University of Bristol & The Linnaeus Group, Bristol Veterinary School, Bristol & Shirley, UK
What Are Mycobacteria?
Mycobacterial infections are a global health problem in animals and humans with geographical variation worldwide. They are intracellular acid-fast aerobic bacilliform bacteria (AFB), usually slow-growing, organisms that can be resistant in the environment. Those of feline importance1,2 belong to the following groups:
- Tuberculosis (TB) complex—these form tubercles seen on pathology
- Non-tuberculous mycobacteria (NTM) including feline leprosy (FL) organisms
- Tuberculosis (TB) complex
Tuberculosis (TB) Complex
- These result in tuberculosis (TB), forming tubercles, and comprise three species, all of which are obligate pathogens and slow-growing: M. tuberculosis, M. bovis and M. microti. Cats are primarily affected by M. bovis and M. microti with M. tuberculosis cases very rare, as cats are naturally resistant to infection.
M. bovis and M. microti are thought to be most commonly acquired via bites from infected rodents (voles/mice), but M. bovis can also be acquired via ingestion of unpasteurised milk or infected meat (ingestion of infected carcasses may be a reason M. bovis infection hunting dogs3,4) and via direct or indirect contact with badgers. Recently a short report5 has described suspected6 M. bovis infection in 3 young (<2 years old) indoor-only pedigree cats in England that were fed a commercial raw diet, inferring that this could have been involved in transmission. Indirect contact/environmental transmission is possible as M. bovis and M. microti can survive for several months in organic material (e.g., faeces, carcasses) although they generally survive poorly outside mammalian hosts (4 days in summer, up to 28 days in the winter). Despite M. bovis being zoonotic and infecting humans7, cat-to-human transmission is of very low risk and very rarely reported8. M. microti is less of a zoonotic concern than M. bovis and cat-to-human transmission has never been reported9.
TB is primarily seen in adult male cats with outdoor access (likely due to hunting and fighting). M. bovis tends to affect younger cats (median age 3 years) than M. microti (median age 8 years). No evidence of immunosuppression is present in most cats with TB.
Cats usually present with cutaneous signs: nodules (± ulceration) or non-healing draining wounds, primarily on the head, extremities or tail base, possible sites of rodent bites. Regional or generalised lymphadenopathy is common. Systemic pulmonary involvement occurs quite frequently, although outward signs of respiratory disease (coughing, tachypneoa/dyspneoa) may not be present. Pulmonary involvement is usually via haematogenous spread of infection c.f. inhalation. Weight loss and anorexia may occur with systemic disease. Bone involvement can result in lameness and/or pain. Recently joint involvement has been reported in 4 cats (2 with M. bovis and 2 with M. microti)10. Occasionally ocular uveitis is seen. Systemic involvement is more common with M. bovis than M. microti.
Non-tuberculous Mycobacteria (NTM), Including Feline Leprosy (FL)
These are opportunistic environmental bacteria (in the soil, water and decaying plants), comprising many species. Some are slow-growing (>7 days to grow in culture) e.g., M. genavese, whilst others are fast-growing (≤7 days to grow in culture) e.g., M. fortuitum. Mycobacterium avium (a member of the Mycobacterium avium-intracellular complex [MAC]) is also a slow-growing NTM; MAC infections are important as they can be zoonotic. FL was assumed to be due to only M. lepraemurium11 but other species are now known to be involved, e.g., Mycobacterium visibile, and others more recently12,13. FL organisms are also opportunistic environmental and are usually unculturable.14 FL organisms are also NTM organisms as they do not form tubercles15.
Infection usually occurs following soil contamination of wounds, especially when adipose tissue becomes infected. MAC transmission may be possible via ingestion of infected meat or via contact with bird faeces. Infection with FL organisms occurs following rodent bites or soil contamination of wounds. Of the NTM, only M. avium can be zoonotic (immunosuppressed people) but there are no records of cat-human transmission of NTM. Outdoor cats, and those that are obese, are at increased risk of infection of non-FL NTM infections. Occasionally infection is associated with immunosuppression (e.g., retroviruses, toxoplasmosis). Siamese, Abyssinians and Somalis are at increased risk of disseminated MAC infection. Adult male cats with outdoor access are most at risk of FL.
