Global distribution of Leptospira serovar isolations and detections from animal host species: A systematic review and online database.

OBJECTIVES: Leptospira, the spirochaete causing leptospirosis, can be classified into >250 antigenically distinct serovars. Although knowledge of the animal host species and geographic distribution of Leptospira serovars is critical to understand the human and animal epidemiology of leptospirosis, current data are fragmented. We aimed to systematically review, the literature on animal host species and geographic distribution of Leptospira serovars to examine associations between serovars with animal host species and regions and to identify geographic regions in need of study. METHODS: Nine library databases were searched from inception through 9 March 2023 using keywords including Leptospira, animal, and a list of serovars. We sought reports of detection of Leptospira, from any animal, characterised by cross agglutinin absorption test, monoclonal antibody typing, serum factor analysis, or pulsed-field gel electrophoresis to identify the serovar. RESULTS: We included 409 reports, published from 1927 through 2022, yielding data on 154 Leptospira serovars. The reports included data from 66 (26.5%) of 249 countries. Detections were from 144 animal host species including 135 (93.8%) from the class Mammalia, 5 (3.5%) from Amphibia, 3 (2.1%) from Reptilia, and 1 (0.7%) from Arachnida. Across the animal host species, Leptospira serovars that were detected in the largest number of animal species included Grippotyphosa (n = 39), Icterohaemorrhagiae (n = 29), Pomona (n = 28), Australis (n = 25), and Ballum (n = 25). Of serovars, 76 were detected in a single animal host species. We created an online database to identify animal host species for each serovar by country. CONCLUSIONS: We found that many countries have few or no Leptospira serovars detected from animal host species and that many serovars were detected from a single animal species. Our study highlights the importance of efforts to identify animal host species of leptospirosis, especially in places with a high incidence of human leptospirosis. We provide an updated resource for leptospirosis researchers.

Diagnostic immunohistochemistry of primary and secondary central nervous system neoplasms of dogs and cats.

The diagnosis of primary and secondary CNS neoplasms of dogs and cats relies on histologic examination of autopsy or biopsy samples. In addition, many neoplasms must be further characterized by immunohistochemistry (IHC) for a more refined diagnosis in specific cases. Given the many investigations assessing the diagnostic and prognostic IHC profile of CNS neoplasms in the veterinary literature, it may be difficult for the diagnostic pathologist or pathology trainee to narrow the list of reliable diagnostic IHCs when facing a challenging case. Here we compile a comprehensive list of the most diagnostically relevant immunomarkers that should be utilized for the diagnostic support or confirmation of the most common primary and secondary CNS neoplasms of dogs and cats.

Global distribution of Leptospira serovar isolations and detections from animal host species: a systematic review and online database.

Objectives: Leptospira, the spirochaete causing leptospirosis, can be classified into >250 antigenically distinct serovars. Although knowledge of the animal host species and geographic distribution of Leptospira serovars is critical to understand the human and animal epidemiology of leptospirosis, currently data are fragmented. We aimed to systematically review the literature on animal host species and geographic distribution of Leptospira serovars to examine associations between serovars with animal host species and regions, and to identify geographic regions in need of study. Methods: Nine library databases were searched from inception through 9 March 2023 using keywords including Leptospira, animal, and a list of serovars. We sought reports of detection of Leptospira, from any animal, characterized by cross agglutinin absorption test, monoclonal antibody typing, serum factor analysis, or pulsed-field gel electrophoresis to identify the serovar. Results: We included 409 reports, published from 1927 through 2022, yielding data on 154 Leptospira serovars. The reports included data from 66 (26.5%) of 249 countries. Detections were from 144 animal host species including 135 (93.8%) from the class Mammalia, 5 (3.5%) from Amphibia, 3 (2.1%) from Reptilia, and 1 (0.7%) from Arachnida. Across the animal host species, Leptospira serovars that were detected in the largest number of animal species included Grippotyphosa (n=39), Icterohaemorrhagiae (n=29), Pomona (n=28), Australis (n=25), and Ballum (n=25). Of serovars, 76 were detected in a single animal host species. We created an online database to identify animal host species for each serovar by country. Conclusions: We found that many countries have few or no Leptospira serovars detected from animal host species and that many serovars were detected from a single animal species. Our study highlights the importance of efforts to identify animal host species of leptospirosis, especially in places with a high incidence of human leptospirosis. We provide an updated resource for leptospirosis researchers.

