Field assessment of potential exposure of dogs to leptospirosis by measuring antibody titers in dogs: a multisite study in five geographic regions of the United States.

Leptospirosis vaccine for dogs in the United States is considered a lifestyle or non-core vaccine, making individual veterinary practitioners responsible for determining if vaccination is necessary for their patients. Veterinary professionals often base their vaccination decisions on local rates of clinical cases. However, even subclinical leptospirosis infections have zoonotic potential. The microscopic agglutination test (MAT) is effective for screening unvaccinated animals, but previous vaccination can lead to inconsistent results and variable MAT titers over time. This prospective research survey evaluated if local experience was sufficient to justify selective vaccination for leptospirosis. MAT analyses were performed on sera collected from well-cared-for, unvaccinated dogs residing in five different geographies across the United States: South-Central (East Texas), New England, the Mid-Atlantic (North Carolina and Virginia), Midwest (Wisconsin/northern Illinois), and Southwest (southern California). Thirty-eight clinics participated, submitting a total of 1345 qualified samples from unvaccinated dogs over 1 year of age. 11.6% of these unvaccinated dogs had MAT titers for one or more serogroups of Leptospira. While seropositivity does not necessarily indicate that disease will result or that a specific serovar is involved, these MAT-positive cases do indicate that the potential for exposure exists and clinical signs or a carrier-state could result from infection. These survey results would indicate that a more aggressive vaccination protocol for leptospirosis should be considered.

Examining the role of macrolides and host immunity in combatting filarial parasites.

Macrocyclic lactones (MLs), specifically the avermectins and milbemycins, are known for their effectiveness against a broad spectrum of disease-causing nematodes and arthropods in humans and animals. In most nematodes, drugs in this class induce paralysis, resulting in starvation, impaired ability to remain associated with their anatomical environment, and death of all life stages. Initially, this was also thought to be the ML mode of action against filarial nematodes, but researchers have not been able to validate these characteristic effects of immobilization/starvation of MLs in vitro, even at higher doses than are possible in vivo. Relatively recently, ML receptor sites exclusively located proximate to the excretory-secretory (ES) apparatus were identified in Brugia malayi microfilaria and an ML-induced suppression of secretory protein release by B. malayi microfilariae was demonstrated in vitro. It is hypothesized here that suppression of these ES proteins prevents the filarial worm from interfering with the host's complement cascade, reducing the ability of the parasite to evade the immune system. Live microfilariae and/or larvae, thus exposed, are attacked and presented to the host's innate immune mechanisms and are ultimately killed by the immune response, not the ML drug. These live, exposed filarial worms stimulate development of innate, cellular and humoral immune responses that when properly stimulated, are capable of clearing all larvae or microfilariae present in the host, regardless of their individual sensitivity to MLs. Additional research in this area can be expected to improve our understanding of the relationships among filarial worms, MLs, and the host immune system, which likely would have implications in filarial disease management in humans and animals.

Assessment of afoxolaner efficacy against Otodectes cynotis infestations of dogs.

BACKGROUND: The efficacy of a single 2.5 mg/kg dose of afoxolaner (NexGard®, Merial) against induced Otodectes cynotis infestations was assessed in eight afoxolaner-treated dogs, compared to eight untreated dogs. METHODS: After O. cynotis infestations were established and confirmed by otoscopic assessments in 16 dogs, all of the dogs were included in the study and allocated to two separate treatment groups. The first group of eight ear mite-infested dogs remained untreated, while afoxolaner was administered orally to the second group of dogs at the minimum recommended dose once on Day 0. Otoscopic assessments performed on all dogs (Days -7, -2, 14 and 28) confirmed the presence or absence of live mites throughout the study. No serious adverse events were recorded throughout the study, and no adverse events were likely related to the administration of NexGard. RESULTS: By Day 28, seven out of eight untreated dogs were still infested with ear mites, while only two out of eight afoxolaner-treated dogs were infested, with one and four ear mites, respectively. On Day 28, the reductions of mite counts in the afoxolaner-treated group versus those of the control dogs were 98.5% based on geometric means, and 99.4% based on arithmetic means. Significantly fewer (P < 0.05) live mites were present in the afoxolaner-treated group than the untreated group on Day 28. CONCLUSION: The results of this study demonstrated that a single oral administration of afoxolaner at the minimum recommended dose is highly effective (>98%) in treating dogs with induced O. cynotis infestations.

Efficacy of a proprietary formulation of fipronil/(S)-methoprene/cyphenothrin against Ixodes scapularis tick infestations on dogs.