NTM infections usually present as cutaneous/subcutaneous nodules ± ulceration (which resembles localised TB) and/or granulomatous panniculitis (multiple punctate draining tracts; ‘pepper pot’ appearance) which can progress to involve significant areas of painful, ulcerated and non-healing tissue (inguinal fat pads, flanks and/or tail base). Systemic signs are uncommon other than with M. avium infection, which tends to be particularly pathogenic, causing cutaneous skins in association with lymphadenopathy and other systemic (e.g., neurological16, pulmonary) signs. Cats with FL NTM have nodular cutaneous signs; typically alopecic or ulcerated non-painful nodules that are mobile on palpation on the head or limbs. Regional lymphadenopathy may occur.
Approach to Diagnosis
Most cats affected by mycobacterial disease are outdoor cats, often with a history of hunting or fighting, from a non-urban area, although a recent report suspected M. bovis infection in three indoor-only cats5, possibly via ingestion of raw food. The clinical presentation is similar with all mycobacterial species; cutaneous lesions (especially around the ‘fight and bite’ sites: face/legs, areas bitten when playing with prey), which may be multiple due to local or haematogenous spread. Local or generalised lymphadenopathy (often submandibular and/or prescapular) is common. Systemic signs, typically involving the lungs, are far less common than cutaneous signs, but may occur with M. bovis or M. avium (and occasionally M. microti). Systemic signs include generalised lymphadenopathy, splenomegaly, hepatomegaly, renal abnormalities, ocular signs and bone lesions. Pyrexia is not a consistent feature. Abdominal lymphadenopathy was the primary sign in the indoor-only cats reported with suspected M. bovis infection5.
An anaemia of inflammatory disease may occur. Hypercalcaemia can occur with extensive disease or severe panniculitis. Testing for retroviruses may be indicated for NTM cases.
Imaging is useful. Thoracic radiography may show pulmonary involvement and/or osteolytic/proliferative changes with overlying soft tissue changes. Abdominal radiographic changes are less common but include hepatomegaly and/or splenomegaly. Ultrasonography may show abdominal lymphadenopathy, hepatomegaly, splenomegaly or renal changes, and may provide a window for sampling tissues for diagnostic purposes. Computed tomography (CT) abnormalities17 are primarily pulmonary but abdominal or peripheral lymphadenopathy, osteolytic/proliferative lesions and cutaneous/subcutaneous soft tissues masses and nodules are reported. Mild lymphadenopathy was more appreciated in post-contrast CT studies, so use of contrast should be considered.
Feline interferon-gamma (IFN-) release assay blood testing shows promise for the ante-mortem diagnosis of TB. The test18 measures the T-cell response (IFN-production) in peripheral blood mononuclear cells to three different antigens; the pattern of any positive results is said to identify whether the cat is infected with a pathogenic or less pathogenic TB complex species or whether it has been exposed to environmental NTM species. It is useful to determine whether M. bovis and M. microti infection is most likely to determine the zoonotic risk to guide treatment in suspected cases. The test may also be useful for monitoring treatment15. Mycobacterial organisms may be visible following Ziehl-Neelsen (ZN) staining for AFB in fine needle aspirates or biopsies collected from affected tissues (e.g., lymph nodes, skin, liver) or bronchoalveolar lavage (BAL) or draining wound/cutaneous lesion samples. Cytology and histopathology from affected cases reveals pyogranulomatous/granulomatous inflammation ± AFB in macrophages. If no AFB are present, but cytology or pathology changes are consistent with mycobacterial infection, mycobacterial disease should remain a differential diagnosis and culture should be performed. Whenever biopsies are taken from cats in which mycobacterial disease is suspected, some should be reserved out of formalin (wrap in sterile gauze moistened with sterile saline) and frozen at -20°C for mycobacterial culture and polymerase chain reaction (PCR) if required, pending other investigations. NB. Gloves and aseptic practice are required to handle the biopsy (and biopsy site) zoonotic risk. Culture is required to confirm a diagnosis and is done in specialist laboratories but can take a long time (2–4 months) and is costly. Some species (e.g., FL NTM and some M. microti) are impossible to grow. Culture is performed on the same samples obtained for cytology or histopathology. PCR may allow diagnosis whilst awaiting culture or with unculturable organisms but is costly.
It is important to discuss whether cases should be treated at all, especially cases of disseminated M. bovis infection due to zoonotic implications and worries around antimicrobial resistance developing in human TB cases as a result of antimicrobial use in feline cases. The current advice in the UK is that cats diagnosed with M tuberculosis and M. bovis should be euthanased, but this can be hard to persuade owners to do. The cat should be kept indoors and the costs and compliance issues of treatment need to be carefully discussed with owners. It is recommended that specialist advice is sought before embarking on treatment. Additionally, owners should be advised to contact their doctor, informing them of the diagnosis in their pet cat so that screening can be arranged.
References are available upon request.