Outcome of chronic inflammatory enteropathy in cats: 65 cases (2011-2021).

OBJECTIVES: Feline chronic inflammatory enteropathy is an idiopathic disease with limited information on variables that might affect treatment outcome and survival. The aim of this study was to determine if clinicopathological variables were associated with death due to gastrointestinal disease in cats with chronic inflammatory enteropathy. MATERIALS AND METHODS: Three medical records databases were retrospectively searched for cats diagnosed with chronic inflammatory enteropathy at the Royal Veterinary College between June 2008 and November 2021. Intestinal biopsy specimens of eligible cases were re-reviewed by one board-certified veterinary pathologist. Outcome information was obtained by contact with the referring veterinary surgeon. Two univariable binary logistic regression models and a Fisher's exact test were performed to assess the association between the outcome of death due to gastrointestinal disease or its short-term survival (≤ versus >1 year) with clinicopathological variables and the attainment of clinical remission. RESULTS: Sixty-five cats diagnosed with chronic inflammatory enteropathy between September 2011 and August 2021 were included in the study with follow-up information available for 54 cats (83%). Of these 54 cats, 20 (37%) were euthanised due to gastrointestinal disease (median 129.5 days; range 8 to 2970 days). Twenty-five (46%) cats were alive and in clinical remission (median 916 days; range 78 to 2113 days) with 16 (64%) diagnosed with food-responsive enteropathy. Attaining clinical remission reduced the likelihood of subsequent death due to gastrointestinal disease. CLINICAL SIGNIFICANCE: Measured physical and laboratory variables at the time of histopathological diagnosis of chronic inflammatory enteropathy were not predictors of death. Alternative diagnostic measures are required to definitively investigate outcome and survival in cats with chronic inflammatory enteropathy.

Scent (Apocrine) Gland Adenocarcinoma in a Wedge-Capped Capuchin Monkey (Cebus olivaceus): Histological and Immunohistochemical Features.

In humans, apocrine gland tumours encompass a heterogeneous group of uncommon neoplasms with varied and unpredictable biological behaviour. They can be slow-growing lesions, recur after excision, produce lymph node metastasis in up to 50% of cases or lead to tumour-related death. We document a malignant scent adenocarcinoma in a wedge-capped capuchin monkey (Cebus olivaceus). Immunohistochemical labelling revealed complete absence of myoepithelial cells, a finding usually considered a hallmark of malignancy in humans; however, after a 2-year follow-up, the neoplasm had not recurred. This is the first detailed report of the pathology of a spontaneous scent (apocrine) gland adenocarcinoma in a non-human primate.

Aberrant Expression of Cell Cycle Regulator 14-3-3-σ and E-Cadherin in a Metastatic Cholangiocarcinoma in a Vervet Monkey (Chlorocebus pygerythrus).

We present a unique case of metastatic cholangiocarcinoma with concurrent abdominal cestodiasis in an African green monkey (Chlorocebus pygerythrus) that presented with respiratory insufficiency and abdominal discomfort. There were multiple white-grey masses in the liver and colonic serosa alongside intra-abdominal parasitic cysts. Histopathologically, the liver masses were composed of poorly-differentiated epithelial cells that formed densely cellular solid areas and trabeculae. The neoplastic cells were strongly immunopositive for CK7 but negative for Hep-Par1 antigen, which confirmed a diagnosis of cholangiocarcinoma. Interestingly, there was strong and diffuse neoexpression in the tumour of the cell cycle regulator 14-3-3σ, which is not constitutively expressed in normal liver. There was aberrantly strong expression of E-cadherin, a key cell-cell adhesion protein, in neoplastic cells with evidence of cytoplasmic internalization. This is the first immunohistochemical analysis of 14-3-3σ and E-cadherin in a liver neoplasm in an animal species and the use of these markers requires further investigation in animal liver neoplasms.

Histiocytic sarcoma in miniature schnauzers: 30 cases.