BACKGROUND: Efficacy of FRONTLINE TRITAK For Dogs (fipronil/(S)-methoprene/cyphenothrin, Merial, Inc., Duluth, GA) against Ixodes scapularis was evaluated in two separate, but concurrent laboratory studies. METHODS: One day after topical treatment with placebo or active, dogs (n = 24) were infested with 50 unfed adult Ixodes scapularis ticks, with repeat infestations on Days 7, 14, 21 and 28. The number of live ticks was counted at 6 hours post-infestation in the first study (n = 12) and at 24 hours post-infestation in the second study (n = 12). RESULTS: Observed efficacies in study 1 were 93-99% at 6 hour assessments on Day 1 through Day 28 and in the second study, 98-100% at 24 hour assessments, occurring on Day 2 through Day 29. CONCLUSIONS: A single dose of FRONTLINE TRITAK For Dogs (fipronil/(S)-methoprene/cyphenothrin) (0.67 ml or 1.34 ml) prevented the establishment of a new infestation following treatment, as well as the repeated weekly re-infestations with Ixodes scapularis ticks, for 4 weeks.

Evaluation of afoxolaner chewables to control flea populations in naturally infested dogs in private residences in Tampa FL, USA.

BACKGROUND: A study was conducted to evaluate the effectiveness of afoxolaner chewables to control flea populations in naturally infested dogs in private residences in Tampa FL, USA. Evaluations of on-animal and premises flea burdens, flea sex structure and fed-unfed premises flea populations were conducted to more accurately assess flea population dynamics in households. METHODS: Thirty seven naturally flea infested dogs in 23 homes in Tampa, FL were enrolled in the study and treated with afoxolaner chewables. Chewables (NexGard® Chewables; Merial) were administered according to label directions by study investigators on study day 0 and once again between study days 28 and 30. Flea infestations on pets were assessed using visual area thumb counts and premises flea infestations were assessed using intermittent-light flea traps on days 0, 7, 14, 21, and once between study days 28-30, 40-45, and 54-60. RESULTS: Within 7 days of administration of afoxolaner chewable tablets, flea counts on dogs were reduced by 99.3%. By one month post-treatment, total flea counts on dogs were reduced by 99.9%, with 97.3% (36/37) of the dogs being flea free. Following the second dosing on study day 28-30, total on-dog flea burden was reduced by 100% on days 40-45 and 54-60. On day 0, the traps collected a geometric mean of 18.2 fleas. Subsequent reductions in emerging flea populations were 97.7 and 100% by days 28-30 and 54-60, respectively. There were 515 total fleas (Ctenocephalides felis felis) collected in the intermittent light flea traps on day 0, and 40.4% of those fleas displayed visual evidence of having fed. Seven days after initial treatment, only 13.1% of the fleas contained blood and by day 14 only 4.9% of the fleas collected in traps displayed evidence of having fed. On day 0, prior to treatment, 60% of the unfed fleas collected in intermittent-light flea traps were females, but by days 28-30, unfed males accounted for 78% of the population. CONCLUSIONS: This in-home investigation conducted during the summer of 2014 in subtropical Tampa, FL demonstrated that afoxolaner chewables rapidly and effectively eliminated flea populations in infested dogs and homes.

Efficacy of a single dose of a novel topical combination product containing eprinomectin to prevent heartworm infection in cats.

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.

Switching NSAIDs in practice: insights from the Previcox (firocoxib) Experience Trial.

Veterinarians currently have a choice of six registered NSAIDs for use in the management of canine osteoarthritis. There is a need for data to clarify whether there is an increased risk of side effects occurring in the event of a switch between different members of the NSAID class. In this retrospective analysis of extensive data collected in the 1,000 dog Previcox (firocoxib, Merial) Experience Trial, the incidence of side effects in dogs reported as treated with an NSAID 7 days or less before enrollment was compared with that in dogs reported as not having received an NSAID in the equivalent period. Statistical analysis of the data indicates that observation of an interval of up to 1 week between beginning treatment with firocoxib and cessation of treatment with a different NSAID was not associated with any increased risk of adverse events.

Clinical effectiveness and safety of a new NSAID, firocoxib: a 1,000 dog study.

For the Previcox (firocoxib, Merial) Experience Trial, practicing veterinarians across the United States were asked to enroll dogs diagnosed with osteoarthritis (OA). At an initial visit, owners of dogs deemed suitable for NSAID therapy were given Previcox and instructed to maintain a daily diary and to return 10 and 40 days after treatment began. Approximately 86% of the 1,002 enrolled dogs completed the study. The withdrawal rate associated with gastrointestinal side effects was low (2.9% of dogs), and no serious drug-related adverse events were reported. Investigators and Owners rated 93% and 91% of dogs, respectively, as improved, and 86% of owners rated their dogs "happier" or "more active" after treatment with firocoxib. The improvements observed following initiation of firocoxib therapy were independent of gender, breed, starting body weight, age, and prior NSAID use. These results support previous findings indicating that firocoxib is well tolerated and effective when used under field conditions.