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

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)

Alternative Names (Synonyms)

Disease Type

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)

Mycobacterium spp. are gram-positive, acid-fast bacteria 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

References

Disease Author

Referees

Major References / Reviews

Code and Title List

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

P1.1988.w2, P1.1990.w2

Badgers 

Meles meles - Eurasian Badger

• B209.21.w21, 
• J3.105.w4, J3.149.w1, J60.2.w2
• P27.5.w5

Hedgehogs 

Erinaceus europaeus - West European Hedgehog

• J10.43.w1, J10.48.w1, J18.53.w1, J46.1933.w1, J46.1936.w1, J127.63.w1, J195.26.w1
• P23.1999S.w8

Elephants

• B10.49.w21, B16.18.w18, B64.27.w4, B214.3.7.w3, B336.53.w53, B450.16.w16
• J12.76.w1, J54.19.w4, J84.4.w1, J98.350.w2, J133.969.w1, J196.60.w1
• P1.2002.w1, P5.39.w1, P5.39.w3, P502.1.w1, P502.1.w5

• J2.14.w4, J2.32.w1, J3.93.w1, J4.183.w2, J12.5.w3, J42.38.w1, J46.1875.w1, J353.124.w1, J353.125.w1, J357.11.w1, J358.19.w1
• P1.1981.w1, P1.1997.w4, P6.4.w2, P20.1998.w3, P501.1.w2

Loxodonta africana - African Elephant

• J25.14.w1
• P1.1997.w4

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

• B214.3.4.w16, B407.w18
• J1.37.w6, J64.21.w18
• P1.1990.w1, P6.1.w5

Lagomorphs

• B602.17.w17, B614.8.w8

Other References

Code and Title List

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

Elephants

• J2.31.w1, J93.40.w3, J93.41.w5
• P5.39.w4, P20.1998.w4, P30.1.w7
• D301.3.w3

Detailed Clinical and Pathological Characteristics

Clinical Characteristics

• 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.
  • 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.

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)

In Erinaceus europaeus - West European Hedgehog:

• Fatal pneumonia recorded in one individual (Erinaceus europaeus - West European Hedgehog). (J18.53.w1)
• Sub-clinical infection reported following experimental intraperitoneal inoculation in hedgehogs (Erinaceus europaeus - West European Hedgehog). (J127.63.w1)
• Infection reported following experimental intraperitoneal or subcutaneous inoculation of hedgehogs (Erinaceus europaeus - West European Hedgehog) with the "bovine virus" (probably Mycobacterium bovis), but many animals died due to inadequate diet and "no clinical picture emerged". (J18.53.w1)
• Fatal infection recorded in one Erinaceus europaeus - West European Hedgehog after 11 weeks in captivity (J46.1933.w1) and in another after a year in captivity. (J46.1936.w1)

Clinical pathology in Erinaceus europaeus - West European Hedgehog):

• Following experimental inoculation of five individuals:
  • No response to the intradermal tuberculin test up to 56 days after inoculation. (J127.63.w1)
  • No detectable antibodies by complement fixation test or passive haemagglutination test. (J127.63.w1)
  • No detectable cell mediated immunity reaction. (J127.63.w1)

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)

• 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)

Incubation

• The strain of the organism, the dose and the route of exposure may affect the time to produce progressive disease. (P1.1990.w2)

Mortality / Morbidity

• Apparently very rare in bears. (B407.w18)
• There is one report of fatal tuberculosis in an Ursus maritimus - Polar bear at a Swiss zoo. (P6.1.w5)
• There is one report of a Ursus maritimus - Polar bear which died due to acute miliary tuberculosis (human type) at Frankfurt Zoo, and another report of TB as an incidental finding at necropsy in a Ursus maritimus - Polar bear. (B214.3.4.w16)

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)

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.

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)

• 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)

• 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)

• In one Ursus maritimus - Polar bear:
  • Lesions in both lungs and one kidney. (B214.3.4.w16)
• In another Ursus maritimus - Polar bear, at Frankfurt Zoo:
  • Acute miliary lesions. (B214.3.4.w16)
• In wild Ursus americanus - American black bear, no gross lesions. (J64.21.w18)

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)

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)

• 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

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

• A wide range of mammal species.