Virulent Brucella nosferati infecting Desmodus rotundus has emerging potential due to the broad foraging range of its bat host for humans and wild and domestic animals.

Desmodus rotundus, vampire bats, transmit dangerous infections, and brucellosis is a hazardous zoonotic disease, two adversities that coexist in the subtropical and tropical areas of the American continent. Here, we report a 47.89% Brucella infection prevalence in a colony of vampire bats inhabiting the tropical rainforest of Costa Rica. The bacterium induced placentitis and fetal death in bats. Wide-range phenotypic and genotypic characterization placed the Brucella organisms as a new pathogenic species named Brucella nosferati sp. nov., isolated from bat tissues, including the salivary glands, suggesting feeding behavior might favor transmission to their prey. Overall analyses placed B. nosferati as the etiological agent of a reported canine brucellosis case, demonstrating its potential for infecting other hosts. To assess the putative prey hosts, we analyzed the intestinal contents of 14 infected and 23 non-infected bats by proteomics. A total of 54,508 peptides sorted into 7,203 unique peptides corresponding to 1,521 proteins were identified. Twenty-three wildlife and domestic taxa, including humans, were foraged by B. nosferati-infected D. rotundus, suggesting contact of this bacterium with a broad range of hosts. Our approach is appropriate for detecting, in a single study, the prey preferences of vampire bats in a diverse area, demonstrating its suitability for control strategies where vampire bats thrive. IMPORTANCE The discovery that a high proportion of vampire bats in a tropical area is infected with pathogenic Brucella nosferati and that bats forage on humans and many wild and domestic animals is relevant from the perspective of emerging disease prevention. Indeed, bats harboring B. nosferati in their salivary glands may transmit this pathogenic bacterium to other hosts. This potential is not trivial since, besides the demonstrated pathogenicity, this bacterium possesses all the required virulent arsenal of dangerous Brucella organisms, including those that are zoonotic for humans. Our work has settled the basis for future surveillance actions in brucellosis control programs where these infected bats thrive. Moreover, our strategy to identify the foraging range of bats may be adapted for exploring the feeding habits of diverse animals, including arthropod vectors of infectious diseases, and therefore of interest to a broader audience besides experts on Brucella and bats.

Granulomatous mural folliculitis in 16 domestic goats: Infection with malignant catarrhal fever viruses and colocalization with ovine herpesvirus-2 using in situ hybridization.

Granulomatous mural folliculitis (GMF) is an uncommon reaction pattern occasionally observed in nonadapted ruminant hosts infected with malignant catarrhal fever viruses. This report characterizes GMF and concurrent cutaneous lesions in 16 goats with crusting dermatitis using histochemistry including hematoxylin and eosin, periodic acid-Schiff, and Grocott's methenamine silver, and immunohistochemistry for CD3, CD20, ionized calcium binding adaptor molecule 1, and cytokeratin AE1/3. Infiltrates in all 16 GMF cases consisted of macrophages and fewer T lymphocytes, and variably included eosinophils, multinucleated histiocytic giant cells, and/or neutrophils. Formalin-fixed paraffin-embedded skin and fresh skin samples from caprine GMF cases were tested using pan-herpesvirus nested conventional polymerase chain reaction (PCR) and partial sequencing, ovine herpesvirus-2 (OvHV-2) real-time PCR, and OvHV-2 colorimetric in situ hybridization (ISH). Five of 16 goats with GMF (31%) were PCR positive for malignant catarrhal fever viruses, including caprine herpesvirus 3 in 1 goat and OvHV-2 in 4 goats. Three goats also had positive intranuclear OvHV-2 hybridization signal in follicular keratinocytes, among other cell types, localized to areas of GMF. Herpesviruses were not detected in the formalin-fixed paraffin-embedded skin of 9 goats without GMF. This case series describes relatively frequent detections of malignant catarrhal fever viruses in the skin of goats with GMF, including the first report of caprine herpesvirus 3, and localizes OvHV-2 infected follicular keratinocytes within areas of GMF.