OBJECTIVES: To summarise the clinical presentation and outcomes in a series of miniature schnauzers diagnosed with histiocytic sarcoma. MATERIALS AND METHODS: Retrospective review of medical records of miniature schnauzers diagnosed with histiocytic sarcoma between 2008 and 2019 at two referral centres in the UK. Signalment, clinical signs at initial presentation, imaging results and clinico- and histopathological findings, treatment type and outcome were recorded. Progression-free survival and overall survival time were calculated. RESULTS: Thirty dogs were included. Twenty-four of 29 dogs undergoing imaging of the thorax had lung and/or mediastinal involvement. The median overall survival time for dogs that were not euthanased within 3 days of diagnosis was 117 days (range 10 to 790). Three dogs underwent surgery; 13 received treatment with lomustine as a sole therapy - with partial responses documented on imaging in five of six dogs and 11 of 13 showing clinical improvement. CLINICAL SIGNIFICANCE: Histiocytic sarcoma should be considered as a differential diagnosis for miniature schnauzers with pulmonary masses. Although responses to treatment were common, they were usually short-lived because of the aggressive nature of the disease.

Avian Papilloma and Squamous Cell Carcinoma: a Histopathological, Immunohistochemical and Virological study.

In this retrospective study, we describe the histopathological findings in seven papillomas and 45 squamous cell carcinomas (SCCs) from psittacine birds, raptors and domestic fowl. The age of affected birds ranged from 3 to 40 years, with median age significantly higher in psittacines (P = 0.014). The majority of tumours were located in the skin (24/52, 46.2%) or uropygial gland (10/52, 19.2%). Thirty of the SCCs (66.7%) were well differentiated and 15 (33.3%) were poorly-differentiated. SCCs exhibited a significantly higher degree of nuclear pleomorphism (P = 0.005) and a greater proportion were ulcerated (P = 0.001) compared with papillomas; however, there was no significant difference in mitotic count (MC) or inflammation score. The expression of cyclo-oxygenase (COX)-2 and E-cadherin was investigated by immunohistochemistry. The COX-2 total score (TS) was significantly higher in SCCs compared with papillomas (P = 0.002), but the difference between COX-2 TS of well- and poorly-differentiated SCCs was not significant. COX-2 labelling was predominantly cytoplasmic, but some tumours had concurrent membranous and/or perinuclear labelling. SCCs with membranous labelling had a significantly higher MC (P = 0.028). A significantly higher proportion of SCCs were negative for E-cadherin compared with papillomas (P = 0.042), but there was no significant difference between well- and poorly-differentiated SCCs. Fourteen papillomas and SCCs from psittacines were also tested by polymerase chain reaction for the presence of Psittacus erithacus papillomavirus 1 and Psittacid herpesvirus 1, but all samples tested negative. We demonstrate for the first time the expression of COX-2 and E-cadherin in avian tissues, and suggest that these markers may be useful in differentiating papillomas from SCCs, particularly when sample size is small.

Eubacterial fluorescence in situ hybridisation and histologic features in 25 dogs with gallbladder mucocele.

OBJECTIVES: To detect and localise bacteria in gallbladder mucoceles using fluorescence in situ hybridisation (FISH). To report clinical signs, clinicopathologic abnormalities, sonographic findings and histopathological findings in FISH+ and FISH- dogs with gallbladder mucoceles. MATERIALS AND METHODS: Retrospective review of signalment, clinical signs, clinicopathologic and sonographic findings of 25 cases of histopathologically confirmed gallbladder mucocele. Histopathological sections of gallbladder mucocele were evaluated for cystic mucinous hyperplasia, cystic mucinous hyperplasia with cholecystitis and rupture. The number and spatial distribution of bacteria was determined by eubacterial FISH. Gallbladder contents were cultured in 21 dogs. RESULTS: Bacteria were detected within or adherent to the gallbladder wall in eight of 25 (32%) cases. Bacterial culture was positive in one dog. Cystic mucinous hyperplasia with concurrent cholecystitis was found in 17 of 25 (68%) of dogs with gallbladder mucocele. CLINICAL SIGNIFICANCE: FISH was more sensitive for detection of bacteria in gallbladder mucoceles when compared to bacterial culture of bile. Cholecystitis was common in dogs with gallbladder mucocele. Further study is required to elucidate the relationship of cystic mucinous hyperplasia, bacteria and cholecystitis in the aetiopathogenesis and progression of gallbladder mucocele.

Surgical management of chronic otitis secondary to craniomandibular osteopathy in three West Highland white terriers.

