DISEASE SUMMARY PAGE

Atypical Mycobacterial Infection in Ferrets and Cranes

Summary Information

Diseases / List of Bacterial Diseases / Disease summary
Alternative Names  
Disease Agents
  • In ferrets: Mycobacterium celatum, (J26.38.w2, J42.144.w1, J84.17.w4) Mycobacterium microti, (J84.13.w6) Mycobacterium genavense (J24.78.w3)
  • In cranes: Mycobacterium flavescens. (B702.19.w19)
    • In general, bacterial diseases are seen in cranes which are predisposed to infection due to population or environmental stressors. (B336.20.w20)
Infectious Agent(s) Mycobacterium spp.
Non-infectious Agent(s) --
Physical Agent(s) --
General Description
Clinical signs
Ferrets
  • In a four-year-old male ferret in Norway in 1999: (J26.38.w2)
    • Weight loss, depression for at least six months, gradual decline in condition, cough for three months. On examination, depression, emaciation, dehydration and poor hair coat as well as dyspnoea. 
    • On auscultation, dry, harsh pulmonary sounds.
    • Radiography: throughout both lungs, disseminated nodular and peribronchial increased densities, also within the lung parenchyma, a cystic structure.
  • In a three-year-old neutered male ferret in Germany in 2009: (J84.17.w4)
    • Coughing, weight loss, general reduction in condition, vomiting and mild diarrhoea, over a period of five months.
    • Radiography: in the lungs, multiple nodular densities. (J84.17.w4)
  • In five-year-old neutered male ferret in Italy. (J42.144.w1)
    • Over a period of two months, anorexia and weight loss. Examination revealed poor body condition with muscle atrophy, slight hair loss on the tail, pale mucous membranes and an enlarged spleen. (J42.144.w1)
    • Clinical pathology: marked macrocytic hypochromic anaemia (haematocrit only 13.6%, normal range 40.2 - 46.8%), haemoglobin 4.0 g/dL (normal range 13.1 - 15.6 g/dL), also slight anocytosis and polychromasia and a few acanthocytes. There was a moderate leucopaenia (1.10 x 109/L) with marked lymphopaenia (0.022 x 109/L, normal range 1.23 - 3.74 x 109/L) and moderate hypoalbuminaemia (2.1 g/L, normal range 3.0 - 3.6 g/dL). (J42.144.w1)
  • In a five-year-old castrated male ferret in Australia, eye lesion with hyperplasia of the conjunctiva on the palpebral surface of the third eyelid, also slight generalised peripheral lymphadenopathy. Otherwise well. (J24.78.w3)
  • In a four-year-old female ferret, conjunctival swelling, serous ocular discharge, also slight swelling of the bridge of the nose. (J24.78.w3)
Cranes
Pathological findings
Cranes
Gross pathology

Ferrets

  • In a four-year-old male ferret in Norway in 1999: (J26.38.w2)
    • General: poor body condition.
    • Respiratory: Throughout the lung parenchyma, firm pale grey 2-10 mm nodules, also around the distal trachea.
    • GIT: On the stomach, a 15x15 mm section of wall thickened, seros roughened; on the cut surface pale grey. 
    • Hepatic: in the liver parenchyma, multiple grey 1-2 mm foci.
    • Splenic: spleen normal size, pale.
    • Lymph nodes: moderate to severe enlargement.
  • In a three-year-old neutered male ferret in Germany in 2009: (J84.17.w4)
    • Respiratory: in the lungs, multiple 6-10 mm firm light-brown nodules.
    • Splenic: splenomegaly.
    • Lymph nodes: enlarged cervical, retropharyngeal, bronchial, gastric, mesenteric and popliteal lymph nodes.
Histopathology

