Intracellular survival of virulent Mycobacterium bovis and M. bovis BCG in ferret macrophages

The intracellular survival of virulent Mycobacterium bovis and avirulent M. bovis BCG in ferret alveolar macrophages was investigated. In addition, the effects of endogenous and exogenous modulators of macrophage oxidative function on bacterial survival and growth in vitro were determined. Ferret macrophages limited the initial growth of BCG, while virulent M. bovis replicated within macrophages. Intracellular bacterial survival was unaffected by the addition of specific inhibitors of macrophage oxidative function. A T-cell supernatant (TCS), derived from mitogen-stimulated lymphocyte cultures, activated ferret macrophages for heightened oxidative burst performance. However, macrophages activated by TCS, bacterial LPS or a combination of both, failed to control infection, and actually enhanced the intracellular survival of M. bovis. These results are discussed in relation to the role of macrophages in mediating tuberculosis-related pathogenesis, with respect to the fact that ferrets are important wildlife vectors of bovine tuberculosis in New Zealand.     

Exocrine pancreatic carcinoma and carcinomatosis with abdominal effusion containing mast cells in a ferret (Mustela putorius furo).

This case describes the clinical presentation and findings of exocrine pancreatic carcinoma in a 9-year-old female sprayed ferret (Mustela putorius furo). Transcoelomic metastasis and hemorrhagic abdominal effusion were secondary to the neoplasm. The finding of mast cells in abdominal effusion, with a leukocyte component composed primarily of lymphocytes and lesser numbers of neutrophils and macrophages, is an atypical finding, never before reported in ferrets.     

The First Case of Feline Infectious Peritonitis-like Pyogranuloma in a Ferret Infected by Coronavirus in Japan

A male ferret, which was purchased from abroad at 9 months of age, had shown significant weight loss starting at 13 months of age. The ferret subsequently showed decreasing motor activity and recumbency and was euthanized at 14 months of age. At necropsy, a white, quail egg-sized mass was found in the mesentery. Histopathologically, multifocal granulomas consisting of necrotic foci, macrophages, fibroblasts and plentiful fibrous connective tissues were observed in the mesenteric mass. Surrounding the granulomas, inflammatory cell infiltration consisting of neutrophils, lymphocytes and plasmacytes was observed diffusely and significantly. Immunohistochemistry revealed small numbers of macrophages around necrotic foci that were positively stained for anti-mouse feline coronavirus. Electron microscopically, the cytoplasm of the macrophages contained viral particles, which were identified as coronavirus. The histopathological features in this ferret were similar to those in cats with feline infectious peritonitis (FIP). This was the first case in ferrets in Japan.     

Ferrets. Examination and preventive medicine.

As ferrets are anatomically and physiologically similar to dogs and cats, the basic elements of ferret examination, disease processes, and preventive health are familiar to small-animal practitioners. Like other domestic carnivores, ferrets are tolerant of handling and medical procedures, especially compared with rabbits, rodents, and most nondomestic mammals. These characteristics make ferrets amenable to many of the highly specialized diagnostic and therapeutic techniques that are now available in small-animal practice. Veterinarians who wish to add ferrets to their practices should be familiar with the ferret literature, but they should not forget to draw from the wealth of knowledge in canine and feline medicine when managing unusual or difficult ferret cases.     

Isolation and chemiluminescent properties of ferret (Mustela putorius furo) polymorphonuclear cells

Ferret polymorphonuclear cells (PMNs) and peripheral blood mononuclear cells (PBMCs) were separated from whole blood by density gradient centrifugation. Using a 50% Percoll solution (density=1.066), PMNs and PBMCs were successfully isolated after centrifugation; the purities of the PMNs and PBMCs were 94.2% and 95.6%, respectively. To evaluate the function of isolated ferret PMNs, we measured the superoxide generation with a MCLA-dependent chemiluminescence assay. The isolated ferret PMNs responded to phorbol 12-myristate 13-acetate (PMA) with kinetics similar to that of human PMNs. The ferret PMNs did not respond to N-formyl-Met-Leu-Phe (fMLF), unlike human PMNs, which rapidly responded. Thus, authors established a method for the rapid separation of highly purified populations of functional PMNs from the whole blood of ferrets.     

Effect of field capture on the measurement of cellular immune responses in wild ferrets (Mustela furo), vectors of bovine tuberculosis in New Zealand.

