A randomized, blinded, negative controlled study was conducted to determine whether treatment with afoxolaner (NexGard, Merial, Inc.) would prevent the transmission of Borrelia burgdorferi to dogs by wild caught Ixodes scapularis ticks. Twenty healthy dogs were randomly assigned to two groups of ten dogs each. Ten dogs were treated orally on Day 0 at a dose near the minimum recommended dose of afoxolaner of 2.5mg/kg (actual doses 2.5-3.1mg/kg) and ten control dogs were not treated. On Day 28, each dog was infested with approximately 50 adult unfed wild caught I. scapularis that had a 67% B. burgdorferi infection rate (determined by polymerase chain reaction). On Day 33, live ticks were counted and removed. No ticks were found on treated dogs while control dogs had an average of 21.4 ticks. To detect infection, the B. burgdorferi-specific C6 antibody SNAP 4Dx test (IDEXX) was performed on serum collected before infestation (all dogs seronegative on Days -6 and 27) and on Days 48, 63, 77 and 92. The ten treated dogs remained seronegative through the end of the study (Day 92), while nine out of the ten control dogs were infected, as demonstrated by their seroconversion to being positive for the presence of the B. burgdorferi-specific C6 antibody starting on Day 48. In this study, all dogs treated with NexGard 28days prior to challenge with wild caught I. scapularis ticks were protected from B. burgdorferi infection, while nine out of the ten untreated control dogs were infected.
Cats may be infected by heartworm, Dirofilaria immitis, through mosquito bites. They can develop severe heartworm disease when infective D. immitis larvae migrate and develop into adults in the pulmonary vasculature or other tissues. As there is no curative treatment for feline heartworm infection, the monthly administration of preventative treatment is recommended in endemic areas. Three controlled, blinded laboratory studies were conducted to evaluate the preventative efficacy of BROADLINE(®), a novel combination of fipronil, (S)-methoprene, eprinomectin, and praziquantel against D. immitis in cats. In each study, 28 cats were inoculated with approximately 100 (studies 1 and 2) or 40 (study 3) infective third stage D. immitis larvae by subcutaneous injection, thirty days prior to treatment. The larvae were from recent field isolates from naturally infected dogs from three distinct geographic areas (two in the USA and one in Europe). In each study, the cats were allocated randomly to two study groups of 14 cats each. The control group remained untreated. On Day 0, each cat in the treated group received one topical application of the novel topical formulation, delivering the minimum intended dose of 0.5mg of eprinomectin per kilogram of body weight. At 6 months after infection, all cats were humanely euthanized and examined for adult D. immitis. Across all three studies, 28 (68%) of the 41 untreated cats harbored one or more heartworms, while 100% of the 42 treated cats remained free of heartworm infection, demonstrating the 100% preventive efficacy of BROADLINE(®) against D. immitis in cats. The treatment was well tolerated and no health abnormality was observed in any treated cat.
The efficacy of a novel topical combination of fipronil 8.3% (w/v), (S)-methoprene 10% (w/v), eprinomectin 0.4% (w/v), and praziquantel 8.3% (w/v) (BROADLINE(®), Merial) was evaluated against adult and larval Toxocara cati in four controlled studies. All studies included experimentally infected, purpose-bred, short-haired cats. In two studies, 22 or 20 cats harbouring patent infections as confirmed by pre-treatment faecal examination, were included. Within each study, cats were allocated to one of two groups: control or treated. In a further two studies, 30 cats were included in each; cats were allocated to one of three groups: control, treated when T. cati were expected to be either migrating third and/or fourth-stage larvae, or treated when T. cati were expected to be fourth-stage larvae. Cats allocated to the treated groups received a single topical application of the combination product at 0.12 mL/kg bodyweight (10mg fipronil+12 mg (S)-methoprene+0.5mg eprinomectin+10mg praziquantel per kg). For parasite recovery and count, cats were euthanized humanely at different intervals after treatment. In the studies targeting adult T. cati, ascarids were recovered from all controls (range 1-150) while only two worms were isolated from one treated cat. Thus, the efficacy of the novel combination was 99.4% and 100% against adult T. cati. For studies targeting larval T. cati, up to 21 worms were recovered from each of seven or eight of the control cats per study. No T. cati were recovered from the treated cats in two studies, corresponding to 100% efficacy against both, migrating third and/or fourth-stage larvae and luminal fourth-stage larvae. All cats accepted the treatment well and no adverse experiences or other health problems were observed throughout the studies.
