Diseases / List of Bacterial Diseases / Disease description:

Mammalian Tuberculosis (with special reference to Badgers, Hedgehogs, Elephants, Bears, Lagomorphs, Ferrets and Bonobos)

INFORMATION AVAILABLE

GENERAL INFORMATION

CLINICAL CHARACTERISTICS & PATHOLOGY

INVESTIGATION & DIAGNOSIS

TREATMENT & CONTROL

SUSCEPTIBILITY & TRANSMISSION

ENVIRONMENT & GEOGRAPHY

..

 

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General and References

Disease Summary

  • Mammalian tuberculosis is an important infectious disease of mammals including humans. (B101)
  • Mammalian tuberculosis caused by Mycobacterium bovis may occur in most warm-blooded vertebrates. (B101)
  • Mammalian tuberculosis caused by Mycobacterium tuberculosis is the most specific type that generally affects humans, nonhuman primates, and zoo species such as elephants, seals and sea lions. It has also been reported in psittacine birds. (B101, B336.66.w66)
  • Chronic granulomatous lesions which may become necrotic, caseous and calcified are typical of infection. (B101)
BADGERS --
HEDGEHOGS --
ELEPHANTS Tuberculosis in elephants is commonly regarded as a disease of captivity, that most likely occurs subsequent to contact with infected human beings. It is often asymptomatic. It generally affects Elephas maximus - Asian Elephant, and seems to be rarer in Loxodonta africana - African Elephant. (B336.66.w66, J64.20.w1)
BEARS Reported as a rare fatal infection. (B214.3.4.w16, B407.w18)
LAGOMORPHS Tuberculosis is reported as a rare disease of domestic rabbits. (B614.8.w8)
FERRETS Ferrets may develop tuberculosis, most commonly associated with Mycobacterium bovis.
BONOBOS/GREAT APES Bonobos and other great apes, like other non-human primates, may develop tuberculosis.

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Alternative Names (Synonyms)

TB

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Disease Type

Bacterial Infection

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Infectious/Non-Infectious Agent associated with the Disease

  • Mycobacterium bovis (principle host cattle but may infect and cause progressive disease in most warm-blooded vertebrates including humans). (B101, J64.20.w1)
    • This is the main organism involved in tuberculosis of rabbits. (B614.8.w8)
  • Mycobacterium tuberculosis (main cause in humans). (J64.20.w1)
    • This organism has been isolated from some cases of rabbit tuberculosis. (B614.8.w8)
  • Mycobacterium africanum (rarer cause in humans). (J64.20.w1)
  • Mycobacterium microti (in voles and some other rodents). (J64.20.w1)
  • In nonhuman primates, either Mycobacterim bovis or Mycobacterium tuberculosis, with no differences between disease or pathology caused by these two organisms. (B644.2.w2, D390.96.w96)
    • In great apes: both Mycobacterium tuberculosis and Mycobacterium bovis. Mycobacterium tuberculosis may be involver most often. (P1.1974.w4)
    • In two gorillas (as well as various other mammals on the same premises) in the UK, a proposed new species, Mycobacterium pinnipedii. (J384.53.w1, P503.2203.w11)

Mycobacterium spp. are gram-positive, acid-fast bacteria (B501.12.w12) that have the following characteristics: 

  • slender
  • rod-shaped
  • non-motile
  • aerobic
  • slow growing.
  • (B614.8.w8)
Pathogenesis
  • Mycobacteria are facultative intracellular pathogens that accumulate in significant numbers in macrophages in the area of the lesion. The bacteria provoke a granulomatous inflammatory response; this is partly due to the high lipid content of the cell walls of this organism. (B614.8.w8)
  • Infection also provokes an intense cell-mediated immune response which usually inhibits dissemination of the organisms and so blocks the progression of the disease. However, in some cases there is an aberrant immune response which is characterised by hypersensitivity. This response accelerates the development of the lesions and induces clinical disease. (B614.8.w8)
  • The host genotype influences the nature of the immune response and thus the consequent level of resistance to this organism. (B614.8.w8)

Infective "Taxa"

  • Mycobacterium spp.
    • Mycobacterium bovis
    • Mycobacterium tuberculosis
    • Mycobacterium africanum
    • Mycobacterium microti

Non-infective agents

--

Physical agents

Indirect / Secondary

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References

Disease Author

Debra Bourne MA VetMB PhD MRCVS (V.w5), Nikki Fox BVSc MRCVS (V.w103), Gracia Vila-Garcia DVM, MSc, MRCVS (V.w67
Click image for main Reference Section

Referees

William Lewis BVSc CertZooMed MRCVS (V.w129)

Major References / Reviews

Code and Title List

B22.11.w8, B58.22.w22, B101, B336.66.w66

J4.170.w1, J4.193.w1, J64.20.w1

P1.1988.w2, P1.1990.w2

Badgers 

Meles meles - Eurasian Badger

Hedgehogs 

Erinaceus europaeus - West European Hedgehog

Elephants

Elephas maximus - Asian Elephant

Loxodonta africana - African Elephant

Further guidance on the control of TB in elephants is provided in: D303 - Guidelines for the control of tuberculosis in elephants 2003 - Full text provided

Bears

Lagomorphs

Ferrets

Bonobos/Great Apes

Other References

Code and Title List

J4.179.w2, J13.16.w1, J13.41.w1, J84.8.w15

P1.1990.w1, P1.1997.w2, P1.1997.w3, P503.1.w1, P30.1.w6

Elephants

Ferrets

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Clinical Characteristics and Pathology

Detailed Clinical and Pathological Characteristics

General Mammalian tuberculosis is normally a chronic debilitating disease but is occasionally acute and rapidly progressive.
  • The primary focus (start of the disease) is usually in the lungs in cattle and in humans. Caseous lesions form in adjacent lymph nodes. The "primary complex" (primary focus plus primary lymph node lesions) may progress slowly or rapidly.
  • Tuberculous lesions form where organisms localise. These may become very large, the central area becomes necrotic and the lesion may become a caseous mass which may then mineralise. When tubercles become enclose by dense fibrous connective tissue the disease is arrested. 
  • Tubercles may form in other organs when numerous bacilli from a local lesions invade the bloodstream. Acute generalised miliary tuberculosis, with many small foci of infection developing, is frequently rapidly fatal. Alternatively, one or more isolated lesions may form in organs other than the lungs; such lesions may remain small for long periods, becoming encapsulated and not causing clinical illness.
(B22.11.w8, B101)

Clinical Characteristics

  • Clinical signs vary depending on the extent of the lesions and their location.
    • General signs include:
      • weakness,
      • dyspnoea,
      • weight loss and emaciation despite good feeding,
      • low-grade fluctuating fever.
    • With extensive lung lesions, an intermittent hacking cough may be noted.
(B22.11.w8, B101)
BADGERS

In Meles meles - Eurasian Badger:

  • Often no clinical signs.
  • Loss of body condition, emaciation.
  • In terminally ill animals there may be behavioural changes; they may wander erratically and enter farm buildings.
  • Clinical progression may sometimes be faster in cubs than in adults.
  • (B209.21.w21, J60.2.w2)
(B209.21.w21, J60.2.w2)
HEDGEHOGS

In Erinaceus europaeus - West European Hedgehog:

Clinical pathology in Erinaceus europaeus - West European Hedgehog):

ELEPHANTS In Elephas maximus - Asian Elephant:

General signs

  • The following signs have been noted:
  • Reluctance to do any strenuous work. (J3.93.w1)
  • Exercise intolerance. (B214.3.7.w3, J196.60.w1, P6.4.w2, P502.1.w5)
  • Depression. (J12.5.w3, J42.38.w1, P1.1981.w1)
  • Weight loss. (B10.49.w21)
  • Loss of condition. (J2.32.w1, J4.183.w2, J42.38.w1, J196.60.w1, P1.1981.w1, P1.1997.w4)
  • Weakness. (J196.60.w1)
  • Anorexia. (J4.183.w2, J42.38.w1)
  • Subcutaneous oedema that extended from the neck along the mid-ventral body wall. (J3.93.w1)
  • Polydipsia. (J4.183.w2, P6.4.w2)
  • Polyuria. (J4.183.w2)
  • Gradual deterioration, prostration and death. (J3.93.w1, J42.38.w1, J196.60.w1)
  • Note: signs may be aggravated by parasitism. (J42.38.w1, J196.60.w1)

Respiratory signs

  • Panting. (J196.60.w1)
  • Trunk discharge, mucopurulent in one case. (J2.32.w1, P1.1997.w4, P502.1.w5)
  • Harsh cough. (J3.93.w1, P502.1.w5)
  • Dry cough. (B214.3.7.w3)
  • Dyspnoea. (J12.5.w3, J196.60.w1)
  • Mucopurulent discharge from the eyes. (P1.1981.w1)
  • Signs of chronic pneumonia concurrent with severe helminthiasis and subsequently anaemia was reported in a 25-year-old male elephant. On thoracic auscultation this animal demonstrated an expiratory effort and ronchi (respiratory noises). Two weeks later, the heart was muffled on auscultation and noises suggestive of pulmonary oedema were detected. (J196.60.w1)

Clinical pathology

  • Haematology revealed anaemia in a suspected case of tuberculosis and severe parasitism. (J196.60.w1)
  • Haematology revealed a low leucocyte count in a case of confirmed tuberculosis. (J3.93.w1)
  • Biochemistry of an infected Elephas maximus - Asian Elephant confirmed by culture, revealed increased beta- and gamma globulins and decreased of the albumin:globulin ratio. (P6.4.w2)
BEARS No details available.
LAGOMORPHS General signs
  • Anorexia (B614.8.w8)
  • Weight loss (B614.8.w8)
  • Pallor (B614.8.w8)

