. immitis antibody were enrolled and received 9 monthly topical treatments with selamectin plus sarolaner during the period of April to December 2015. Efficacy was assessed by testing post-treatment blood samples collected 8, 12, and 15 months after initiation of treatment for the presence of D. immitis antigen and anti-D. immitis antibody. Eighty-seven cats completed the entire study and were included in the determination of efficacy. No D. immitis antigen or anti-D. immitis antibody were detected in any of the post-treatment samples. In the roundworm field study, completed in the period from April to November 2015, 64 cats with ≥100 roundworm eggs per gram (EPG) of feces were enrolled and allocated randomly in a 1:1 ratio, to receive either selamectin plus sarolaner or emodepside plus praziquantel (Profender®, Bayer). Treatments were administered topically on Days 0 and 30, and efficacy was assessed by fecal EPG counts conducted on Days 14, 30, and 60. All cats completed the entire study. At enrollment, all cats were infected with Toxocara cati. Compared to pre-treatment, geometric mean T. cati EPG counts on Days 14, 30, and 60 were reduced by >99.9% in both treatment groups. There were no treatment-related adverse events in either study. Monthly topical administration of Revolution® Plus / Stronghold® Plus providing a minimum of 6 mg/kg selamectin and 1 mg/kg sarolaner was safe and effective in the prevention of heartworm disease and the treatment of roundworm infection in cats enrolled as veterinary patients in Japan.

Efficacy of a new topical formulation of selamectin plus sarolaner for the control of fleas and ticks infesting cats in Japan.

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.

Efficacy of a new topical formulation containing selamectin plus sarolaner against three common tick species infesting cats in the United States.

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.

Efficacy and safety of a new topical formulation of selamectin plus sarolaner in the treatment and control of natural infections of Ancylostoma tubaeforme and Toxocara cati in cats presented as veterinary patients in the United States.

A new topical formulation of selamectin plus sarolaner (Revolution® Plus/Stronghold® Plus, Zoetis) was evaluated in the treatment and control of naturally occurring infections of Ancylostoma tubaeforme and Toxocara cati in cats presented as veterinary patients in the United States. Three thousand three hundred three (3303) cats were screened in 25 veterinary practices in 15 states and 153 hookworm-positive cats (A. tubaeforme and/or A. braziliense), mainly from Alabama, Mississippi, Texas, and Hawaii, were identified; 135 cats met all the criteria for enrollment and were included on study. The cats were randomly assigned to treatment with Revolution® (at the label dosage, to provide a minimum dosage of 6 mg/kg selamectin) or selamectin plus sarolaner (at a dosage of 6-12 mg/kg plus 1-2 mg/kg, respectively). Treatments were administered at the time of enrollment and repeated 30 days later. Fecal samples were collected for differential fecal egg count prior to the first treatment (Day 0), prior to the second treatment (Day 30), and approximately 30 days later (Day 60). Efficacy was based on the percentage reductions in geometric mean fecal egg count for A. tubaeforme on Day 30 and Day 60 compared with Day 0. Where cats were co-infected with T. cati, efficacy against this species was also evaluated. Efficacy data were evaluated for A. tubaeforme for 40 cats on both Day 30 and Day 60 for the group treated with the selamectin/sarolaner combination and reductions in geometric mean fecal egg counts of 99.4% and 99.7% were demonstrated for Day 30 and Day 60, respectively. For the group treated with selamectin alone, 44 and 40 cats were evaluated and percent reductions for Day 30 and Day 60 were 99.5% and 99.9%, respectively. For T. cati, 14 cats were evaluated in the selamectin/sarolaner-treated group for Day 30 and for Day 60, and the reduction in geometric mean fecal egg count was 100% for both days. There were 11 and 9 cats evaluated for Day 30 and Day 60, respectively, for the selamectin-treated group and the reduction was again 100% for both days. The geometric mean fecal egg counts post-treatment were significantly lower than pre-treatment for both A. tubaeforme and T. cati, for both treatments, and for both periods of interest (P < 0.0001). No serious adverse events related to treatment with either product occurred during the study. Thus, both selamectin alone and the combination product of selamectin/sarolaner were safe and effective when administered on a monthly basis for the treatment and control of natural infections of A. tubaeforme and T. cati. The addition of sarolaner to the formulation did not interfere with the efficacy of selamectin against these nematodes.

