Tuberculosis

Epidemiology

In the UK, tuberculosis in cats is infrequent and usually caused by either Mycobacterium bovis or M. microti (the vole bacillus). The VLA has released recent figures: of 89 feline samples received during 2005 which had Ziehl-Neelsen (ZN) -positive organisms on histopathology; culture revealed M. bovis in 12, M. microti 9, M. avium 4, M. malmonoense 1, M. celatum 1, inconclusive 2. A positive culture was only gained in 30%. M. avium and M. avium-intracellulare complex (MAC) organisms are saprophytic, but are considered with the tuberculosis complex as they can cause identical clinical disease.

Tuberculosis in cats most commonly affects their skin, where it causes non-healing sores and lumps, with or without lymphadenopathy. In the UK wild mice and voles often carry M. microti, while moles and rats can carry M. bovis. Cats may therefore become infected when hunting these rodents. This accounts for the distribution of the lesions on areas most likely to be bitten when playing with prey. In some areas of Britain M. bovis is endemic in badgers and other free-ranging wildlife, e.g., deer, so they may potentially infect cats through environmental contamination.

All members of the tuberculosis complex are potentially zoonotic. However, to date, there have been no reported cases of cats infecting humans. M. bovis can be a reverse zoonosis and there have been a small number of cases where humans have infected their cats.

Predisposition

Infection occurs after protracted exposure, e.g., repeated exposure to infected small mammals, living on a farm housing tuberculous cattle, or living for prolonged periods with infected humans/ poultry. Tuberculosis is seen mainly in adult cats (typically males), that are feline immunodeficiency virus (FIV) and feline leukaemia virus (FeLV) negative. Siamese, Abyssinian and Somalis appear to be predisposed to MAC infection.

Clinical Signs

Depending on the route of infection, affected cats may present with cutaneous, respiratory and commonly, alimentary signs.

Cutaneous lesions often involve the face, extremities, tail base or perineum. They are typically firm raised dermal nodules, or non-healing wounds with draining sinus tracts. Extension of granulomatous tissue may involve the subcutaneous structures. Skin lesions are commonly associated with either local or generalised lymphadenopathy. Occasionally, submandibular or prescapular lymphadenopathy is the only clinical finding.

Infection in the lungs and/or hilar lymph nodes can cause weight loss, dyspnoea and coughing. Infection in the intestines and/or mesenteric lymph nodes can cause intestinal malabsorption, weight loss, anaemia, vomiting and diarrhoea. Disseminated disease can lead to splenomegaly, hepatomegaly, pleural or pericardial effusions, generalised lymphadenopathy, weight loss and fever. Lameness may result from bone involvement. Granulomatous uveitis and central nervous system involvement have been seen.

Diagnostics

Non-specific tests can be used. Hypercalcaemia may correlate with poor prognosis. Radiography can be useful to assess lung involvement. Changes are variable: tracheobronchial lymphadenopathy; interstitial or miliary lung infiltration; localised lung consolidation; or pleural effusion. Abdominal radiography may reveal hepato- or splenomegaly, abdominal masses, mineralised mesenteric lymph nodes or ascites. Bone lesions tend to consist of areas of bony lysis and sclerosis, osteoarthritis, discospondylitis or periostitis.

Specific tests have proved unhelpful in cats.

To confirm mycobacterial involvement, aspirates and/or biopsy samples should be stained with ZN. The number of acid-fast bacilli seen within affected macrophages varies, depending on the species of mycobacteria, the location of the granuloma and the nature of the cat's immune response. Culture is needed to identify the exact species involved and so evaluate zoonotic risk, potential sources of infection and feasible treatment options. Unfortunately, many ZN-positive samples fail to culture, and even those that do typically take ~2 months. While molecular polymerse chain reaction (PCR) techniques are now available, they are expensive, and have still to be perfected.

Whenever handling potentially tuberculous material, take precautions. In the UK, the law requires the use of specialist laboratories when dealing with material known to be tuberculous. However, the law relating to material taken from animals where tuberculosis is only one of the differentials is different. In the latter routine asepsis is adequate, plus the use of gloves. Collect a biopsy, cut it into three pieces, fix one in formalin for histopathology and ZN staining and, pending results, place one in a sterile container and freeze it. Where other bacterial infections are suspected, the third sample should be sent unfixed for routine bacterial culture. If the sample is found to be ZN positive, the frozen portion can be sent to the VLA for specialist culture.

Under the tuberculosis orders in England, Wales, and Scotland, the identification of M. bovis in clinical or pathological samples taken from any mammal (except humans) is notifiable to the VLA. The same orders impose a duty on any veterinary surgeon who suspects tuberculosis in a domestic cat to immediately notify the Divisional Veterinary Manager at the local office of the State Veterinary Service.

Histopathology reveals granulomatous inflammation, with foamy macrophages containing variable numbers of acid-fast bacilli.

Treatment

Deciding to treat suspected feline tuberculosis is contentious:

 Consider potential zoonotic risk. We strongly advise against treatment where potentially immunosuppressed individuals may be exposed, or if the affected cat has generalised disease, respiratory tract involvement or extensive draining cutaneous lesions.

 Treatment is long term and difficult to maintain given patient non-compliance, inherent drug toxicity and financial costs. In some cases indefinite treatment may be required.

 Surgical excision of small cutaneous lesions may be considered, but debulking larger lesions risks wound dehiscence and recurrence.

Pending definitive diagnosis, interim therapy with a fluoroquinolone has been recommended for localized cutaneous infections. However, double or triple therapy gives the best chance of clinical resolution, and decreases the potential for developing mycobacterial resistance.

