Nephrology in Veterinary Medicine.

Veterinary nephrology is a specialized field of veterinary medicine providing a high level of care for animals with all types of kidney disease. Veterinarians complete extensive training to become board-certified in veterinary nephrology-urology. Companion animal nephrology is the most advanced field; however, all species are afflicted by a variety of renal disorders. Most naturally occurring animal kidney diseases have similar disorders found in people; where veterinary research is lacking, clinical management is often modified from standard of care in people. Veterinarians have become adept at scaling down procedures to safely perform them on dogs and cats weighing only a few kilograms. Advanced diagnostics (renal biopsy, cystoscopy, fluoroscopic studies, etc. ) and therapeutics (renal replacement therapy, interventional endourology, etc. ) are commonly performed within the practice of veterinary nephrology-urology. Collaboration between veterinary and human nephrologists may advance both disciplines and improve care for people and animals alike.

The differentiation state of the Schwann cell progenitor drives phenotypic variation between two contagious cancers.

Contagious cancers are a rare pathogenic phenomenon in which cancer cells gain the ability to spread between genetically distinct hosts. Nine examples have been identified across marine bivalves, dogs and Tasmanian devils, but the Tasmanian devil is the only mammalian species known to have given rise to two distinct lineages of contagious cancer, termed Devil Facial Tumour 1 (DFT1) and 2 (DFT2). Remarkably, DFT1 and DFT2 arose independently from the same cell type, a Schwann cell, and while their ultra-structural features are highly similar they exhibit variation in their mutational signatures and infection dynamics. As such, DFT1 and DFT2 provide a unique framework for investigating how a common progenitor cell can give rise to distinct contagious cancers. Using a proteomics approach, we show that DFT1 and DFT2 are derived from Schwann cells in different differentiation states, with DFT2 carrying a molecular signature of a less well differentiated Schwann cell. Under inflammatory signals DFT1 and DFT2 have different gene expression profiles, most notably involving Schwann cell markers of differentiation, reflecting the influence of their distinct origins. Further, DFT2 cells express immune cell markers typically expressed during nerve repair, consistent with an ability to manipulate their extracellular environment, facilitating the cell's ability to transmit between individuals. The emergence of two contagious cancers in the Tasmanian devil suggests that the inherent plasticity of Schwann cells confers a vulnerability to the formation of contagious cancers.

Pathology of the Bearded Dragon (Pogona vitticeps): a Retrospective Analysis of 36 Cases.

The bearded dragon (Pogona vitticeps) is a common species in the pet reptile trade and in zoological collections. Despite this, only a few reviews detailing common causes of mortality have been published. The goal of this retrospective study was to compile information related to the presence and prevalence of various diseases in bearded dragons in several private and one zoological collection. Findings from 36 animals, necropsied over a 20-year period were categorized on the basis of the cause of death or euthanasia and the organ system affected. Multiple contributors to death were identified in a subset of animals (n = 12; 33.33%) and were counted in more than one category. The most common contributors to death by category were inflammatory (infectious or non-infectious) diseases (n = 25; 69.44%), followed by chronic/degenerative diseases (n = 17; 47.22%). Diseases or conditions that were systemic, or affected the hepatobiliary system, were the most commonly implicated in death. The most frequent histological findings included hepatic fatty change, renal tubular epithelial pigmentation and the presence of faveolar hyaline-like material. Although Chi square testing did not reveal an association between these common findings and comorbidities, a statistically significant association was found between chronic/degenerative causes of death and renal tubular epithelial pigment. Chi square testing of categorical variables, including contributors to death, primary organ(s) affected, sex, age class and institution, identified statistically significant associations between males and chronic/degenerative disease (P = 0.043) and inflammatory contributors to death and private collection animals (P = 0.039). Death due to inflammatory contributors was significantly higher in the 1-5-year-old and >5-year-old age classes (P = 0.02).

Age and Infectious Dose Significantly Affect Disease Progression after RHDV2 Infection in Naïve Domestic Rabbits.