Occasionally, there may be clinical signs referable to a particular organ system including:

Ocular lesions

  • Uveitis has occasionally been seen. (B614.8.w8)

Gastrointestinal signs

  • Diarrhoea (B614.8.w8)

Musculoskeletal signs

  • Swollen joints (B614.8.w8)

Pneumonia (B602.17.w17)

FERRETS
  • The ferret may be asymptomatic, or show vague clinical signs. (B627.14.w14)
  • Signs may only occur at the late stages of infection. (B501.12.w12)

General signs

  • Weight loss, emaciation. (B501.12.w12, B627.14.w14, J4.195.w5, J215.23.w1, )
  • Loss of appetite. (B627.14.w14, J4.195.w5)
  • Lethargy. (B627.14.w14, J215.23.w1)

Gastrointestinal signs

  • Diarrhoea. (J215.23.w1)

Musculoskeletal signs

  • Initial difficulty in walking and splaying of the hind legs due to paralysis of the pelvic adductor muscles; progression of paralysis, eventually affecting all the limbs. (B501.12.w12, B627.14.w14, J4.195.w5)

Other

  • Hepatosplenomegaly and enlarged mesenteric lymph nodes may be detected on abdominal palpation. (B501.12.w12, B627.14.w14, B628.11.w11)
BONOBOS/GREAT APES In primates: (B644.2.w2)
  • Variable.
    • Death without prior clinical signs.
    • General signs: easily fatigued, anorexia, chronic weight loss, hair coat ungroomed, loss of hair.
    • Respiratory signs: persistent cough, dyspnoea during/after exercise.
    • Peripheral lymphadenopathy, sometimes draining tracts or cutaneous abscesses.
    • On palpation sometimes hepatomegaly, splenomegaly.
    • Diarrhoea with enteric infection.
    • Clinical pathology: mild normochromic normocytic anaemia, leucocytosis with neutrophilia and lymphopaenia, increased serum globulin, increased erythrocyte sedimentation rate.

(B16.1.w1, B644.2.w2, B680.w1)

  • The disease usually progresses rapidly in rhesus monkeys and in baboons, slower in cynomolgus monkeys. In great apes it is usually more chronic than in Old World monkeys. (D390.96.w96)

In Pan troglodytes - Chimpanzee: (B569.w4)

  • General: inactivity, weight loss, poor hair coat.
  • Chronic cough sometimes.
  • Occasionally sudden death.
  • Note: clinical signs may be minor despite extensive lesions.

(B569.w4)

Incubation

  • The strain of the organism, the dose and the route of exposure may affect the time to produce progressive disease. (P1.1990.w2)
BADGERS --
HEDGEHOGS --
ELEPHANTS --
BEARS --
LAGOMORPHS --
FERRETS --
BONOBOS/GREAT APES
  • Usually considered a chronic infection, although rapid progression of disease has been recorded occasionally in other primates. (B680.w1)
  • Tuberculin test conversion usually occurs less than three weeks after infection in primates. (D390.96.w96)

Mortality / Morbidity

--
BADGERS --
HEDGEHOGS --
ELEPHANTS --
BEARS
LAGOMORPHS --
FERRETS Morbidity
  • This disease is currently rare in ferrets and was seen more commonly in the early 1900's, probably due to the feeding of raw meat. (B628.11.w11)

Mortality

  • Tuberculosis can be fatal. (B627.14.w14, J4.195.w5)
BONOBOS/GREAT APES
  • Tuberculosis was very prevalent in zoo primates in the past due to high levels in the human population and ease of transfer from members of the public. Transfer was reduced by use of glass-fronted displays. (B569.w4)
  • Prior to the 1960s, tuberculosis was a significant cause of morbidity and mortality in captive great apes. (B336.39.w39)
  • Tuberculosis was reported as the cause of death of one bonobo listed in the 1975 bonobo studbook. (J23.20.w2)
  • Tuberculosis is now uncommon in great apes in zoos in North America. [1993](B22.31.w31c)

Pathology

Gross Pathology:
  • Nodular lesions with caseous necrosis may involve entire organs of one or both body cavities. (B58.22.w22)
  • Tuberculous lesions typically appear as yellowish, caseous, necrotic areas in nodules of firm white to light grey fibrous tissue. (B58.22.w22)
  • Some lesions may have purulent consistency and others may be partially dry with caseation or extensive fibrosis. (B58.22.w22)
  • Calcification or caseocalcification may occur in lesions. (B58.22.w22)

Histopathology:

  • A tubercle lesion is described as a granuloma composed of a caseous, necrotic centre surrounded by epithelioid cells. Some of these cells may have formed multinucleated giant cells of lymphocytes and granulocytes. The granuloma is commonly encapsulated by fibrous connective tissue. (B58.22.w22)
BADGERS

In Meles meles - Eurasian Badger:

  • 70-80% of Mycobacterium bovis infected animals may show no gross lesions at post mortem examination. (P27.5.w5)
  • Lesions mainly in lungs and associated lymph nodes, lymph nodes of the head and in the kidneys.
  • Primary foci may be 0.5mm diameter with mineralisation and fibrosis.
  • In non-contained disease, chronic progressive pneumonia with early tubercles 1-2 mm diameter, central necrosis with surrounding epithelioid cells and only scarce tubercle organisms. Later more extensive coagulative necrosis, greater numbers of organisms, with lesions coalescing giving 3-4mm diameter tubercles.
  • May be localised spread by extension into bronchioles.
  • May be haematogenous spread (through the blood) resulting in spread to some organs such as the kidney or to generalised miliary TB.
  • May be miliary lung lesions in the end stages.
  • In infected bite wounds: abscesses or extensive ulceration.
    • May be associated acute tuberculous pneumonia.
(B209.21.w21, J60.2.w2, J3.105.w4, P27.5.w5)
HEDGEHOGS

Gross Pathology in Erinaceus europaeus - West European Hedgehog:

  • Gross pulmonary lesions. (J10.43.w1)
    • Lungs: grey nodules, about 2-6 mm diameter, spherical or with irregular borders, sometimes bulging from the pleural surface, firm and homogenous when incised. (J10.43.w1)
    • Pharyngeal lymph node (one individual): enlarged, with normal tissue replaced by yellow caseous material with some mineralisation. (J10.43.w1)
    • Kidney (one individual): abscess in the medulla and pelvis causing thinning and atrophy of the cortex. (J10.43.w1)
    • Prostate (one individual): enlarged and abscessated with extensive yellow caseous foci. (J10.43.w1)
    • Liver (one individual: Pin-point grey foci visible on the surface. (J10.43.w1)
  • Following experimental intraperitoneal or subcutaneous inoculation of hedgehogs (Erinaceus europaeus - West European Hedgehog) with the "bovine virus" (probably Mycobacterium bovis), the spleen often contained numerous bacilli, while "the lungs, liver and kidneys were also reported to have lesions but less bacilli". (J18.53.w1)
  • Following experimental infection with Mycobacterium bovis:
    • In six animas injected parenterally, caseous lesions in local lymph nodes and small non-caseous granulomas in the liver, spleen, kidney and lungs were noted. 
    • Following oral dosing of ten animals, four failed to develop gross or microscopic lesions. The remaining six animals developed in four cases caseous lesions in the retropharyngeal or cervical lymph nodes, in three cases small grey lesions in the lungs, in one case haemorrhagic lesions of the intestines and in one case small calcified omental lesions. Some mesenteric lymph nodes contained acid-fast organisms, but without associated gross lesions. 

    (J10.43.w1)

  • No gross (macroscopic) lesions were visible in the lungs, liver, kidney, spleen, mesenteric lymph nodes or mesentery of five hedgehogs following experimental intraperitoneal inoculation with Mycobacterium bovis. (J127.63.w1)
Histopathological changes in Erinaceus europaeus - West European Hedgehog:
  • Renal: 
    • Kidneys had a few microscopic lesions, "a small, poorly defined focus comprising a few necrotic cells including polymorphonuclear leucocytes, bordered by small numbers of epithelioid cells." Also occasional acid-fast bacilli in the kidneys without associated pathological changes in the tissues (following experimental intraperitoneal inoculation with Mycobacterium bovis). (J127.63.w1)
  • Pulmonary:
    • Pulmonary lesions described as being of the ""grey hepatization" type" in a hedgehog (Erinaceus europaeus - West European Hedgehog) after eleven weeks in captivity. (J46.1933.w1)
    • Pulmonary and intestinal tuberculosis recorded. (J46.1936.w1)
    • Focal, locally-infiltrative, non-encapsulated, non-caseating granulomatous inflammation of the lungs. Destruction of the normal parenchyma by dense accumulations of macrophages (dominant cell type) and leucocytes; numerous Langhans' type multinucleated giant cells throughout the area of reaction.. (J10.43.w1)
  • Other:
    • Occasional acid-fast bacilli in various organs, without associated pathological changes in the tissues (following experimental intraperitoneal inoculation with Mycobacterium bovis). (J127.63.w1)
ELEPHANTS Gross pathology reported in affected Elephas maximus - Asian Elephant:
  • Lungs:
    • Solid granulomatous pneumonia. (P1.1981.w1, P6.4.w2)
    • Extensive areas of consolidation and distended septa. (J196.60.w1)
    • Collapsed lung. (J4.183.w2)
    • Chronic tuberculous lesions of up to 7 cm diameter, with central caseous material surrounded by dense fibrous tissues. (J3.93.w1)
    • Numerous small tubercles distributed in the lung parenchyma and subpleurally. (J3.93.w1, J12.5.w3, J46.1875.w1, J196.60.w1, P6.4.w2)
    • Bronchioles and alveoli contained calcified and caseous material. (J42.38.w1)
    • Pulmonary abscess. Mycobacterium tuberculosis and Pseudomona aeroginosa was isolated. (J4.183.w2)
    • Regions of compensatory emphysema. (J196.60.w1)
    • Thickened pleura. (J3.93.w1, J12.5.w3)
  • Thoracic lymph nodes: Lung-associated lymph nodes were enlarged, caseated and nodular. (J2.32.w1, J196.60.w1, P6.4.w2)
  • Heart:
    • Enlarged, with right ventricular dilatation. (J3.93.w1)
    • Pericardial effusion. (J2.32.w1, J196.60.w1)
    • Thickened pericardium. (J4.183.w2)
  • Liver: 
    • Enlarged. (J42.38.w1)
    • Granulomatous lesions. (P1.1981.w1)
  • Spleen: 
    • Enlarged. (J42.38.w1)
    • Granulomatous lesions. (P1.1981.w1)
  • Kidneys: Pale. (J4.183.w2)

