Mycobacteria are aerobic, non-spore forming bacteria that are capable of causing disease in animals and man. Several species of mycobacteria can cause disease in veterinary species, being either primary pathogens, or becoming pathogenic (disease causing) under certain circumstances. Mycobacterial infections generally cause one of three different types of disease:
- Tuberculosis: formation of granulomas (inflammatory nodules)
- Leprosy: formation of granulomas in the skin
- Opportunistic mycobacterial infections: primarily involving the subcutaneous tissues (just below the skin)
Mycobacterium tuberculosis causes over 90 per cent of tuberculosis in man. Other than dogs, this organism rarely infects other mammals. Other species of mycobacteria that can infect people include:
M bovis, the main cause of tuberculosis in cattle, can also infect mammals including people, dogs, cats and pigs.
M avium complex (MAC), the cause of tuberculosis in birds, may also infect man, dogs and cats.
Infection is most commonly acquired through spending prolonged periods in an environment where the air is contaminated by a person with untreated TB who is coughing. Although TB is generally spread through the air, it can also be transmitted through drinking unpasteurised milk or milk products obtained from infected cattle. Northern Ireland, the West of England, the West Midlands and parts of South Wales have had the highest incidence of TB cases reported in cattle in the UK .
In cats, tuberculosis is classically caused by infection with M bovis. Historically, infection resulted from the ingestion of milk from tuberculous cattle. Although there has been an increase in tuberculosis in the national herd, there has been a marked decline in the prevalence of the disease seen in cats and it is currently considered to be rare. When it is diagnosed, feline tuberculosis is usually caused by infection with either the cattle form of the infection (M bovis [41 cases]) or the vole form ( M microti [22 cases - recent figures from Keith Jahans, Veterinary Laboratories Agency, 2004, data collected since 1980]). The VLA has just released more recent figures: They received 98 feline samples during 2005, of which the culture results are available for all but 9; M bovis 12 cases, M microti 9 cases, M avium 4 cases, M malmonoense 1 case, inconclusive culture 2 cases).
Infection of cats with M tuberculosisis incredibly rare, probably because cats are naturally very resistant to this organism. (Interestingly, this is quite different from the picture seen in humans; where over 90 per cent of cases result from infection with M tuberculosis, approximately 1 per cent is caused by M bovis and disease due to M microti is incredibly rare). Cats can occasionally develop disease due to infection with MAC.
The current epidemiology of tuberculosis in cats is still unclear. While occasional clinical cases are reported, few are believed to relate to direct infection from cattle. Tuberculosis may arise after drinking contaminated cows' milk when the infection establishes within the cat's intestines, resulting in diarrhoea and weight loss. As almost all cows' milk is now pasteurised this type of tuberculosis is currently very rare. The tuberculosis that we now see most frequently in cats affects their skin; where it causes nonhealing sores and lumps that fail to heal. This is often associated with swollen lymph nodes, especially those under the chin, and some cases show only the swollen lymph nodes. In chronic cases, where the infection has spread to the cat's lungs, it may develop a soft cough or have difficulty breathing.
It is believed that most cats become infected via hunting small wild rodents. For this reason, most affected cats are adult males and keen hunters, regularly catching small rodents. Studies have shown that in the UK wild mice and voles quite often carry M microti, while moles and rats can carry M bovis. Affected cats most commonly suffer from skin lesions on the face and legs, ie, the areas most likely to be bitten when playing with prey.
In some areas of Britain M bovis has become endemic in badgers. While cats and badgers rarely interact directly, there may be a potential risk for cats to become infected via local environmental contamination. Most cases of feline TB caused by M bovis in recent years have been diagnosed in parts of Great Britain where this infection is considered endemic in cattle and badgers (see above).
Infection usually occurs after protracted exposure, eg, repeated exposure to infected small mammals, living on a farm housing tuberculous cattle, or living for prolonged periods with infected humans or poultry. There is no current evidence to suggest that immunosuppression increases a cat's susceptibility to TB – for example most cats with TB tested for the immunosuppressive viruses FIV and FeLV have been negative.
Depending on the route of infection, affected cats may present with systemic signs related to the gastrointestinal, and/or respiratory tracts, or with localised disease affecting the skin. Currently, the most usual presentation for tuberculosis in cats is the cutaneous (skin) form, with respiratory and gastrointestinal forms being seen less frequently.
In the cutaneous form the lesions probably arise from infected bite wounds, local spread or spread via the bloodstream. The lesions most commonly involve the face, limb extremities and tail base areas ie, ‘fight and bite sites'. They generally take the form of firm, raised skin nodules, ulcerated areas, or non-healing wounds with draining sinus tracts. Extension of granulomatous tissue may in some cases involve the subcutaneous structures, muscle and/or bone. Skin lesions are commonly associated with either local or generalised lymph node enlargement. In some cases, lymph node enlargement may be the only clinical finding.
When the infection spreads to the lungs, or where it is acquired through inhalation, infection can establish within the lungs and/or internal lymph nodes and affected cats may present with weight loss, loss of appetite, breathlessness and coughing.