The speed of kill of a topical combination of selamectin plus sarolaner against induced infestations of Ixodes scapularis ticks on cats.

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.

Efficacy and safety of a combination of selamectin plus sarolaner for the treatment and prevention of flea infestations and the treatment of ear mites in cats presented as veterinary patients in the United States.

Two randomised, single-masked, multi-center field studies were conducted in the United States in cats presented as veterinary patients. The first study evaluated the efficacy and safety of a topically applied formulation of selamectin plus sarolaner (Revolution® Plus/Stronghold® Plus, Zoetis) against natural flea infestations; the second study evaluated its efficacy against natural ear mite infestations. The product was administered topically by the cats' owners at the dose range provided in the market product of 6.0-12.0 mg selamectin and 1.0-2.0 mg sarolaner per kg bodyweight. Imidacloprid plus moxidectin (Advantage® Multi for Cats, Bayer) was used as a positive control in both studies at the label dosage. In the flea study, treatments were administered on Days 0, 30, and 60. Efficacy was calculated based on the mean percent reduction of live flea counts on Days 30, 60, and 90 relative to the pre-treatment count. In the ear mite study, a single treatment was applied on Day 0 and efficacy was determined on Days 14 and 30 based on the presence or absence of ear mites. In both studies, patients were randomly allocated to treatments in the ratio of 2:1, selamectin plus sarolaner: imidacloprid plus moxidectin. In the two studies, 405 cats received treatment with selamectin plus sarolaner; of these, 256 cats received three monthly treatments in the flea study. There were no serious adverse reactions to treatment with selamectin plus sarolaner; health issues noted were typical of the normal ailments or minor traumatic injuries expected in the general cat population and were similar in both treatment groups. Efficacy against fleas based on geometric (arithmetic) means was 97.2% (95.9%), 99.5% (99.4%), and 99.8% (99.8%) in the selamectin plus sarolaner group and was 79.7% (70.5%), 91.4% (77.3%), and 95.5% (87.4%) in the imidacloprid plus moxidectin group on Days 30, 60, and 90, respectively. Flea counts for the selamectin plus sarolaner group were significantly lower than the counts for the imidacloprid plus moxidectin group at all time-points after treatment administration on Day 0 (P < 0.001). Treatment reduced the clinical signs of flea allergy dermatitis (alopecia, dermatitis/pyodermatitis, erythema, pruritus, scaling, and papules) in affected cats by 86.7%-100% in the selamectin plus sarolaner group and by 66.7%-100% in the imidacloprid plus moxidectin group. In the ear mite study, a single application of selamectin plus sarolaner resulted in the clearance of mites from 87.5% of cats within 14 days and 94.4% of cats within 30 days of treatment. The respective percentages of mite-free cats in the imidacloprid plus moxidectin group were 64.0% and 72.0%. There were significantly more cats with no mites noted in the selamectin plus sarolaner group than in the imidacloprid plus moxidectin group on Day 14 and Day 30 (P ≤ 0.018). Selamectin plus sarolaner (Revolution® Plus/Stronghold® Plus) administered topically at monthly intervals for three months was well tolerated and highly effective for the treatment and prevention of natural infestations of fleas on cats presented as veterinary patients. Clinical signs of flea allergy dermatitis improved in affected cats following treatment administration. A single topical treatment was also safe and highly effective for the treatment of ear mite infestations in naturally infested cats.

Efficacy of oral moxidectin against susceptible and resistant isolates of Dirofilaria immitis in dogs.