Histopathology reported in affected Elephas maximus - Asian Elephant:

  • Lungs: 
    • Hematoxylin and eosin staining
      • Pulmonary oedema with acute to chronic tuberculous lesions and presence of Langerhans type giant cells. Acute lesions tuberculous lesions consisted of caseous area surrounded by fibrous tissue. Some healing areas presented dense fibrosis and calcification. (J3.93.w1)
      • Alveoli filled with necrotic eosinophilic and homogenous material. Numerous rounded mononuclear cells were present in the alveoli and the interstitial tissue. Lymphocytes, plasma cells and phagocytic cells were present. Endothelial cells were found outside the alveoli. No Langerhans type giant cells were seen. (J196.60.w1)
      • Small granulomas composed of macrophages and epithelioid cells surrounded by connective tissue. Eosinophils and lymphocytes were abundant, and a few plasma cells and multinucleated giant cells were seen. Larger tubercles were caseous and mineralised. (J4.183.w2)
      • Granulomatous consolidation of the tissue consisted of epithelioid cells surrounded by macrophages, eosinophils and lymphocytes. Multiple small foci of caseous necrosis and microabscesses within the consolidated areas. Calcification was mild. No Langerhans type giant cells were seen. (P6.4.w2)
    • Ziehl-Neelsen's staining: 
      • A stained tissue section revealed acid-fast rods, both within macrophages and epithelioid cells and outside cells. A smear of the caseous material showed large numbers of acid-fast bacilli. (J3.93.w1)
      • Large numbers of acid-fast organisms morphologically resembling Mycobacterium tuberculosis. (J196.60.w1)
      • Acid fast bacilli were seen occasionally in caseous granulomas. (J4.183.w2, P1.1981.w1)
      • Large necrotic granulomas with numerous acid fast bacilli were present in the trachea and lungs. (J2.32.w1, P6.4.w2)
  • Liver: Centrilobular areas were atrophied and hepatocytes were filled with haemosiderin. (J4.183.w2)
  • Kidney: Small granulomas composed of macrophages and epithelioid cells surrounded by connective tissue. Eosinophils and lymphocytes were abundant, and a few plasma cells and multinucleated giant cells were seen. The kidneys were atrophied, with loss of tubules and moderate interstitial fibrosis. Some tubules contained protein or cellular casts, others contained mineral material ,and in some cases the epithelium was necrotic. (J4.183.w2)
BEARS
LAGOMORPHS Gross pathology 

Tan to grey caseous nodules may be seen in various organs particularly the lungs, bronchial lymph nodes, liver and kidneys. (B614.8.w8)

  • Gastrointestinal tract: caseous nodules may be seen particularly at sites of lymphoid tissue. The mucosa overlying these nodules may be ulcerated. (B614.8.w8)
  • Skeletal: caseous necrosis of bone with areas of osseous proliferation. (B614.8.w8)
  • Central nervous system: caseous nodules may be seen in the cerebrum, medulla, and leptomeninges. (B614.8.w8)
  • Ocular: lesions such as uveitis have also been seen. (B614.8.w8)
  • Pulmonary: pneumonia. (B602.17.w17)

Histopathology

  • Foci of caseous necrosis encircled by epithelioid macrophages, lymphocytes, and fibrous tissue. (B614.8.w8)
  • Multi-nucleated giant cells are usually scarce and mineralisation of lesions is uncommon. (B614.8.w8)
  • Acid-fast organisms can be found in histological sections of the lesions or in impression smears. (B614.8.w8)
FERRETS Usually, Mycobacterium tuberculosis infection produces only localised lesions in ferrets, whereas Mycobacterium bovis infection is more likely to be disseminated. (B627.14.w14)

Gross pathology 

Tuberculous lesions may be found in many organs; localised lesions may be found in the liver, spleen, mesenteric lymph nodes, peritoneum and brain. (J195.11.w2)
  • Muscular: Adductor muscles yellow and soft. (B501.12.w12)
  • Hepatic: Hepatomegaly. (J4.195.w5)
  • Splenic: Splenomegaly. (J4.195.w5)
  • GIT:  
    • Multifocal areas of necrosis: (B501.12.w12)
    • Intestinal nodule formation. (J4.195.w5) 
  • Lymph nodes: mesenteric lymph nodes enlarged. (B501.12.w12)

In feral ferrets in New Zealand. (J10.43.w2)

  • Respiratory: only 2.9% of lesions. (J10.43.w2)
  • Lymph nodes: Mesenteric lymph node lesions (34.5% of all lesions and 60.4% of all single-site lesions). Other lymph nodes less commonly (retropharyngeal 17% of lesions; prescapular 16.4%). Peripheral lymph node involvement was noted in 24.5% of cases. (J10.43.w2)

In ferrets experimentally infected by the oral route: (J42.123.w1)

  • Lungs, liver, spleen, kidney: No gross lesions at 20 weeks post infection.
  • Mesenteric lymph nodes: lesions >1 mm diameter visible in 3/9 ferrets.

Histopathology

Tubercles with extensive caseation, sometimes liquefaction; cellular response limited. (J195.11.w2)

  • Gastrointestinal tract: Multifocal areas of coagulative necrosis: (B501.12.w12)
  • Histiocytes with acid-fast bacilli may be seen in the abdominal organs. (B501.12.w12)
  • Minimal cellular reactions with numerous acid-fast bacilli in the lesions produced by Mycobacterium bovis. (B627.14.w14)
  • Zeihl-Neelsen staining of sections or smears may reveal numerous acid-fast bacilli. (J195.11.w2)

In feral ferrets in New Zealand. (J10.45.w4)

  • Hepatic: granulomas present in the liver commonly. (J10.45.w4)

In ferrets experimentally infected by the oral route: (J42.123.w1)

  • Mesenteric lymph node: 9/9 had microscopic lesions (infiltration by macrophages, extensive necrosis of tissue). (J42.123.w1)
  • Ziehl-Neelsen staining: Acid-fast organisms in the mesenteric lymph nodes of 8/9 ferrets. (J42.123.w1)
BONOBOS/GREAT APES There are relatively few published pathological descriptions of tuberculosis in great apes. (B569.w4) Chronic lung lesions are the most common findings. (B680.w1) The hilar nodes are commonly involved associated with lung lesions. Disseminated infection also occurs. (P1.1974.w4)
Gross pathology

In primates

  • Any affected organ: yellow-while caseous granulomas, sometimes confluent. (D390.96.w96)
  • Pulmonary: Pneumonia may be evident. (D390.96.w96)

In great apes

  • Disseminated: Tuberculous lesions in the lungs, liver, spleen, kidneys, adrenals, intestines and peritoneum. (B569.w4)
  • Respiratory: Caseous lesions in the lungs. (B569.w4)
  • GIT: In one chimpanzee, numerous flattened caseous lesions in the peritoneum, matting the abdominal organs together. (B569.w4)
  • Lymph nodes: Lymph nodes associated with affected tissues may be enlarged and are sometimes caseous. (B569.w4)
  • Reproductive: large tuberculous masses filling the vagina and involving the cervix in one Pan troglodytes - Chimpanzee (also with gastrointestinal lesions). (B569.w4)
Histopathology

In primates

  • Tuberculous granulomas with relatively few Langhans' giant cells and little or no calcification. (D390.96.w96)
  • Pulmonary: Giant cellular pneumonia. (D390.96.w96)

In great apes

  • Granulomas with giant cells; acid-fast bacilli present in the lesions.
  • Granulomas may coalesce.
  • Infiltration of lymphocytes around pulmonary blood vessels.
  • Alveoli filled with reticuloendothelial cells; occasional giant cells found.