Ferrets are recognised as significant wildlife vectors of bovine tuberculosis (Tb) in New Zealand. Disease management strategies, such as the development of a protective wildlife vaccine, could be assisted by the ability to measure pertinent cellular immune responses among wild animals. In the present study, we investigated whether it is possible to measure in vitro lymphocyte reactivity in wild-caught ferrets, and also determined levels of physiological stress in these animals, and we compared these responses to those observed in laboratory-maintained domesticated ferrets. Over a 12-month period, 80 ferrets were live-captured from a Tb-endemic region (Otago, southern New Zealand); cardiac blood was withdrawn on-site, and mononuclear cell cultures were successfully established from 75 of these animals. Lymphocyte transformation (LT) responses to T cell and T/B cell mitogens (Concanavalin A [Con A] and pokeweed mitogen) were measured via uridine incorporation assay. The magnitude of these responses did not differ significantly between animals that had been captured in wire-framed cage traps and those captured using soft-jawed leg-hold traps. Levels of serum cortisol and glucose (as indicators of physiological and oxidative stress, respectively) were highest in animals captured using leg-hold traps. In comparison to domesticated ferrets, wild-caught ferrets had lower overall LT responses to Con A, but significantly higher levels of serum cortisol. Finally, 10/80 animals captured from the wild were severely diseased (Tb+), as evidenced by gross tuberculous lesions at autopsy. Successful mononuclear cell cultures were established from nine of these animals; LT responses to Con A were significantly lower in Tb+ ferrets than in either wild-caught/non-diseased (Tb-) or domesticated ferrets. These results demonstrate that it is possible to measure cellular immune responses from the blood of wild-caught ferrets, but that field capture and disease status may have detrimental effects on in vitro T cell function, possibly due to the influence of physiological stress.     

ADRENAL NEOPLASIA IN SEVEN FERRETS

Medical records from 7 ferrets presented to the VMTH with histologically confirmed adrenal neoplasia were reviewed. Three neutered female ferrets had adrenal cortical adenoma; four ferrets (2 neutered females, 2 neutered males) had adrenal cortical carcinoma. Ultrasound identified unilateral enlargement or abnormal shape of the adrenal gland in all ferrets. Only 1 ferret had adrenomegaly on abdominal radiographs. Adrenomegaly was identified in 1 ferret by magnetic resonance imaging (MRI). All ferrets were treated by adrenalectomy followed by a tapered dose of prednisone. Surgical complications were limited to fatal hemorrhage from the caudal vena cava in 1 ferret. Remission of clinical signs occurred in all 6 ferrets which survived surgery. The time of follow up varied from 3 to 16 months. The 3 ferrets with adrenal adenomas were still alive 3 to 7 months after surgery. AH 3 ferrets with adrenal carcinoma developed metastasis and were euthanized from 2 to 16 months after surgery.     

Cultured bovine monocytes exhibit decreased release of superoxide anion and increased levels of lysosomal enzymes but do not secrete detectable lysozyme activity

In this study we determined the effects of in vitro maturation on the phagocytic activity, lysosomal enzyme content and oxidative response of bovine monocytes. Intracellular levels of the lysosomal enzymes acid phosphatase, beta glucuronidase, and beta glucosaminidase increased as bovine monocytes matured in vitro. However, in marked contrast to the mononuclear phagocytes of other mammalian species, lysozyme activity was undetectable in the culture supernatants and cell lysates of adherent bovine blood monocytes cultured for one to fifteen days. In vitro maturation of bovine monocytes also increased their phagocytic activity as determined by the ingestion of opsonized yeast. A greater percentage of monocyte-derived macrophages that were stimulated with opsonized yeast and phorbol myristic acetate (PMA) reduced nitroblue tetrazolium than did similarly treated monocytes. Monocyte-derived macrophages stimulated with PMA released significantly less superoxide anion than did PMA-stimulated monocytes. Bovine monocytes and macrophages also failed to bind the monoclonal antibody Mac-1, which binds to human and mouse macrophages. Bovine monocytes demonstrated both similarities and differences with other mammalian mononuclear phagocytes, thus making them a useful model for further study of the comparative and developmental biology of mononuclear phagocytes.     