Ferrets

  • In a four-year-old male ferret in Norway in 1999: (J26.38.w2)
    • Respiratory: in the lung and in the tracheal mucosa, submucosa and adventitia, multiple inflammatory foci of epitheliod cells with abundant eosinophilic cytoplasm, macrophages, lymphocytes and neutrophils; some foci contained necrotic areas. (J26.38.w2)
    • GIT: in the gastric lamina propria, submucosa, muscle wall and serosa, large areas of granulomatous inflammation. (J26.38.w2)
    • Hepatic: in the liver parenchyma, small scattered foci of macrophages and neutrophils; in periportal areas, a lymphoplasmacytic infiltrate with some macrophages. In the areas which had been visible macroscopically as grey foci, vacuolated hepatocytes, probably containing lipid. (J26.38.w2)
    • Lymph nodes: in both the cortex and medulla, architecture distorted by large granulomatous inflammatory foci. (J26.38.w2)
    • Immunohistochemistry: staining with polyclonal antibodies against both Mycobacterium bovis and Mycobacterim avium subsp. paratuberculosis. (J26.38.w2)
    • PCR: 16S rRNA sequence identical to Mycobacterium celatum. (J26.38.w2)
    • Culture: positive cultures for mycobacteria. (J26.38.w2)
  • In a three-year-old neutered male ferret in Germany in 2009: (J84.17.w4)
    • Lung, liver, spleen, lymph nodes, brain: granulomatous inflammation; mainly macrophages epitheliod cells and multinucleate giant cells. With Ziehl-Neelsen staining, acid-fast bacilli seen, mainly in epitheliod cells. (J84.17.w4)
    • Culture: acid-fast bacilli grown in suitable media for mycobacteria. (J84.17.w4)
    • PCR: 510 bp fragment of 16S rRNA sequence confirmed as Mycobacterium celatum. (J84.17.w4)
  • In two ferrets with ocular lesions: (J24.78.w3)
    • Ocular: conjunctival biopsy showed numerous macrophages containing many lymphocytes and large numbers of negatively-staining bacilli (DiffQuick stain). (J24.78.w3)
    • Lymph node: In the ferret with enlarged lymph nodes, lymph node aspirate contained lymphoid cells and a few macrophages, some of which contained negatively-staining bacilli. (J24.78.w3)
    • Ziehl-Neelsen: acid fast bacilli within macrophages. (J24.78.w3)
    • PCR of a region of the 16S rRNA gene matched Mycobacterium genervase. (J24.78.w3)
Further Information
  • Mycobacterium microti was isolated from a ferret in Scotland [no clinical details were available]. (J84.13.w6)
  • Mycobacterium celatum has been isolated from:
    • A four-year-old male ferret in Norway in 1999. (J26.38.w2)
    • A three-year-old neutered male ferret in Germany in 2009. (J84.17.w4)
    • A five-year-old neutered male ferret in Italy. (J42.144.w1)
  • A study of 21,481 feral ferrets from wildlife areas of New Zealand, 2004-2008 detected the following Mycobacterium spp.: Mycobacterium triplex (15), Mycobacterium fortuitum (1), Mycobacterium florentinum (1), Mycobacterium interjectum (3), Mycobacterium intracellulare (3), Mycobacterium septicum/Mycobacterium peregrinum (identical 16s rRNA sequences) 2, MCR0 24 (1), Mycobacterium sp. (3) (as well as 175 isolates of Mycobacterium avium and 268 of Mycobacterium bovis). (J238.132.w2)
Diagnosis
Diagnosis is based on finding of acid-fast bacilli in lesions and immunohistochemical staining for mycobacteria, and conformed by culture and PCR with sequencing of part of the 16S rRNA gene.
  • In a four-year-old male ferret in Norway in 1999: (J26.38.w2)
    • Radiography: throughout both lungs, disseminated nodular and peribronchial increased densities, also within the lung parenchyma, a cystic structure. (J26.38.w2)
    • Immunohistochemistry: staining with polyclonal antibodies against both Mycobacterium bovis and Mycobacterim avium subsp. paratuberculosis. (J26.38.w2)
    • Culture: positive cultures for mycobacteria. (J26.38.w2)
