Preliminary Study on the Efficacy of a Recombinant, Subunit SARS-CoV-2 Animal Vaccine against Virulent SARS-CoV-2 Challenge in Cats.

The objective of this work was to evaluate the safety and efficacy of a recombinant, subunit SARS-CoV-2 animal vaccine in cats against virulent SARS-CoV-2 challenge. Two groups of cats were immunized with two doses of either a recombinant SARS-CoV-2 spike protein vaccine or a placebo, administered three weeks apart. Seven weeks after the second vaccination, both groups of cats were challenged with SARS-CoV-2 via the intranasal and oral routes simultaneously. Animals were monitored for 14 days post-infection for clinical signs and viral shedding before being humanely euthanized and evaluated for macroscopic and microscopic lesions. The recombinant SARS-CoV-2 spike protein subunit vaccine induced strong serologic responses post-vaccination and significantly increased neutralizing antibody responses post-challenge. A significant difference in nasal and oral viral shedding, with significantly reduced virus load (detected using RT-qPCR) was observed in vaccinates compared to mock-vaccinated controls. Duration of nasal, oral, and rectal viral shedding was also significantly reduced in vaccinates compared to controls. No differences in histopathological lesion scores were noted between the two groups. Our findings support the safety and efficacy of the recombinant spike protein-based SARS-CoV-2 vaccine which induced high levels of neutralizing antibodies and reduced nasal, oral, and rectal viral shedding, indicating that this vaccine will be efficacious as a COVID-19 vaccine for domestic cats.

Intracranial inflammatory polyp with cerebellopontine compression and leptomeningitis secondary to chronic otitis in a red kangaroo.

CNS lesions associated with chronic otitis have not been reported in red kangaroos (Macropus rufus), to our knowledge. Here we describe an intracranial inflammatory polyp secondary to chronic otitis in a 6-y-old female red kangaroo with right auricular discharge, loss of balance, and head tilt. Autopsy highlighted a pale-yellow, firm, intracranial polypoid growth that extended from the right tympanic cavity through the internal acoustic meatus and intracranially, with compression of the right cerebellopontine angle. Anaerobic bacterial culture yielded Bacteroides pyogenes from fresh brain and a right external ear swab. Histologically, the tympanic cavity was effaced by neutrophils and macrophages surrounded by lymphocytes and plasma cells, as well as edematous fibrovascular tissue. The epithelial lining of the mucoperiosteum was hyperplastic, with epithelial pseudoglands surrounded by fibrovascular tissue. Areas of temporal bone lysis and remodeling were associated with the inflammatory changes, which occasionally surrounded adjacent nerves. Fibrovascular tissue and inflammatory cells extended from the tympanic cavity through the internal acoustic meatus and into the intracranial cavity, forming the polypoid growth observed grossly; the polyp consisted of a dense core of fibrovascular tissue with scattered clusters of neutrophils and foamy macrophages. Lymphocytes and plasma cells surrounded the leptomeningeal perivascular spaces in the brainstem, cerebellum, and occipital lobe.

Intraluminal Uropygial Gland Epithelioma in an African Grey Parrot (Psittacus erithacus).

A 27-year-old female African grey parrot (Psittacus erithacus) presented as a referral for surgical removal of an enlarged uropygial gland that was first observed by the owner 6 months prior. Antibiotic therapy was attempted by the referring veterinarian with limited treatment response. No abnormalities were noted in the results of a complete blood count and plasma biochemistry panel. Computed tomographic imaging of the parrot showed a left-sided uropygial gland mass with no evidence of metastasis or invasion into the underlying soft tissue or bone. The uropygial gland was surgically excised in an attempt to obtain clean margins devoid of tumor cells. Histopathological evaluation of the submitted tissue was suggestive of an intraluminal uropygial gland epithelioma. Intraluminal epithelioma should be considered as a differential diagnosis in psittacine species that are presented with an asymmetrically enlarged uropygial gland.

Investigation of suspected gadolinium neurotoxicity in a dog.

Gadolinium-based contrast agents are used across species to better visualize abnormalities during MRI and are considered generally safe in clinical practice. The aim of this study was to investigate central nervous system (CNS) gadolinium deposition in 11 dogs that had an MRI performed, received 0.22 mL/kg (0.1 mmol/kg) of gadopentetate dimeglumine, and were necropsied on the same hospital admission. The index case was a 5-year-old castrated male Australian Shepherd that presented for ataxia and following MRI developed seizure-like activity that became refractory to anticonvulsant therapy. Gadolinium concentration was quantified in CNS tissues by inductively-coupled plasma mass spectrometry and was 43-fold higher in the index case. These findings suggest the possibility of gadolinium toxicity in select patients.

