Tuberculosis (TB) is a disease that arises from infection with mycobacteria of the Mycobacterium tuberculosis complex (MTBC). It has affected humans and animals from ancient times to the modern day. Until the COVID-19 pandemic, TB was the leading infectious cause of death around the world, with up to a quarter of the global population infected according to data from the World Health Organization. In the UK, the devastating effect of TB among cattle and the farming industry is sadly well documented and remains a significant challenge.
Due to the proximity of pets to their owners, TB in companion animals can have important health consequences and potential zoonotic implications. Therefore, the aim of this article is to summarise key aspects of this disease in cats, including the cause, presentation and diagnosis to treatment and prognosis. It will also highlight when the zoonotic risk should be considered.
Aetiology of feline tuberculosis
The causative agents of feline TB are the species of the MTBC. The taxonomy of mycobacteria is debated, but there are 10 generally accepted species within this group. Notably, cats can become infected with mycobacteria other than these accepted species, so not every cat with a mycobacterial infection has TB. Culture data in the UK identified that feline TB is caused by just two MTBC organisms: Mycobacterium microti, which was found in 19 percent of cases, and Mycobacterium bovis, which was identified in a further 15 percent.
Mycobacterium tuberculosis infection, the leading cause of human tuberculosis, is reported as “very rare” in the feline population. Critically, it is now suspected that the small numbers of cases reported in the literature are very likely to have been due to other MTBC mycobacteria, as historic typing methods are now widely accepted to have been inaccurate for the sub-classification of the MTBC. Furthermore, it has been demonstrated that cats have a natural resistance to M. tuberculosis based on experimental challenge studies. Therefore, it should not be a concern for a clinician or owner, and a TB diagnosis in a cat does not necessitate immediate euthanasia on public health grounds.
The prevalence of TB in the UK cat population is unknown, but 1 percent of all feline biopsy samples submitted to UK laboratories were consistent with mycobacterial infection
The prevalence of TB in the UK cat population is unknown, but 1 percent of all feline biopsy samples submitted to UK laboratories were consistent with mycobacterial infection (though not necessarily TB infections, as discussed). Infected cats can be of any age, with the majority being young to middle-aged adults (three to seven years), with a male bias but no breed predisposition.
A strong geographical predilection exists for cases of TB in the UK: M. bovis infections are strongly coincident with high levels of endemic infection in local bovine and wildlife populations, such as in the south-west of England. By comparison, M. microti infections are much more common in areas with high prevalence in the wild rodent population, typically south-east of London, the north of England and throughout Scotland. This co-localisation is thought to reflect the putative mechanism of infection: hunting infected prey.
How does tuberculosis present in cats?
Most feline TB cases present with localised nodular cutaneous disease (Figure 1), some of which present with ulceration and, occasionally, draining sinus tracts. Lesions are typically distributed around the face, extremities and tail base (ie around “fight and bite sites”). Cases can have localised or, occasionally, a generalised lymphadenomegaly. Alternatively, lymphadenomegaly, usually of the submandibular or popliteal nodes, may be the only presenting sign.
Less frequently observed signs include coughing, dyspnoea, gastrointestinal disease, insidious weight loss and ocular changes (eg chorioretinitis).
How can we diagnose feline tuberculosis?
Making a diagnosis of TB is challenging as the clinical signs are often non-specific. However, making a subspecies-specific diagnosis is important because the treatment for other mycobacterial infections is sometimes different, as is the zoonotic risk between M. bovis and M. microti.
General haematology and serum biochemistry tests are usually normal, and any abnormalities seen are frequently non-specific signs of inflammation. Typically, the initial test that raises the clinical suspicion of TB is the histology of a removed cutaneous mass or lymph node that reveals granulomatous or pyogranulomatous inflammation and, possibly, the presence of mycobacteria using acid-fast staining techniques. Histology cannot discriminate between the infecting species, so further specific tests are subsequently needed.