(B569.w4)

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Human Health Considerations

  • Potential zoonosis. (P5.39.w3)
  • Notifiable disease in the UK
  • Human tuberculosis caused by Mycobacterium tuberculosis is the most important infectious cause of death worldwide, affecting approximately one third of the world population and killing three million people each year. (J64.20.w1)
    • Outbreaks of Mycobacterium tuberculosis have been recorded in environments such as hospitals, schools, factories, homeless shelters, prisons, circuses and exotic animal facilities. (J84.8.w15)
    • The most important sources of human tuberculosis have been non-human primates. (J64.20.w1)
    • Most recently, Mycobacterium tuberculosis has been reported as a zoonotic disease of Elephas maximus - Asian Elephant in the USA. (J64.20.w1)
    • Zoo gardens are a particular public health concern due to the close contact between TB-susceptible animals and humans, specifically animal handlers and visitors. (J4.170.w1, J84.8.w15)
    • Transmission to humans occurs most commonly through aerosols. (P1.1997.w2)
    • Only animals with active disease present a risk of spreading the disease to humans. (P1.1997.w2)
  • Non-tuberculous species of mycobacteria may also cause infection in man, particularly in immunosuppressed individuals. (P1.1997.w2)
  • Mycobacterium elephantis, a newly described elephant isolate, have been isolated in humans showing signs of diseases but with no history of contact with animals. (J93.40.w3, J93.41.w5)
  • Active disease in humans is diagnosed by culture and identification, by detection of thoracic radiographic lesions consistent with tuberculosis or by PCR and other nucleic acid (DNA, RNA) amplification methods. Tuberculin skin test only detects tuberculosis infection. Other indirect methods, such as ELISA and Lymphocyte transformation (Blood Tuberculosis test) cannot differentiate infection from active disease. (P1.1997.w2)
  • In human medicine a combination treatment of isoniazid, ethambutol and rifampin is commonly used. Treatment is nine months with rifampin included and 18 to 24 months without it. (B88)
  • Bacillus of Calmette-Guerin (BCG) vaccination has been used in humans in some high risk areas. (B101)
Elephants
  • In 1973, three cases of tuberculosis were diagnosed in humans from the  elephant keepers' community in Ceylon. However, no investigations were pursued to compare the human strain with the elephant isolate. (J3.93.w1)
  • Phage typing of mycobacteria was used to compare the Mycobacterium tuberculosis isolate in a circus Elephas maximus - Asian Elephant with the one from her infected keeper. The phage types were different and therefore it is likely that both elephant and keeper were infected from different sources. (J353.125.w1)
  • Between 1994 and 1996, Mycobacterium tuberculosis was isolated from four elephants. These animals came from an exotic animal farm in Illinois. All the employees in contact with the elephants were tested. Of 22 handlers screened on the farm, 11 had a positive tuberculin test and one handler had a positive culture result. DNA fingerprinting demonstrated that the isolate from the four elephants and the handler were the same strain. (J84.4.w1)
  • Between 1997 and 2000, Mycobacterium tuberculosis was diagnosed in two Elephas maximus - Asian Elephant and four more animals from two different species in Los Angeles Zoo. DNA tests suggested recent transmission. An investigation found no active tuberculosis of the zoo employees, however, tuberculin skin test conversions in humans were significantly associated with training elephants and attending an elephant necropsy. (J84.8.w15)
Measurements to prevent and decrease zoonotic spread of tuberculosis include:
  • Regular human testing of handlers or keepers. (J84.8.w15)
  • Handlers should wear HEPA filtered masks when working close to known positive elephants and during procedures that generate aerosols in elephant herds with a previous history of the disease or exposure. Handlers should also wear protective clothing such as gloves, gowns and adequate footwear. (P1.2002.w1)
  • All new personnel should be tested before contact with elephants. (J54.19.w4)
  • Any employee with active tuberculosis should not be in contact with elephants. (J54.19.w4)
  • Animals should be kept in well ventilated enclosures. (P1.2002.w1)
  • Any elephants showing unexplained weight loss, coughing or trunk discharge should be considered highly suspicious. (J84.8.w15)
  • Public health measurements include contact tracing and notification. (J84.8.w15)
  • Zoos should establish protocols for elephant-visitor interactions. (J54.19.w4)
  • Active and effective treatment of infected staff and animals. (J84.8.w15)
  • Ensure there are areas with access to ultraviolet light - either direct sunlight or with UV ceiling lights. (P1.1997.w2)

Also see: D303 - Guidelines for the control of tuberculosis in elephants 2003 - Full text provided

Ferrets
  • Due to zoonotic risks (P1.1997.w11, B631.29.w29), ferrets should be euthanased if positive for this disease. (J215.23.w1, B627.14.w14, B628.11.w11)
  • Infected ferrets may be asymptomatic or show vague clinical signs; this may increase the potential for spread of the disease to humans and other animals. (B627.14.w14)
  • There is a reported case of a human having a swollen hand after being bitten by a ferret with tuberculosis, resulted in a swelling of the right palm. This developed into a swelling above the wrist joint and impaired mobility of the fingers. A Mycobacterium sp. was isolated, but treatment did not eradicated this as infection recurred. This highlights the potential zoonotic risks of this disease. (B627.14.w14)
Great Apes
  • Tuberculosis in primates is a zoonotic risk to humans. (D390.96.w96)

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Susceptibility / Transmission

General information on Susceptibility / Transmission

Susceptibility:
  • Typically affects captive and domestic animals. (B88)
  • In wild populations, tuberculosis is rarer. (B88)
  • Immature individuals often develop more severe lesions than older ones. (B88)
  • Some animal breeds may be more susceptible than others, e.g. zebu cattle are more resistant than European breeds. (B88)

Transmission:

  • Sources include:
    • Aerosol or droplets containing tubercle bacilli. (B88, B58.22.w22, J4.170.w1)
    • Feed or water contaminated with urine, faeces, or exudates from an infected animal. (B88, B58.22.w22)
    • Milk from infected mammary glands. (B88)
    • Fomites such as thermometers, cages, masks and containers used for contaminated food or water. (B58.22.w22)
  • Crowding appears to increase the risk the risks of transmission. (B58.22.w22)
BADGERS
  • Tuberculosis in badgers is considered important due to the potential for transmission to cattle. (B209.21.w21)
  • Infection is often dormant; active infection may be stress-related. (P27.5.w5)

Transmission in Meles meles - Eurasian Badger:

  • Excreted in sputum, urine, faeces, discharges from infected bite wounds, discharges from submandibular abscesses.
  • Inhalation, assisted by close contact within sets is thought to be the main route of infection.
  • Infection is also transmitted by bite wounds.
  • (B209.21.w21)
HEDGEHOGS Erinaceus europaeus - West European Hedgehog:
  • Direct transmission hedgehog-to-hedgehog is considered unlikely due to the solitary habits of this species. However, hedgehogs scavenge carcasses and dead hedgehogs may in turn be eaten by scavengers. Such scavenging may allow transmission to and from individual hedgehogs. (J10.48.w1, J195.26.w1)
  • Hedgehogs in the UK to date have not been found infected with Mycobacterium bovis. (P23.1999S.w8)
ELEPHANTS Susceptibility:
  • Tuberculosis in elephants appears to be a disease of  captivity. (B336.66.w66, J46.1875.w1)
  • It has been suggested that tuberculosis may occur in captivity as a result of malnutrition, parasitism and overwork. (J196.60.w1)
  • Mycobacterium tuberculosis has been the microorganism identified in all elephant cases reported from which isolates were obtained. (J64.20.w1)
  • Elephants are likely to contract the disease from infected humans. (J64.20.w1)
  • Tuberculosis generally affects Elephas maximus - Asian Elephant, and seems to be uncommon in Loxodonta africana - African Elephant. This may only reflect the closer association of the first species with man. (J64.20.w1)

Transmission:

  • Infection is likely to occur subsequent to contact with infected humans. (J64.20.w1, J84.4.w1)
  • Exposure to farm infected animals. (J98.350.w2)
  • The transmission of a shared strain of Mycobacterium tuberculosis isolated from an elephant and its handler has been documented. (J84.4.w1)
  • Between 1997 and 2000, Mycobacterium tuberculosis was diagnosed in two Elephas maximus - Asian Elephant and four more animals from two different species in Los Angeles Zoo. DNA tests suggested recent transmission. An investigation found no active tuberculosis of the zoo employees, however, tuberculin skin test conversions in humans were significantly associated with training elephants and attending an elephant necropsy. (J84.8.w15)
  • The method of transmission of the disease between elephants is currently undetermined. However, it probably occurs by aerosol of contaminated respiratory droplets. (B336.66.w66)
BEARS
LAGOMORPHS
Susceptibility
  • Tuberculosis is a rare disease in rabbits. However, in the early 1900s there were a large number of reports of tuberculosis in rabbits and it is thought that this may have be due to the common practice of feeding cow's milk to rabbits to promote growth. This practice has since been discontinued and along with control programs for bovine tuberculosis, is likely to have contributed to the decline in the prevalance of this disease in rabbits. (B614.8.w8)
Transmission
  • Inhalation: inhaled organisms will colonise the lungs and the bronchial lymph nodes. Organisms may also be coughed up and swallowed resulting in a second exposure via the gastrointestinal tract. (B614.8.w8)
  • Ingestion: ingested organisms will penetrate the gastrointestinal epithelium and then colonise the intestinal wall or the mesenteric lymph nodes. (B614.8.w8)

In either method of transmission, organisms may occasionally be able to enter the systemic circulation and disseminate around the body. (B614.8.w8)

FERRETS
Susceptibility
  • Ferrets are highly susceptible to mammalian tuberculosis. (P20.1992.w7, J4.195.w5, B627.14.w14, B628.11.w11)
  • Farm and hunting ferrets have been reported with tuberculosis. (J215.23.w1)
  • Ferrets are susceptible to various mycobacteria including Mycobacterium bovis, Mycobacterium tuberculosis and Mycobacterium microti; the most common organism involved in ferrets is Mycobacterium bovis. (B627.14.w14, B631.29.w29)
  • Occurs in all ages of ferrets. (J195.11.w2)
Transmission
  • Inhalation, ingestion and wound infections are ways in which the organism can be transmitted. (J4.195.w5, B501.12.w12, B628.11.w11)
  • Ingestion of raw meat products/byproducts, milk or infected prey is thought to be a route of infection. (P20.1992.w7, J215.23.w1, J195.11.w2)
    • Tuberculosis was reported in ferrets when they were being fed raw meat/meat byproducts and milk; reductions of TB in the domestic livestock population have reduced this source of infection for ferrets. (B627.14.w14)
  • Experimental tests have shown that tuberculosis can be transmitted through infected milk and carcases. (J4.195.w5, B627.14.w14)
  • Feral ferrets in New Zealand have been reported to transfer the disease to domestic livestock and humans. (B631.29.w29)
  • In feral ferrets in New Zealand, initial lesions tend to be associated with the gastrointestinal tract, suggesting oral exposure. Sampling showed that Mycobacterium bovis could be isolated from the oral cavity (15/64, 23%), faeces (10/63, 16%), tracheobronchial lavage (4/64, 6%), urine (2/29, 7%) and mammary gland (1/8, 12.5%). Despite the oral excretion, intraspecific infection via biting (wounds) appears to be minor. (J10.45.w5)
BONOBOS/GREAT APES
  • All nonhuman primates (B644.2.w2) including all of the apes are susceptible to tuberculosis. (B214.3.1.w18)
  • Infection is by direct contact including respiratory transmission and bites, and indirect via contaminated food and fomites. (B680.w1)
  • Transmission is via the respiratory tract, gastrointestinal tract or from bites. Both primary respiratory and primary gastrointestinal lesions have been seen in the great apes. (B569.w4)
  • Aerogenous (respiratory) transmission is the main route in primates, with oral transmission much rarer. (D390.96.w96)

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Disease has been reported in either the wild or in captivity in:

  • A wide range of mammal species.