BACKGROUND: Monthly topical and sustained-release injectable formulations of moxidectin are currently marketed; however, an oral formulation, while approved at a dose of 3 µg/kg, is not currently marketed in the United States. Although resistance of heartworms to all macrocyclic lactone (ML) heartworm preventives (ivermectin, milbemycin, selamectin and moxidectin) has been demonstrated, to date no data have been reported on the effectiveness of oral moxidectin against recent isolates of Dirofilaria immitis. METHODS: A total of nine studies were conducted to determine the efficacy of moxidectin against a range of older and recently sourced heartworm isolates. Dogs (groups of three to eight) were inoculated with 50 D. immitis infective larvae (L3) from nine different isolates (MP3, Michigan, JYD-34, ZoeMO-2012, ZoeKy-2013, ZoeLA-2013, GCFL-2014, AMAL-2014 and ZoeAL-2015) and treated 28-30 days later with single oral doses of 3 µg/kg of moxidectin. Additionally, one group of dogs that was inoculated with JYD-34 was treated monthly for 3 consecutive months beginning 30 days post inoculation. Dogs were held for approximately 4 months after the initial (or only) treatment and then necropsied for recovery of adult heartworms. RESULTS: A single dose of 3 µg/kg of moxidectin was 100% effective in preventing the development of five of nine heartworm isolates (MP3, Michigan, ZoeKy, GCFL and ZoeAL isolates), confirming their susceptibility to oral moxidectin at this dose. MP3 and Michigan are isolates sourced from the field more than 9 years ago, while ZoeKy, ZoeAL and GCFL were isolated from the field within the past 2 to 3 years. Against JYD-34, ZoeMO, ZoeLA and AMAL isolates, a single dose of 3 µg/kg of moxidectin was not completely effective, with efficacies of 19%, 82%, 54% and 62%, respectively, demonstrating resistance of these heartworm isolates to oral moxidectin at this dosage. Three consecutive monthly doses of 3 µg/kg of moxidectin were also incompletely effective against the JYD-34 isolate, with an efficacy of 44%. JYD-34 was originally isolated in 2010, while ZoeMO, ZoeLA and AMAL were isolated within the past 2 to 3 years. CONCLUSIONS: A single oral dose (3 µg/mg) of moxidectin was 100% effective in preventing the development of ML-susceptible heartworm isolates while being incompletely effective against ML-resistant isolates.

Efficacy and safety of a new spot-on formulation of selamectin plus sarolaner in the treatment of naturally occurring flea and tick infestations in cats presented as veterinary patients in Europe.

Two randomised, blinded, multi-centre field studies were conducted in Europe (Germany, Italy, France, Hungary) to demonstrate the efficacy and safety of three monthly applications of a new spot-on formulation of selamectin plus sarolaner (Stronghold® Plus, Zoetis) against natural flea or tick infestations in cats presented as veterinary patients. The spot-on formulation was administered at the commercial dose range of 6.0-12.0mg selamectin and 1.0-2.0mg sarolaner per kg bodyweight. In the flea study, the improvement in clinical signs associated with flea allergy dermatitis (FAD) was also monitored. Imidacloprid plus moxidectin (Advocate® for Cats, Bayer) and fipronil (Frontline® Spot on, Merial) were used as positive control products in the flea and tick studies, respectively. Treatments were administered on Days 0, 30 and 60. Efficacy was calculated based on the mean percent reduction of live parasite counts on post-treatment days 14, 30, 60 and 90 versus the pre-treatment count on Day 0. Non-inferiority of selamectin/sarolaner to the control products was assessed at each time-point using a non-inferiority margin of 15% at the one-sided 0.025 significance level. Cats were enrolled in a 2:1 ratio (selamectin/sarolaner:comparator). In the flea study, 277 cats were assessed for efficacy and safety, and an additional 170 cats were assessed for safety only. On days 14, 30, 60 and 90, efficacy against fleas was 97.4%, 97.3%, 98.8% and 99.4% in the selamectin/sarolaner-treated group and was 90.0%, 83.6%, 87.7% and 96.3% in the imidacloprid/moxidectin-treated group, respectively. Selamectin/sarolaner was non-inferior to imidacloprid/moxidectin at all time-points. For the 16 cats identified as having FAD at enrolment, clinical signs related to FAD improved following treatment administration. In the tick study, 200 cats were assessed for efficacy and safety, and a further 70 cats were assessed for safety only. Four tick species were identified. Overall efficacy against ticks was 96.7%, 92.6%, 98.8% and 99.5% in the selamectin/sarolaner-treated group and was 90.2%, 74.6%, 83.0% and 93.4% in the fipronil-treated group on Days 14, 30, 60 and 90, respectively. Selamectin/sarolaner was non-inferior to fipronil at all time-points, and was superior on Days 30 and 60. There were no serious treatment-related adverse events in any study. Thus, the new spot-on formulation of selamectin plus sarolaner administered at monthly intervals was safe and highly effective against natural infestations of fleas and ticks on cats, and improved clinical signs of FAD.