Rabbit haemorrhagic disease virus 2 (RHDV2 or GI.2, referring to any virus with lagovirus GI.2 structural genes) is a recently emerged calicivirus that causes generalised hepatic necrosis and disseminated intravascular coagulation leading to death in susceptible lagomorphs (rabbits and hares). Previous studies investigating the virulence of RHDV2 have reported conflicting results, with case fatality rates ranging from 0% to 100% even within a single study. Lagoviruses are of particular importance in Australia and New Zealand where they are used as biocontrol agents to manage wild rabbit populations, which threaten over 300 native species and result in economic impacts in excess of $200 million AUD annually to Australian agricultural industries. It is critically important that any pest control method is both highly effective (i.e., virulent, in the context of viral biocontrols) and has minimal animal welfare impacts. To determine whether RHDV2 might be a suitable candidate biocontrol agent, we investigated the virulence and disease progression of a naturally occurring Australian recombinant RHDV2 in both 5-week-old and 11-week-old New Zealand White laboratory rabbits after either high or low dose oral infection. Objective measures of disease progression were recorded through continuous body temperature monitoring collars, continuous activity monitors, and twice daily observations. We observed a 100% case fatality rate in both infected kittens and adult rabbits after either high dose or low dose infection. Clinical signs of disease, such as pyrexia, weight loss, and reduced activity, were evident in the late stages of infection. Clinical disease, i.e., welfare impacts, were limited to the period after the onset of pyrexia, lasting on average 12 h and increasing in severity as disease progressed. These findings confirm the high virulence of this RHDV2 variant in naïve rabbits. While age and infectious dose significantly affected disease progression, the case fatality rate was consistently 100% under all conditions tested.

Global mRNA and miRNA Analysis Reveal Key Processes in the Initial Response to Infection with WSSV in the Pacific Whiteleg Shrimp.

White Spot Disease (WSD) presents a major barrier to penaeid shrimp production. Mechanisms underlying White Spot Syndrome Virus (WSSV) susceptibility in penaeids are poorly understood due to limited information related to early infection. We investigated mRNA and miRNA transcription in Penaeus vannamei over 36 h following infection. Over this time course, 6192 transcripts and 27 miRNAs were differentially expressed-with limited differential expression from 3-12 h post injection (hpi) and a more significant transcriptional response associated with the onset of disease symptoms (24 hpi). During early infection, regulated processes included cytoskeletal remodelling and alterations in phagocytic activity that may assist WSSV entry and translocation, novel miRNA-induced metabolic shifts, and the downregulation of ATP-dependent proton transporter subunits that may impair cellular recycling. During later infection, uncoupling of the electron transport chain may drive cellular dysfunction and lead to high mortalities in infected penaeids. We propose that post-transcriptional silencing of the immune priming gene Dscam (downregulated following infections) by a novel shrimp miRNA (Pva-pmiR-78; upregulated) as a potential mechanism preventing future recognition of WSSV that may be suppressed in surviving shrimp. Our findings improve our understanding of WSD pathogenesis in P. vannamei and provide potential avenues for future development of prophylactics and treatments.

Pathology, bacteriology and molecular studies on caseous lymphadenitis in Camelus dromedarius in the Emirate of Abu Dhabi, UAE, 2015-2020.

Caseous lymphadenitis (CLA) or pseudotuberculosis is a chronic zoonotic bacterial disease caused by Corynebacterium pseudotuberculosis, which affects livestock and humans. This study aimed to describe the pathology, bacteriology and confirm the identity of the pathogen by 16S rRNA gene sequencing in Camelus dromedarius. A total of 12 camels with suspected CLA in three regions of Abu Dhabi Emirate (Abu Dhabi, Al Ain and Al Dhafra), United Arab Emirate (UAE) were subjected to clinical and postmortem examinations from January 2015 to December 2020. Clinically, camels were emaciated and showed the presence of external caseous abscesses suggestive of CLA. Postmortem examination showed multiple abscesses of variable sizes with caseous material encapsulated by fibrous tissue in the liver, lungs, muscle, and lymph nodes. Following clinical and postmortem examination, blood, pus and different tissue samples were collected for subsequent analysis. Histopathological examination of all organs stained with Hematoxylin and Eosin (H&E) indicated a central caseo-necrotic core that was admixed with bacterial colonies and infiltration of chronic inflammatory cells, surrounded by a pyogenic membrane, and an outer fibrous connective tissue capsule. Bacterial culture identified the isolates of Corynebacterium pseudotuberculosis biotype ovis strain, and these isolates were shown to be sensitive to all antibiotics tested (penicillin, ampicillin, Co-trimoxazole, enrofloxacin and tetracycline). Moreover, the identity of the isolates was confirmed by partial sequencing of the 16S rRNA gene which showed a 100% identity to Corynebacterium pseudotuberculosis. Phylogenetic analysis based on 16S rRNA gene sequence clearly differentiates Corynebacterium pseudotuberculosis from other species of Corynebacterium. Briefly, this study provided the basic information for infection of Corynebacterium pseudotuberculosis in Camels and will help in controlling of this pathogen in the region.