Bilateral tympanokeratomas (cholesteatomas) with bilateral otitis media, unilateral otitis interna and acoustic neuritis in a dog.

BACKGROUND: An aural cholesteatoma, more appropriately named tympanokeratoma, is an epidermoid cyst of the middle ear described in several species, including dogs, humans and Mongolian gerbils. The cyst lining consists of stratified, keratinizing squamous epithelium with central accumulation of a keratin debris. This case report describes vestibular ganglioneuritis and perineuritis in a dog with chronic otitis, bilateral tympanokeratomas and presumed extension of otic infection to the central nervous system. CASE PRESENTATION: An 11-year-old intact male Dalmatian dog with chronic bilateral otitis externa and sudden development of symptoms of vestibular disease was examined. Due to the dog's old age the owner opted for euthanasia without any further examination or treatment and the dog was submitted for necropsy. Transection of the ears revealed grey soft material in the external ear canals and pearly white, dry material consistent with keratin in the tympanic bullae bilaterally. The brain and meninges were grossly unremarkable. Microscopical findings included bilateral otitis externa and media, unilateral otitis interna, ganglioneuritis and perineuritis of the spiral ganglion of the vestibulocochlear nerve and multifocal to coalescing, purulent meningitis. A keratinizing squamous epithelial layer continuous with the external acoustic meatus lined the middle ear compartments, consistent with bilateral tympanokeratomas. Focal bony erosion of the petrous portion of the temporal bone and squamous epithelium and Gram-positive bacterial cocci were evident in the left cochlea. The findings suggest that meningitis developed secondary to erosion of the temporal bone and ganglioneuritis and/or perineuritis of the vestibulocochlear nerve. CONCLUSIONS: Middle ear tympanokeratoma is an important and potentially life-threatening otic condition in the dog. Once a tympanokeratoma has developed expansion of the cyst can lead to erosion of bone and extension of otic infection to the inner ear, vestibulocochlear ganglion and nerve potentially leading to bacterial infection of the central nervous system.

Characterization of cardiac lesions in calves after ingestion of Japanese yew (Taxus cuspidata).

Plants of the genus Taxus are common ornamental shrubs that contain cardiotoxic alkaloids. Gross lesions consistent with heart failure are frequently reported in fatal cases; however, microscopic lesions in the heart have not been well characterized. The current report describes 2 related outbreaks in which 7 of 30, 250-kg calves died after confirmed exposure to clippings of Japanese yew (Taxus cuspidata). Three calves died 24 hr after initial exposure, with no significant gross or histologic lesions. Leaves of the yew plant were identified within the rumen contents, and Taxus alkaloids were confirmed by gas chromatography-mass spectrometry. Following the initial diagnosis, the yew clippings were burned. Two days later, the remaining calves were reintroduced to the enclosure. Within 24 hr, 3 additional calves began to show clinical signs of depression (3/3) or labored breathing (1/3), and by the fourth day, these 3 calves and an additional calf were found dead. Partially burnt yew leaves were found during close inspection of the enclosure. Two of 3 calves submitted for necropsy were severely autolyzed; the third had pulmonary edema and mild fibrinous pleural effusion. Histologic lesions in the latter included multifocal cardiac myocyte hypereosinophilia, sarcolemma fragmentation, pyknosis, karyolysis, myocyte loss, and a mild interstitial lymphoplasmacytic infiltrate with edema. Moderate fibrinosuppurative interstitial pneumonia was the only other significant finding. Cardiac changes were attributed to damage from the initial exposure to Taxus 6 days prior to death.

Practical otic anatomy and physiology of the dog and cat.

Knowledge of the normal structure and function of the canine and feline ear is critical to be able to diagnose abnormalities that either involve the ear or originate within one or more of the ear compartments. In addition, a veterinarian must be aware of various structures within or associated with the ear so that they are not damaged or destroyed while treating an animal with otic disease. This article provides a brief discussion of the various anatomic features of the ear and normal physiology of portions of the ear.

Collection and preparation of dog and cat ears for histologic examination.