The reference test for TB remains specialist culture, which, in the UK, can currently only be performed by the Animal and Plant Health Agency. The disadvantages of this test are:
- It has relatively poor sensitivity, with no growth in 53 percent of samples submitted in one study
- It requires fresh tissue, which may not be available
- TB mycobacteria are very slow growing, meaning results can take approximately eight weeks, so action must be taken in the interim
Alternatively, PCR testing is offered by Leeds University Teaching Hospital (a reference laboratory for human infections in England), which can be conducted on fresh or fixed tissue sections. This service can be accessed via veterinary diagnostic service providers such as Idexx.
Biobest Laboratories in Edinburgh have over a decade of experience using an interferon-gamma release assay (IGRA) to diagnose feline TB. The IGRA is a blood test that detects the patient’s immune response to mycobacterial antigens. As more data have been accumulated, recent adjustments to the interpretation methodology have increased the overall test sensitivity for MTBC infections to 90.2 percent with 100 percent specificity. It can also identify M. bovis to the species level with 68 percent sensitivity.
What’s next?
Once a diagnosis has been reached, staging for systemic spread is imperative. Many cases have secondary pulmonary involvement. The inflammation in the lungs affects the interstitial space, making it impossible to detect by auscultation, thoracic compression or percussion, so thoracic radiography is an essential step when investigating cases of feline TB (Figure 2).
How do we treat feline tuberculosis?
Once a diagnosis has been achieved, the next challenge for clinicians and owners is management of the disease. If treatment is to be attempted, obtaining a successful outcome requires a prolonged course of multi-antibiotic therapy.
Good antibiotic stewardship requires clinicians to have a clear discussion with clients about the importance of appropriate adherence to treatment from the outset
The success of this treatment is dramatically influenced by owner and patient compliance. Drug toxicity and the costs associated with medications and disease monitoring can make optimal regimes difficult to maintain. Furthermore, good antibiotic stewardship requires clinicians to have a clear discussion with clients about the importance of appropriate adherence to treatment from the outset. If this cannot be achieved, then treatment must be discouraged to avoid generating antibiotic resistance.
Surgical treatment
Complete surgical resection of solitary skin nodules may be curative; however, this cannot be guaranteed, and adjunctive medical therapy is always indicated. Surgery may be considered for any lesions that remain at the time of diagnosis and those that may have subsequently arisen, but there is a significant risk of wound dehiscence. There is no evidence that revision surgery confers a benefit to rigorous medical management.
Medical treatment
The standard first-line therapy for feline TB should comprise a fluoroquinolone, a macrolide/azalide and rifampicin (Table 1).
| Drug | Product | Dosing | Contraindications | Side effects |
|---|---|---|---|---|
| Pradofloxacin (fluoroquinolone) | Veraflox – 25mg/ml suspension or 15mg tablets | 3 to 5mg/kg PO q24h | Not in cats under six weeks of age due to potential adverse effects on cartilage Do not use in animals with epilepsy | Neutropenia with high doses and/or long courses |
| Marbofloxacin (fluoroquinolone) | Marbocyl – 20mg tablets | 2mg/kg PO q24h | (As for pradofloxacin) | Intermittent vomiting and transient diarrhoea on instigation of treatment |
| Moxifloxacin (fluoroquinolone) | Avelox – 400mg tablets | 10mg/kg PO q24h | (As for pradofloxacin) | Occasional vomiting Ocular toxicity has not been thoroughly assessed |
| Ciprofloxacin (fluoroquinolone) | 5 to 15mg/kg PO q12h | (As for pradofloxacin) | Occasional vomiting | |
| Azithromycin (azalide/macrolide) | Zithromax – 250mg capsule or 50mg/ml suspension | 5 to 15mg/kg PO q24h | Pre-existing cardiopathy, especially arrhythmogenic diseases Pre-existing hepatopathy | Intermittent vomiting Diarrhoea possible but uncommon |
| Clarithromycin (macrolide) | (Generic) 500mg tablet or 50mg/ml suspension | 7.5mg/kg PO q12h | Concurrent use of non-steroidal anti-inflammatory drugs or antacids Pre-existing hepatopathy | Pinnal erythema Generalised erythema Hepatotoxicity |
| Rifampicin | Rifadin – 300mg capsule or 20mg/ml suspension | 5 to 10mg/kg PO q24h | Pre-existing hepatopathy Pregnant queens | Hepatotoxicity – induction of liver enzymes, anorexia, generalised erythema and pruritus Central nervous system signs Discoloration of body fluids |
The fluoroquinolone of choice is pradofloxacin (where available) due to its excellent safety profile in the cat and known in vitro activity against mycobacteria.Enrofloxacin is an unacceptable choice for the treatment of TB in cats due to its association with acute irreversible retinopathy. The macrolide/azalide of choice is azithromycin due to a once-daily dosage pattern which eases compliance.