Broad-scale possum and ferret correlates of macroscopic Mycobacterium bovis infection in feral ferret populations

AIMS: To examine the relationships between the prevalence of macroscopic Mycobacterium bovis infection (bovine tuberculosis) in feral ferrets (Mustela furo), the abundance of ferrets, and the abundance of brushtail possums (Trichosurus vulpecula) . METHODS: Data on the prevalence of macroscopic M. bovis infection in ferrets, abundance of ferrets, and abundance of possums were analysed from 12 comparable independent broad-scale surveys. RESULTS: The prevalence of macroscopic M. bovis infection in ferrets was positively correlated with possum abundance but unrelated to ferret abundance, suggesting that possums are an important source of M. bovis infection in ferrets. The lack of any positive relationship between the prevalence of M. bovis infection in ferrets and ferret abundance does not support the hypothesis that per capita transmission rates, and therefore disease prevalence, should be higher at higher ferret abundance. CONCLUSION: The results support the hypothesis that tuberculous possums are the major underlying source of M. bovis infection for feral ferrets in New Zealand.     

Comparison of the blood coagulation profiles of ferrets and rats

The aim of this study was to examine the blood coagulation profiles of ferrets and compare them with those of rats. The ferret activated partial thromboplastin time (aPTT) was slightly longer than the rat aPTT. In contrast, the ferret prothrombin time and thrombin time were profoundly shorter than the corresponding rat values. The fibrinogen level in ferret plasma was 2 times higher than that in rats. Heparin prolonged all blood coagulation times in a concentration-dependent manner in both ferret and rat plasma. A significantly (P<0.01) higher concentration of heparin was required to double the aPTT in ferrets than rats. These blood coagulation data for ferrets will be useful in experimental animal studies.     

Pancreatic adenocarcinoma with metastasis in two ferrets.

Exocrine pancreatic adenocarcinoma with carcinomatosis was diagnosed in 2 ferrets. Clinical signs included abdominal distention and hind limb weakness. Ultrasonography revealed moderate ascites in both ferrets, an irregular abdominal mass in 1 ferret, and multiple abdominal masses in the other ferret. The ferrets were euthanatized, and necropsy of 1 ferret revealed carcinomatosis without visceral metastasis.     

Acetaminophen UDP-glucuronosyltransferase in ferrets: species and gender differences, and sequence analysis of ferret UGT1A6

The principal objective of this study was to determine whether ferrets glucuronidate acetaminophen more slowly compared with other species, and if so investigate the molecular basis for the difference. Acetaminophen-UDP-glucuronosyltransferase (UGT) activities were measured using hepatic microsomes from eight ferrets, four humans, four cats, four dogs, rat, mouse, cow, horse, monkey, pig and rabbit. Gender differences between male and female ferret livers were explored using enzyme kinetic analysis. Immunoblotting of microsomal proteins was also performed using UGT-specific antibodies. Finally, the exon 1 region of UGT1A6, a major acetaminophen-UGT, was sequenced. Glucuronidation of acetaminophen was relatively slow in ferret livers compared with livers from all other species except cat. Gender differences were also apparent, with intrinsic clearance (Vmax/Km) values significantly higher in male compared with female ferret livers. Furthermore, Vmax values correlated with densitometric measurements of two protein bands identified with a UGT1A subfamily-specific antibody. No deleterious mutations were identified in the exon 1 or flanking regions of the ferret UGT1A6 gene. In conclusion, like cats, ferret livers glucuronidate acetaminophen relatively slowly. However, unlike cats, in which UGT1A6 is encoded by a pseudogene and dysfunctional, there are no defects in the ferret UGT1A6 gene which could account for the low activity.     

The scavenging behaviour of ferrets (Mustela furo), feral cats (Felis domesticus), possums (Trichosurus vulpecula), hedgehogs (Erinaceus europaeus) and harrier hawks (Circus approximans) on pastoral farmland in New Zealand: implications for bovine tuberculosis transmission