Badgers:

Hedgehogs:

Elephants:

Elephas maximus - Asian Elephant

  • Not recorded in free-living Elephas maximus - Asian Elephant. (J64.20.w1)
  • In 1875, a case of tuberculosis was described in a 25-year-old Elephas maximus - Asian Elephant and associated with the conditions of captivity in London's cold climate. (J46.1875.w1)
  • Presumptive diagnosis of tuberculosis based on the pulmonary histopathological lesions, numerous numbers of acid fast organism resembling Mycobacterium tuberculosis and numerous endothelioid cells in the alveolar exudates, was reported in a 25-year-old captive male elephant. (J196.60.w1)
  • Mycobacterium tuberculosis was isolated from a 24-year-old domesticated Elephas maximus - Asian Elephant. (J3.93.w1)
  • Mycobacterium tuberculosis was isolated post mortem from a 35-year-old female circus Elephas maximus - Asian Elephant. (J353.124.w1, P1.1981.w1)
  • Two working elephants from Kerala were found to be infected with Mycobacterium tuberculosis. (P502.1.w5)
  • Mycobacterium tuberculosis was isolated from an 11-year-old circus Elephas maximus - Asian Elephant in the USA. Pseudomonas aeruginosa was isolated from a lung abscess in the same animal. (J4.183.w2)
  • Between 1996 and 1997, Mycobacterium tuberculosis was isolated from several Elephas maximus - Asian Elephants in the USA. (P1.1997.w4)
  • Mycobacterium tuberculosis was isolated from two Elephas maximus - Asian Elephants in Los Angeles Zoo in 1997. One of the animals died of salmonellosis. (J2.32.w1, J84.8.w15)
  • From 1996 to 2000, a study of tuberculosis in North America based on 539 elephant samples revealed a estimated prevalence of 3.3%. Mycobacterium tuberculosis was isolated in 17 elephants from eight different herds in Illinois, California, Arkansas, Missouri and Florida. Elephants from five of the herds had been in contact in the past. (J54.19.w4)
  • From 1996 to 2002, a more recent study of tuberculosis in North America based on 539 elephant samples has revealed a estimated prevalence of 4.8%. Mycobacterium tuberculosis was isolated in 25 Elephas maximus - Asian Elephants and Mycobacterium bovis was isolated in one Loxodonta africana - African Elephant. (P1.2002.w1)
  • In 2002, Mycobacterium tuberculosis was isolated on trunk wash in two female Elephas maximus - Asian Elephants in a Swedish zoo. (P6.4.w2)

Loxodonta africana - African Elephant

Bears:

  • Mycobacterium bovis was cultured from the lymph nodes of a free-living 1.5 year old male Ursus americanus - American black bear from Michigan, United States. The animal did not showed any gross pathological of histopathological lesions characteristic of tuberculosis. The bear came from an area where the disease is known to be endemic in free-ranging Odocoileus virginianus - White-tailed deer. (J1.37.w6)
  • Using an ELISA, a single tested bear had a titre of <5 (in the negative range, based on a comparison of result from various TB-positive and TB-negative animals). (P1.1990.w1)
  • There is one report of fatal tuberculosis in an Ursus maritimus - Polar bear at a Swiss zoo. (P6.1.w5)

Lagomorphs:

  • Oryctolagus cuniculus domesticus - Domestic European rabbit: Tuberculosis was recognised in rabbits in 1884 by Robert Koch. There were a large number of cases reported in the 1900s but tuberculosis is now a rare disease in this species. Most cases have been attributed to Mycobacterium bovis but Mycobacterium tuberculosis has also been isolated. (B614.8.w8)
  • Both Mycoacterium bovis and Mycobacterium tuberculosis have been reported as causes of pneumonia in rabbits. (B602.17.w17)

Ferrets:

  • Tuberculosis has been reported in domestic ferrets. (P20.1992.w7)
  • In feral ferrets in New Zealand. (J10.43.w2 J10.45.w4, J10.45.w5)
  • Mycobacterium bovis infects 32% of feral ferrets in New Zealand. (B631.29.w29)
  • Mycobacterium bovis was isolated from 1.25% of ferrets (268/21,481), 2004-2007 in wildlife areas (and from 2/1,056 stoats). (J238.132.w2)

Bonobos/Great Apes

Further information on Host species has only been incorporated for species groups for which a full Wildpro "Health and Management" module has been completed (i.e. for which a comprehensive literature review has been undertaken). Host species with further information available are listed below:

Host Species List

(List does not contain all other species groups affected by this disease)

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Disease has been specifically reported in Free-ranging populations of:

Badgers:

Bears:

Ferrets:

  • Mycobacterium bovis infects 32% of feral ferrets in New Zealand. (B631.29.w29)
  • Mycobacterium bovis was isolated from 1.25% of ferrets (268/21,481), 2004-2007 in wildlife areas (and from 2/1,056 stoats). (J238.132.w2)

Further information on Host species has only been incorporated for species groups for which a full Wildpro "Health and Management" module has been completed (i.e. for which a comprehensive literature review has been undertaken). Host species with further information available are listed below:

Host Species List

(List does not contain all other species groups affected by this disease)

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Environment/Geography

General Information on Environmental Factors/Events and Seasonality

  • A case of tuberculosis in a 25-year- old Elephas maximus - Asian Elephant in 1875 was considered to be associated with the conditions of captivity in London's cold climate. (J46.1875.w1)

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Regions / Countries where the Infectious Agent or Disease has been recorded

  • Worldwide.

In Meles meles - Eurasian Badger:

  • Europe, including Eire, Switzerland and the UK. (B209.21.w21, J3.149.w1, J60.2.w2)

In Elephants:

In Ferrets:

  • Ferrets in Europe, maintained for research between the years 1929 and 1953, were commonly diagnosed tuberculosis positive. (J4.195.w5, B627.14.w14)
  • In New Zealand, farmed ferrets have been recognised with this disease. (J4.195.w5, B627.14.w14, B631.29.w29)
  • Pet ferrets in the USA have been diagnosed with a Mycobacterium sp. infection. (B627.14.w14)

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Regions / Countries where the Infectious Agent or Disease has been recorded in Free-ranging populations

  • 32% of feral ferrets have been found to carry Mycobacterium bovis in New Zealand. (B631.29.w29)

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General Investigation / Diagnosis

General Information on Investigation / Diagnosis

  • Active disease in humans is diagnosed by culture and identification, by detection of thoracic radiographic lesions consistent with tuberculosis, or by PCR and other nucleic acid amplification methods. The tuberculin skin test only detects tuberculosis infection. Other indirect methods, such as the ELISA and lymphocyte transformation test (blood tuberculosis test) cannot differentiate infection from active disease. (P1.1997.w2)

Clinical and pathological findings

  • Consider tuberculosis in the differential diagnosis list for any individual with chronic weight loss or emaciation, weakness, dyspnoea, cough, or enlarged lymph nodes. (B519.2.w2)
  • Clinical signs are of limited value in diagnosis. (B58.22.w22)
  • Note: Many infected animals are asymptomatic until a late stage in the disease. (B519.2.w2)
  • Presumptive diagnosis may be made on post-mortem examination from gross and microscopic pathology. (B58.22.w22, B64.27.w4, P1.1990.w2)

Further direct testing

  • Smears of specimen sediment or tissue are stained with Ziehl-Neelsen for detection of acid-fast bacilli, or with auramine-rhodamine where fluorescence microscopy is available. Positive result should be confirmed by culture. (B88, J4.170.w1)
  • Isolation and identification from tissues and other specimens e.g. sputum, urine, faeces. (B88, B22.11.w8, B58.22.w22, B214.3.7.w3, J4.193.w1, P1.1990.w2)
  • Isolation and identification is the definitive method to confirm tuberculosis infection in animals. (B58.22.w22, P1.1997.w3)
  • Nucleic acid tests based on amplification and detection of the mycobacterial nucleic acids are highly specific for the TB-complex organism but cannot differentiate between species. (P1.1997.w3)
  • Spoligotyping, a special form of PCR, has been developed for formalin-fixed tissues to differentiate Mycobacterium tuberculosis from other mycobacteria in histological sections of tuberculous lesions. (J64.20.w1)

Indirect testing

Tests are available based on either cell-mediated immunity reactions or serology. (B519.2.w2)

