History
A 3-year-old spayed female ferret was evaluated at the Louisiana State University Veterinary Teaching Hospital and Clinics because of a 3-week history of weight loss, lethargy, decreased appetite, nonproductive hacking cough, and abnormal feces (described by the owner as softer than normal for this ferret).
Clinical and Gross Findings
On physical examination, the ferret was in poor body condition (body condition score, 2/5). It was bright, alert, and responsive but tachypneic (100 breaths/min). Findings of abdominal palpation were suggestive of a possible abdominal mass and splenomegaly. No cutaneous lesions were observed. Results of a CBC and serum biochemical analysis were unremarkable. The ferret was anesthetized, and thoracic and abdominal radiography and ultrasonography were performed. Thoracic radiography revealed a severe diffuse alveolar pulmonary pattern with multiple air bronchograms and complete consolidation of the left cranial lung lobe. Diffuse splenic enlargement was evident on the abdominal radiographic views. Thoracic and abdominal ultrasonography revealed diffuse consolidation of the left lateral and dorsal lung lobes, diffusely enlarged intra-abdominal lymph nodes, and loss of wall layering in several intestinal segments. Fine-needle aspirate samples from the lung lesions were obtained for evaluation. Because of the grave prognosis, the owner decided to take the ferret home without treatment. The ferret died a day after discharge from the hospital and was submitted for necropsy.
On gross examination, the lungs contained multifocal to coalescing, raised, pale tan nodules ranging from 0.3 to 2 cm in diameter in all lung lobes (Figure 1). Approximately 90% of the left cranial lung lobe was obliterated by coalescing nodules, and the sections from the affected areas sank when placed in formalin solution. The intestines contained nodular intramural thickenings up to 5 mm in diameter. The spleen was enlarged (11 × 4 × 0.5 cm) and was meaty on cut surface. Tracheobronchial and mesenteric lymph nodes were also enlarged. No other notable gross lesions were detected.
Photograph (dorsal view) of the lungs from a 3-year-old spayed female ferret that was evaluated because of a 3-week history of weight loss, lethargy, anorexia, nonproductive cough, and soft feces. Notice that the lungs containing multifocal to coalescing, raised, pale tan nodules in all lung lobes.
Citation: Journal of the American Veterinary Medical Association 240, 12; 10.2460/javma.240.12.1427
Photograph (dorsal view) of the lungs from a 3-year-old spayed female ferret that was evaluated because of a 3-week history of weight loss, lethargy, anorexia, nonproductive cough, and soft feces. Notice that the lungs containing multifocal to coalescing, raised, pale tan nodules in all lung lobes.
Citation: Journal of the American Veterinary Medical Association 240, 12; 10.2460/javma.240.12.1427
Photograph (dorsal view) of the lungs from a 3-year-old spayed female ferret that was evaluated because of a 3-week history of weight loss, lethargy, anorexia, nonproductive cough, and soft feces. Notice that the lungs containing multifocal to coalescing, raised, pale tan nodules in all lung lobes.
Citation: Journal of the American Veterinary Medical Association 240, 12; 10.2460/javma.240.12.1427
Formulate differential diagnosis from the history, clinical findings, and Figure 1—then turn page →
Cytologic and Histopathologic Findings
Microscopic examination of the fine-needle aspirate samples from the lung lesions obtained during the ultrasonographic examination of the ferret contained high numbers of well-preserved nucleated cells with small amounts of blood contamination. Large numbers of macrophages, including many epithelioid macrophages and multinucleated giant cells, few degenerate neutrophils, and some small mature lymphocytes, were present. Frequently, macrophages contained large numbers of phagocytosed nonstaining (clear), rod-shaped (approx 5- to 7-μm-long) bacteria (Figure 2). The cytologic interpretation was marked granulomatous inflammation with intracellular organisms (consistent with Mycobacterium sp).
Photomicrograph of a fine-needle aspirate specimen obtained from the lung lesions in the ferret in Figure 1. Notice the large numbers of epithelioid macrophages containing many nonstaining, rod-shaped bacteria consistent with Mycobacterium sp. Wright-Giemsa stain; bar = 20 μm.