Nocardia and Streptomyces keratitis in dogs: In vivo detection of filamentous bacteria by confocal microscopy.

OBJECTIVE: To describe the clinical features of dogs with Nocardia and Streptomyces keratitis, including the results of in vivo confocal microscopy examinations. ANIMAL STUDIED: A 15-year-old, male-castrated, miniature Schnauzer was presented with a multilobulated, cystic, pink, ulcerated corneal mass with surrounding dense leukocyte infiltrates. Cytologic evaluation of a corneal scraping identified pyogranulomatous inflammation and filamentous bacteria. Nocardia nova was cultured from corneal samples. Anterior lamellar keratectomy was performed to excise the affected corneal region and histopathologic evaluation confirmed the diagnosis of pyogranulomatous keratitis. A 10-year-old, male-castrated, Yorkshire terrier was presented for evaluation of a chronic anterior stromal corneal ulcer associated with a brown corneal plaque. Cytologic evaluation of a corneal scraping identified suppurative inflammation and filamentous bacteria. A Streptomyces sp. was cultured from corneal samples. The keratitis in both dogs resolved with therapy. PROCEDURES: In vivo confocal microscopy examination of the corneal lesions in both dogs revealed dense accumulations of leukocytes and clusters of hyperreflective, slender, branching bacterial structures that were approximately 1.5-2.0 µm in diameter and 25-50 µm in length. Confocal microscopy imaging of the Nocardia isolate in vitro, and ex vivo canine corneas experimentally infected with the bacteria, was performed to corroborate the in vivo findings. The morphology of the filamentous bacteria was similar between the in vivo, in vitro, and ex vivo confocal microscopy examinations. CONCLUSIONS AND CLINICAL RELEVANCE: Nocardia and Streptomyces spp. can be associated with infectious keratitis in dogs. In vivo detection of filamentous bacteria in the cornea can be accomplished by confocal microscopy.

Histiocytic sarcoma with central nervous system involvement in 6 cats.

Here we characterize 6 cases (4 autopsies and 2 biopsies) of histiocytic sarcoma in the CNS of cats. All affected cats had chronic, progressive clinical signs. Three autopsied cats were euthanized because of a poor prognosis, and one died. The clinical outcome for the biopsy cases remains unknown. Tumors occurred in the brain (4 cases), spinal cord (1 case), and brain and spinal cord (1 case). Neoplasms were restricted to the CNS in 3 cases. Reported gross changes in the 4 autopsy cases consisted of neuroparenchymal swelling with or without tissue pallor or gray discoloration (2 cases) and a yellow or dark-gray mass (2 cases). Histologically, pleomorphic, round-to-elongate neoplastic cells with typical histiocytic morphology effaced the neuroparenchyma and leptomeninges. Multinucleate neoplastic cells were observed in all cases. The mitotic count was 1-24 in 2.37 mm2 (10 FN22 40× fields). Neoplastic cells in all cases had positive immunolabeling for Iba1; immunolabeling was negative for E-cadherin, CD3, CD79, and MUM1, confirming their histiocytic origin.

Delayed puberty, gonadotropin abnormalities and subfertility in male Padi2/Padi4 double knockout mice.