Efficacy and speed of kill of a new spot-on formulation of selamectin plus sarolaner against flea infestations in cats.

The efficacy of a new spot-on formulation of selamectin plus sarolaner against induced flea infestations in cats was confirmed in three placebo-controlled, blinded studies. Purpose-bred adult cats (n=8/group) were blocked by pre-treatment flea counts and randomly allocated to treatment with either a placebo or with the spot-on formulation at the minimum dose of 6.0mg selamectin and 1.0mg sarolaner per kg bodyweight. Treatments were applied topically once on Day 0. All cats were infested with approximately 100 unfed, adult Ctenocephalides felis prior to treatment and at weekly intervals for 5 weeks. In Studies 1 and 2 comb counts were conducted to determine the numbers of viable fleas 24h after treatment and subsequent weekly infestations. In Study 3, flea counts were conducted at 6, 12, 24 and 48h after treatment and 3, 6, 12 and 24h after subsequent weekly infestations to evaluate the speed of kill against fleas. Cats in the placebo-treated groups maintained flea infestations throughout all studies. In Study 1, no live fleas were found on any of the treated cats, resulting in 100% efficacy for 5 weeks after a single treatment (P≤0.0001). In Study 2, selamectin/sarolaner reduced flea counts by 92.4% immediately after treatment and by 97.7%-100% after re-infestations for five weeks (P≤0.0001). In the speed of kill study, selamectin/sarolaner started killing fleas within 12h after treatment administration and within 6h following re-infestation for at least 28days. Efficacy was 98.1% by 24h after treatment and 100% within 24h after re-infestations for 5 weeks. A single topical administration of a new spot-on formulation of selamectin plus sarolaner at the minimum dose rapidly and consistently kills fleas on cats for at least 5 weeks.

Efficacy of a new spot-on formulation of selamectin plus sarolaner for cats against adult Ctenocephalides felis, flea egg production and adult flea emergence.

