Heterogeneous immunoreactivity of axonal spheroids in focal symmetrical encephalomalacia produced by Clostridium perfringens type D epsilon toxin in sheep.

Since axonal injury (AI) is an important component of many veterinary neurologic disorders, we assessed the relative ability of a panel of antibodies (amyloid precursor protein, 3 subunits of neurofilament protein, protein gene product 9.5, ubiquitin, and synaptophysin) to detect axonal swellings or spheroids. Abundant axonal spheroids found in necrotic internal capsule foci produced in 4 sheep by chronic Clostridium perfringens type D epsilon neurotoxicity provided a model system in which to evaluate this important diagnostic tool. There was heterogeneous labeling of subsets of spheroids by the respective antibodies, suggesting that, in order to detect the complete spectrum of AI in diagnostic cases, a range of antibodies should be used, not only when spheroids are plentiful but also when they are few in number or incompletely developed. The application of insufficient markers in the latter cases can potentially lead to the contribution of AI to lesion pathogenesis being underappreciated.

A Splice Site Variant in ADAMTS3 Is the Likely Causal Variant for Pulmonary Hypoplasia with Anasarca in Persian/Persian-Cross Sheep.

Pulmonary hypoplasia with anasarca, or hydrops fetalis, is characterized by stillbirth, diffuse oedema, and generalized lymph node hypoplasia. The enlarged fetus frequently causes dystocia. The disease has been reported in cattle and sheep as an inherited condition with a recessive mode of inheritance. This is the first report of the disease in Persian/Persian-cross sheep in Australia. Affected fetuses were reported from three flocks, and a total of eleven affected, eleven obligate carrier, and 188 related Persian/Persian-cross animals were available for analysis, as well as unrelated control animals. SNP genotyping revealed a region of homozygosity in affected animals on ovine chromosome six, which contained the functional candidate gene ADAMTS3. Whole genome sequencing of two affected fetuses and one obligate carrier ewe revealed a single nucleotide deletion, ENSOARG00000013204:g.87124344delC, located 3 bp downstream from a donor splice site region in the ADAMTS3 gene. Sanger sequencing of cDNA containing this variant further revealed that it is likely to introduce an early splice site in exon 14, resulting in a loss of 6 amino acids at the junction of exon 14 and intron 14/15. A genotyping assay was developed, and the ENSOARG00000013204:g.87124344delC segregated with disease in 209 animals, allowing for effective identification of carrier animals.

Red neurons in ovine polioencephalomalacia (cerebrocortical necrosis) are strongly amyloid precursor protein immunopositive.

The signature pathological feature of the pseudolaminar cerebrocortical necrosis found in polioencephalomalacia (PEM) of ruminants is the development of red (eosinophilic) neurons. These neurons are generally considered to be irredeemably injured but we have shown, for the first time, in ovine PEM cases, that most strongly express amyloid precursor protein (APP), which has a neuroprotective role in the brain. By contrast, neurons in unaffected cerebral cortices from control sheep were APP immunonegative. This finding suggests that, rather than being inevitably destined to die, some of these APP immunoreactive cortical neurons may survive and regain structural and functional integrity.

Clinical and pathologic features of acute bovine liver disease in Australia.

Acute bovine liver disease (ABLD) is a sporadic hepatic disease affecting cattle in southern Australia, characterized histologically by striking periportal hepatocellular necrosis. The cause of ABLD is unknown; however, the seasonality and acute presentation of outbreaks suggest mycotoxin involvement. We describe here the clinical and pathologic findings of ABLD in 45 naturally affected cattle from 13 outbreaks occurring from 2010 to 2019 in Victoria, Australia. Outbreaks occurred in herds located along the southern coastal plain of Victoria and were observed most frequently in lactating dairy cattle. Clinical signs commonly included a combination of mild photosensitization, progressive neurologic signs, and hypogalactia, which preceded death by ≤ 48 h. All affected animals had marked elevations in activities of glutamate dehydrogenase, aspartate aminotransferase, and gamma-glutamyl transferase. At autopsy, the most common lesions were serosal petechiae and/or gastrointestinal hemorrhage, and hepatomegaly with a pronounced hepatic reticular pattern. The principal histologic lesion was widespread-severe periportal hepatocellular coagulative necrosis and erythrocyte pooling-which often extended to massive necrosis. Lesions in other organs were uncommon. Our study of ABLD suggests involvement of a potent hepatotoxin that is either directly cytopathic or requires bioactivation by periportal-specific enzymes.

An idiopathic upper alimentary tract ulcerative syndrome in weaned dairy calves in Victoria, Australia.