BACKGROUND: Peptidylarginine deiminase enzymes (PADs) convert arginine residues to citrulline in a process called citrullination or deimination. Recently, two PADs, PAD2 and PAD4, have been linked to hormone signaling in vitro and the goal of this study was to test for links between PAD2/PAD4 and hormone signaling in vivo. METHODS: Preliminary analysis of Padi2 and Padi4 single knockout (SKO) mice did not find any overt reproductive defects and we predicted that this was likely due to genetic compensation. To test this hypothesis, we created a Padi2/Padi4 double knockout (DKO) mouse model and tested these mice along with wild-type FVB/NJ (WT) and both strains of SKO mice for a range of reproductive defects. RESULTS: Controlled breeding trials found that male DKO mice appeared to take longer to have their first litter than WT controls. This tendency was maintained when these mice were mated to either DKO or WT females. Additionally, unsexed 2-day old DKO pups and male DKO weanlings both weighed significantly less than their WT counterparts, took significantly longer than WT males to reach puberty, and had consistently lower serum testosterone levels. Furthermore, 90-day old adult DKO males had smaller testes than WT males with increased rates of germ cell apoptosis. CONCLUSIONS: The Padi2/Padi4 DKO mouse model provides a new tool for investigating PAD function and outcomes from our studies provide the first in vivo evidence linking PADs with hormone signaling.

OLIG2 immunolabeling in feline ependymoma.

Ependymoma, one of the most common gliomas in cats, occurs most often in the lateral and third ventricles and has variable histologic patterns that often form rosettes and pseudorosettes. Oligodendrocyte transcription factor (OLIG2) is expressed in oligodendrocyte precursor cells and mature oligodendrocytes. Although widely used as a diagnostic marker for most gliomas, OLIG2 is reported to have minimal immunolabeling in ependymomas. Here we characterize the OLIG2 immunolabeling pattern in 19 cases of feline ependymoma, which occurred predominantly in the lateral and third ventricles. Immunohistochemistry for GFAP was variable in 14 cases and was typically localized in the cytoplasmic processes of the neoplastic ependymal cells, especially in the rosettes and pseudorosettes. Nuclear OLIG2 immunolabeling was present in 17 cases and varied in intensity from weak (4 cases) to strong (13 cases). The distribution of OLIG2 immunolabeling within the neoplasms included none (2 cases), <25% (7 cases), 25-50% (6 cases), 51-75% (2 cases), and >75% (3 cases). OLIG2 immunolabeling intensity and distribution is widespread in feline ependymoma, in contrast to ependymomas in other species, and should not be relied upon as a specific marker for feline oligodendroglioma.

Pathology in Practice.

In collaboration with the American College of Veterinary Pathologists.

Osteogenesis Imperfecta in Two Finnish Lapphund Puppies.

Two 8-week-old Finnish Lapphund dogs presented with pain on manipulation, abnormal long bone conformation, retrognathism, and stunted growth compared to their litter mates. Multiple long bone fractures were evident on radiographs. Clinical pathology showed an atypically normal serum alkaline phosphatase activity for dogs this age. Due to poor quality of life, the dogs were humanely euthanized and subjected to a complete necropsy. On necropsy, all bones were soft and easily broken. Histologic examination revealed that the secondary spongiosa was diminished with abnormal bony trabeculae embedded in abundant loose vascular stroma. No Haversian canals were observed and the cortices contained abundant woven bone separated by fibrovascular tissue consistent with the diagnosis of osteogenesis imperfecta (OI). Inbreeding of the sire and female offspring led to a suspicion of recessive inheritance and the particular genetic collagen disorder remains to be identified in this breed.

In vivo detection of microstructural spinal cord lesions in dogs with degenerative myelopathy using diffusion tensor imaging.