Three West Highland white terriers were presented for investigation of left-sided para-aural abscessation. CT revealed chronic otitis media with extensive osseous proliferation surrounding the horizontal and vertical ear canals contiguous with the expanded temporal bone, consistent with a unilateral variant of craniomandibular osteopathy. A left total ear canal ablation with lateral bulla osteotomy was performed in all dogs. An ultrasonic bone curette (Sonopet; Stryker) proved useful when removing the osseous proliferation in two dogs. Histopathological examination of the ear canals was consistent with craniomandibular osteopathy and the treatment led to resolution of the presenting clinical signs in all dogs. To our knowledge, this is the first report of craniomandibular osteopathy engulfing the external ear canal, presumably leading to chronic otitis media and para-aural abscess formation. This is also the first reported use of an ultrasonic bone curette in canine otic surgery.

Malignant Cutaneous Peripheral Nerve Sheath Tumour with Rhabdomyosarcomatous Differentiation (Triton Tumour) in a Domestic Cat.

Divergent differentiation is encountered frequently within human malignant peripheral nerve sheath tumours (MPNSTs). The new component is often a rhabdomyosarcoma, but in animals this specific form of divergent differentiation within MPNSTs has only been reported once (in a dog). Incisional wedge biopsy of a locally extensive, ventral abdominal wall mass, which extended from the dermis to the subcutis, from a 12-year-old female domestic shorthaired cat, was performed. The tissue was examined with routine haematoxylin and eosin staining and immunohistochemical methods. A malignant neoplasm with spindle and polygonal cell components and progression towards a rhabdomyosarcomatous phenotype was observed. Both neoplastic cell populations exhibited strong expression of vimentin and there was multifocal expression of S100 and desmin. There was strong cytoplasmic labelling for α-sarcomeric actin and muscle actin and weak labelling for myoglobin within the cells positive for desmin. There was multifocal positive nuclear labelling for myogenin. Glial fibrillary acidic protein, α-smooth muscle actin, microphthalmia-associated transcription factor and melanoma antigen recognized by T cells were not expressed. Microscopical features, aided by immunohistochemistry, identified a MPNST with progression towards a rhabdomyosarcomatous phenotype, a so-called 'triton tumour'. A Schwann cell component could account for the divergent patterns of growth, given the plasticity of the neural crest. Nerve sheath tumours have been reported in the skin and subcutis of cats and are a differential diagnosis of feline cutaneous spindle cell neoplasms.

Canine NAPEPLD-associated models of human myelin disorders.

Canine leukoencephalomyelopathy (LEMP) is a juvenile-onset neurodegenerative disorder of the CNS white matter currently described in Rottweiler and Leonberger dogs. Genome-wide association study (GWAS) allowed us to map LEMP in a Leonberger cohort to dog chromosome 18. Subsequent whole genome re-sequencing of a Leonberger case enabled the identification of a single private homozygous non-synonymous missense variant located in the highly conserved metallo-beta-lactamase domain of the N-acyl phosphatidylethanolamine phospholipase D (NAPEPLD) gene, encoding an enzyme of the endocannabinoid system. We then sequenced this gene in LEMP-affected Rottweilers and identified a different frameshift variant, which is predicted to replace the C-terminal metallo-beta-lactamase domain of the wild type protein. Haplotype analysis of SNP array genotypes revealed that the frameshift variant was present in diverse haplotypes in Rottweilers, and also in Great Danes, indicating an old origin of this second NAPEPLD variant. The identification of different NAPEPLD variants in dog breeds affected by leukoencephalopathies with heterogeneous pathological features, implicates the NAPEPLD enzyme as important in myelin homeostasis, and suggests a novel candidate gene for myelination disorders in people.

Endocardial Peripheral Nerve Sheath Tumour with Features of a Benign Schwannoma in a Donkey.

A peripheral nerve sheath tumour, with features of a benign schwannoma and arising from the endocardium of the right ventricle, was found incidentally during routine post-mortem examination of a 28-year-old gelding donkey. Macroscopically, five round to oval, white to grey and red, firm masses, firmly attached to the endocardium were identified. Microscopically, the endocardium and adjacent subendocardium were infiltrated by a variably demarcated, non-encapsulated mesenchymal neoplasm with features of a benign schwannoma, including concurrent presence of Antoni A and Antoni B areas, nuclear palisading, neoplastic cells with enlarged bizarre nuclei ('ancient change') and the formation of Verocay-like bodies. Immunohistochemically, the tumour cells were variably strongly positive for expression of S100 and glial fibrillary acidic protein. This is the first cardiac tumour reported in a donkey and is macroscopically, histologically and immunohistochemically similar to endocardial schwannoma occurring in Wistar rats.