An idiopathic clinical syndrome had been described in weaned dairy calves in the state of Victoria, Australia, where affected animals presented with diarrhoea, ill-thrift, enteritis and ulceration of the upper alimentary tract, with occasional oral/nasal ulcers. Between 7 November 2016 and 31 March 2019, 34 Victorian cattle herds were investigated, after each reported five or more weaned calves with diarrhoea and/or ill-thrift, or at least one calf with oral/nasal ulceration. Primary study objectives included the development of a detailed case definition for the clinical syndrome, termed upper alimentary tract ulcerative syndrome (UAUS) and the identification of potential causative virus(es) using metagenomics. A diagnosis of UAUS could not be made based solely on clinical signs and required histopathological assessment of post-mortem samples. Specifically, this included the identification of multifocal to coalescing areas of mucosal epithelial necrosis at all depths of the stratified squamous epithelium of the oesophagus, along with exclusion of bovine viral diarrhoea virus. Based on this case definition, twelve herds were diagnosed with clinical UAUS across the three dairying regions of Victoria, while thirteen were ruled UAUS-negative. The status of the nine remaining herds was unresolved due to a lack of required post-mortem samples. Metatranscriptomic analysis on oral swabs and oesopharyngeal samples from confirmed UAUS cases did not detect a virus common to the cross-sectional sample collection.

Plant and Fungal Hepatotoxicities of Cattle in Australia, with a Focus on Minimally Understood Toxins.

Plant- and fungus-derived hepatotoxins are a major cause of disease and production losses in ruminants in Australia and around the world. Many are well studied and described in the literature; however, this is not the case for a number of hepatotoxicities with economic and animal welfare impacts, such as acute bovine liver disease (ABLD), brassica-associated liver disease (BALD) and Trema tomentosa, Argentipallium blandowskianum and Lythrum hyssopifolia toxicity. Additionally, significant overlap in the clinical presentation and pathology of these conditions can present a diagnostic challenge for veterinarians. This review summarizes the current and most recently published knowledge of common plant- and fungus-associated hepatotoxins affecting cattle in Australia, with a focus on the mechanisms of toxicity and distinguishing diagnostic features. Consolidation of the current understanding of hepatotoxic mechanisms in cattle provides insight into the potential mechanisms of lesser-known toxins, including cellular and subcellular targets and potential metabolic pathways. In the absence of specific etiological investigations, the study of epidemiological, clinical and pathological features of hepatotoxicity provides valuable insights into potential toxic mechanisms and is integral for the successful diagnosis and management of these conditions.

Diagnostic investigation of new disease syndromes in farmed Australian saltwater crocodiles (Crocodylus porosus) reveals associations with herpesviral infection.

Since 2006, 3 new disease syndromes have emerged in farmed saltwater crocodiles (Crocodylus porosus) in the Northern Territory of Australia. We describe the syndromes through a retrospective study of laboratory findings from 187 diagnostic cases submitted to Berrimah Veterinary Laboratories between 2005 and 2014. The first syndrome was characterized by conjunctivitis and/or pharyngitis (CP), primarily in hatchlings. Herpesviruses were isolated in primary crocodile cell culture, or were detected by PCR directly from conjunctiva or pharyngeal tissue, in 21 of 39 cases of CP (54%), compared with 9 of 64 crocodiles without the syndrome (14%, p < 0.0001). Chlamydiaceae were detected by PCR in conjunctiva or pharyngeal tissue of 55% of 29 CP cases tested, and of these, 81% also contained herpesvirus. The second syndrome occurred in juveniles and growers exhibiting poor growth, and was characterized histologically by systemic lymphoid proliferation and nonsuppurative encephalitis (SLPE). Herpesviruses were isolated or detected by PCR from at least 1 internal organ in 31 of 33 SLPE cases (94%) compared with 5 of 95 crocodiles without the syndrome (5%, p < 0.0001). The third syndrome, characterized by multifocal lymphohistiocytic infiltration of the dermis (LNS), occurred in 6 harvest-sized crocodiles. Herpesviruses were isolated from at least 1 skin lesion in 4 of these 6 cases. Although our study revealed strong associations between herpesvirus and the CP and SLPE syndromes, the precise nature of the role of herpesvirus, along with the pathogenesis and epidemiology of the syndromes, requires further investigation.

Primary ocular melioidosis due to a single genotype of Burkholderia pseudomallei in two cats from Arnhem Land in the Northern Territory of Australia.

Melioidosis was diagnosed in two domestic crossbred cats presented for unilateral ocular disease. One patient was born and bred in Nhulunbuy, Arnhem Land, while the other had moved there 6 months previously from Townsville, Queensland. Both patients were presented with sudden onset of a 'red eye' and blepharospasm, which progressed to an enlarged, painful, firm globe with loss of pupillary light reflexes and vision. An obvious primary focus of infection outside the eye was not detected in either cat. In both patients, the affected eye was surgically removed and vitreal culture revealed a pure growth of Burkholderia pseudomallei. In each instance, the infection had penetrated the sclera to produce retrobulbar cellulitis, and in one case frank retrobulbar abscessation. Histologically, there was a pyogranulomatous uveitis with extensive destruction of intraocular structures. The first case was still alive approximately 1 year following enucleation and limited antimicrobial therapy using amoxicillin clavulanate and doxycycline. The second was euthanased when a localised abscess developed on the same side of the face as the healed surgical incision, despite appropriate antimicrobial therapy. Both cases were caused by the same multilocus sequence type of B pseudomallei (ST 116), which had only been isolated previously from two human patients, both living in the same isolated geographical area as the cats of this report. Apart from the geographical clustering, no epidemiological links were evident between the two cats and/or the two people. The presumptive pathogenesis of these infections is discussed in relation to current knowledge about melioidosis in northern Australia.