Citation: Journal of the American Veterinary Medical Association 240, 12; 10.2460/javma.240.12.1427
Photomicrograph of a fine-needle aspirate specimen obtained from the lung lesions in the ferret in Figure 1. Notice the large numbers of epithelioid macrophages containing many nonstaining, rod-shaped bacteria consistent with Mycobacterium sp. Wright-Giemsa stain; bar = 20 μm.
Citation: Journal of the American Veterinary Medical Association 240, 12; 10.2460/javma.240.12.1427
Photomicrograph of a fine-needle aspirate specimen obtained from the lung lesions in the ferret in Figure 1. Notice the large numbers of epithelioid macrophages containing many nonstaining, rod-shaped bacteria consistent with Mycobacterium sp. Wright-Giemsa stain; bar = 20 μm.
Citation: Journal of the American Veterinary Medical Association 240, 12; 10.2460/javma.240.12.1427
Samples of tissues (including the lungs, jejunum, tracheobronchial and mesenteric lymph nodes, and spleen) collected at necropsy were subsequently fixed in neutral-buffered 10% formalin and processed for histologic examination. Histologically, > 95% of the lung parenchyma was expanded and obliterated by a granulomatous infiltrate of primarily epithelioid macrophages admixed with fewer multinucleated giant cells (foreign body type), multiple aggregates of lymphocytes, and scattered neutrophils and plasma cells (Figure 3). Large numbers of macrophages and multinucleated giant cells contained numerous nonstaining, rod-shaped bacteria that yielded positive results following staining with Fite acid-fast stain (Figure 4). Multifocal areas of necrosis with numerous acicular cholesterol clefts were present. The alveolar spaces in the less affected areas of lungs contained eosinophilic fluid. The lamina propria and submucosa of jejunum and the tracheobronchial and mesenteric lymph nodes contained multifocal areas of granulomatous infiltrates with acid-fast bacilli similar to the organisms detected in the lung sections. The spleen was hyper-cellular with marked extramedullary hematopoiesis; no bacterial organisms were evident in the sections of spleen examined. Samples of lung and spleen tissue underwent microbiological culture on Lowenstein-Jensen medium at 36° to 37°C with 5% (± 1%) CO2 and yielded growth of a slow-growing mycobacterium. By use of a 16S PCR assay,a the culture organisms yielded a 554-bp product with 99% similarity to Mycobacterium xenopi and 95% similarity to Mycobacterium celatum.
Photomicrograph of a section of lung tissue with lesions obtained from the ferret in Figure 1. The lung parenchyma has been replaced by large numbers of macrophages, low numbers of multinucleated giant cells (arrows) with intracellular multiple acicular cholesterol clefts (arrowheads), and few neutrophils and lymphocytes. H&E stain; bar = 100 μm.
Citation: Journal of the American Veterinary Medical Association 240, 12; 10.2460/javma.240.12.1427
Photomicrograph of a section of lung tissue with lesions obtained from the ferret in Figure 1. The lung parenchyma has been replaced by large numbers of macrophages, low numbers of multinucleated giant cells (arrows) with intracellular multiple acicular cholesterol clefts (arrowheads), and few neutrophils and lymphocytes. H&E stain; bar = 100 μm.
Citation: Journal of the American Veterinary Medical Association 240, 12; 10.2460/javma.240.12.1427
Photomicrograph of a section of lung tissue with lesions obtained from the ferret in Figure 1. The lung parenchyma has been replaced by large numbers of macrophages, low numbers of multinucleated giant cells (arrows) with intracellular multiple acicular cholesterol clefts (arrowheads), and few neutrophils and lymphocytes. H&E stain; bar = 100 μm.
Citation: Journal of the American Veterinary Medical Association 240, 12; 10.2460/javma.240.12.1427
Photomicrograph of a section of jejunum obtained from the ferret in Figure 1. Notice the large numbers of stained bacteria within epithelioid macrophages. Fite acid-fast stain; bar = 20 μm. Inset—Numerous epithelioid macrophages with intracellular nonstaining, rod-shaped bacteria are visible. H&E stain; bar = 20 μm.
Citation: Journal of the American Veterinary Medical Association 240, 12; 10.2460/javma.240.12.1427
Photomicrograph of a section of jejunum obtained from the ferret in Figure 1. Notice the large numbers of stained bacteria within epithelioid macrophages. Fite acid-fast stain; bar = 20 μm. Inset—Numerous epithelioid macrophages with intracellular nonstaining, rod-shaped bacteria are visible. H&E stain; bar = 20 μm.