Badgers:

• Meles meles - Eurasian Badger (B209.21.w21, J3.149.w1, J60.2.w2)

Hedgehogs:

• Erinaceus europaeus - West European Hedgehog (J10.43.w1, J18.53.w1)
• Mycobacterium bovis was isolated from the lungs of four hedgehogs Erinaceus europaeus with gross pulmonary lesions in New Zealand. (J10.43.w1)

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

• Not recorded in free-living Loxodonta africana - African Elephant. (J64.20.w1)
• A case of suspected tuberculosis in Loxodonta africana - African Elephant in Uganda was not confirmed by culture. (J25.14.w1)
• One case of tuberculosis caused by Mycobacterium tuberculosis in a captive Loxodonta africana - African Elephant was confirmed by culture. (B450.16.w16, J64.20.w1) 
• Recently, Mycobacterium bovis was isolated in one Loxodonta africana - African Elephant in North America. (P1.2002.w1)

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)

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

• Erinaceus europaeus - West European Hedgehog
• Elephants (Elephantidae - Elephants (Family))
  • Elephas maximus - Asian Elephant
  • Loxodonta africana - African Elephant
• Meles meles - Eurasian Badger  
• Oryctolagus cuniculus domesticus - Domestic European rabbit
• Ursus americanus - American black bear

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

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

Badgers:

• Meles meles - Eurasian Badger, in Europe, including Eire, Switzerland and the UK. (B209.21.w21, J3.149.w1, J60.2.w2)

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)

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

• Meles meles - Eurasian Badger
• Ursus americanus - American black bear

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

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)

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:

• India: two working elephants from Kerala were found to be infected with Mycobacterium tuberculosis. (P502.1.w5)
• Sweden, in two Elephas maximus - Asian Elephants in a zoo. (P6.4.w2)
• UK in 1875 in one Elephas maximus - Asian Elephant. (J46.1875.w1)
• USA, Mycobacterium tuberculosis in Elephas maximus - Asian Elephants and Mycobacterium bovis  in one Loxodonta africana - African Elephant. (J2.32.w1, J4.183.w2, J54.19.w4, J84.8.w15, P1.1997.w4, P1.2002.w1)

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

General Information on Investigation / Diagnosis

• Clinical signs are of limited value in diagnosis. (B58.22.w22)
• Radiographic studies have been found to be of value in identify  the occurrence of lesions in nonhuman primates. (B58.22.w22)
• Presumptive diagnosis may be made on post-mortem examination from gross and microscopic pathology. (B58.22.w22, B64.27.w4, P1.1990.w2)
• Tuberculin test, 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 0.1ml 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)
• 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)
• 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)
• 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)
• 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) 

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)

• 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

• 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)

• Environmental Assessment
• History & Documentation
• Physical Examination of Mammals
• Necropsy of Mammals
• Imaging in Lagomorph Diagnosis and Treatment
• Clinical Pathology of Lagomorphs
• Chapter 2 - B36 Field Manual of Wildlife Diseases - Specimen Collection and Preservation
• Chapter 3 - B36 Field Manual of Wildlife Diseases - Specimen shipment
• Appendix A - B36 Field Manual of Wildlife Diseases - Sample specimen history form
• Trunk Wash of Elephants

Similar Diseases (Differential Diagnosis)

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)

• 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 µg/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)

• "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)

• Treatment and Care
• Medicating Elephants
• Intramuscular Injection of Elephants
• Oral Medication of Elephants
• Rectal Administration in Elephants

General Nursing and Surgical Techniques

• Pyridoxine (B Vitamin) has been given to counter the side-effects of isoniazid and prevent peripheral neuropathy. (J54.19.w4, P1.1997.w4)

• Treatment and Care

Preventative Measures

• 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)

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)

--

• 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)

• Medicating Elephants
• Oral Medication of Elephants

Environmental and Population Control Measures

• 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

• 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) 

• 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

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.

• 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)

• 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)

• 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)

• Environmental Assessment
• Treatment and Care - Euthanasia
• Environmental and Population Management
• Euthanasia of Elephants