Mycobacterioses in cats

 

Updated March, 2021

 

The Mycobacterioses in cats guidelines were first published in the J Feline Med Surg 2013; 15: 591-597 by Albert Lloret et al. and updated by Albert Lloret in 2015. The present update was authored by Albert Lloret and Séverine Tasker.

 

Agent properties

 

Mycobacteria are intracellular, acid-fast, slow-growing bacilliform Gram-positive aerobic bacteria, highly resistant to environmental conditions (Greene and Gunn-Moore, 2006; Gunn-Moore, 2010). Mycobacterial taxonomy is complex, and many species can infect cats and cause different clinical presentations. Different classifications have been suggested in the past based on features and ability to growth in culture as well as biochemical properties (Gunn-Moore, 2010). The use of molecular techniques has led to taxonomic changes, and some species have been classified into different groups (Gunn-Moore, 2010).

 

For practical purposes, mycobacteria will be classified in this guideline on the basis of their biologic behaviour, including aspects of clinical presentation, diagnosis and culture, their response to treatment and zoonotic aspects.

 

Tuberculosis (TBC) complex group

 

This group includes Mycobacterium tuberculosis (mainly infecting humans and dogs, rarely cats and other species), Mycobacterium bovis (infecting cattle, dogs, cats and rarely humans) and Mycobacterium microti (infecting small rodents like voles and shrews as well as cats). These bacteria are obligate pathogens and can be grown only in specific culture media. Tuberculosis in cats most commonly arises due to M. bovis or M. microti infections. Infection with these species can result in systemic disease with disseminated internal lesions (mainly digestive or respiratory), especially with M. bovis (Gunn-Moore et al., 1996; Rüfenacht et al., 2011); infections with M. microti are more commonly associated with localized or disseminated cutaneous disease (Gunn-Moore et al., 2011a).

 

Nontuberculous mycobacteria (NTM) group

 

This group includes a large number of species that have pathogenic potential but are generally saprophytic or opportunistic. NTM slow-growing and rapid-growing species causing infections in cats are listed in Table 1. NTM infections in cats typically involve skin and subcutaneous tissues (either focal, multifocal or diffuse lesions), rarely progressing to systemic disease (Baral et al., 2006; Pekkarinen et al., 2018) with the exception of MAC (Mycobacterium avium-intracellulare complex) infections, which are more frequently systemic in nature (Gunn-Moore et al., 1996; Malik et al., 2002; Munro et al., 2021).

 

Feline leprosy

 

Mycobacterium lepraemurium, and several other species that cause feline leprosy, cannot be grown in culture. Infection in cats is restricted to the skin where it produces localized and rarely disseminated cutaneous nodules (Horne and Kunkle, 2009; O’Brien et al., 2017a, b, c; Krug et al., 2018).

 

Knowledge on this group of species is evolving rapidly, particularly in Australia and New Zealand where most cases are diagnosed and reported. Novel species and associated disease have been detected in recent years, such as ‘Candidatus Mycobacterium tarwinense’ and ‘Candidatus Mycobacterium lepraefelis’ (O’Brien et al., 2017a, c) (Table 1).

 

Mycobacteria species TransmissionClinical presentation Treatment Zoonotic risk
References
Tuberculosis complex
Mycobacterium tuberculosisInhalation respiratory secretions from infected humans Pulmonary

Mesenteric / gastrointestinal

Lymphadenopathy

Systemic
Not advisedAnthropozoonosis

Cats naturally resistent
Mycobacterium bovisIngestion unpasteurized milk

Ingestion or contact with wild species (badgers)

Cutaneous inoculation contaminated soil

Cat-to-cat

Commercial raw food
Cutaneous lesions (nodules, ulcers)

Lymphadenopathy

Mesenteric / gastrointestinal

Ocular lesions

Systemic disease
Clarithromycin (azithromycin), pradofloxacin and rifampicine

Surgical removal skin nodules

Other alternative drugs in some cases
Potential zoonotic risk (low)

Humans infected
by cats in two
reports


O’Connor et al., 2019
Attig et al., 2019
Cerna et al., 2019
O’Halloran et al., 2019
Murray et al., 2015
Ramdas et al., 2015
Mycobacterium microti Ingestion or contact with prey species, (voles, mice)