    • PCR: 16S rRNA sequence identical to Mycobacterium celatum. (J26.38.w2)
  • In a three-year-old neutered male ferret in Germany in 2009: (J84.17.w4)
    • Radiography: in the lungs, multiple nodular densities. (J84.17.w4)
    • Histopathology: acid-fast bacilli visible with Ziehl-Neelsen staining. (J84.17.w4)
    • Culture: acid-fast bacilli grown in suitable media for mycobacteria. (J84.17.w4)
    • PCR: 510 bp fragment of 16S rRNA sequence confirmed as Mycobacterium celatum. (J84.17.w4)
  • In five-year-old neutered male ferret in Italy. (J42.144.w1)
    • Ultrasonography: small amount abdominal fluid, spleen markedly enlarged and hyperechoic. (J42.144.w1)
    • Cytology: splenic fine needle aspirate stained with Wright's stain revealed high cellularity with numerous background rbc, occasional cellular debris. Mostly there were haematopoitic cell precursors (erythroid and myeloid, with normal maturation) and inflammatory cells. There were numberous histiocytic cells, often found in epitheliod aggregates and some containing negative staining intracytoplasmic rods, short to medium in length. there were occasional multinucleate giant cells, moderate quantities of neutrophils and small numbers of lymphocytes. Using Ziehl-Neelsen staining, some macrophages were found to contain acid-fast bacilli. Overall, the cytological picture was considered to show a macrophage-dominated inflammation associated with an infection with a Mycobacterium sp., plus extramedullar haematopoiesis. (J42.144.w1)
    • Culture: from splenic samples produced colonies of acid-fast bacilli. (J42.144.w1)
    • PCR: after inactivation and DNA extraction, a 500 bp segment of the 16s RNA gene was amplified and the resultant product found to have 99.7% identity with a Mycobacterium celatum strain. (J42.144.w1)
  • In two ferrets with ocular lesions: (J24.78.w3)
    • In biopsy specimens, within macrophages, numerous small negatively-staining bacilli with DiffQuick, shown to be acid-fast bacilli by Ziehl-Neelsen staining. (J24.78.w3)
    • PCR of a region of the 16S rRNA gene matched Mycobacterium genervase. (J24.78.w3)
Treatment
  • A four-year-old male ferret in Norway in 1999 and a three-year-old neutered male ferret in Germany in 2009 were euthanised due to the poor prognosis. (J26.38.w2, J84.17.w4)
  • In five-year-old neutered male ferret in Italy, enrofloxacin 5 mg/kg orally daily, rifampicin 20 mg/kg orally every 12 hours and azithromycin 10 mg/kg orally every 12 hours. This regime was recommended to be used for at least six months. Clinical improvement was notable by 40 days, with reduced spleen size on ultrasonography and absence of the macrophage inflammation or mycobacteria detectable on cytology of a splenic sample. Treatment continued for another two months, however, problems developed regarding drug administration, treatment ceased and the ferret then rapidly deteriorated and died. (J42.144.w1)
  • In two ferrets with ocular lesions: (J24.78.w3)
    • Rifampin 30 mg, clofazimine 12.5 mg and clarithromycin 31.25 mg, orally, once daily (all suspended in a palatable gel), plus chloramphenicol eye ointment. Continued for 2-3 months with clinical cure. Deterioration ten months after treatment started due to end-stage renal disease. (J24.78.w3)
    • Rifampin 14 mg/kg orally once daily, with evident improvement within two weeks, clinically normal by four weeks, treatment continued for a further four weeks. The ferret deteriorated two months after treatment stopped, with an abdominal mass which appeared to be an ovarian tumour. (J24.78.w3)
Associated Techniques
Host taxa groups /species
Author Dr Debra Bourne MA VetMB PhD MRCVS (V.w5)
Referees  

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