A rapid phenotype change in the pathogen Perkinsus marinus was associated with a historically significant marine disease emergence in the eastern oyster.

The protozoan parasite Perkinsus marinus, which causes dermo disease in Crassostrea virginica, is one of the most ecologically important and economically destructive marine pathogens. The rapid and persistent intensification of dermo in the USA in the 1980s has long been enigmatic. Attributed originally to the effects of multi-year drought, climatic factors fail to fully explain the geographic extent of dermo's intensification or the persistence of its intensified activity. Here we show that emergence of a unique, hypervirulent P. marinus phenotype was associated with the increase in prevalence and intensity of this disease and associated mortality. Retrospective histopathology of 8355 archival oysters from 1960 to 2018 spanning Chesapeake Bay, South Carolina, and New Jersey revealed that a new parasite phenotype emerged between 1983 and 1990, concurrent with major historical dermo disease outbreaks. Phenotypic changes included a shortening of the parasite's life cycle and a tropism shift from deeper connective tissues to digestive epithelia. The changes are likely adaptive with regard to the reduced oyster abundance and longevity faced by P. marinus after rapid establishment of exotic pathogen Haplosporidium nelsoni in 1959. Our findings, we hypothesize, illustrate a novel ecosystem response to a marine parasite invasion: an increase in virulence in a native parasite.

MORBIDITY AND MORTALITY OF TAKIN (BUDORCAS TAXICOLOR) IN NORTH AMERICAN ZOOLOGICAL INSTITUTIONS FROM 1997 TO 2017.

Takin (Budorcus taxicolor) are classified as "Vulnerable" on the International Union for the Conservation of Nature Red List. Thus, ex situ conservation efforts provide assurance populations for future survival of this species. The objective of this study was to identify common causes of morbidity and mortality in takin populations in human care. Twenty North American institutions that housed takin from 1997 to 2017 completed a survey requesting medical and husbandry data. Data were examined broadly, by sex and age groups. There were 206 morbidity events (male = 133; female = 73) submitted across 102 takin (male = 62; female = 40). The most common causes of morbidity were infectious or inflammatory diseases (50%; 104/206), degenerative diseases (22%; 46/206), and traumatic events (17%; 34/206). Necropsy reports were provided for 42 takin that died during the study period. The most common causes of mortality were infectious or inflammatory diseases (26%; 11/42), traumatic events (24%; 10/42), and degenerative disease (12%; 5/42). Sixty-two percent of infectious or inflammatory diseases causing morbidity were associated with endoparasites (64/104). Degenerative joint diseases more commonly affected males (78%; 36/46) as well as forelimbs (48%; 22/46) when compared to hindlimbs (30%; 14/46) and unspecified limbs (22%; 10/46). The prevalence of trauma as a cause of morbidity and mortality was higher in neonate and juvenile takin groups combined (morbidity = 19%; mortality = 50%) as compared to adult and senior takin groups combined (morbidity = 15%; mortality = 11%). Older takin were euthanatized more often (57%; 16/28) than younger takin (29%; 4/14). Correlations between husbandry and health were difficult as a result of the inherent limitations of the survey. These data will inform takin-holding zoologic institutions and contribute to the successful management of takin in human care.

Highly divergent herpesviruses in threatened river dolphins from Brazil.