BACKGROUND: Degenerative myelopathy (DM) in dogs is a progressive neurodegenerative condition that causes white matter spinal cord lesions. These lesions are undetectable on standard magnetic resonance imaging (MRI), limiting diagnosis and monitoring of the disease. Spinal cord lesions cause disruption to the structural integrity of the axons causing water diffusion to become more random and less anisotropic. These changes are detectable by the technique of diffusion tensor imaging (DTI) which is highly sensitive to diffusion alterations secondary to white matter lesion development. OBJECTIVE: Perform spinal DTI on cohorts of dogs with and without DM to identify if lesions caused by DM will cause a detectable alteration in spinal cord diffusivity that correlates with neurological status. ANIMALS: Thirteen dogs with DM and 13 aged-matched controls. METHODS: All animals underwent MRI with DTI of the entire spine. Diffusivity parameters fractional anisotropy (FA) and mean diffusivity (MD) were measured at each vertebral level and statistically compared between groups. RESULTS: Dogs with DM had significant decreases in FA within the regions of the spinal cord that had high expected lesion load. Decreases in FA were most significant in dogs with severe forms of the disease and correlated with neurological grade. CONCLUSIONS AND CLINICAL IMPORTANCE: Findings suggest that FA has the potential to be a biomarker for spinal cord lesion development in DM and could play an important role in improving diagnosis and monitoring of this condition.

Microtubule-Associated Protein 2 Expression in Canine Glioma.

Canine glioma is considered a potential model for human glioma, with recent studies of occurrence, therapy, and reclassification supporting the value of the canine model. The current diagnosis of canine glioma is based on morphologic criteria and immunohistochemistry (IHC), including oligodendrocyte transcription factor 2 (Olig2), glial fibrillary acidic protein (GFAP), and 2', 3' cyclic nucleotide phosphatase (CNPase). Microtubule-associated protein 2 (MAP2) is a proven marker of human glioma and is used to complement the diagnosis and its specific immunoreactivity pattern contributes to the differentiation of astrocytomas from other glial tumors. The objective of this study was to evaluate whether canine gliomas express MAP2 and to explore differences in the pattern of immunolabeling between different gliomas. Seventy-eight cases of canine glioma were evaluated for MAP2 expression by immunohistochemistry. A glial origin was supported by Olig2 IHC in all cases. MAP2 immunolabeling was evaluated on a semi-quantitative basis, including the percentage of immunolabeled neoplastic cells, as well as the signal intensity, distribution, and pattern of immunolabeling. MAP2 was expressed in all cases, with significant correlation between diagnosis and signal intensity (P = 0.04). MAP2 immunolabeling distribution was dominated by diffuse (34/78; 44%), followed by patchy (20/78; 26%), multifocal to coalescing (16/78; 21%), and scattered (8/78; 10%). All oligodendrogliomas (53/53; 100%) and undefined gliomas (12/12; 100%) revealed a combination of perinuclear and cytoplasmic immunolabeling, and all but 3 astrocytomas had a combination of perinuclear and cytoplasmic processes immunolabeling (10/13; 77%). Significant correlation between immunolabeling pattern and diagnosis was obtained (P = 0.001). The study demonstrates that MAP2 is expressed in canine gliomas and the pattern of expression can also be applied to help distinguish astrocytomas from oligodendrogliomas and undefined gliomas.

Single-Stage Craniectomy and Cranioplasty for Multilobular Osteochondrosarcoma Managed with a Custom Additive Manufactured Titanium Plate in a Dog.

A 9-year-old spayed female dachshund presented with a large multilobular osteochondrosarcoma of the crania, with obliteration of approximately 70% of the surface area of the dorsal calvaria and intracranial extension. The mass was excised with histologically clean lateral bone margins (2-4 mm) and invasion at the deep margin. The resulting defect was reconstructed with a custom titanium plate. The patient recovered routinely and was asymptomatic until 7 months postoperatively. The patient developed intractable seizures 7 months postoperatively and was euthanized. Post-mortem examination showed tumor regrowth within the brain parenchyma. No abnormalities were seen associated with the plate. The patient-specific, custom additive manufactured titanium plate provided an excellent option for anatomic reconstruction and protection of the brain over a relatively large area with no complications noted.