  • The intradermal skin test or tuberculin test is based on the results of delayed-type hypersensitivity skin responses to purified protein derivative (PPD) tuberculins prepared from Mycobacterium bovis or Mycobacterium avium. Old tuberculin prepared from Mycobacterium tuberculosis  has been used nonhuman primates. When the tuberculin is administered intradermally, subcutaneously or conjunctivally, a local inflammatory reaction is detected in infected animals within 72 hours. The dose used in mammals is 0.1 mL of a suitable PPD tuberculin (containing 50,000 tuberculin U/ml). False-negatives may occur in animals recently infected and in advance cases. (B88, B22.11.w8, B58.22.w22, J4.193.w1, P1.1990.w2)
  • ELISA is recommended for supplemental use to detect tuberculous animals with progressive disease. (B22.11.w8)
  • ELISA is a valuable diagnostic tool in zoo animals. (P1.1990.w1, P1.1990.w2)
  • Antigen 85 immunoassay detects a serum protein complex (Ag85) produce by mycobacteria in the early stages of infection. This method has been suggested to be useful for nonhuman primates and captive hoofstock species. (P503.1.w1)
  • Lymphocyte blastogenic assays (LBAs) have been used in nonhuman primates and other species. (B22.11.w8)
  • A blood TB test is based on two assays, a lymphocyte transformation assay and an ELISA to quantify antibody formation against antigens. (P1.1997.w3)
  • Gamma interferon test measures the release of the cytokine gamma interferon after exposure of peripheral blood mononuclear cells to mycobacterial antigens, commonly PPD-bovis. (P1.1997.w3)
BADGERS

Diagnosis in Meles meles - Eurasian Badger:

  • Post-mortem examination and culture of bacteria from tissue samples.
    • This is the most reliable method of identifying Mycobacterium bovis infection in badgers (J3.149.w1)
  • Isolation from e.g. sputum, urine, faeces (requires several samples taken at different times to increase sensitivity of diagnosis).
  • Skin testing is not sufficiently sensitive.
  • ELISA on blood samples from live animals.
    • Neither sensitivity (40.7%) nor specificity (94.3%) is as high as would be preferred.
    • [For any test an increase in sensitivity reduces the chance of false negative results (infected animals wrongly classified as uninfected). An increase in specificity reduces the chance of false-positive results (uninfected animals wrongly classified as infected)].
    • Sensitivity is higher in males than in females and in animals with gross lesions.
  • (J3.149.w1, B209.21.w21)

Further information regarding ELISA and testing protocols:

  • The use of the ELISA blood test is extremely important for decision making when badger cubs are being hand-reared and may be released at a site distant from their origin.
  • At present, the recommended procedure is test by ELISA blood samples from all hand-reared cubs three times between their arrival at a rehabilitation centre and their release six to nine months later.
  • Using this protocol an animal may be classified as infected if one of the three test results is positive.
  • This approach increases the sensitivity of the test to 79.2% although with a concomitant decrease in sensitivity to 83.9%. Repeating the test on blood samples taken from a given individual on more occasions gives a further increase in sensitivity for each additional blood test, however while an increase from one to two tests increases the sensitivity by 24.1% and increasing to three tests gives an additional 14.3% sensitivity, a fourth test would increase the sensitivity by only a further 8.3%. Additional tests also continue to give a decrease in specificity (i.e. more false positive results with uninfected animals wrongly classified as infected).
  • For animals with progressive lesions (potentially infective animals) the sensitivity of a single ELISA test has a sensitivity of 60%; carrying out the test three times as above increases the sensitivity for detecting such animals to approximately 94%.

(J3.149.w1)

HEDGEHOGS --
ELEPHANTS
  • Note: a thoracic radiographic study is not feasible in adult elephants. (B450.16.w16)
  • Presumptive diagnosis of tuberculosis based on the pulmonary histopathological lesions, numerous numbers of acid fast organism resembling Mycobacterium tuberculosis and numerous endothelioid cells in the alveolar exudates, was reported in a 25-year-old captive male. (J196.60.w1)
  • Ziehl-Neelsen staining of clinical or histopathology specimens for detection of acid-fast bacilli. (P1.1997.w4)
  • In the past, tuberculin testing has been used as a screening test of tuberculosis in elephants. (B450.16.w16, J2.32.w1, J357.11.w1, J358.19.w1) 
    • 0.1ml of bovine purified protein derivative tuberculin is administered intradermally in the caudal fold or base of the ear. The thickness of the skin is measured after 48 and 72 hours. (B450.16.w16, J2.32.w1, J357.11.w1, J358.19.w1)
  • The tuberculin skin test is unreliable for the diagnosis of tuberculosis in elephants. Results of this test correlate poorly with serological assays and mycobacterial culture: (J54.19.w4)
    • An ELISA has been developed, using protein A labelled with horseradish peroxidase for detecting antibodies in tuberculous elephants, among other zoo species. In this study, some tuberculin negative animals had suspicious ELISA results. There were no animals with positive tuberculin reactions and negative ELISA results. (J13.41.w1)
    • A correlation study of several diagnostic tools in large zoo animals showed that both species of elephant may be nonspecific reactors  to the intradermal tuberculin injection, as these animals had a positive tuberculin response but the ELISA tests were negative and tracheal culture of one of the elephants was negative. (J4.179.w2)
    • Tuberculin testing and passive haemagglutination test (PHA) were studied in elephants to evaluate their efficacy for screening tuberculosis in wild captive animals. Both tests were found not to be reliable. For the tuberculin test, 0.1 ml of purified protein derivative (PPD) tuberculin (mammalian) was injected intradermally on the base of the dorsal aspect of the ear and skin fold measurements were recorded before and 72 hours after injection. The PHA test was performed for the detection of antibodies in the serum. Elephants that reacted to the tuberculin test had no significant PHA titers and those elephants with high PHA titers were not positive for the tuberculin test. (J12.76.w1)
    • In some elephants given a series of tuberculin skin tests, the results change from positive to negative, and then back to positive. (J98.350.w2)
    • Two elephant cases of Mycobacterium tuberculosis infection, confirmed on trunk wash culture, were tuberculin skin test negative or inconclusive. Both animals seroconverted and showed a weak positive ELISA antibody titer. (P6.4.w2)
    • Mycobacterium tuberculosis was isolated post mortem from a captive elephant that was negative to the skin test before death. (J4.183.w2)
  • A multiple-antigen ELISA has been recently documented as a valuable screening test of Mycobacterium tuberculosis in elephant herds. The study evaluated the seroreactivity to six antigens of 47 elephant serum samples (32 Asian and 15 African elephants). The specificity and sensitivity of this test were both 100% (95% confidence interval 91.9%-100% and 54.4%-100%, respectively). (J2.31.w1, J2.32.w1)
  • Nucleic acid amplification test (NAAT). Laboratories employ the Gen- Probe Amplified Mycobacterium tuberculosis Direct Test (MTD) that has been used in elephants and showed a sensitivity of 66.6% and specificity of 96.2%. However, validation of this test in elephants has not been reported. (J2.32.w1, J54.19.w4)
  • Blood TB test (BTB). Whole elephant blood is submitted for two tests: an ELISA against mycobacterial antigens and a lymphocyte stimulation test. This test showed a sensitivity of 83.3% and specificity of 51.6%, however was found less reliable in elephants that had previous tests. (J2.32.w1)
  • Restriction fragment length polymorphism (RFLP) has been used in elephants as a molecular evaluation test of Mycobacterium tuberculosis. (J2.32.w1) 
  • Isolation and identification is the only definitive test to diagnosed TB in elephants. (J54.19.w4)
    • Isolation and identification of Mycobacteria sp. from affected tissues. (J3.93.w1, J4.183.w2, P1.1981.w1, P1.1997.w4)
    • Samples collected on culture swabs are not adequate. (P1.2002.w1)
    • Trunk wash culture of Mycobacteria sp. (J2.32.w1, J54.19.w4, J133.969.w1, P5.39.w4, P6.4.w2, P20.1998.w3, P20.1998.w4)
      • Sixty ml of sterile 0.9% saline are instilled in one or both trunk nostrils. The elephant's trunk is elevated. A one gallon plastic zip lock back is applied over the trunk tip before lowering the trunk and allowing the fluid to drain in the bag. The elephant is allowed to exhale into the bag. (P5.39.w4)
      • Three samples should be collected in different days. (J54.19.w4)
      • Details are provided in: Trunk Wash of Elephants
  • It is very important to perform multiple comparative testing in elephants. (P20.1998.w4)
  • The interpretation of the results may be influence by several factors, such as cross-reactivity, sampling etc.: 
    • Three trunk cultures performed in an elephant within a week were negative. However, the same animal had a previous reaction to the PPD-bovis skin test, this result was attributed to a cross-reaction to a non-tuberculous Mycobacteria sp. ELISA and blood tuberculosis (BTB) test were also considered false positives after tuberculin skin test exposure. (P20.1998.w4)
    • Many factors may cause a false negative culture result, such as inadequate number of bacteria, inadequate collection, sample contamination and/or incorrect sample handling. (P30.1.w7)
    • Some elephants that had a negative trunk culture were positive by the ELISA test. This may occur due to an undetected case of infection or nonspecific reactions with other Mycobacterium spp., such as Mycobaterium avium, Mycobacterium intracellulare or saprophytic environmental mycobacteria. (J2.32.w1)
    • When using ELISA and other serological tests it is important to request that both Mycobacterium tuberculosis (and/or Mycobacterium bovis) and Mycobaterium avium antigens are compared to study cross-reactivity. (P20.1998.w4, P30.1.w7)
  • A virulence test by inoculation in experimental animals has been used in the past. (J3.93.w1)

