Tuberculosis

Aetiopathogenesis

In cats, tuberculosis can be caused by Mycobacterium bovis or M. microti (the vole form). Data from the Veterinary Laboratories Agency (VLA) shows 337 Ziehl Neelsen (ZN)-positive feline samples received during 2005-7: M. microti 19%, M. bovis 12%, M. avium (MAC) 7%, M. malmonoense 1%, unclassified mycobacterium 4%, negative culture 55%. Infection with M. tuberculosis is incredibly rare, probably because cats are naturally resistant to it.

Current epidemiology is unclear. Few cases relate to direct infection from cattle (as drinking tuberculous milk typically results in GI disease). Most current cases are cutaneous in nature, spreading to the lungs in chronic cases. So how are cats infected? Most cases are keen hunters. In the UK, wild mice and voles can carry M. microti and M. bovis so it is likely that cats become infected by hunting wild rodents. In some areas of Britain M. bovis has become endemic in badgers. While cats and badgers rarely interact directly, there is potential risk from environmental contamination.

All members of the tuberculosis complex pose potential zoonotic risks.

Predisposition

Infection usually requires protracted exposure so disease is mainly seen in adults. No evidence of immunosuppression has been found. Certain breeds appear to be predisposed to MAC: Siamese and Abyssinian cats.

Clinical Signs

Depending on the route of infection, affected cats present with local cutaneous disease or systemic signs related to the alimentary, and/or respiratory tracts.

Cutaneous lesions probably arise from bite wounds, local spread or haematogenous dissemination. They often involve the face, extremities, tail base or perineum, i.e., the areas most likely to be bitten when playing with prey. They generally form firm raised dermal nodules, or non-healing wounds with draining sinus tracts. Extension of granulomatous tissue may involve the subcutaneous structures. Local or generalised lymphadenopathy is common, and is often the only clinical finding.

Pulmonary infection may cause weight loss, anorexia, dyspnoea and coughing. GI infection may cause intestinal malabsorption, weight loss, anaemia, vomiting and diarrhoea. Disseminated disease may cause splenomegaly, hepatomegaly, pleural or pericardial effusions, generalised lymphadenopathy, weight loss and fever. Lameness may result from bone involvement. Granulomatous uveitis and CNS signs may occur.

Diagnosis

Most changes are non-specific: hypercalcaemia, tracheo-bronchial lymphadenopathy, interstitial or miliary lung infiltration, localised lung consolidation, pleural effusion, hepato- or splenomegaly, mineralised mesenteric lymph nodes, ascites, bony lysis/sclerosis, osteoarthritis, discospondylitis or periostitis. Intra-dermal skin testing and serology are unreliable.

To confirm mycobacteria, aspirates and/or biopsy samples should be ZN-stained. The number of acid fast bacilli (AFB) seen in macrophages of the granulomatous response is variable, depending on the species of mycobacteria involved, the location of the granuloma and the cat's immune response. While finding AFB confirms mycobacteria, culture is needed to determine which species is involved. Unfortunately, many samples fail to culture, even after two months. Molecular techniques are now available, but they are expensive and not very sensitive.

Under the Tuberculosis Orders (England, Wales, and Scotland) the suspicion and/or identification of M. bovis in clinical or pathological samples taken from any mammal (except humans) is notifiable to the VLA.

Management

Interim

Deciding to treat suspected feline tuberculosis is contentious:

 Consider the potential zoonotic risk. Treatment is not advised if the cat lives with anyone immuno-suppressed, or if it has generalised disease, respiratory tract involvement, or extensive draining cutaneous lesions (these may increase the risk of transmission).

 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.

 Surgical debulking risks wound dehiscence.

Pending definitive diagnosis, interim therapy with a fluoroquinolone has been recommended. However, this should only be considered in cases of localized cutaneous infection. It is more sensible to recommend double or triple therapy (Table); this gives the best chance of clinical resolution, and decreases the potential for mycobacteria resistance.

Before deciding on continued treatment we need to know which mycobacterium is involved. Unfortunately, ~55% fail to culture so it is essential to counsel owners carefully, making them aware of all of the potential risks and complications.

Treatment

Ideally, anti-tuberculosis treatment should consist of an initial and a continuation phase. The initial phase requires two or three drugs and lasts for two months, while the continuation phase requires two drugs and lasts for a further four months, depending on the type and extent of the disease. Fluoroquinolones have potential in the treatment of tuberculosis and non-tuberculous Mycobacteria, but do not appear to be effective against MAC, except possibly some newer preparations e.g., moxifloxacin. Clarithromycin is best included when treating MAC. A potentially useful once daily alternative to this is azithromycin, although it may not be as effective. From clinical experience gained over >10 years we recommend an initial phase of rifampicin-fluoroquinolone-clarithromycin or azithromycin, followed by a continuation phase of rifampicin and either fluoroquinolone or clarithromycin/azithromycin (Table).