AIMS: To identify species that scavenge carcasses in pastoral habitats in New Zealand; to determine whether there were interspecific or intraspecific differences in scavenging behaviour and; to document any interspecific or intraspecific interactions occurring at carcasses. METHODS: Scavenging by ferrets (Mustela furo), feral cats (Felis domesticus), possums (Trichosurus vulpecula), hedgehogs (Erinaceus europaeus) and harrier hawks (Circus approximans) was studied from autumn to midwinter on pastoral farmland near Palmerston (45S, 170E), Otago, New Zealand. Time-lapse video recorders and camera lens mounted with infra-red light illumination were used to monitor carcasses of 10 ferrets, 12 possums, 2 hedgehogs and 7 rabbits (Oryctolagus cuniculus) until they were totally scavenged. RESULTS: Ferrets scavenged 5/8 ferret carcasses, 8/9 possum carcasses and 6/7 rabbit carcasses encountered. Feral cats scavenged 3/8 ferret carcasses, 5/7 rabbit carcasses, and 3/8 possum carcasses encountered. Possums scavenged 1/2 ferret carcasses and 3/4 rabbit carcasses encountered. The proportion of encounters resulting in feeding on ferret carcasses differed between ferrets (45.7%) and possums (6.3%), and between possums and cats (29.7%). Similarly, for possum carcasses, differences were found between ferrets (76.6%) and possums (0%), ferrets and cats (60.6%) and possums and cats. No interspecific differences were found in the proportion of encounters that resulted in feeding on rabbit carcasses between ferrets (85.2%), possums (75%) and cats (73.1%). In 8/12 instances of ferrets coming into contact with other ferrets whilst feeding, ferrets fed together at the carcass. On 1 occasion, 4 ferrets were recorded feeding together. In 7/8 instances where cats and ferrets came into contact over carrion, ferrets maintained possession or displaced the cat from the carcass. CONCLUSIONS: Communal carrion feeding by ferrets may facilitate intraspecific and interspecific transmission of bovine tuberculosis (caused by Mycobacterium bovis) by the consumption of contaminated carrion, fighting, or close-contact activities. Cannibalism may be one mechanism by which tuberculosis is transmitted within ferret populations. Our results also suggest that possums may acquire infection from carrion, despite being mainly herbivorous.     

Behavior of Mustela putorius furo (the domestic ferret).

Behavior patterns exhibited by the domestic ferret, although similar to its wild cousins, are distinctly domestic in nature. Domestic ferrets use many different types of behaviors, including body posturing, animations, vocalizations, and scent markings. These behaviors may differ somewhat from ferret to ferret. The domestic ferret is best understood by observation and recognition of its behavior patterns and interactions as it plays and communicates with both humans and animals within its home environment. As with all other species of animals kept as pets, the clinician will be greatly benefited by urging the pet owner to regularly note typical behavior patterns for their individual pet. Following is a brief summary of behavioral changes noted in domestic ferrets that may aid the owner or keeper in the detection of potential illness or injury: A normally active ferret suddenly becoming quiet or vice-versa Any sudden increase or decrease in daily food and water intake Routine behaviors performed out of context or order, especially in older animals Any sudden increase or decrease in the speed at which routine behaviors are performed (such as urination, defecation, grooming, food, or water intake) Any sudden increase in the effort required to perform normal or routine behaviors Any sudden changes in personality or attitude toward other ferrets or toward other animals or people. The previous information was gathered over the last 15 years from personal observations, experiences, and studies of ferrets in the shelter, home, and animal hospital environments. This information regarding ferret behavior can assist the veterinarian in differentiating between normal and abnormal behaviors in domestic ferrets. This increased understanding of ferret behavior can aid in the diagnosis of injury and disease and assist the veterinarian in educating clients regarding ferret behavior, care, and recognition of potential disease.     

The relationship between prevalence of Mycobacterium bovis infection in feral ferrets and possum abundance

AIM: To determine the relationship between the prevalence of macroscopic Mycobacterium bovis infection in feral ferrets (Mustela furo) and the abundance of brushtail possums (Trichosurus vulpecula). METHODS: The predictive power of a previously reported positive association between the prevalence of macroscopic M. bovis infection in ferrets and possum abundance was examined by undertaking surveys of M. bovis infection in ferrets at sites of low and high possum abundance. The association was then tested by a manipulative experiment that measured changes in the prevalence of macroscopic M. bovis infection in feral ferrets after reducing possum abundance. RESULTS: The positive relationship between the prevalence of macroscopic M. bovis infection in ferrets and possum abundance remained valid for new survey data, although the goodness of fit of the relationship was reduced. Experimentally reducing possum abundance reduced the odds of macroscopic M. bovis infection in ferrets by 80% in the years immediately following possum control (Odds Ratio=0.23, p=0.003). CONCLUSIONS: There is a causal link between possum abundance and the prevalence of macroscopic M. bovis infection in feral ferrets in areas in which M. bovis infection is known to occur in ferret populations. This suggests that possum-to-ferret transmission of disease occurs and accounts for most of the disease evident in ferret populations, though does not determine whether ferrets are spillover or maintenance hosts of M. bovis. Management to reduce the prevalence of M. bovis infection in ferrets should consider reducing possum abundance as a control tactic. KEY WORDS: Mustela furo, ferret, Trichosurus vulpecula, brushtail possum, Mycobacterium bovis, bovine tuberculosis.     

