One Health: Animal Models of Heritable Human Bleeding Diseases.

Animal models of human and animal diseases have long been used as the lynchpin of experimental and clinical research. With the discovery and implementation of novel molecular and nano-technologies, cellular research now has advanced to assessing signal transduction pathways, gene editing, and gene therapies. The contribution of heritable animal models to human and animal health as related to hemostasis is reviewed and updated with the advent of gene editing, recombinant and gene therapies.

Early Life Vaccination of Companion Animal Pets.

Development of the immune system of mammalian animal species parallels that of humans and involves the innate and adaptive (acquired) immune responses acting together with the thymus gland. Consequently, issues surrounding the adequacy and safety of vaccinations to protect pet animals from their relevant infectious diseases need to be addressed just as they are for humans. Pet animals, especially canines, also have unique needs because of the wide diversity of purebred and mixed breeds that vary greatly in size, type, temperament, and even maturation rates. Furthermore, pets in early life encounter a series of changes that can affect their development and induce stressors including parasite control, new homes and environment, novel foods, and the socialization that is essential at a time when vaccinations need to be given. While recognizing that this overall need is becoming more understood, current vaccination policy guidelines for companion animals are still only adhered to by about 40% of veterinarians worldwide. Clearly, vaccination of pets should no longer be considered as "one size fits all".

Survey of canine use and safety of isoxazoline parasiticides.

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.

Duration of immunity after rabies vaccination in dogs: The Rabies Challenge Fund research study.

A prospective study of 65 research beagles kept in a rabies-free environment was undertaken to determine the duration of immunity after they received licensed rabies vaccines. The eventual goal was to extend mandated rabies booster intervals to 5 or 7 years and help reduce the risk of vaccine-associated adverse events. Three groups of dogs were vaccinated with 1 of 2 commercial rabies vaccines or saline at 12 and 15 weeks of age. Beginning 5 years 5 months later, vaccinated and unvaccinated dogs were challenged with virulent rabies virus and observed for 90 days over a series of 3 trials. Humoral and cellular immune responses were examined by serology and flow cytometry. Brain tissue from all challenged dogs was tested for rabies virus. Challenge trial 1 was confounded due to insufficiently virulent virus. In trials 2 and 3 virulent challenge provided 100% mortality in controls. Vaccinate survival was 80% (4/5) after 6 years 7 months, 50% (6/12) after 7 years 1 month, and 20% (1/5) after 8years 0 months. Antibody responses 12 days post-challenge correlated strongly with survival. In a separate non-challenge trial, administration of either a recombinant or a killed rabies vaccine demonstrated memory antibody responses 6 years 1 month after initial vaccination compared with unvaccinated controls. Our data demonstrated that i) duration of immunity to rabies in vaccinated dogs extends beyond 3 years; ii) immunologic memory exists even in vaccinated dogs with serum antibody titer < 0.1 IU/mL; and iii) non-adjuvanted recombinant rabies vaccine induces excellent antibody responses in previously vaccinated dogs 14 days after administration.

Une étude prospective sur 65 chiens beagle de recherche gardés dans un environnement exempt de rage fut entreprise afin de déterminer la durée de l'immunité après qu'ils reçurent un vaccin homologué contre la rage. Le but éventuel était d'allonger l'intervalle requis du rappel du vaccin contre la rage à 5 ou 7 ans et aider à réduire le risque associé aux réactions adverses au vaccin. Trois groupes de chiens furent vaccinés avec un des deux vaccins commerciaux contre la rage ou de la saline à 12 et 15 semaines d'âge. Débutant 5 ans et 5 mois plus tard, les chiens vaccinés et non-vaccinés furent soumis à une infection défi avec un virus de la rage virulent et observés pendant 90 jours lors d'une série de trois essais. Les réponses immunitaires humorale et cellulaire furent examinées par sérologie et cytométrie de flux. Du tissu cérébral de tous les chiens infectés fut testé pour la présence du virus rabique. L'essai 1 était décevant étant donné la quantité insuffisante de virus virulent. Lors des essais 2 et 3, l'infection défi a entrainé 100 % de mortalité chez les témoins. Le taux de survie des animaux vaccinés était de 80 % (4/5) après 6 ans et 7 mois, 50 % (6/12) après 7 ans et 1 mois et 20 % (1/5) après 8 ans 0 mois. La réponse en anticorps 12 jours post-infection corrélait fortement avec la survie. Dans un essai séparé sans infection défi, l'administration de soit un vaccin recombinant ou un vaccin tué a mis en évidence une réponse anamnestique en anticorps 6 ans et 1 mois après la vaccination initiale comparativement aux témoins non-vaccinés. Nos résultats démontrent que (1) la durée de l'immunité contre la rage chez les chiens vaccinés va au-delà de 3 ans, (2) une mémoire immunologique existe même chez les chiens vaccinés avec des titres d'anticorps sériques < 0,1 IU/mL, et (3) un vaccin antirabique recombinant sans adjuvant induit d'excellentes réponses en anticorps chez des chiens préalablement vaccinés 14 jours après son administration.(Traduit par Docteur Serge Messier).

Diagnosis of Feline Food Sensitivity and Intolerance Using Saliva: 1000 Cases.

This prospective study assessed the efficacy of a novel saliva-based immunoassay of IgA- and IgM-antibodies in predicting feline food sensitivities and intolerances. Clinical samples were obtained from 1000 cats proven or suspected to have food intolerances. Most were of domestic shorthair breed type, over 10 years of age, and weighed around 5 kg; they were equally distributed between spayed females and neutered males. Saliva was collected after at least an 8-h fast with a dental cotton rope, placed in a double-sleeved saliva collection tube, and sent to the laboratory. Salivary antibodies elicited by 24 common foods were measured with goat anti-canine IgA and IgM. Low reacting foods were lamb, cow milk, pork, turkey, wheat (lowest) and white-colored fish, whereas high reacting foods were millet, white potato, rice (highest) and salmon. Thus, the novel salivary-based food sensitivity and intolerance test, described previously for canines, also provided a reliable and clinically predictive alternative to food elimination trials, serum-based food allergy testing, and skin patch testing in cats. Manufacturers of commercial cat foods and treats, as well as those making homemade diets and treats for cats, should consider avoiding the more highly reactive foods as determined by the present study.