Cutaneous inoculation contaminated soil
Localized or generalized cutaneous lesions (nodules, ulcers)

Lymphadenopathy
Same Low potential risk
In immuno-
competent humans


Rüfenacht et al., 2011
Smith et al., 2009
Gunn-Moore et al., 1996
Nontuberculous mycobacterial disease (NTM)
Slow-growing bacteria
Mycobacterium avium-intracellullare complex (MAC)Cutaneous inoculation contaminated cat fights

Ingestion of contaminated water or prey species (birds)
Mesenteric lymphadenopathy

Pulmonary

Systemic involvement

Ocular lesions

Meningoencephalitis

Maybe associated with immunodeficiency in some cats

Breed predisposition
Clarithromycin (azithromycin) and one or two of the following pradofloxacin, rifampicine or clofazimine Low potential risk
In immuno-
competent humans



Pekkarinen et al., 2018
Madarame et al., 2017
Rivière et al., 2011
De Groot et al., 2010
Sieber-Ruckstuhl et al., 2007
Baral et al., 2006
Griffin et al., 2003
Kaufman et al., 1995
Jordan et al., 1994
Mycobacterium genavenseRespiratory and systemic in a FIV catHughes et al., 1999
Mycobacterium malmoenseLocal muscular


Disseminated disease
Enrofloxacin, rifampicin and azithromycinPekkarinen et al., 2018
Hetzel et al., 2012
Mycobacterium celatum
Mycobacterium terraeSkin noduleEnrofloxacin, rifampicin, clarithromycinHenderson et al., 2003
Mycobacterium simiaeDietrich et al., 2003
Mycobacterium xenopiTracheal granuloma in a FIV cat


Chronic disseminated in a cat with primary CD4+ lymphocytopenia



Peritonitis and lymphadenopathy
Surgery


Enrofloxacin, rifampicin, clarithromycin, clofazimide
De Lorenzi and Solano-Gallego, 2009

Meeks et al., 2008




MacWilliams et al., 1998
Mycobacterium ulceransSkin nodule Surgery
clarithromycin
Elsner et al., 2008
Mycobacterium heckeshornenseGastrointestinal and systemic disease in a FIV cat Elze et al., 2013
Mycobacterium branderi/shimoideiDisseminated diseasePekkarinen et al., 2018
Mycobacterium kansasiSystemicLee et al., 2017
Mycobacterium sp strain MFM001Unknown, water suggestedGastrointestinal and systemic disease in an immunosuppressed catKayanuma et al., 2019
Mycobacterium nebraskenseNodular skin lesions, panniculitisClarithromycin
Rifampicin
Surgery
Niederhäuser et al., 2018
Rapid-growing bacteria
Mycobacterium fortuitumCat bite Skin lesions, panniculitis





Respiratory disease


No response
Ngan et al., 2005
Jang and Hirsch, 2002 Krajewska-Wędzina et al., 2019

Couto and Artacho, 2007
Mycobacterium chelonae-abscessusSkin lesions Jang and Hirsch, 2002
Mycobacterium mageritenseSkin lesions Govendir et al., 2011a, b
Mycobacterium smegmatisSkin lesions


Panniculitis
Bennie et al., 2015


Alander-Damsten et al., 2003
Mycobacterium flavescensSkin lesions Jang and Hirsch, 2002
Mycobacterium mucogenicum
Mycobacterium massilienseSkin lesionsAlbini et al., 2007
Mycobacterium phlei
Mycobacterium thermoresistibleContamination by soil Panniculitis in surgical wounds No

Vishkautsan et al., 2016
Suy et al., 2013
Foster et al., 1999
Willemse et al., 1985
Mycobacterium porcinum PanniculitisPradofloxacin and doxycyclineCox and Udenberg, 2020
Mannion et al., 2020
Feline leprosy syndrome
Mycobacterium lepraemuriumRodent bites

Soil contamination
Skin nodules head and forelimbs


Rarely disseminated skin nodules
Surgical excision


Two or three of the following drugs: rifampicin, clofazimine, clarithromycin,
Pradofloxacin