Hepatobiliary inflammation,neoplasia, and argyrophilic bacteria in a ferret colony

Hepatobiliary disease was diagnosed in eight of 34 genetically unrelated cohabitating pet ferrets (Mustela putorios furo) during a 7-year period. The eight ferrets ranged in age from 5 to 8 years and exhibited chronic cholangiohepatitis coupled with cellular proliferation ranging from hyperplasia to frank neoplasia. Spiral-shaped argyrophilic bacteria were demonstrated in livers of three ferrets, including two with carcinoma. Sequence analysis of a 400-base pair polymerase chain reaction product amplified from DNA derived from fecal bacteria from one ferret demonstrated 98% and 97% similarity to Helicobacter cholecystus and Helicobacter sp. strain 266-1 , respectively. The clustering of severe hepatic disease in these cohabitating ferroes suggests a possible infectious etiology. The role of Helicobacter species and other bacteria in hepatitis and/or neoplasia in ferrets requires further study.     

Common procedures in the pet ferret.

The domestic ferret is an increasingly popular pet in North America and Europe and may easily be incorporated into the structure and workings of most small animal hospitals. Not only does treatment of ferrets provide case diversity and intellectual challenges to the veterinarian but it may increase revenue, because most ferret owners have several ferrets. The diagnostic and supportive care procedures used commonly in ferrets are similar to those used in dogs and cats. This article presents the common diagnostic and supportive care procedures used in ferrets, with special emphasis on some of the unique aspects that make these procedures easier to learn and perform.     

Emerging Ferret Diseases

There are a number of newly described and emerging disease syndromes affecting the domestic ferret, and the purpose of this article is to make veterinarians aware of these diseases. A recently described systemic coronavirus infection appears to be a variant of the ferret enteric coronavirus and is currently termed “ferret infectious peritonitis.” Disseminated immunopathologic myositis, aplastic anemia/bone marrow aplasia, acute hemorrhagic syndrome, and oral ulcerations are also described, although the exact etiologies for these diseases have yet to be determined. There appears to be at least 2 important amino acid metabolism deficiencies in ferrets: hindlimb weakness in older ferrets (L-carnitine) and cysteine urolithiasis. Ferrets have recently been found to be susceptible to H1N1 influenza, so knowledge regarding this zoonotic disease is essential for veterinarians working with these animals. A novel Mycoplasma spp. has also recently been identified in ferrets with chronic respiratory problems that originated from one breeding colony. Because these diseases are still being investigated, practitioners who treat a ferret patient exhibiting clinical signs consistent with any of the conditions mentioned are encouraged to contact people who are knowledgeable of that particular illness.     

Circumcaval ureter in two ferrets

BackgroundCircumcaval ureter is an anomaly in the development of the caudal vena cava, rarely reported in ferrets.Materials and methodsInclusion criteria for ferrets were circumcaval ureter confirmed on surgery or post-mortem examination. Data collection of ferrets with circumcaval ureters presented between January 2014 and January 2021 included signalment, medical history, clinical signs, laboratory diagnostics, diagnostic imaging results, treatments, and clinical outcomes.ResultsTwo ferrets met the inclusion criteria. One presented following diarrhea, and one was found on routine examination that revealed a right nephromegaly. Abdominal ultrasound revealed severe unilateral hydronephrosis associated with hydroureter in both ferrets. No obvious cause of obstruction was identified. Biochemical results were unremarkable in both patients. Hydronephrosis was investigated through CT scans, revealing Type 1 circumcaval ureter in both ferrets. Section and relocation of the right ureter by uretero-vesical anastomosis was performed in one ferret. This ferret died 48 hours later following a nephrectomy performed due to persistent hydronephrosis. The second cas underwent right nephrectomy andd ureter resection due to severe hydronephrosis and stenosis of the circuncaval segment. This ferret has remained healthy on followup with no abnormalities found in biochemistries or ultrasound examination.Conclusion and case relevanceFindings suggest that circumcaval ureter should be suspected in ferrets with unilateral hydronephrosis and associated hydroureter without any identified cause of obstruction on abdominal ultrasonography. It should be confirmed with CT scan and/or urography and treated surgically.