Benign Bilateral Adenomyoepithelioma of the Mammary Gland in a Ring-tailed Lemur (Lemur catta).

Naturally occurring mammary tumours are uncommon in prosimians. A 20-year-old female ring-tailed lemur (Lemur catta) developed bilateral enlargement of the mammary glands. Surgical removal revealed that both masses were comprised of multiple nodules and cystic areas that entirely replaced the normal glands. Histologically, a benign neoplastic biphasic cellular proliferation, composed of luminal-epithelial and basal-myoepithelial components, was identified. Immunohistochemical analysis for expression of cytokeratin (CK) AE1/AE3, CK7, CK5 + 8, CK14, vimentin, p63 and 14-3-3σ highlighted the biphasic nature of the neoplasm. A low mitotic count, low Ki67 labelling index, expression of oestrogen receptor-α, lack of expression of human epidermal growth factor receptor and a 3-year disease-free period without recurrence supported the benign nature of the tumour. Macroscopically, histologically and immunohistochemically this neoplasm resembled benign adenomyoepithelioma of the breast in women. This is the first complete report of a naturally occurring mammary tumour in a ring-tailed lemur.

Prevalence of FoxP3+ Cells Does Not Correlate With Ki67 Expression in Canine Diffuse Large B-cell Lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is the most common type of canine lymphoma and survival times are currently <1 year. Manipulation of the tumour microenvironment, of which the regulatory T cell (Treg) is a principal player, represents a potentially exciting way to curb the rapid proliferation of neoplastic cells. Tregs, characterized by the stable expression of the transcription factor FoxP3, suppress innate and adaptive arms of the immune response and represent a potential therapeutic target within neoplastic lymph nodes. This retrospective study explored the hypothesis that Tregs promote the proliferation of neoplastic large B cells, employing immunohistochemistry to assess both FoxP3 and Ki67 expression within canine lymph nodes. Fifty-seven biopsy samples of canine nodal DLBCL were examined. There were significantly fewer FoxP3+ cells in lymph nodes effaced by DLBCL than in reactive lymph nodes (27 versus 369 cells/mm2; Mann-Whitney U = 16, P = 0.011). There was no relationship between the number of intratumoural FoxP3+ cells and neoplastic cell proliferation (Spearman's rank r = 0.058, P = 0.670, 95% confidence interval). The results of this study show that FoxP3+ cells are reduced in lymph nodes effaced by DLBCL and that this change is unrelated to the expression of Ki67. This study also describes a robust digital method to standardize cell counts and facilitate future comparative studies.

Histopathologic Characteristics of Intestinal Biopsy Samples from Dogs With Chronic Inflammatory Enteropathy With and Without Hypoalbuminemia.

BACKGROUND: Previous studies have identified hypoalbuminemia as a risk factor for negative outcome in dogs with chronic enteropathy (CE), but it has not been determined whether histopathology differs between CE dogs with and without hypoalbuminemia. OBJECTIVE: To compare histopathologic findings in dogs with biopsy-diagnosed inflammatory CE with and without hypoalbuminemia. ANIMALS: 83 dogs that had intestinal biopsy performed between January 2010-July 2015. Dogs had signs compatible with CE of at least 3-weeks' duration and no evidence of clinically relevant extra-gastrointestinal (GI) disease or potential non-GI causes of hypoalbuminemia. Dogs had primary diagnosis of inflammatory enteritis based on histopathology. METHODS: Dogs were grouped into CE with normoalbuminemia (CEN; serum albumin concentration ≥3.0 g/dL, N = 46) or chronic enteropathy with hypoalbuminemia (CEH; serum albumin concentration <3.0 g/dL, N = 37). A pathologist (SLP) blinded to the groups reviewed biopsy samples and applied the World Small Animal Veterinary Association scoring system to all samples. RESULTS: Intestinal biopsy samples from dogs in the CEH group were significantly more likely to display villous stunting, epithelial injury, crypt distension, and lacteal dilatation, and were more likely to have intraepithelial lymphocytes and lamina propria neutrophils than biopsy samples from dogs in the CEN group. Additionally, higher scores for each of the above listed histopathologic criteria were associated with a lower serum albumin concentration. CONCLUSIONS AND CLINICAL IMPORTANCE: Histopathologic features of chronic inflammatory enteropathy differ between dogs that are hypo- versus normoalbuminemic. Additional work is needed to elucidate the clinical relevance of these differences.