Rifampicin is a cornerstone of anti-tuberculosis medical therapy due to its efficacy against both intra- and extracellular mycobacteria. However, it should never be used as a monotherapy as resistance develops rapidly. Rifampicin has the potential to be significantly hepatotoxic when used chronically. Before starting treatment, obtaining a baseline serum biochemistry is advisable. Treatment with rifampicin should be stopped if patients become unwell on therapy, and additional management advice sought. Rifampicin is excreted in all bodily fluids and may cause urine, tears and saliva to discolour and become red-orange. While not clinically significant, this side effect can be distressing for unprepared clients, as there is the potential for discoloration to be mistaken for haemorrhage. Deposition of the drug in the skin can cause discoloration, irritation and, occasionally, hyperaesthesia. Rifampicin is potentially teratogenic, so should be handled by owners appropriately and should not be administered to pregnant queens.
The duration of treatment is dependent on the clinical signs present at the time of diagnosis. Three months of triple therapy, as outlined, is considered the minimum in all cases. Treatment should be extended for two months beyond the resolution of clinical signs, which includes any pulmonary dissemination detectable on radiographs.
Prognosis
If dosing is maintained, then the prognosis for feline TB is considered fair, with one review stating that 40 percent of cases reached and maintained complete clinical remission. The remaining 60 percent of cases showed variable responses from temporary or partial remission to no response to treatment. However, these data relate to a retrospective cohort not treated with optimal therapies. With the approach outlined above, unpublished clinical experience of the author suggests a positive prognosis in 80 to 85 percent of feline TB cases.
If dosing is maintained, then the prognosis for feline TB is considered fair, with one review stating that 40 percent of cases reached and maintained complete clinical remission
Zoonotic risk
When it comes to feline TB, the degree of zoonotic risk is dependent on four key factors:
- The species of mycobacteria
- The nature of the cat’s infection (eg subcutaneous non-ulcerated lesions versus wounds draining large quantities of pus)
- The susceptibility of individuals in close contact with the animal(s)
- The degree and nature of contact between the animal and its owner
M. bovis is a known zoonosis with around 1 percent of human TB cases in the UK caused by M. bovis infection. There are sporadic but low numbers of confirmed or highly suspected zoonotic cases of feline origin. Overall, the UK public health agencies consider the risk to people from cats to be “very low”, so treatment in pets can be considered. A number of risk factors have been compiled from public health organisations to identify people who are considered at heightened risk. In these circumstances, euthanasia of an M. bovis-infected cat would be indicated to protect human health unless the cat can be removed and treated elsewhere. This should be considered if individuals in contact with the infected cat:
- Are under five years old
- Are pregnant
- Are HIV positive (untreated)
- Suffer from substance abuse
- Have been diagnosed with diabetes mellitus, cystic fibrosis or kidney disease
- Have received an organ transplant
- Are a cancer patient receiving chemotherapy or radiotherapy
- Require treatment with systemic corticosteroids
- Require tumour necrosis factor-alpha antagonists, such as infliximab
By comparison, the risk posed by M. microti is considered negligible, with only 27 human cases reported globally. There is also no evidence linking infections in people to cats.
Summary
Feline TB is increasingly recognised in UK cats, and updated diagnostic and treatment protocols have significantly improved the prognosis of the disease. Appropriate specific investigations can aid clinical decision making with regard to optimal treatment strategies and inform owners about the zoonotic risks.