Spontaneous remission in some cats
No zoonotic risk

No cat-to-cat transmission

Krug et al., 2018
O’Brien et al., 2017b
Malik et al., 2002
Roccabianca et al., 1996
Candidatus “Mycobacterium tarwinense”Cat aggression

Self-inoculation grooming

Rodent bites

Soil contamination
Ocular lesions (proliferative lesions in conjunctiva, cornea, eyelids, nictitating membrane)


Nasal and periocular skin nodules

Forelimbs nodules
Surgical excision (especially cornea)




Two or three of the following drugs: rifampicin, clofazimine, clarithromycin,
Pradofloxacin
No zoonotic risk

O’Brien et al., 2017c
Candidatus “Mycobacterium lepraefelis”Cat aggression

Rodent bites
Skin nodules with tendency to progress to generalized skin disease

Systemic involvement and haematogenous dissemination
Poor response to treatment

Surgical excision and/or debulking of lesions

Two or three of the following drugs; dapsone, rifampicin, clofazimine, moxifloxacin, minocycline
No zoonotic risk

O’Brien et al., 2017a
Malik et al., 2002

 

Epidemiology

 

The true prevalence of mycobacterial infections in cats is unknown. They are considered rare, but case series or case reports from the USA, Australia, New Zealand and several European countries have been reported or published. In recent years, more cases have been recognised, suggesting that infection has been under-diagnosed previously (Malik et al., 2002; Smith et al., 2009; Gunn-Moore et al., 2013). A survey (2009) from diagnostic laboratories in the UK evaluating the prevalence of tissue samples with a final histological diagnosis of mycobacterial infection showed a relatively high incidence of approximately 1% (Gunn-Moore et al., 2013).

 

Data on the importance of the different mycobacterial species are also lacking. A retrospective study from the UK, evaluating 339 cases of mycobacterial disease in cats, found that 53% could not be identified following culture; 19% were M. microti, 15% M. bovis, 7% MAC and 6% NTM (Gunn-Moore et al., 2011a). Most cats with mycobacterial infections have an outdoor lifestyle (Horne and Kunkle, 2009; Gunn-Moore et al., 2011a), but infection has also been reported in indoor cats. Living in a non-urban area seems to increase the risk of infection (Gunn-Moore et al., 2013). Adult male cats are likely predisposed to become infected (Gunn-Moore et al., 1996; Gunn-Moore et al., 2011a), and Siamese, Somali and Abyssinian breeds seem to be predisposed specifically for MAC infections (Malik et al., 2002; Burthe et al., 2008; Gunn-Moore et al., 2011a).

 

Tuberculosis complex group

 

M. microti infection is mainly related to ingestion or direct contact (bites) with small rodents like voles and mice (Aranaz et al., 1996). M. tuberculosis infection is rare in cats (Hartmann et al., 2000), probably due to their natural resistance to infection (Biet et al., 2005). M. tuberculosis and M. bovis can be directly transmitted to cats by several methods such as direct contact with an infected human (M. tuberculosis), ingestion of milk from infected cattle or by direct or environmental contact with badgers (M. bovis; Malik et al., 2000).

 

M. bovis infection can also be transmitted cat-to-cat by direct contact as it has been reported in recent years. In the UK, a nosocomial infection with M. bovis was reported in a cluster of cats which had attended a veterinary practice in Ireland for routine surgery (Murray et al., 2015). In a recent outbreak in Italy, five indoor Abyssinian cats living in a breeding cattery were infected by a kitten imported from Ukraine. All of the cats died with respiratory, gastrointestinal and systemic clinical signs (Černá et al., 2019).

 

Recently, several cats have been diagnosed with M. bovis infection associated with the ingestion of a commercial raw food. Thirteen indoor cats in 5 different households from different areas were diagnosed with mycobacteriosis by culture, PCR and/or interferon-gamma release assay (IGRA). Six cats were presented with severe clinical disease, five of them dying. Seven cats tested positive by IGRA without showing clinical signs at the time the report was submitted for publication. Following publication, the authors identified up to 30 more infected cats. All the cats had been fed with the same raw food and so, while still not definitively proven, the food was the likely source of M. bovis infection. No cat-to-owner transmission was reported so far associated with those outbreaks (O’Halloran et al., 2019).