River dolphins are a highly threatened polyphyletic group comprised of four odontocete families: Iniidae, Pontoporiidae, Lipotidae, and Platanistidae, the first two endemic to South America. To address the knowledge gap regarding infectious agents in this cetacean group, we surveyed the presence of herpesviruses by PCR in skin and/or blood samples of live-captured Amazon (Inia geoffrensis, n = 25) and Bolivian (Inia boliviensis, n = 22) river dolphins of the Amazon basin and in selected tissue samples of franciscanas (Pontoporia blainvillei, n = 27) stranded or bycaught in southeastern Brazil. Additionally, available franciscana tissue samples were examined by histopathology. Herpesvirus DNA was amplified in 13 Bolivian river dolphins (59.1%, 95% CI 38.5-79.6%) and 14 franciscanas (51.9%, 95% CI 33.0-70.7%). All Amazon river dolphins were herpesvirus-negative. Two different herpesviruses were found in Bolivian river dolphins: a previously known gammaherpesvirus detected in blood and/or skin samples of all positive individuals and a novel alphaherpesvirus in the skin of one animal. A new gammaherpesvirus was found in several franciscana samples-the first herpesvirus recorded in Pontoporiidae. Intranuclear inclusion bodies consistent with herpesvirus were observed in the lymph node of one franciscana. The high divergence among the obtained herpesviruses and those previously described can be explained by viral-host coevolution, and by the fact that these populations are fairly isolated.

Deep pemphigus (pemphigus vulgaris, pemphigus vegetans and paraneoplastic pemphigus) in dogs, cats and horses: a comprehensive review.

Pemphigus is the term used to describe a group of rare mucocutaneous autoimmune bullous diseases characterized by flaccid blisters and erosions of the mucous membranes and/or skin. When the autoantibodies target desmosomes in the deep layers of the epidermis, deep pemphigus variants such as pemphigus vulgaris, pemphigus vegetans and paraneoplastic pemphigus develop. In this article, we will review the signalment, clinical signs, histopathology and treatment outcome of pemphigus vulgaris, pemphigus vegetans and paraneoplastic pemphigus in dogs, cats and horses; where pertinent, we compare the animal diseases to their human homologue. Canine, feline and equine pemphigus vulgaris, pemphigus vegetans and paraneoplastic pemphigus have many features similar to the human counterpart. These chronic and often relapsing autoimmune dermatoses require aggressive immunosuppressive therapy. In animals, the partial-to-complete remission of pemphigus vulgaris and pemphigus vegetans has been achieved with high dose glucocorticoid therapy, with or without adjunct immunosuppressants; the prognosis is grave for paraneoplastic pemphigus.

A review of pathological findings in impalas (Aepyceros melampus) in South Africa.

Impalas (Aepyceros melampus) are common African antelope. A retrospective study was conducted of 251 impala cases from game farms, national parks and zoos submitted by veterinarians and pathologists in South Africa (2003-2016). Histopathology slides as well as records of macroscopic lesions and additional diagnostic tests performed were examined. Non-infectious conditions, such as acute pulmonary congestion and oedema, cachexia, traumatic injury and anaesthetic-related mortality were the most common causes of morbidity and mortality. Bacterial sepsis was the most common infectious disease, whilst skeletal muscle and myocardial sarcocystosis and verminous cholangitis and pneumonia were the most common parasitic diseases. Although the retrospective nature of this study limits the significance of the relative prevalence of lesions in the three locations, management decisions and diagnostic plans may be informed by the results. Impala from game farms had significantly more cachexia cases than those from other locations. Impala from zoos had significantly more lymphoid depletion than those from other locations. These findings suggest that nutrition and pasture management, enclosure design, management of intra- and interspecies aggression and improved anaesthetic protocols could improve animal welfare and survival of impala on game farms and in zoos. This report presents a detailed survey of diseases and conditions found in impala that provides baseline data for veterinary pathologists.

Chronic whipworm infection exacerbates Schistosoma mansoni egg-induced hepatopathology in non-human primates.

BACKGROUND: Schistosomiasis continues to inflict significant morbidity and mortality in the tropical and subtropical regions of the world. The disease endemicity overlaps with the transmission of other parasitic diseases. Despite the ubiquity of polyparasitism in tropical regions, particularly in rural communities, little is known about the impact of multiple helminth infections on disease progression. In this pilot study, we describe the influence of chronic Trichuris trichiura infection on Schistosoma mansoni egg-induced hepatopathology in infected baboons. METHODS: Baboons with or without underlying whipworm infection were challenged with S. mansoni cercariae to establish schistosomiasis. Adult S. mansoni worms were recovered by perfusion and enumerated, hepatic granulomas were quantified via light microscopy, and transcriptional profiling of tissues were completed using RNA sequencing technologies. RESULTS: Co-infection with both S. mansoni and T. trichiura resulted in higher female schistosome worm burden and significantly larger liver granuloma sizes. Systems biology analyses of peripheral blood mononuclear cells (PBMC) revealed pathways associated with increased liver damage in co-infected baboons. CONCLUSIONS: Underlying chronic whipworm infection intensified schistosome egg-induced liver pathology in infected baboons. RNA-Seq analysis provided insight into pathways associated with increased liver damage, corroborating histological findings.