Citation: Journal of the American Veterinary Medical Association 240, 12; 10.2460/javma.240.12.1427
Photomicrograph of a section of jejunum obtained from the ferret in Figure 1. Notice the large numbers of stained bacteria within epithelioid macrophages. Fite acid-fast stain; bar = 20 μm. Inset—Numerous epithelioid macrophages with intracellular nonstaining, rod-shaped bacteria are visible. H&E stain; bar = 20 μm.
Citation: Journal of the American Veterinary Medical Association 240, 12; 10.2460/javma.240.12.1427
Morphologic Diagnosis
Severe pyogranulomatous pneumonia, enteritis, and lymphadenitis with numerous acid-fast bacteria (M xenopi).
Comments
Pathogenic mycobacterial organisms are classified into 3 known types: slow-growing organisms with and without production of tubercles (tuberculous or nontuberculous mycobacteria), leproid granuloma-producing organisms (lepromatous mycobacteria), and rapidly growing organisms (atypical mycobacteria).1 Ferrets are susceptible to various mycobacterial infections, including infections with Mycobacterium avium, Mycobacterium bovis, Mycobacterium genavense, Mycobacterium microti, Mycobacterium abscessus, Mycobacterium triplex, and M celatum.2–4 In New Zealand, ferrets, along with opossums and stoats, are considered an important reservoir host for M bovis, the causative agent of tuberculosis in cattle.2 Mycobacterium avium infection in a ferret with lymphoma has been reported.5
Mycobacterium xenopi is a slow-growing, saprophytic, nontuberculous, acid-fast bacterium that grows optimally at 45°C and grows very slowly at 37°C.6 Mycobacterium xenopi was first isolated in 1959 from a skin abscess of a South African toad (Xenopus laevis).7 The organism has been isolated from water supplies in homes and hospitals.8 Mycobacterium xenopi is a recognized cause of pulmonary disease in humans with chronic lung disease and is frequently isolated from individuals with preexisting lung disease or HIV infection.9 Mycobacterium xenopi has been reported to cause lymphadenitis and peritonitis6 and chronic disseminated infection10 in cats. To the authors' knowledge, infection with M xenopi in ferrets has not been reported. For the ferret of this report, the source of infection was unknown and there was no prior history of illness. There was no evidence of mycobacterial disease (human or animal) in the owner's household. Although transmission of M xenopi infection in humans from person to person and transmission from animal reservoirs are controversial,8 the owner was strongly advised to take extra precautions when handling the ferret following the cytologic diagnosis of mycobacterial infection.
Mycobacterium celatum has similar biochemical characteristics to M xenopi and members of the M avium complex. The identification of M celatum was first reported in 1993, and the organism has a unique 16S rRNA sequence.11 Mycobacterium celatum is pathogenic in humans, particularly immunocompromised individuals,12 and has been reported as a cause of disseminated granulomatous infection in a bird13 and a ferret.14
Murine macrophages efficiently kill or inhibit the growth of intracellular M bovis, Mycobacterium tuberculosis, Mycobacterium leprae, and M avium.15 However, ferret macrophages activated with T-cell–derived supernatant, lipopolysaccharide, or both fail to have increased ability to control M bovis infection.15 Moreover, survival of the intracellular bacteria within the activated ferret macrophages is enhanced.15
Other differential diagnoses for the gross lesion in the ferret of the present report included neoplasia and bacterial and fungal infections. A diagnosis of mycobacteriosis can be made on the basis of findings of cytologic evaluation of acid-fast–stained fine-needle aspirate samples and histologic examination of acid-fast–stained biopsy specimens obtained from apparent masses and radiographic and ultrasonographic detection of enlarged lymph nodes (mostly hilar lymphadenopathy).1 Bacteria can be isolated via mycobacterial culture, and PCR procedures can be used for organism identification. Single-antimicrobial treatment of any mycobacterial infection is not advised. There is a paucity of literature regarding the treatment of M xenopi infection. In a report10 of a cat with disseminated M xenopi infection, a survival time of approximately 7 years was achieved by use of a combination of antimicrobials. The ferret of the present report died shortly after the cytologic diagnosis and did not receive any treatment.
Athens Diagnostic Laboratory, Athens, Ga.
References
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