Clinical Features, Imaging Characteristics, and Long-term Outcome of Dogs with Cranial Meningocele or Meningoencephalocele.

BACKGROUND: The term meningoencephalocele (MEC) describes a herniation of cerebral tissue and meninges through a defect in the cranium, whereas a meningocele (MC) is a herniation of the meninges alone. HYPOTHESIS/OBJECTIVES: To describe the clinical features, magnetic resonance imaging (MRI) characteristics, and outcomes of dogs with cranial MC and MEC. ANIMALS: Twenty-two client-owned dogs diagnosed with cranial MC or MEC. METHODS: Multicentric retrospective descriptive study. Clinical records of 13 institutions were reviewed. Signalment, clinical history, neurologic findings and MRI characteristics as well as treatment and outcome were recorded and evaluated. RESULTS: Most affected dogs were presented at a young age (median, 6.5 months; range, 1 month - 8 years). The most common presenting complaints were seizures and behavioral abnormalities. Intranasal MEC was more common than parietal MC. Magnetic resonance imaging identified meningeal enhancement of the protruded tissue in 77% of the cases. Porencephaly was seen in all cases with parietal MC. Cerebrospinal fluid (CSF) analysis identified mild abnormalities in 4 of 11 cases. Surgery was not performed in any affected dog. Seventeen patients were treated medically, and seizures were adequately controlled with anti-epileptic drugs in 10 dogs. Dogs with intranasal MEC and mild neurologic signs had a fair prognosis with medical treatment. CONCLUSION AND CLINICAL IMPORTANCE: Although uncommon, MC and MEC should be considered as a differential diagnosis in young dogs presenting with seizures or alterations in behavior. Medical treatment is a valid option with a fair prognosis when the neurologic signs are mild.

Intra- and inter-observer agreement in histological assessment of canine soft tissue sarcoma.

BACKGROUND: The diagnosis of canine soft tissue sarcoma (STS) is based on histological assessment. Assessment of criteria such as, degree of differentiation, necrosis score and mitotic score, gives rise to a final tumour grade, which is important in the recommendation of treatment and prognosis of patients. MATERIALS AND METHODS: Previously diagnosed cases of STS were independently assessed by three board-certified veterinary pathologists. Participating pathologists were blinded to the original results. For the intra-observer study, the cases were assessed by a single pathologist six months apart and slides were randomized between readings. For the inter-observer study, the whole case series was assessed by a single pathologist before being passed onto the next pathologist. Intraclass correlation coefficient (ICC) and Fleiss's Kappa (ƙ) for the intra- (single observer) and inter-observer agreement. RESULTS: Strong agreement was observed for the intra-observer assessment in necrosis score, mitotic score, total score and tumour grading (ICC between 0.78 to 0.91). The intra-observer agreement for differentiation score was rated perfect (ICC 1.00). The agreement between pathologists for the diagnosis and grading of canine STS was moderate (ƙ = 0.60 and 0.43 respectively). CONCLUSION: Histological assessment of canine STS had high reproducibility by an individual pathologist. The agreement of diagnosis and grading of canine STS was moderate between pathologists. Future studies are required to investigate further assessment criteria to improve the specificity of STS diagnosis and the accuracy of the STS grading in dogs.

Retrospective evaluation of COX-2 expression, histological and clinical factors as prognostic indicators in dogs with renal cell carcinomas undergoing nephrectomy.