Ideally, treatment should consist of an initial phase with three drugs for 2 months (e.g., rifampicin-fluoroquinolone-clarithromycin/ azithromycin), then a continuation phase with two drugs for ~4 months (e.g., rifampicin and either fluoroquinolone or clarithromycin/azithromycin) (Figure 1). Where triple therapy is not feasible, two drugs should be given for a minimum of 6-9 months. Fluoroquinolones are useful for the treatment of feline tuberculosis and opportunistic mycobacteriosis, but are often not effective against MAC infection (except possibly some newer preparations, e.g., moxifloxacin). MAC infections are best treated with clarithromycin, typically in combination with rifampicin and/or another antibiotic as per culture results, e.g., doxycycline. A potentially useful once-daily alternative to clarithromycin is azithromycin, although it may not be as effective.

Prognosis depends on the type of mycobacteria and the severity of disease. While many cases (especially M. microti) respond well to treatment giving cure or long-term remission, the prognosis should always be stated as guarded.

Feline Leprosy

Epidemiology

Infection with M. lepraemurium is assumed, as the organism cannot be easily cultured. Reports from Australia show that disease can take two forms; in younger cats it is caused by M. lepraemurium, while in older cats it is caused by a novel undefined mycobacterium. Infection is believed to be gained through bite wounds from rodents. There is no known zoonotic potential. Adult cats are typically affected. Prevalence is higher in temperate maritime climates, e.g., Australia, New Zealand, Europe (UK, Channel Islands, Netherlands), western Canada and USA.

Clinical Signs

Leprosy is primarily cutaneous, causing single or multiple nodules, which may be haired, alopecic or ulcerated, on the head, limbs and occasionally trunk; they are non-painful and freely mobile. Regional lymphadenopathy may be present; systemic disease is rare. In Australia there are two forms: young cats initially developing localised nodular, often ulcerated, lesions on the limbs, which progress rapidly, and have few acid fast organisms on histopathology; and older cats, which develop more generalised skin involvement with no ulceration and a slower clinical progression, with lesions containing large numbers of acid-fast organisms, which can be clearly seen within macrophages.

Treatment

Fluoroquinolone is given, pending diagnosis. Surgical removal of small nodules can be carried out. Clofazimine has been used in a limited number of cases where surgical removal was difficult. Dapsone is too toxic for cats.

Prognosis

The prognosis is good and spontaneous resolution may occur.

Opportunistic Mycobacteria

Epidemiology

This syndrome is caused by saprophytic, usually non-pathogenic, organisms which are found in soil. 'Fast-growing' mycobacteria are most commonly implicated but specialist laboratories are growing slow-growing variants more frequently; e.g., M. chelonae-abscessus, M. fortuitum/peregrinum group, M. smegmatis, M. phlei, M. genavense, M. simiae, M. thermoresistible, M. flavescens, M. xenopi, M. malmoense and M. terrae complex. All can cause disease through contamination of cutaneous wounds and are particularly pathogenic if inoculated into adipose tissue. Entry through the gastrointestinal or respiratory tracts is rare. Adult cats with a hunting/fighting lifestyle are more typically affected. Viral immunosuppression is rare.

Clinical Signs

The most common clinical syndromes is panniculitis, where multiple, punctate draining tracts occur with a 'salt and pepper shaker' appearance. These are associated with subcutaneous nodules and coalescence produces large areas of ulcerated, non-healing tissue. Affected areas can be painful. Inguinal fat pads, flanks and tail base are affected most frequently. The lesions may be exacerbated by surgery and dehiscence with satellite lesions is common. Although systemic spread is rare, fever and anorexia 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.

Histopathology

Pyogranulomatous panniculitis is found, but organisms are difficult to identify even with special stains.

Culture

Organisms are usually relatively easy to grow on Lowenstein Jensen media, but molecular PCR techniques are also being investigated.

Treatment

Fluoroquinolone is used pending culture. Treatment of choice is controversial and evaluation of individual cases is required. Ideally, treatment is determined by culture and sensitivity as different species have differing sensitivity patterns: e.g., M. chelonae-abscessus and M. fortuitum are sensitive to amikacin (100%), cefoxitin (94%), ciprofloxacin (75%--presume other fluoquinolones are similar), clarithromycin (71%) and doxycycline (29%). M. smegmatis is usually sensitive to fluoquinolones. It is possible that double or triple therapy with a combination of fluoroquinolone, clarithromycin or azithromycin and/or rifampicin should be considered as for tuberculosis. Antibiotic therapy should be continued for 6-12 weeks. Surgical intervention should be radical. Antibiotic therapy in combination with surgery has been recommended.

Prognosis

This is poor to guarded, and deteriorates with previous unsuccessful surgery.

Figure 1. Potentially useful drugs for the treatment of feline mycobacterial disease.

Drugs given in italics are not licensed for use in cats. Second line treatments for tuberculosis should be reserved for resistant infections. Potentially useful drugs for the treatment of feline mycobacterial disease. Drugs given in italics are not licensed for use in cats. Second line treatments for tuberculosis should be reserved for resistant infections.

All potential cases should be reported to the VLA, which is willing to undertake mycobacterial culture free of charge in appropriate cases. Contact Mr Jahans prior to sending samples and enclose case details: Mr Keith Jahans, TB Diagnostic Laboratory, Veterinary Laboratories Agency (DEFRA)--Weybridge, New Haw, Addlestone, Surrey, KT15 3NB. Telephone number: 01932 357280. email: k.jahans@vla.defra.gsi.gov.uk. Also please contact Danielle.Gunn-Moore@ed.ac.uk as I am trying to collate cases of mycobacterial infection in cats in the UK.