 

NTM group

 

The main risk for infection with these species is wound contamination by NTM present in the environment, soil, water and in decaying vegetation (Jang and Hirsch, 2002; Baral et al., 2006; Smith et al., 2009).

 

Infection with MAC species can also be acquired by ingestion or contact with prey species such as birds (M. avium subsp. avium).

 

Feline leprosy

 

The main risk for infection with leprosy-causing bacteria is direct contact or rodent bites, but infection can also result from wound contamination by mycobacteria present in soil or on plants (McIntosh, 1982; Horne and Kunkle, 2009). 

Other means of transmission, such a cat fights and grooming, have been proposed for Candidatus “Mycobacterium tarwinese” (O’Brien et al., 2017c).

 

Pathogenesis

 

Mycobacteria infect macrophages and induce granulomatous and pyogranulomatous inflammatory responses to the affected persistent stimuli of the pathogen in the organs (Kipar et al., 2003; O’Halloran et al., 2018). The mycobacterial species, route of infection and immune responses determine the extent, location and severity of the lesions.

 

The inflammatory cascade induced by mycobacterial infection is complex and poorly characterised in the cat. Inhibition of phagosome-lysosome fusion enables the intracellular survival of mycobacteria which stimulates macrophage invasion of tissues. Cytokine production is also stimulated, predominantly TNF-α, which drives the recruitment of mononuclear cells and neutrophils from surrounding blood vessels. Additionally, each group of recruited cells also releases its own assortment of cytokines and chemokines, which perpetuate the inflammatory cascade and lead to the formation of stable granuloma (O’Halloran et al., 2018).

 

The cytokine pattern in feline mycobacterioses has recently been studied for the first time, revealing that seven critically important cytokines were increased (GM-CSF, IL-2, PDGF-BB, IL-8, KC, RANTES and TNF-α) compared to control cats (healthy cats and ill cats with other diseases), showing a sensitive and specific cytokine indication/pattern of mycobacterial infection in this study population. Three cytokines were significantly reduced (sFAS, IL-13 and IL-4). This pattern is suggestive of a pro-inflammatory process which is dominated by the recruitment and maturation of monocyte-macrophage lineage cells, the recruitment of cytotoxic T-cells, the proliferation of fibroblasts and the suppression of humoral immunity. These results were obtained retrospectively from a small number of cats. Further prospective studies are required to evaluate whether the cytokine pattern could be of diagnostic use for feline mycobacteriosis. For example, TBC infections seemed to be associated with significant elevations of GM-CSF, IL-2 and Flt3-L, in contrast to NTM infections (O’Halloran et al., 2018).

 

Tuberculosis complex group

 

The primary site of infection by M. tuberculosis and M. bovis can be the alimentary tract, the lungs or skin (Malik et al., 2000; Gunn-Moore, 2010), largely dependent on the route of infection (ingestion, inhalation or contact, respectively). From these sites, dissemination and systemic infection can occur, e.g. haematogenous spread to the lungs from cutaneous lesions. Only rarely is the infection primarily systemic. With M. microti infection the route of entry is the skin, in locations commonly affected by wild rodent bites (the face and legs) (Gunn-Moore et al., 2011a).

 

NTM group

 

The primary site of infection is the skin, mainly through traumatic or surgical wounds contaminated with mycobacteria (Baral et al., 2006; Smith et al., 2009; Vishkautsan et al., 2016). Some fast-growing mycobacteria show a predilection to replicate in lipid-rich tissues, such as the ventral abdominal and inguinal areas, particularly after surgical wound contamination, causing cutaneous panniculitis (Fig. 1).