A new spot-on formulation of selamectin plus sarolaner was evaluated against fleas for adulticidal efficacy, and for the effect on egg production and hatching when applied to flea-infested cats. Ten male and ten female adult domestic shorthair cats were randomly assigned to one of two treatment groups based on pre-treatment flea counts. Cats received topical treatment on Day 0 in a single spot to the dorsal scapular area with either a placebo formulation or with the combination formulation at the minimal dose of 6.0mg selamectin plus 1.0mg sarolaner per kg bodyweight. On Days -1, 5, 12, 19, 26 and 33, cats were infested with approximately 100 (±5) unfed Ctenocephalides felis fleas. At 24h after treatment or 48h after subsequent flea infestation, cats were housed for a 20-h period in a cage to allow collection of flea eggs. At the end of this period, flea eggs were collected from the cages and cats were combed to remove and count live fleas. Emerged viable larvae and emerged adult fleas were counted 3days and 35days, respectively, after egg collection. The new spot-on formulation of selamectin plus sarolaner provided 100% efficacy against adult fleas up to Day 36 following a single application. Fleas on placebo-treated cats produced large numbers of eggs throughout the study, with individual counts ranging from 110 to 1256 eggs. Following treatment, four flea eggs were collected from a single selamectin/sarolaner-treated cat on Day 29, but there were no eggs collected from any other selamectin/sarolaner-treated animal during the study. No larvae or adult fleas developed from these four eggs. From the eggs collected from the placebo-treated cats, the mean percentage of live larvae and adults that emerged ranged from 67.3% to 84.2% and from 50.7% to 81.8%, respectively. A single topical treatment with a new spot-on formulation of selamectin plus sarolaner at the minimum label dose thus controlled fleas on cats and was 100% effective in preventing flea reproduction for over one month after treatment.

Efficacy of a new spot-on formulation of selamectin plus sarolaner against four common tick species infesting cats in Europe.

A single application of a new spot-on formulation of selamectin plus sarolaner (Stronghold®Plus, Zoetis) was evaluated for efficacy against the most common tick species infesting cats in Europe. In each of the seven laboratory studies, 16 adult and purpose-bred cats were randomly allocated to one of two treatment groups based on pre-treatment tick counts. Weekly infestations with 50 unfed adult Ixodes ricinus (2 studies), Ixodes hexagonus (1 study), Dermacentor reticulatus (2 studies), or Rhipicephalus sanguineus (2 studies) were scheduled on Days -2, 5, 12, 19, 26 and 33. Cats were treated on Day 0 with the spot-on formulation at the minimum recommended label dose of 6.0mg selamectin and 1.0mg sarolaner per kg bodyweight or with a placebo. Ticks were counted 48h after treatment and after each re-infestation. No treatment-related adverse reactions were recorded in any of the studies. Geometric mean live tick counts were significantly (P≤0.0012) lower in the selamectin/sarolaner-treated group compared to the placebo-treated group at all time-points. Against I. ricinus and I. hexagonus, efficacy was ≥97.2% against existing infestations and ≥97.4% against weekly re-infestations for at least 5 weeks. Treatment was 100% effective against existing R. sanguineus infestations and was ≥95.8% for at least 4 weeks. Against D. reticulatus treatment resulted in ≥94.4% efficacy for at least 4 weeks. Thus, a single application of the new spot-on formulation of selamectin plus sarolaner at the minimum dose provides rapid treatment of existing infestations and is at least one month effective against re-infestation by all relevant European tick species in cats.

Efficacy of a new spot-on formulation of selamectin plus sarolaner against Ancylostoma tubaeforme and Toxocara cati in cats.

The efficacy of a new spot-on formulation of selamectin plus sarolaner for cats was evaluated against induced infections with Ancylostoma tubaeforme (hookworm) and Toxocara cati (roundworm). Five laboratory studies were conducted using adult, purpose-bred cats. Four of the studies were designed to evaluate efficacy of the combination against A. tubaeforme, the dose-limiting gastrointestinal nematode species for selamectin. In two of these studies non-interference between selamectin and sarolaner was also evaluated. The fifth study evaluated efficacy of the combination against mixed infections of A. tubaeforme and T. cati. The hookworm isolates in three studies were of US origin, as was the roundworm isolate. In the two remaining studies, cats were inoculated with a hookworm isolate of European origin. Cats were inoculated with 150 (±50) to 200 (±50) infective hookworm larvae 30-42days prior to treatment and with 400 infective roundworm eggs 60days prior to treatment. Cats were ranked by pre-treatment faecal egg counts and randomly allocated to different treatment groups. In all studies, cats were treated at the minimum label dose to provide 6.0mg selamectin per kg bodyweight. All animals were euthanized 7-10days after treatment for worm counts. Efficacy was calculated based on the reduction of the geometric mean worm counts in the treated groups versus the placebo-treated control groups. The efficacy against adult hookworms was 99.2%, 94.3% and 100% in three of these studies, and was lower in the remaining two studies. The efficacy against T. cati was 100%. Furthermore, non-interference between sarolaner and selamectin was demonstrated. Thus, a single topical application of the new spot-on formulation of selamectin plus sarolaner at the minimum label dose is effective in the treatment of adult hookworm and roundworm infections in cats.