Lesions Observed Post Mortem in Post-hatchling Loggerhead Sea Turtles (Caretta caretta) from a Head Start Programme.

Head start programmes are ex-situ conservation procedures consisting of the captive rearing of sea turtle hatchlings for several months in order to avoid high mortality rates in the first year of life. Studies of the diseases of hatchling and post-hatchling turtles belonging to these programmes are scarce. We describe the gross and histological lesions found in 78 post-hatchling loggerhead sea turtles (Caretta caretta) that died during captive rearing in the conservation programme of the Cape Verde-Canary Islands, initiated with 113 hatchlings. The main organ systems affected were respiratory (57.69%), integumentary (41.02%) and digestive (41.02%), affecting 94.87% of the animals. Other less frequently affected organ systems were cardiovascular (3.85%), excretory (3.85%), muscular (2.56%) and reproductive (1.28%). The most common lesions were different types of dermatitis (41.02%), mainly ulcerative and/or heterophilic ulcerative dermatitis; these lesions were compatible with a traumatic origin caused by biting and subsequent infection with gram-positive cocci. Purulent and/or fibrinonecrotizing rhinitis associated with mixed populations of bacteria were commonly detected respiratory lesions (21.79%). Acute interstitial pneumonia was the most common form of pneumonia diagnosed (20.51%). Fibrinonecrotizing stomatitis associated with sparse gram-negative rods was the most common digestive tract lesion (29.49%). A possible explanation for the high mortality rate (88.50%) observed in this study could be the occurrence of a decrease in water temperature during the growth phase of the turtles. Despite the limitations caused by an absence of microbiological studies, the survey provides useful information on the lesions found in post-hatchling loggerhead turtles from this head start programme. In addition to maintaining water temperature above 20°C, attention must be paid to lesions that can easily be detected, such as dermatitis, rhinitis and stomatitis.

MORTALITY INVESTIGATION OF MONITORED EASTERN BOX TURTLES (TERRAPENE CAROLINA CAROLINA) IN CENTRAL ILLINOIS, USA, FROM 2016-18.

Mortality events in eastern box turtles (Terrapene carolina carolina) threaten conservation efforts across the species range. These events are often under-diagnosed and, when observed, predictive health factors are unavailable prior to death. At Kickapoo State Park in central Illinois, USA, ranaviruses caused observed mortality events in amphibians and chelonians in 2014 and 2015. Following these outbreaks, eastern box turtles (n=36) were affixed with radio transmitters and temperature data loggers to obtain repeated location and temperature data from spring 2016-spring 2018. Bimonthly, samples of blood and oral and cloacal swabs were collected to investigate health parameters (hematology and cytokine transcription) and presence of multiple pathogens. Deaths of instrumented turtles occurred in 2016 (n=5), 2017 (n=15), and 2018 (n=2). The largest single die-off occurred in February 2017 (n=7). Seventeen turtles were necropsied and multiple pathologic processes were identified, most frequently decreased adipose stores (n=6). Two turtles had pathologic findings consistent with multisystemic inflammation. In addition, infectious pathogens were identified in turtles prior to death, but no single agent was associated with each mortality event. Ranavirus was not detected in any turtle. Hot spot analysis revealed spatial clustering at the center and edges of the study area for body temperature as well as for relative cytokine transcription of interleukin-1 beta, tumor necrosis factor alpha, and interleukin-10 associated with turtle death. Though no single causal factor could be identified, the information from this mortality event can direct future chelonian mortality investigations by providing baseline longitudinal data prior to death and in surviving turtles.

Review: Other Helicobacter species.