Most veterinary textbooks provide very little guidance regarding ear sampling, processing, and examination. The complexity of the ear, which includes integument, mucosa, cartilage, bone, and neural tissues, and the special procedures required to allow histologic examination are 2 of the more common reasons for reluctance by clinicians and pathologists to thoroughly assess the ear. This article helps demystify both the collection and preparation of ear samples, and briefly describes gross features and key landmarks of the ear. However, it is not the intent to provide an exhaustive account of normal and pathologic findings.

Gross lesions of alimentary disease in adult cattle.

The purpose of the gross necropsy examination of the gastrointestinal tract is to recognize the presence of lesions, thus requiring a basic understanding of its normal appearance and anatomy. This article highlights gross changes to the gastrointestinal tract of adult cattle that help place the disease processes into broad categories. Although few gross lesions reach the zenith of pathognomonic, there are numerous lesions that, when considered in aggregate with history (eg, number of animals affected, environment, duration of signs, time of onset relative to management changes, previous management) and clinical signs, can help narrow the spectrum of causes, provide a basis for a strong presumptive diagnosis, and focus diagnostic test selection.

Clinical approach to abortion, stillbirth, and neonatal death in dogs and cats.

This article reviews post-mortem examination, sample collection, and diagnostic procedures used to determine the cause of abortion, stillbirth, and neonatal death in dogs and cats.

Pseudorabies virus infection in Oklahoma hunting dogs.

Pseudorabies is caused by Suid herpesvirus 1, a member of the Alphaherpesvirinae subfamily. Although pigs are the natural host of Pseudorabies virus (PRV), the virus has a broad host range and may cause fatal encephalitis in many species. The United States obtained PRV-free status in 2004 after the virus was eradicated from domestic swineherds, but the virus is still present in feral swine populations. The current report describes PRV infection in 3 dogs that were used to hunt feral swine. The dogs developed clinical signs including facial pruritus with facial abrasions, dyspnea, vomiting, diarrhea, ataxia, muscle stiffness, and death. Two were euthanized, and 1 died within approximately 48 hr after onset of clinical signs. The salient histologic changes consisted of neutrophilic trigeminal ganglioneuritis with neuronophagia and equivocal intranuclear inclusion bodies. Pseudorabies virus was isolated from fresh tissues from 2 of the dogs, and immunohistochemistry detected the virus in the third dog. Virus sequencing and phylogeny, based upon available GenBank sequences, revealed that the virus was likely a field strain that was closely related to a cluster of PRV strains previously identified in Illinois. Though eradicated from domestic swine in the United States, PRV is present in populations of feral swine, and should therefore continue to be considered a possible cause of disease in dogs and other domestic animals with compatible clinical history and signs. Continued surveillance is necessary to prevent reintroduction of PRV into domestic swine.

The virulence of 1997 H5N1 influenza viruses in the mouse model is increased by correcting a defect in their NS1 proteins.

The NS1 protein of human influenza A viruses binds the 30-kDa subunit of the cleavage and polyadenylation specificity factor (CPSF30), a protein required for 3' end processing of cellular pre-mRNAs, thereby inhibiting production of beta interferon (IFN-ß) mRNA. The NS1 proteins of pathogenic 1997 H5N1 viruses contain the CPSF30-binding site but lack the consensus amino acids at positions 103 and 106, F and M, respectively, that are required for the stabilization of CPSF30 binding, resulting in nonoptimal CPSF30 binding in infected cells. Here we have demonstrated that strengthening CPSF30 binding, by changing positions 103 and 106 in the 1997 H5N1 NS1 protein to the consensus amino acids, results in a remarkable 300-fold increase in the lethality of the virus in mice. Unexpectedly, this increase in virulence is not associated with increased lung pathology but rather is characterized by faster systemic spread of the virus, particularly to the brain, where increased replication and severe pathology occur. This increased spread is associated with increased cytokine and chemokine levels in extrapulmonary tissues. We conclude that strengthening CPSF30 binding by the NS1 protein of 1997 H5N1 viruses enhances virulence in mice by increasing the systemic spread of the virus from the lungs, particularly to the brain.

Canine influenza.

In 2004, the isolation of an influenza virus from racing greyhounds changed the point of reference for discussions about influenza virus in dogs. A virus isolated from greyhounds did not have its origin in a previously described human influenza virus but came from a virus with an equine history. More significantly, evidence emerged to indicate that the virus was capable of transmission from dog to dog. This virus is now referred to as canine influenza virus (CIV) and is the focus of this review. Because the history of CIV is relatively short, the impact of this virus on canine health is yet to be determined.