See: D303 - FULL TEXT Guidelines for the Control of Tuberculosis in Elephants

LAGOMORPHS
  • Clinical signs of tuberculosis are non-specific so diagnosis of this disease is usually made at necropsy. (B614.8.w8) See the pathology section for more details.
  • Culture and identification of the organism are necessary for definitive diagnosis. (B614.8.w8)
FERRETS
  • If ferrets have been exposed to Mycobacteria then a tuberculin-test should be performed as well as other diagnostic tests. (B627.14.w14)
  • Palpation of the abdomen can detect splenomegaly, hepatomegaly and intestinal nodules where there is multiply organ involvement. (B627.14.w14)

Imaging

  • Radiography can reveal nodular lesions, if these are calcified. (B627.14.w14)

Laboratory samples

  • Faeces or a gastrointestinal swab may be sent for analysis to detect a Mycobacterium sp. (B631.20.w20)
  • Detection of acid-fast bacteria from biopsy samples or on histopathological sections. (B627.14.w14, J4.195.w5)
  • In feral ferrets in New Zealand, the presence of hepatic granulomas on histopathological examination was considered pathognomonic for tuberculosis. (J10.45.w4)
  • Culture: isolation and identification of the organism from biopsy or necropsy samples. (B627.14.w14, B628.11.w11)
  • PCR can be used in diagnosis of tuberculosis. (B627.14.w14)

Note: The subcutaneous tuberculin test has not been defined for use in ferrets. (B628.11.w11) Tuberculin skin testing in ferrets is unreliable. (J4.195.w5, P20.1992.w7)

BONOBOS/GREAT APES Diagnosis of tuberculosis in primates is by a combination of the following: (D390.96.w96)
  • Clinical observation.
  • Radiography.
  • Tuberculin test
  • Cultivation of the organism.
  • PCR (although both false-positive and false-negative reactions have been reported)
  • ELISA
  • Primagam interferon-Gamma test. This has been found useful with sera from great apes (gorillas, chimpanzees, orang utans), gibbons, colobids, baboons, mandrills, vervet mokeys, guenons, langurs, squirrel monkeys and marmosets, but not with sera from Macaca sp. (D390.96.w96)

In 1978 it was noted that there were no standardised tests for TB in the great apes. (B680.w18). This is still true. Testing using more than one category of test (direct, serological and cell-mediated immunity based) is recommended; diagnosis can be improved by using at least two types of test in parallel. (B519.2.w2, D390.X.w143)

  • Initially, standard tuberculin test. (B336.39.w39) If a great ape has a positive reaction on the standard tuberculin test, thorough further testing is essential including: (B336.39.w39)
    • Comparative tuberculin testing using balanced mammalian and avian antigens. (B336.39.w39)
    • Horizontal-beam radiograph of the thorax, with the ape in a vertical (hanging) posture. (B336.39.w39)
      • Radiographic studies have been found to be of value in identify the occurrence of lesions in nonhuman primates. (B58.22.w22)
    • Both bronchioalveolar and gastric cultures for acid-fast bacterial culture. (B336.39.w39)
  • A multimodal approach using both more than one test in parallel (e.g. an interferon-gamma releasing test alongside a tuberculin skin test), and repeating tests is recommended for diagnosis. (J543.37.w2, P133.2012.w2)
  • Note: great apes have been known to die from TB despite repeated negative TB tests. (P1.1974.w4)
Direct tests
  • Clinical samples - direct tests: tonsillar swabs, faeces and brochoalveolar lavage samples can be tested by acid-fast stains (e.g. Ziehl-Neelsen), culture and PCR. (P133.2012.w1)
    • Direct tests from clinical samples are relatively insensitive, due to sampling limitations. (P133.2012.w2)
    • In a given animal, intermittent positive and negative results may be found with culture and PCR or tracheal wash samples. (J219.14.w3)
    • At low prevalence of infection, the positive predictive value of a positive PCR result is relatively low. (D390.X.w143)
    • Culture and speciation is still considered to be the "gold standard" but takes up to eight weeks for culture and even longer for speciation. (B519.2.w2)
    • .2.w2)
  • At necropsy - direct tests: characteristic gross and microscopic lesions, with acid-fast bacilli in the lesions. Diagnosis confirmed by culture of the organism. (B569.w4)
  • Non-specific tests include clinical examination and antero-posterior thoracic radiographs to detect typical lesions. (P133.2012.w1)
Serological and other indirect tests
  • A variety of indirect tests are available including:
    • Comparative skin tests with PPD, bovine PPD and avian PPD. (P133.2012.w1)
      • 0.2 mL of bovine PPD is used, injected into either the eyelid or abdominal skin. The dose is at least 2,000 IU per test, which is 1,000 - 10,000 times greater than the amount used in testing humans. The reaction should be read at 24, 48 and 72 hours after injection (D390.X.w143) using calipers. (B519.2.w2)
      • Old mammalian tuberculin (old tuberculin, OT) has been suggested as preferable to PPD for testing nonhuman primates. (B680.w17). However, while this increases sensitivity it decreases specificity compared with bovine ppd. (B519.2.w2, D390.X.w143) It is also more difficult standardise between lots. (B519.2.w2)
      • Both false-positives and false-negatives occur. Species-specific features can result in low specificity, as seen in orangutans, in which false-positive reactions are common; additionally, there can be individual variability in response, anergic responses in individuals with fulminant disease and false positives resulting from contact with other mycobacteria. (B519.2.w2, D390.X.w143)
    • Interferon-gamma release assays (IGRA) e.g. Primagam (Prionics, Schlieren, Switzerland) and Quantiferon-TB Gold (Cellestis, Darmstadt, Germany). (P133.2012.w1)
      • In these tests, standard whole blood aliquots in a culture plate are stimulated by a positive control medium and with various mycobacterial antigens. Following an incubation period, interferon-gamma in the supernatants of the cultures is measured using an ELISA, with positive and negative results determined by comparisons of responses between controls and mycobacterial antigen stimulation. PRIMAGAM uses purified protein derivative (PPD) from Mycobacterium bovis while Quantiferon uses EST-6, which is a protein secreted by Mycobacterium bovis and Mycobacterium tuberculosis, and culture filtrate protein-10 antigens. (J543.37.w2)
      • PRIMAGAM has been shown to have a lower sensitivity but higher specificity than standard primate tuberculin skin testing (e.g. sensitivity 68% specificity 97% versus sensitivity 84% specificity 87%), therefore a negative result from PRIMAGAM has a low negative prediction value but a positive result has a high positive predictive value (i.e. false positives are rare). (J543.37.w2)
        • Whole blood or white cells should be stimulated a maximum of eight hours after the sample has been taken. (D390.X.w143)
    • Lateral flow assays PrimaTB STAT-PAK (Chembio, New York, USA) is used on serum. (J219.14.w3, P133.2012.w1) This is a lateral-flow test using a variety of antigens and was shown to have high sensitivity (90%) and specificity (99%) when tested using Macaca mulatta - Rhesus macaque, cynomolgous monkeys (Macaca fascicularis - Crab-eating macaque) and African green monkeys (Chlorocebus aethiops - Savanna monkey). It was found to detect 100% of infected monkeys tested 4-8 weeks post inoculation. (J219.14.w3)
    • MAPIA (multiantigen print immunoassay), in which antigens are applied to nitrocellulose membranes then incubated with test sera followed by detection of positive reactions using chromogenic immunodevelopment. (B519.2.w2, P133.2012.w1)
    Note: interpretation of the results of TB tests in the great apes is challenging. (B22.31.w31c, P133.2012.w2)
    • Testing of great apes in range state countries found for example that of three chimpanzees later confirmed TB positive by culture following necropsy, one was positive with the tuberculin skin test (using Mammalian Old Tuberculin, bovine and avian), one was positive with the PrimaTB STAT-PAK (Chembio Diagnostic Systems, New York, USA) assay and one was negative with both tests. (P133.2012.w2)
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Similar Diseases (Differential Diagnosis)

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BADGERS --
HEDGEHOGS --
ELEPHANTS --
FERRETS

Other causes of chronic weight loss and lethargy. (J215.23.w1)

For diarrhoea: Other causes of diarrhoea including Salmonellosis and Campylobacter Infection. (J215.23.w1)

For musculoskeletal signs:

  • Hemivertebrae. (B501.12.w12)
  • Vertebral fractures. (B501.12.w12)
  • Intervertebral disc disease. (B501.12.w12)
  • Myelitis. (B501.12.w12)
  • Spinal cord haemorrhage. (B501.12.w12)
BONOBOS/GREAT APES

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Treatment and Control

Specific Medical Treatment

  • Isoniazid (INH). (B88, B58.22.w22)
  • Ethambutol. (B88)
  • Streptomycin. (B58.22.w22)
  • Rifampin (RIF). (B58.22.w22)
  • Resistant often develops under a single drug treatment; in these cases a combination of isoniazid, ethambutol (ETH) and rifampin is commonly used. (B88)
  • The combination of isoniazid, ethambutol and rifampin can be a successful treatment in zoo animals. (P1.1990.w1)
  • Other drugs such as para-amino salicylic acid, pyrazinamide (PZA), kanamycin, capreomycin and ethionamide have been used. (B88, B58.22.w22)
  • In human medicine, a combination treatment of isoniazid, ethambutol and rifampin is commonly used. Treatment lasts nine months with triple drug therapy including rifampin, and 18 to 24 months without rifampin. (B88)
BADGERS --
HEDGEHOGS --
ELEPHANTS
  • Drug therapy should be selected according to the culture and sensitivity results. (B336.53.w53)