This article is a review of the most important, accessible, and relevant literature published between April 2018 and April 2019 in the field of Helicobacter species other than Helicobacter pylori. The initial part of the review covers new insights regarding the presence of gastric and enterohepatic non-H. pylori Helicobacter species (NHPH) in humans and animals, while the subsequent section focuses on the progress in our understanding of the pathogenicity and evolution of these species. Over the last year, relatively few cases of gastric NHPH infections in humans were published, with most NHPH infections being attributed to enterohepatic Helicobacters. A novel species, designated "Helicobacter caesarodunensis," was isolated from the blood of a febrile patient and numerous cases of human Helicobacter cinaedi infections underlined this species as a true emerging pathogen. With regard to NHPH in animals, canine/feline gastric NHPH cause little or no harm in their natural host; however they can become opportunistic when translocated to the hepatobiliary tract. The role of enterohepatic Helicobacter species in colorectal tumors in pets has also been highlighted. Several studies in rodent models have further elucidated the mechanisms underlying the development of NHPH-related disease, and the extra-gastric effects of a Helicobacter suis infection on brain homeostasis was also studied. Comparative genomics facilitated a breakthrough in the evolutionary history of Helicobacter in general and NHPH in particular. Investigation of the genome of Helicobacter apodemus revealed particular traits with regard to its virulence factors. A range of compounds including mulberries, dietary fiber, ginseng, and avian eggs which target the gut microbiota have also been shown to affect Helicobacter growth, with a potential therapeutic utilization and increase in survival.

RETROSPECTIVE ANALYSIS OF MORTALITY IN CAPTIVE BONGO (TRAGELAPHUS EURYCERUS), 1995-2015.

A retrospective histologic study was performed for 96 deceased bongo (Tragelaphus eurycerus) submitted to Northwest ZooPath from 1995 to 2015. Histologic data were assessed for associations with sex, age, cause of death/euthanasia, and affected organ systems. Female bongo lived significantly longer than males. Males were more likely to die from infectious causes (41.2%), whereas most females died from chronic noninfectious conditions (54.4%) and trauma/stress (28.1%). Of those that died from infectious disease, the respiratory tract was the most commonly affected organ system. The most common infectious agents included acid-fast bacteria and fungi. Chronic conditions included amyloidosis (31.0%), inanition/emaciation (23.8%), and neoplasia (21.4%). Of the 31 animals that died with amyloidosis, 58% appeared to be clinically affected, and amyloidosis was likely an underlying cause of death in 42% of the animals. The most commonly affected organs included the liver, kidneys, adrenal glands, and gastrotintestinal tract. Also noteworthy was a high prevalence of adrenal gland hyperplasia and neoplasia, cystic thyroid glands, and aspiration pneumonia, which were not consistently associated with a prior anesthetic event or other obvious predisposing cause.

Is Stem Cell Commerce in Small Animal Therapies Scientifically and Morally Justified?

The lack of clear regulations for the use of veterinary stem cells has triggered the commercialization of unproven experimental therapies for companion animal diseases. Adult stem cells have complex biological characteristics that are directly related to the therapeutic application, but several questions remain to be answered. In order to regulate the use of these cells, well-conducted, controlled scientific studies that generate high-quality data should be performed, in order to assess the efficacy and safety of the intended treatment. This paper discusses the scientific challenges of mesenchymal stem cell therapy in veterinary regenerative medicine, and reviews published trials of adipose-tissue-derived stem cells in companion animal diseases that spontaneously occur.

Transboundary animal diseases as re-emerging threats - Impact on one health.

Transboundary animal diseases are those that can move through a population of animals and cause considerable economic and societal harm. Many have high mortality, and in low-income areas, can quickly destroy herds and flocks of agricultural animals. Although much of One Health, which sits at the intersection of human, animal, and environmental health, focuses on the zoonotic diseases, in fact transboundary animal diseases can harm both humans and the environment through robbing communities of livelihoods and nutrition, and creating environmental contamination through extensive carcass disposal requirements. Transboundary animal diseases continue to circulate in the world, predominantly in low-income regions or in areas with less than optimal biosecurity. This paper will review three prominent emerging and re-emerging transboundary animal diseases, describing their pathology and diagnostics, as well as economic and food security impacts, which are substantial. Attention to these devastating diseases should be a One Health priority.