Emerging viral encephalitides in dogs and cats.

Few viral pathogens resulting in encephalitis in dogs and cats have emerged over the past decade or so. All are the result of penetration through presumed species barriers and all are considered zoonoses or possible zoonotic pathogens. In all cases, encephalitis is a rare event that has low morbidity but high mortality. More viruses are likely to emerge as pathogenic in our domesticated carnivorous companions as our habitats continue to overlap with the shrinking wildlife habitats. Hopefully, however, none reach the level of distinction that was once held by rabies virus.

Cyclooxygenase-2 immunoreactivity in equine ocular squamous-cell carcinoma.

Squamous-cell carcinoma (SCC) is the second most common tumor in horses, and 40%-50% may occur in ocular and adnexal structures. Cyclooxygenase (COX)-2 is an inducible enzyme responsible for the production of prostaglandins that control cell growth and the development and progression of cancer. Mechanisms responsible for the initial upregulation of COX-2 in neoplasia are unclear; prolonged sunlight exposure and mutations in the p53 gene may be possibilities. Because the etiopathogenesis of ocular SCC in horses may involve ultraviolet sunlight and p53 mutations, the purpose of this study was to characterize the immunoreactivity of COX-2 in these tumors. Cyclooxygenase-2 expression was found in 6 of 22 (27%) paraffin-embedded equine SCCs. Cyclooxygenase-2 immunoreactivity was associated with the mitotic index (P < 0.001). Strategies to inhibit COX-2 by the use of topical or systemic COX-2 inhibitors might prove to be a safe and economical treatment in some horses with SCC.

Characterization of rupture of abdominal artery aneurysm in dairy cattle.

In this retrospective study, the authors describe the gross and histologic changes associated with rupture of an abdominal artery aneurysm in 33 mature female Holstein cattle between January 1980 and June 2005 from 29 farms in upstate New York and northern Pennsylvania. Over this period, there was an increase in the number of cases submitted for necropsy per year, and a seasonal trend did not exist. Affected animals ranged from 2.5 to 5.5 years of age. Grossly affected cattle exhibited marked hemoabdomen. There was marked dilation and rupture of the abdominal aorta or one of its branches, including the mesenteric, left gastric, celiac artery, right ruminal artery, or left ruminal artery. Histologically, the tunica media of the affected arteries was often thin and irregular in width with disrupted, fragmented, and coiled elastin. Granulation tissue and hemorrhage was localized at the site of rupture. There was mild-to-marked hyperplasia of the tunica intima that was irregular and disorderly with adjacent smooth-muscle hyperplasia within the tunica media. In addition, in a fraction of cases, there was mild-to-moderate mucinous change (48%) and mineralization (30%) within the tunica media. To the authors' knowledge, this is the first description of the gross and histologic changes in Holstein cows with abdominal artery aneurysm and rupture.

Evaluation of factors associated with survival in dogs with untreated nasal carcinomas: 139 cases (1993-2003).

OBJECTIVE: To evaluate factors associated with survival in dogs with nasal carcinomas that did not receive treatment or received only palliative treatment. DESIGN: Retrospective case series. ANIMALS: 139 dogs with histologically confirmed nasal carcinomas. PROCEDURES: Medical records, computed tomography images, and biopsy specimens of nasal carcinomas were reviewed. Only dogs that were not treated with radiation, surgery, chemotherapy, or immunotherapy and that survived > or = 7 days from the date of diagnosis were included. The Kaplan-Meier method was used to estimate survival time. Factors potentially associated with survival were compared by use of log-rank and Wilcoxon rank sum tests. Multivariable survival analysis was performed by use of the Cox proportional hazards regression model. RESULTS: Overall median survival time was 95 days (95% confidence interval [CI], 73 to 113 days; range, 7 to 1,114 days). In dogs with epistaxis, the hazard of dying was 2.3 times that of dogs that did not have epistaxis. Median survival time of 107 dogs with epistaxis was 88 days (95% CI, 65 to 106 days) and that of 32 dogs without epistaxis was 224 days (95% CI, 54 to 467 days). CONCLUSIONS AND CLINICAL RELEVANCE: The prognosis of dogs with untreated nasal carcinomas is poor. Treatment strategies to improve outcome should be pursued.