 

Fig. 1. Mycobacterial infection in ventral abdomen (courtesy Richard Malik, University of Sydney Veterinary School)

Fig. 1. Mycobacterial infection in ventral abdomen (courtesy Richard Malik, University of Sydney Veterinary School)

 

A case of lipoid pneumonia caused by mycobacterial infection has been reported (Couto and Artacho, 2007). Dissemination from the skin and systemic infections are not commonly caused by bacteria of this group, with exception of MAC infections which easily disseminate (Jordan et al., 1994; Barry et al., 2002; Malik et al., 2002; De Groot et al., 2010; Rivière et al., 2011). However, a recent paper reported three cats with NTM disseminated infections (respiratory, gastrointestinal) in immunocompetent cats (Pekkarinen et al., 2018).

 

Feline leprosy

 

The primary site of infection is the skin, with localised subcutaneous granulomas and less commonly disseminated skin granulomas (Horne and Kunkle, 2009).

 

Clinical signs

 

Although there are some trends in clinical manifestations associated with the type of mycobacterial species involved, it should be noted that it is not possible to determine the mycobacterial species based on clinical presentation alone.

 

Most mycobacterial infections occur in immunocompetent animals (Gunn-Moore et al., 1996; Gunn-Moore et al., 2011a). Cases in cats with primary or acquired immunodeficiency, such as with retrovirus infection, have been reported with disseminated MAC infections and NTM slow-growing mycobacterial infections  (Hughes et al., 1999; De Lorenzi and Solano-Gallego, 2009). One case of an atypical mycobacterial infection in a cat with an idiopathic CD4+ lymphopenia was documented (Meeks et al., 2008). Two cases (MAC disseminated infection and mycobacterial osteomyelitis) have been reported after renal transplantation and long-term immunosuppressive therapy with cyclosporine (Griffin et al., 2003; Lo et al., 2012). One case of disseminated M. avium subspecies hominissuis associated with ascites in a feline immunodeficiency virus infected cat has been described (Paharsingh et al., 2020).

 

Cutaneous forms

 

M. microti, the NTM mycobacteria and feline leprosy species are the most common mycobacteria producing skin lesions. These commonly consist of dermal nodules, non-healing wounds with draining tracts and ulceration (Baral et al., 2006; Horne and Kunkle, 2009; Smith et al., 2009; Gunn-Moore et al., 2011a; Gunn-Moore et al., 2013) (Figs. 2, 3, 4).

 

Fig. 2. Ulcerated skin nodule in M. microti (courtesy of Richard Malik, University of Sydney Veterinary School)

Fig. 2. Ulcerated skin nodule in M. microti (courtesy of Richard Malik, University of Sydney Veterinary School)

 

Fig. 4a. Subcutaneous nodules in lepra (courtesy of Richard Malik, University of Sydney Veterinary School)

Fig. 3. Subcutaneous nodules in lepra (courtesy of Richard Malik, University of Sydney Veterinary School)

Fig. 4b. Subcutaneous nodules in lepra (courtesy of Richard Malik, University of Sydney Veterinary School)

Fig. 4. Subcutaneous nodules in lepra (courtesy of Richard Malik, University of Sydney Veterinary School)

 

 

 

 

 

 

 

 

Common locations are the facial area, extremities, tail base, perineum, ventral thorax and abdomen. Lesions can be solitary or multiple (Smith et al., 2009; Gunn-Moore et al., 2011a). Multiple skin lesions can result from local spread or haematogenous dissemination. Local or generalised lymphadenopathy is present in about half of the cases and can be the only clinical sign (especially submandibular and praescapular) (Gunn-Moore et al., 2011a).

 

Visceral (gastrointestinal or respiratory) or systemic forms

 

The TB complex and MAC species are the most common mycobacteria producing visceral or systemic lesions (Gunn-Moore et al., 1996; Barry et al., 2002; De Lorenzi and Solano-Gallego, 2009; De Groot et al., 2010; Rivière et al., 2011). NTM and leprosy infections rarely produce disseminated disease (Couto and Artacho, 2007), but several case reports of disseminated infection have been reported, even in immunocompetent cats (Lee et al., 2017; O’Brien et al., 2017a; Pekkarinen et al., 2018). Common clinical signs and abnormalities include gastrointestinal (weight loss, mesenteric lymphadenopathy) or respiratory (pneumonia, hilar lymphadenopathy, pneumothorax, pleural or pericardial effusions) signs which can be accompanied by signs of systemic infection such as fever, ocular signs, splenomegaly, hepatomegaly, generalised lymphadenopathy, bone lesions and neurological signs (Hartmann et al., 2000; Barry et al., 2002; Malik et al., 2002; Burthe et al., 2008; De Groot et al., 2010; Rivière et al., 2011; Rüfenacht et al., 2011; Lo et al., 2012; Madarame et al., 2017).