Limited veterinary literature is available regarding prognostic markers for canine renal cell carcinoma (CRCC). We retrospectively evaluated COX-2 expression, histological and clinical features associated with prognosis of CRCC. Sixty-four cases post-nephrectomy were included, 54 had histopathological assessment and 30 had COX-2 immunostaining performed. Eight dogs (13%) had metastatic disease at initial diagnosis. Twenty-seven dogs (42%) received adjuvant therapy after nephrectomy. On univariate analysis, COX-2 expression, mitotic index (MI), histologic type, vascular invasion, neoplastic invasiveness and metastasis at diagnosis were significantly associated with overall median survival time (MST). COX-2 score (COX-2 score > 3 MST 420 days versus 1176 days if COX-2 score <3; P = 0.011) and MI (MI > 30 MST 120 days versus 540 days for MI < 30; P = 0.003) were the only variables associated with CRCC outcome on multivariate analysis. The addition of MI and COX-2 immunostaining to standard histopathological evaluation would help predicting outcome in CRCC patients.

WITHDRAWN: Clinical Signs, Neuroanatomical Distribution and Histopathological Characterisation of Meningoencephalitis in Wild Red Foxes (Vulpes vulpes) Associated with a Novel fox Circovirus.

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Cervical Vertebral Body Chordoma in a Cat.

A 9-year-old, neutered female Maine Coon cat with a 6-week history of progressive ataxia was diagnosed with a cervical vertebral body mass using magnetic resonance imaging. The mass displaced and compressed the cervical spinal cord. The cat was humanely destroyed and necropsy examination confirmed a mass within the second cervical vertebral body. Microscopically, the mass was composed of large, clear, vacuolated ('physaliferous') cells. Immunohistochemically, the neoplastic cells expressed both cytokeratin and vimentin and the final diagnosis was a cervical, vertebral body chordoma. This is only the third report of a chordoma in this species and the first in this location. Chordoma should be considered as a potential differential diagnosis for tumours arising from the cervical vertebrae in the cat.

Pulmonary Veno-Occlusive Disease: A Newly Recognized Cause of Severe Pulmonary Hypertension in Dogs.

Pulmonary hypertension is a well-known though poorly characterized disease in veterinary medicine. In humans, pulmonary veno-occlusive disease (PVOD) is a rare cause of severe pulmonary hypertension with a mean survival time of 2 years without lung transplantation. Eleven adult dogs (5 males, 6 females; median age 10.5 years, representing various breeds) were examined following the development of severe respiratory signs. Lungs of affected animals were evaluated morphologically and with immunohistochemistry for alpha smooth muscle actin, desmin, CD31, CD3, CD20, and CD204. All dogs had pulmonary lesions consistent with PVOD, consisting of occlusive remodeling of small- to medium-sized pulmonary veins, foci of pulmonary capillary hemangiomatosis (PCH), and accumulation of hemosiderophages; 6 of 11 dogs had substantial pulmonary arterial medial and intimal thickening. Ultrastructural examination and immunohistochemistry showed that smooth muscle cells contributed to the venous occlusion. Increased expression of CD31 was evident in regions of PCH indicating increased numbers of endothelial cells in these foci. Spindle cells strongly expressing alpha smooth muscle actin and desmin co-localized with foci of PCH; similar cells were present but less intensely labeled elsewhere in non-PCH alveoli. B cells and macrophages, detected by immunohistochemistry, were not co-localized with the venous lesions of canine PVOD; small numbers of CD3-positive T cells were occasionally in and around the wall of remodeled veins. These findings indicate a condition in dogs with clinically severe respiratory disease and pathologic features resembling human PVOD, including foci of pulmonary venous remodeling and PCH.

Successful treatment of intra-abdominal eumycotic mycetoma caused by Penicillium duponti in a dog.

A 2-year-old female neutered golden retriever was presented for investigation of an intra-abdominal mass. Computed tomography revealed a mass associated with the caudal pole of the right kidney. Incisional biopsy findings were consistent with eumycotic mycetoma. The mass was subsequently removed in conjunction with right ureteronephrectomy. Two years later, the dog re-presented with a splenic mass and fungal plaques located throughout the peritoneum. Splenectomy was performed and the mass was diagnosed as eumycotic mycetoma caused by Penicillium duponti. Indefinite systemic treatment with 10 mg/kg itraconazole orally once a day was initiated. Thirty-two months after the last surgery, there were no clinical signs apart from mild polydipsia. Haematology and biochemistry results were unremarkable. To the authors' knowledge, this is the first report of successful treatment of intra-abdominal eumycotic mycetoma with a combination of surgery and systemic antifungal therapy in the dog. Penicillium duponti has not apparently been reported to cause disease in animals or humans.