In the gastrointestinal form, tubercles (TB granulomas) arise in the intestines and/or mesenteric lymph nodes. Affected cats commonly develop intestinal malabsorption and present with weight loss, anaemia, vomiting and diarrhoea. Occasionally tubercles arise in the tonsils, resulting in signs of oral discomfort.
A range of clinical signs may be seen with disseminated disease. These include enlargement of the spleen and liver, accumulation of fluid within body cavities, generalised enlargement of lymph nodes, weight loss and fever. Lameness may result from bone and/or joint involvement. Inflammatory ocular and neurological disease has been seen in some cases.
All members of the tuberculosis complex pose potential zoonotic risks. Additional cats and other animals in the household are also at risk of infection. However these risks appear to be small and, to date, there have been no reported cases of cats passing tuberculosis onto humans. By far the greatest tuberculosis risk to humans is spending time with infected humans or, less frequently, handling infected cattle.
Interestingly, M tuberculosis and M bovis can both cause reverse zoonoses (transmission from a human to an animal) and there have been a small number of cases where humans have infected their cats (usually with M bovis). This may be significant because with the current increase in human tuberculosis associated with HIV infection and poor housing, we may see a concurrent increase in feline tuberculosis caused by these organisms.
Infection may be suspected on the basis of clinical findings (eg, skin lesions) and there may be some clues on routine blood tests (eg, hypercalcaemia can be seen in some cases). Radiography can be useful in the appraisal of lung involvement. However, changes are very variable and include lymph node enlargement, interstitial or miliary lung infiltration, localised lung consolidation, or free pleural fluid. Abdominal radiography may reveal an enlarged liver and/or spleen, abdominal masses, mineralised mesenteric lymph nodes, or free abdominal fluid. Bone lesions tend to consist of areas of bony lysis and sclerosis, osteoarthritis,
discospondylitis or periosteitis.
Specific tests for the diagnosis of tuberculosis have been investigated in cats, but have generally proved unhelpful. Unlike other species, cats do not react strongly to intradermally administered tuberculin and the results from intradermal skin testing are unreliable. Tests for specific serum antibody responses have also proved unhelpful.
To confirm mycobacterial involvement, aspirates and/or biopsy samples of affected tissue should be stained with Ziehl Neelsen (ZN) stain. Histopathology of affected tissue generally reveals granulomatous inflammation, with foamy macrophages containing variable numbers of acid fast bacilli. The number of ZN staining (acid fast) bacilli seen within affected macrophages may be variable, depending on the species of mycobacteria involved, the location of the granuloma and, probably most importantly, the nature of the cat's immune response. While finding acid fast bacilli confirms the presence of mycobacteria, it is essential to culture the organism to determine the exact species involved. Since these are very slow-growing bacteria, culture typically takes several months and unfortunately, many samples that are seen to have ZN positive organisms fail to culture positive.
More recently there has been much interest in the use of molecular tests such as the polymerase chain reaction (PCR) test for the diagnosis of tuberculosis. At the moment, PCR is only available for some of the organisms causing mycobacterial infections in cats.
Once the species has been identified it is possible to evaluate zoonotic risk, potential sources of infection, and feasible treatment options. Until the organism has been properly characterised, it is important that it is considered a potential human pathogen.
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Deciding to treat a case of suspected feline tuberculosis is always contentious. Before undertaking treatment it is important to address a number of points:
- Consider the potential zoonotic risk. All members of the affected cat's household must be involved in any decision making. Particular consideration should be given to those individuals most susceptible to the infection, eg, household members with HIV infection, children, the elderly, or those undergoing chemotherapy or organ transplantation. Treatment is discouraged in those instances where such individuals may be exposed to an infected cat. Treatment is also discouraged in those cases where the affected cat has generalised disease, respiratory tract involvement, or extensive draining cutaneous lesions, since any of these findings may increase the risk of transmission to people. Owners should also be aware that cats and other animals in the household may be at risk of infection. Uncomplicated cutaneous disease appears to carry the most favourable prognosis for affected cats.
- Where the cat is a suitable candidate, it is important to recognise that treatment is long-term and difficult to maintain given patient non-compliance, the inherent toxicity of some of the drugs and the financial costs involved. In some cases the drugs may at best suppress the disease and indefinite treatment may be required.
- Tailoring treatment is difficult as sensitivity testing does not always correlate with in vivo results.
- Surgical removal of small skin lesions may be considered, but is successful in only a few cases. Debulking larger lesions risks wound break-down and local recurrence of infection.
Pending a definitive diagnosis, interim therapy with enrofloxacin, or another fluoroquinolone, may be recommended in cases with localised lesions. However, if additional signs of regional spread or systemic involvement are present (eg, radiographic changes or hypercalcaemia), it is strongly recommended that double or triple therapy be initiated immediately. This not only gives the best chance of clinical resolution, but also decreases the potential for the mycobacteria to develop resistance to the fluoroquinolone. This is an important consideration since generating drug resistance will be detrimental not only to the individual cat, but may also endanger human patients.