Speed of kill of a new spot-on formulation of selamectin plus sarolaner for cats against induced infestations with Ixodes ricinus.

The speed of kill of a new spot-on formulation containing selamectin plus sarolaner (Stronghold®Plus, Zoetis) for cats was evaluated against Ixodes ricinus ticks in a placebo-controlled, blinded study. Sixteen (16) cats were blocked by pre-treatment tick counts and randomly allocated to the placebo-treated group or the selamectin/sarolaner-treated group. Cats either received a single topical treatment at the minimum dose of 6.0mg selamectin and 1.0mg sarolaner per kg bodyweight or a placebo formulation on Day 0. On Days -2, 7, 14, 21, 28 and 35, cats were infested with approximately 50 unfed, viable and adult I. ricinus ticks. Tick counts were performed in situ 8 and 12h after treatment or re-infestation. Ticks were removed from the cats and counted at the 24h tick count. Acaricidal efficacy at each time point was calculated based on the reduction of mean live tick counts in the selamectin/sarolaner-treated group versus the placebo-treated group. There were no treatment-related adverse reactions during the study. Placebo-treated cats maintained infestations with mean tick counts ranging from 10.3 to 21.9 throughout the study. The new spot-on formulation of selamectin plus sarolaner demonstrated 99.3% efficacy (P<0.0001) within 24h after treatment against pre-existing infestations. For subsequent re-infestations, efficacy was >97.9% for at least 3 weeks and was 89.0% after the re-infestation on Day 28. Mean live tick counts were significantly reduced by 12h after re-infestation for at least 28 days (P<0.0338). Thus, a single application of the new spot-on formulation of selamectin plus sarolaner at the minimum label dose started killing ticks within 24h after treatment and within 12h after re-infestations for 4 weeks. High acaricidal efficacy was achieved within 24h after treatment and this persisted following subsequent re-infestations for a month.

Confirmation of the efficacy of a novel fipronil spot-on for the treatment and control of fleas, ticks and chewing lice on dogs.

A novel spot-on formulation containing fipronil (Eliminall(®)/Exproline vet™) Spot-on Solution for Dogs, Pfizer Animal Health, registered and manufactured by Krka, d.d, Novo mesto) was evaluated in three laboratory studies to confirm efficacy against fleas, ticks and chewing lice on dogs for at least one month. Control of two laboratory strains of cat flea (Ctenocephalides felis), two tick species (Rhipicephalus sanguineus and Dermacentor reticulatus) and the chewing louse (Trichodectes canis) was evaluated. In all studies, dogs were randomly allocated to treatment groups and compared with untreated dogs. The studies also included a commercial, comparator product containing fipronil (Frontline(®) spot-on, Merial Limited). All treatments were applied to the skin at one spot between the scapulae on Day 0. In the studies, dogs were infested with fleas and/or ticks prior to treatment and then reinfested at weekly intervals for up to 8 weeks after treatment and evaluated for efficacy at 2 days (48 h) after treatment and each reinfestation. These studies confirmed that treatment with the novel fipronil spot-on at the proposed commercial dose rate rapidly reduced existing infestations of fleas, ticks and chewing lice on dogs. Treatment provided control of reinfesting fleas for up to 8 weeks, up to 4 weeks control of ticks, and control of chewing lice.

Efficacy of a novel fipronil spot-on for the treatment and control of induced infestations of adult cat fleas (Ctenocephalides felis) and castor bean ticks (Ixodes ricinus) on cats.