Prognosis

This depends on the type of mycobacteria involved, and the extent and severity of the infection. Many cases, especially those caused by M. microti infection, respond favourably. However, the prognosis should always be stated as poor to guarded.

Feline Leprosy

Aetiopathogenesis

Infection with M. lepraemurium is largely assumed as the organism cannot be cultured using standard techniques. However, recent reports from Australia show that feline leprosy can take one of two different forms and that while disease in younger cats does appear to be caused by M. lepraemurium, the disease seen in older cats appears to be caused by an as yet undefined mycobacteria. Infection is believed to arise through bite wounds from rodents. However, this is not proven and it is also possible that infection is gained via soil contamination of cutaneous wounds. There is no known zoonotic potential.

Predisposition

There is no breed or gender predisposition but adult cats are more often affected. Prevalence is higher in areas with a temperate maritime climate, e.g., Australia, New Zealand, Europe (UK, Channel Islands, Netherlands), western Canada and western parts USA.

Clinical Signs

This is primarily a cutaneous syndrome; single or multiple nodules, which may be haired, alopecic or ulcerated; on the head, limbs and occasionally the trunk. They are non-painful and freely mobile. Regional lymphadenopathy may be present; systemic disease is rare. In Australia this disease appears to have two different forms: 1) young cats, which initially develop localised nodular, often ulcerated, lesions on the limbs, which progress rapidly, 2) older cats, which develop more generalized skin involvement with no ulceration and a slower clinical progression.

Diagnosis

This requires cytology and histopathology (with special stains). In young cats there are typically few AFB; in older cats lesions often contain large numbers of AFB within macrophages. Culture is usually unrewarding, but should be performed in all cases because feline leprosy can mimic feline tuberculosis. Molecular PCR techniques are currently being investigated and show promise.

Management

A fluoroquinolone can be used pending diagnosis. Surgical removal of small nodules is recommended. Clofazimine has been used in a limited number of cases where surgical removal was difficult. Dapsone is considered too toxic for use in cats.

Prognosis

Is good and spontaneous resolution may occur.

Non-tuberculous Mycobacteria (NTM)

Aetiopathogenesis

These are caused by saprophytic, usually non-pathogenic, organisms which are found in soil, water and decaying vegetation. The 'fast growing' representatives of this group are most commonly implicated in 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 are being 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 NTM that have also been found causing disease in cats include M. genavense, M. simiae, M. thermoresistible, M. flavescens, M. xenopi, M. malmoense, M. alvei and M. terrae complex. All of these organisms 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.

Predisposition

In general, cats appear to be predisposed to infection with this group of mycobacteria. 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.

Clinical Signs

Many of the different species of NTM produce similar clinical syndromes. The most common of which is typified by 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 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, anorexia and reluctance to move may be seen. Primary pulmonary infection with M. fortuitum and disseminated infections with M. smegmatis and M. xenopi have been reported and may have arisen from non-cutaneous routes of entry.

Diagnosis

Pyogranulomatous panniculitis is seen and should automatically warrant a search for mycobacteria. Culture is the diagnostic test of choice. Some of the organisms are relatively easy to grow, but molecular PCR techniques are also currently being investigated.

Management

A fluoroquinolone is the drug of choice while waiting for culture. Ideally, antimicrobial therapy should be determined by culture and sensitivity. This is because different species of NTM have differing sensitivity patterns. One paper showed M. chelonae-abscessus and M. fortuitum were sensitive to amikacin (100%), cefoxitin (94%), ciprofloxacin (75%--presume other fluoroquinolones are similar), clarithromycin (71%) and doxycycline (29%). M. smegmatis is usually sensitive to fluoroquinolones, and M. xenopi may be sensitive to fluoroquinolones, clarithromycin, rifampicin and clofazimine. It is possible that double or triple therapy with a combination of fluoroquinolone, clarithromycin or azithromycin, and/or rifampicin should be considered as for the tuberculosis syndromes (Table). Antibiotic therapy should be continued for protracted periods of time: 6-12 weeks. Surgical intervention should be radical and planned as though for a locally invasive neoplasm. Antibiotic therapy in combination with surgery has been recommended.

Prognosis

Poor to guarded and deteriorates further with previous unsuccessful surgery.

Table. Drugs for the treatment of feline mycobacterial disease.

Tx--treatment, TB--tuberculosis, im--intramuscularly, sc--subcutaneously, non-tuberculous mycobacteria--NTM.
a. Not effective against MAC infection
b. Not licensed for use in cats.
c. Not effective against M. bovis infection.
d. Can be difficult to obtain. Second line treatments for tuberculosis should be reserved for resistant infections only. Drugs licensed for human use can be obtained by veterinary prescription from larger chemists.

References

References are available upon request.