The efficacy of a novel topical combination of fipronil 8.3% (w/v), (S)-methoprene 10% (w/v), eprinomectin 0.4% (w/v) and praziquantel 8.3% (w/v) (BROADLINE(®)) was tested against adult and immature stages of Ctenocephalides felis fleas in six studies. For that purpose, fleas from different colonies from North America, Germany and South Africa were used to induce infestations in cats under laboratory conditions. In each study, between 12 and 16 cats were allocated randomly to 2 groups. Cats in Group 1 were not treated and served as controls. Cats in Group 2 were treated once on Day 0 with BROADLINE(®) at the minimum recommended dosage of 0.12 mg/kg body weight. In 4 studies, all animals were infested experimentally with unfed C. felis (100 ± 5) on Days 2 (or 1), 7, 14, 21, 28 and 35. Live fleas were counted 24h post-treatment or infestation. In 2 additional studies, animals were infested at the same frequency with gravid C. felis fleas (100 ± 5) that were fed previously on an untreated host. Forty-eight hours post-infestation, flea eggs were collected, counted and incubated for the evaluation of the reduction of emergence of adults. The combined curative efficacy against adult fleas at 24h after treatment was 94.3% and the combined preventive efficacy values remained greater than 95.9% at 24h after 5 subsequent weekly infestations. In addition, the product reduced dramatically the emergence of new adult fleas for at least 5 weeks (>98.1% for one month and 93.2% at 5 weeks after infestation), demonstrating its efficiency in preventing environmental contamination by immature stages.
NexGard® Combo, a novel topical antiparasitic product for cats, combines the insecticide/acaricide esafoxolaner with the nematocide eprinomectin and cestodicide praziquantel. The efficacy of this combination product was evaluated against two common endoparasites of global occurrence in cats, the nematode Toxocara cati and the cestode Dipylidium caninum, in five controlled studies using naturally or experimentally infected cats with parasites of North American, South African or European origin. Cats evaluated in these studies harbored patent infection of the target parasite confirmed through a pre-treatment fecal examination. In each study, cats were allocated randomly to two groups of equal size (8 or 10 cats per group per study), one group treated with a placebo (mineral oil) and the other with NexGard® Combo. Both treatments were administered once as a spot-on at 0.12 mL per kg body weight to deliver the minimum label dosage (1.44 mg/kg esafoxolaner, 0.48 mg/kg eprinomectin, and 10.0 mg/kg praziquantel) to the NexGard® Combo-treated cats. To determine efficacy, geometric mean parasite counts seven to 12 days after treatment of placebo-treated (control) cats and NexGard® Combo-treated cats were compared. The efficacy of NexGard® Combo was 98.8% and 100% against adult T. cati in two studies; and 98.0%, 98.3% and 93.2% against D. caninum in three studies. No adverse events related to treatment were observed throughout the studies. These studies demonstrate high efficacy against these major feline endoparasites and excellent acceptability of the novel topical antiparasitic combination of esafoxolaner, eprinomectin and praziquantel.
NexGard® Combo is a novel topical endectoparasiticide formulation for cats combining the insecticide/acaricide esafoxolaner, the nematodicide eprinomectin and the cestodicide praziquantel. The efficacy of this novel formulation for the prevention of heartworm disease in cats was tested in two experimental studies using an induced infection model and a randomized, blinded, placebo-controlled study design, and two USA isolates of Dirofilaria immitis. In each study, 20 naïve cats were each inoculated sub-cutaneously with 100 third-stage larvae of D. immitis 30 days before treatment. Following randomization to two treatment groups of ten cats, each cat was treated topically once, either with the minimum recommended dose of the novel formulation, or with an identical volume of placebo. Five months after treatment (6 months after infections), the cats were humanely euthanized for parasite recovery and count. Efficacy was calculated by comparison of the numbers of adult D. immitis recovered in the control and in the novel formulation groups. In the control groups of each study, D. immitis were recovered in seven and nine cats (respective worm counts ranges 1–7 and 1–16, respective geometric means 1.6 and 5.1). In both studies, none of the treated cats harbored any D. immitis at necropsy and the calculated efficacy of the novel formulation was 100%. There were no adverse reactions related to treatment with the novel formulation. The results of these two studies demonstrate that a topical NexGard® Combo application at the minimum label dose is well-tolerated and efficacious in preventing heartworm disease in cats.
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