BackgroundMonthly 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.MethodsA 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.ResultsA 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.ConclusionsA 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.

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A novel spot-on formulation containing metaflumizone plus amitraz (ProMeris/ProMeris Duo for Dogs, Fort Dodge Animal Health, Overland Park, KS) was evaluated for efficacy against demodectic mange mites in naturally infested dogs. Sixteen dogs were allocated to two equal groups and individually housed. Eight of the dogs were treated topically with metaflumizone plus amitraz at the proposed minimum dose rate (20mg/kg of each of metaflumizone and amitraz, 0.133ml/kg) on Days 0, 28, and 56. The other eight were treated with metaflumizone plus amitraz at the proposed minimum dose rate on Days 0, 14, 28, 42, 56, and 70. Mite numbers were estimated from skin scrapings taken on Days -3 to -1, 28, 56, and 84. Clinical signs of mange and the extent of demodectic lesions on each dog were evaluated when skin scrapings were conducted. Efficacy of the treatment was based on a reduction in mite numbers and an assessment of the clinical signs associated with canine demodectic mange. Treatment at monthly or two-weekly intervals for 3 months resulted in a rapid reduction in mite numbers (>94 and >99% for the monthly and two-weekly treatments, respectively) and an improvement in clinical signs. Success rates, based on zero mite counts in skin scrapings at Day 84 were 42.9 and 62.5% of dogs for the monthly and two-weekly regimens, respectively.

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.

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