Cat fleas (Ctenocephalides felis) and the castor bean tick (Ixodes ricinus) cause discomfort and health effects due to bites and ingestion of blood and they serve as vectors for several animal and human pathogens. Effectiveness of a novel 10 % w/v fipronil spot-on (Eliminall®/Exproline vet™, marketed by Pfizer Animal Health and registered and manufactured by Krka, d.d., Novo mesto) was confirmed against these parasites on experimentally infested cats. Two parallel, unicentre and masked controlled studies were conducted with European mixed breed and mixed sex cats. Cats were allocated randomly to one of two treatment groups based on either pre-treatment flea counts (study 1) or pre-treatment tick counts (study 2). In each of the study, eight animals served as control, while another eight animals were treated once topically with the unit label dose of 50 mg fipronil per cat (10.6-23.8 mg/kg). At each reinfestation, animals were infested with approximately 100 fleas or 60 ticks to achieve adequate infestation rates. Parasites were removed and counted on days 2, 9, 16, 23, 30 and 37, 48 h after the treatment or experimental infestation. Excellent effectiveness was demonstrated on day 2 (100 and 94 % efficacy against fleas and ticks, respectively) and lasted for up to 5 weeks (efficacy ≥96 %) against fleas and up to 4 weeks against ticks (efficacy ≥94 %). The product was well tolerated and no adverse reactions were observed.

Persistent efficacy of a long acting injectable formulation of moxidectin against natural infestations of the sheep nasal bot (Oestrus ovis) in Spain.

Cydectin(®) 2% LA Solution for Injection for Sheep (Pfizer Animal Health) is a long-acting (LA) formulation of moxidectin for the treatment and prevention of mixed infections of gastro-intestinal nematodes, respiratory nematodes and certain arthropod parasites in sheep. To evaluate the duration of persistent efficacy against nasal bots (Oestrus ovis), a natural exposure study was conducted in Spain during the summer of 2011. One hundred and twenty nasal bot-free, Rasa Aragonesa sheep were randomly allocated to eight groups of 15 animals each. On Day 0, four groups were treated at the recommended dose rate of 1 mg moxidectin/kg bodyweight. Four groups remained untreated as negative controls. All animals were held in nasal bot-proof housing except for exposure to natural challenge when one group of treated sheep and one of group of control animals were transferred to a local pasture at either 0-20, 20-40, 40-60, or 60-80 days after treatment. Following challenge, sheep were scored for clinical signs of bot infestation, necropsied and the heads sectioned for larval recovery. Nasal bot larvae were retrieved from 7 to 11 control sheep following each exposure period indicating that adult bots were active throughout the study. In the first challenge up to 20 days after treatment, when sheep were slaughtered immediately after exposure, the majority of larvae were first instar (L1) and only 3 of the 15 control sheep were infested with second instars (L2). There was 100% efficacy against L2 and 38.1% reduction in the number of live L1 in the treated sheep but mean counts were not significantly different between treatment and control groups (P ≥ 0.05). For the subsequent exposure periods 20-80 days after treatment (necropsies 7-9 days after challenge), 6-10 sheep were infested with L1 and 9-11 control sheep were infested with L2 and third instars (L3). There was negligible efficacy against L1, but treatment with moxidectin resulted in 100% control of L2 and L3. These results are consistent with the biology of nasal bots and control with a systemic agent, as the slower growing L1 have limited feeding and are therefore less susceptible to systemic parasiticides. The study demonstrated that the persistent efficacy of this long-acting injectable formulation of moxidectin protects against the development of active O. ovis infestations for at least 80 days after treatment.

Evaluation of the comparative efficacy of a moxidectin plus triclabendazole pour-on solution against adult and immature liver fluke, Fasciola hepatica, in cattle.