Recent treatment regimes:

  • A combination of isoniazid, rifampin and pyrazinamide orally has been used in "high-risk" elephants, based upon multiple positive tests results. Body weight, liver function, mycobacterial trunk cultures and diagnostic blood test were monitored. The treatment was well tolerated and the only culture-positive elephant converted to culture-negative. (P1.1997.w4)
  • Recently, a combination of isoniazid, rifampin, pyrazinamide and ethambutol have been used in elephants. Oral and rectal route of administration have been used, however only isoniazid and pyrazinamide seemed to be absorbed by both routes. (J54.19.w4)
  • Currently the recommended treatment for infected elephants is: (J54.19.w4, P20.1998.w3)
    • Isoniazid 2.5-5 mg/kg orally or rectally plus rifampin 7.5-10 mg/kg orally daily for two months, then alternate days for ten months. (J54.19.w4)
    • Pyrazinamide 25-35 mg/kg orally or rectally daily for first two months. (J54.19.w4)
    • An isoniazid blood level of 1-2 g/ml is recommended. (J54.19.w4)
    • Side effects such as anorexia, lethargy and colitis may be seen. Isoniazid toxicity may cause raised liver enzymes. Leukopaenia was observed in one case. (J54.19.w4)
  • Note: Shedding of the tuberculous Mycobateria sp. generally stops when elephants are receiving adequate treatment. (J54.19.w4)
  • N.B. Antibiotic resistant strains of Mycobacterium tuberculosis isolates have been identified recently. Isolates from four animal have been confirmed resistant, one to isoniazid, one to rifampin and two to isoniazid and streptomycin. Treatment should include three or four anti-tuberculosis drugs to which the strains are sensitive. Therapeutic drug concentration monitoring is also recommended. (J2.32.w1, P1.2002.w1)
  • See: D303 - FULL TEXT - Guidelines for the Control of Tuberculosis in Elephants

Older treatment regimes:

  • Penicillin G (10,000,000 units) and streptomycin (5 g) daily for five days (route of administration not specified). (J196.60.w1)
  • Streptomycin given intramuscularly on alternate days for four weeks was used on a suspected tuberculosis case. (J54.19.w4)
  • Streptomycin 100g intramuscularly on alternate days for four weeks was used successfully in adult working elephants. (P502.1.w5)
LAGOMORPHS
  • "There have been no reports of treatment of naturally occurring tuberculosis in rabbits". (B614.8.w8)
  • Theoretically, drugs that should be effective include isoniazid and rifampin. (B614.8.w8)
FERRETS
  • Due to zoonotic risks, ferrets should be euthanased if tuberculosis positive. (J4.195.w5, J215.23.w1, B627.14.w14, B628.11.w11) There is no common treatment for tuberculosis in ferrets. (B501.12.w12) 
  • Infected ferrets should be isolated or preferably euthanased. (B501.12.w12)

Note: Humans in contact with infected ferrets should be referred to a doctor for tuberculosis testing. (J4.195.w5)

BONOBOS/GREAT APES Generally, infected nonhuman primates are euthanised. However, in the case of valuable individuals, treatment may be given. (D390.96.w96)
  • A multi-drug regime should be used based on current standards for human practice. (B644.2.w2)
  • The regime should be chosen based on culture and sensitivity testing. (B644.2.w2)
  • Prolonged treatment is required; treatment should be given only if it can be continued for e.g. a year or more. (B644.2.w2)
  • Isoniazid plus para-amino salycylic acid, orally, for 15 months and longer has been used in great apes. (J23.5.w2)
  • Isoniacid (INH) at 22.5 mg/kg plus Ethambutol 20 mg/kg plus Rifampin 22.5 mg/kg. (D390.96.w96)
  • Note: treatment requires that strict rules are followed for drug administration, checking of pharmacokinetics, and follow-up. (D390.X.w143)
    • "Successfully" treated animals are returned to a latent stage of infection and it should be considered that reactivation could occur at any time in the future after treatment is discontinued. (D390.X.w143)
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General Nursing and Surgical Techniques

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BADGERS --
HEDGEHOGS --
ELEPHANTS
FERRETS --
BONOBOS/GREAT APES --
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Preventative Measures

Vaccination
  • Bacillus of Calmette-Guerin (BCG) vaccine has been used in humans in some high risk areas. (B101)
  • Bacillus of Calmette-Guerin (BCG) vaccine does not prevent infection completely in cattle. This preventive measure was abandoned in countries that attempted to use vaccination. (B101)
BADGERS

Meles meles - Eurasian Badger:

  • Studies are ongoing to develop a means of vaccinating badgers for control of the disease in the future. (B209.21.w21)
HEDGEHOGS --
ELEPHANTS --
FERRETS --
BONOBOS
  • BCG vaccine has been used in bonobos and other great apes. Frankfurt Zoo noted that they had no cases of tuberculosis in their apes after starting vaccinating. (B437.w24)
Prophylactic Treatment

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BADGERS --
HEDGEHOGS --
ELEPHANTS
  • Isoniazid, 5 mg/kg/day orally was given in a single dose to a suspected skin tuberculin test case; this was found to be adequate for prophylactic antituberculosis therapy. (J2.14.w4)
  • A combination of isoniazid, rifampin for 12 months and pyrazinamide added for the first two months has been used as a preventive treatment. (P1.1997.w4)
FERRETS --
BONOBOS/GREAT APES --
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Environmental and Population Control Measures

General Environment Changes, Cleaning and Disinfection
  • Personnel working with animals considered at high risk for infection, should wear masks and protective covering. (P1.1997.w2)
  • Avoid overcrowding. (B58.22.w22)
  • When tuberculosis is diagnosed, cleaning and disinfection of the premises where the animals are kept using a 5% cresylic compound or a phenol derivative three times at seven-day intervals is essential. (B22.11.w8)
  • Foot baths of disinfectant are beneficial in limiting the spread of infection. (P1.1997.w2)
  • Infected animals should be kept isolated in well ventilated areas and ideally with access to ultraviolet radiation (natural sunlight or UV lights). (P1.1997.w2)

BADGERS

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HEDGEHOGS --
ELEPHANTS --
FERRETS
  • Commercially prepared cat or ferret diet should be fed to reduce the risk of infection from food sources such as meat and meat byproducts. (J4.195.w5, B627.14.w14)
BONOBOS/GREAT APES  
Population Control Measures
  • In cattle there are two main approaches to the control of tuberculosis: test-and-slaughter and test-and-segregation (the later is more frequently used in developing countries). (B101, J4.193.w1)
In zoos:
  • When tuberculosis has been diagnosed in an animal population, all the exposed animals need to be tested with a tuberculin test of suitable potency. (B22.11.w8)
  • Tuberculin-positive animals should be destroyed. (B22.11.w8) 
    • Valuable tuberculin-positive animals may be isolated and treated for 60 days. (B22.11.w8, J4.193.w1, P1.1988.w2)
  • Animals positive with the tuberculin test should not be included to the collection. (B58.22.w22, P1.1988.w2)

Also see: D303 - Guidelines for the control of tuberculosis in elephants 2003 - Full text provided

BADGERS

Meles meles - Eurasian Badger:

  • Programmes to reduce infection levels in badgers, in order to prevent transmission to cattle, have involved gassing of setts to kill all the badgers in the sett (now discontinued due to welfare considerations), and trapping and killing by shooting of individual badgers.
  • Trials are ongoing regarding the most effective regimes.
(B209.21.w21)
HEDGEHOGS --
ELEPHANTS
  • Euthanasia of positive animals confirmed by culture. (P6.4.w2)
  • Post mortem examination, including a thorough search for tuberculosis lesions even if tuberculosis is not suspected, should be performed on all elephants that die. (J54.19.w4, P1.2002.w1)
  • On post mortem examination, the tonsillar region, submandibular lymph nodes and bronchial lymph nodes should be thoroughly checked for tuberculosis lesions. (B336.53.w53)
  • Lymph nodes should be submitted for culture even if tuberculosis lesions are no evident. (B336.53.w53)
FERRETS Infected ferrets should be euthanased. (B501.12.w12)
BONOBOS/GREAT APES --
Isolation, Quarantine and Screening
  • Quarantine should be imposed on all imports for a minimum period of 60 days and preferably 120 days. (B58.22.w22)
  • Tuberculin skin test. (B58.22.w22)
BADGERS --
HEDGEHOGS --
ELEPHANTS In North America, elephants are grouped based on culture results and exposure history into the following groups: 
  • A: Culture-negative elephants with no known exposure to culture-positive animals in the previous five years. These animals are cultured annually (three samples on separate days) and have no travel restrictions while they are culture negative. 
  • B: Culture-negative elephants exposed to a culture-positive animal one to five years ago. These animals are cultured quarterly (three samples on separate days) and have no travel restrictions.
  • C: Culture-negative elephants exposed to a culture-positive animal in the previous 12 months. These animals may be cultured on alternate months (three samples on separate days) for eighteen months and are not permitted to travel for one year, or alternatively may be treated prophylactically for nine months and are permitted to travel after two months of this treatment if cultures are negative (with treatment continuing).
  • D: Culture-positive elephants. These animals are not permitted to travel while they are on treatment for six months; they are considered culture-positive until two negative culture results are obtained.

(D303 - Guidelines for the control of tuberculosis in elephants 2003 - Full text provided)

FERRETS Infected ferrets should be isolated immediately. (B501.12.w12)
BONOBOS/GREAT APES
  • All primates being imported into a collection should undergo strict quarantine and isolation. (B569.w4, D428.8.2.w8b)
  • Infected animals should be isolated during treatment. (B644.2.w2)
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