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The prognosis depends on the type of mycobacteria involved, and the extent and severity of the infection. While many cases, especially those caused by M. microti infection, have responded very favourably to treatment, and have achieved apparent cure or longterm remission, the prognosis should always be viewed as guarded.
Infection with M lepraemurium is largely assumed as the organism cannot be cultured using standard techniques. However, other types of mycobacteria have also been detected using PCR methods. In cats, introduction of the organism through bite wounds from rodents has been postulated but not proven and it is now considered that soil contamination of cutaneous wounds is more likely.
There is no breed or gender predisposition but young adult cats are more often affected. The prevalence of feline leprosy is higher in areas with a temperate maritime climate, eg, The Channel Islands.
Feline leprosy primarily presents as skin disease. Single or multiple nodules, which may be haired, alopecic (have lost their hair) or ulcerated, may be seen on the head, limbs and occasionally the trunk. They are non-painful and freely mobile. Regional lymph node enlargement may be present but systemic signs of illness are rare.
No – this is not a zoonotic infection. Leprosy in people is caused by infection with a different organism, Mycobacterium leprae, which is not infectious to cats.
Cytology and histopathology with the use of special stains are the major methods of diagnosis. Large numbers of acid fast organisms are usually seen within macrophages. Culture is unrewarding, but should be performed in all suspect cases as the clinical signs and histopathology of feline leprosy can mimic those of feline tuberculosis. Molecular PCR techniques are currently being investigated and do show promise. The diagnostic approach followed should be the same as that for tuberculosis.
As with tuberculosis, interim treatment with a fluoroquinolone antibiotic may be recommended. Following confirmation of the diagnosis, surgical removal of small nodules and/or continued medical management may be advised.
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The prognosis is good and spontaneous resolution may occur.
This syndrome is caused by saprophytic, usually non-pathogenic organisms that are found in soil, water and decaying vegetation. The ‘fast growing' representatives of this mycobacterial group are most commonly implicated in feline skin disease. However, as our ability to recognise the implications of ‘bite site' lesions improves along with our access to the expertise of the specialist laboratories, slow growing variants may be recognised more frequently as they are in human medicine.
The following organisms have been implicated in causing this syndrome; M. chelonae-abscessus, M fortuitum/peregrinum group, M smegmatis and M phlei. Other opportunist mycobacteria that have been found causing disease in cats include M genavense, M simiae, M thermoresistible, M xenopi and M terrae complex. All of these organisms can cause disease through contamination of skin wounds and are particularly pathogenic if inoculated into adipose tissue. Entry through the gastrointestinal or respiratory tracts is rare.
In general, cats appear to be more predisposed to infection with this group of mycobacteria than other domestic animals. Adult cats with a hunting or fighting lifestyle are more likely to be affected. Disease caused by these organisms is rarely reported in the UK and appears more common in tropical and subtropical areas of the world. However, difficulties associated with diagnosis may influence its true prevalence. Unlike the situation in humans, immunosuppression has only been found in a small number of the affected cats.
Many of the different species of opportunistic mycobacteria produce a similar clinical syndrome. This is typified by panniculitis (inflammation of the fat under the skin), where multiple, punctuate draining tracts occur with a ‘salt and pepper shaker' appearance. These are associated with subcutaneous nodules which coalesce to produce large areas of ulcerated, non-healing tissue. Affected areas can be extremely painful. The inguinal fat pads, flanks and the tail base are affected most frequently. However, any area may be affected if it is prone to injury (and has sufficient subcutaneous fat). The lesions may be exacerbated by surgery and dehiscence associated with satellite lesions is common. Although systemic spread is rare, fever, loss of appetite and reluctance to move may be seen. Primary pulmonary infection with M fortuitum and disseminated infection with M smegmatis have been reported and may have arisen from non-cutaneous routes of entry.
Is there any risk of transmission of opportunistic mycobacterial infections from a cat to a person?
Since opportunistic mycobacteria are present in the environment at all times, the risk of transmission from a cat to a human is low. However, it is recommended that people follow normal hygiene measures such as avoiding direct contact with the wound. Precautions are especially important if any immunosuppressed individuals (eg, those receiving anti-cancer chemotherapy) live in the household with the cat. The same advice applies to other cats and animals living in the same household.
Testing for mycobacteria should be pursued in any cases where histopathology reveals a pyogranulomatous panniculitis. Opportunistic mycobacteria are difficult to identify in histopathological sections even when acid fast stained, but the use of modified Fite's or rapid ZN methods increases the sensitivity of detection.
Culture from a biopsy specimen is the diagnostic test of choice. The organisms are usually relatively easy to grow on Lowenstein Jensen media, but molecular PCR techniques are also currently being investigated.
As with tuberculosis and leprosy, interim treatment with a fluoroquinolone may be recommended whilst awaiting culture results. Further treatment following confirmation of the diagnosis varies according to the specific organism isolated.
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The longterm prognosis is poor to guarded. The prognosis deteriorates further when there have been previous unsuccessful attempts at surgery.
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Updated May 2006 |