The objective of this study was to evaluate the efficacy of a pour-on solution containing moxidectin plus triclabendazole (MOX plus TCBZ) against immature and adult stages of the liver fluke in cattle and compare the efficacy with other commercially available preparations. To this end, 104 male Holstein-Friesian calves aged between 3 and 4 months, were randomly allocated to 13 groups of eight animals each, and infected with approximately 500 Fasciola hepatica metacercariae. One group remained untreated, four groups were treated with MOX plus TCBZ at a dose rate of 0.1 mL/kg, four other groups were treated with ivermectin (IVM) plus clorsulon injectable at a dose rate of 0.02 mL/kg, and the remaining four groups were treated with IVM plus closantel pour-on at a dose rate of 0.1 mL/kg. Each treatment was applied to one of the groups at 4 weeks, 6 weeks, 8 weeks and 12 weeks after the experimental infection. At necropsy (99-102 days after infection), all untreated animals were infected with a minimum of 30 flukes. The MOX plus TCBZ treated animals had significantly (P<0.0001) lower fluke counts compared to the untreated control animals at all time points after treatment. Efficacy against 8-week old and adult flukes was >99.5%. For 6-week old immature fluke, the efficacy was 98.0% and for 4-week old immature fluke the efficacy was 90.9%. The IVM plus closantel pour-on treated animals had significantly lower fluke counts compared to the untreated control animals for adult and 8-week old flukes (P<0.0001), and for 6-week old flukes (P=0.002). The efficacy was 26.8%, 68.2%, 90.6% and 99.3% against 4-week, 6-week and 8-week old immature flukes, and adult flukes respectively. The IVM plus clorsulon treated animals had significantly lower fluke counts compared to the untreated control animals for adult (P<0.0001) and 8-week old (P<0.05) flukes. The efficacy was 29.7%, 43.4%, 53.2% and 99.2% against 4-week, 6-week and 8-week old immature flukes, and adult flukes respectively. For treatments at 4, 6 and 8 weeks after infection, the fluke counts were significantly (P<0.0001) lower for the MOX plus TCBZ treatment than for IVM plus closantel or IVM plus clorsulon. The results confirm the high efficacy (>90%) of the MOX plus TCBZ pour-on combination against 4-week old to adult liver fluke in cattle. The IVM plus closantel pour-on combination was effective (>90%) against 8-week old and adult flukes, but had low efficacy against 4- and 6-week old fluke. The IVM plus clorsulon injectable combination was effective (>90%) against adult fluke only.

Efficacy of a topically applied spot-on formulation of a novel insecticide, metaflumizone, applied to cats against a flea strain (KS1) with documented reduced susceptibility to various insecticides.

A spot-on metaflumizone formulation was evaluated in adult domestic short hair cats to determine its adultidical efficacy against a flea strain that has reduced susceptibility to a number of insecticides. Eight cats served as non-treated controls, eight cats were treated with a metaflumizone formulation at 0.2 ml/kg (40 mg metaflumizone/kg) and eight cats were treated with fipronil 10% w/v-(s)-methoprene 12%w/v at 0.075 ml/kg (7.5-7.7 mg fipronil/kg:9.0-9.2 mg (s)-methoprene/kg). On days -1, 7, 14, 21, 28, 35, and 42 each cat was infested with approximately 100 unfed KS1 cat fleas, Ctenocephalides felis. At approximately 48 h after treatment or infestation, each cat was combed to remove and count live fleas. Treatment with metaflumizone provided > or = 99.3% efficacy for 3 weeks post-treatment and then 97.4, 91.4 and 86.2% efficacy at 4, 5 and 6 weeks post-treatment, respectively. Fipronil-(s)-methoprene provided 99.6% efficacy at 1 week post-treatment and then 97.6, 96.4, 71.3, 22.0 and 13.1% efficacy at weeks 2, 3, 4, 5 and 6, respectively. The reductions in flea numbers were significantly greater for the metaflumizone treatment than for fipronil-(s)-methoprene from 3 to 6 weeks after treatment.