 

Neurological disease is usually present in cats with systemic involvement and other clinical signs, but one cat was reported that was presented only with neurological signs due to a pyogranulomatous meningoencephalitis by M. avium subspecies hominissuis. However, following necropsy and histopathological studies, mycobacteria were identified in several organs, and granulomatous lymphadenitis was evident (Madareme et al., 2017).

 

Recently a case series of feline ocular mycobacteriosis has been published. Approximately 25% of the cats were presented only with ocular signs, emphasizing the importance of including these infections in the differential list of potential causes, not only in cats with systemic disease with ocular signs, but also in cats with only ocular signs. The most common ocular signs were uveitis and blindness, but some cats also showed corneal, conjunctival and eyelid proliferative lesions. Cataracts, lens subluxation and glaucoma secondary to uveitis were present in some cats. In 80% of the cats, ocular disease was unilateral at presentation (Stavinohova et al., 2019).

 

Cats in recent outbreaks of M. bovis infection associated with contaminated raw food were presented with unusual, severe and rapidly progressive clinical disease; and there was a high mortality rate even after attempting treatment. Hence, gastrointestinal infection seems to produce more severe disease compared to infections associated with skin exposure. It has been suggested also that these aggressive infections might be caused by more virulent M. bovis strains (O’Halloran et al., 2019).

 

Diagnosis

 

Diagnosis can be difficult, especially when skin lesions are absent, and is based on a clinical suspicion when the presentation is indicative and other diseases have been ruled out. The traditional tuberculin skin-testing technique used in other species is insensitive in domestic cats (Broughan et al., 2013). Therefore, appropriate samples should be collected for cytology and/or histology (including acid-fast staining), culture and PCR. An interferon-gamma release assay (IGRA) is available in some countries and can be used when cytology samples are non-diagnostic, or tissue samples are not available.

 

Haematology and biochemistry changes are non-specific, suggesting a chronic inflammatory condition. Hypercalcaemia due to granulomatous disease has been reported with systemic MAC (Malik et al., 2002) and M. microti infections (Gunn-Moore et al., 2011a). Cats infected with mycobacteria can show reduced levels of vitamin D compared to healthy cats, as occurs in humans (Lalor et al., 2012), although the clinical significance of this is unknown.

 

Thoracic radiographic changes are variable and non-specific, ranging from no abnormalities to bronchial, alveolar or interstitial nodular mixed patterns, pleural effusion and/or mediastinal and perihilar lymphadenopathy (Bennet et al., 2011) (Fig. 5). Appendicular radiographs can show bone osteolytic lesions, and (less frequently) osteoproliferative changes, associated with systemic mycobacterial infections (Bennet et al., 2011; Lo et al., 2012). Abdominal ultrasonography can be useful to find mesenteric lymphadenopathy or granulomatous lesions and as a guide to obtain fine needle aspirates (Griffin et al., 2003).

 

CT scan abnormalities were also reported in a group of 20 cats with mycobacterial infections. Interstitial lung pattern, mediastinal and/or mesenteric lymphadenomegaly and osteolytic or proliferative skeletal lesions were the most frequent abnormalities seen (Major et al., 2016).

 

Fig. 5. Mixed bronchial-interstitial pattern in the lung of a cat with tuberculosis complex group infection (courtesy of Richard Malik, University of Sydney Veterinary School)

Fig. 5. Mixed bronchial-interstitial pattern in the lung of a cat with tuberculosis complex group infection (courtesy of Richard Malik, University of Sydney Veterinary School)

 

Cytology

 

Fine needle aspirates or smears from skin lesions (nodules, ulcers, draining tracts) or granulomatous lymph nodes should always be stained for acid-fast bacteria using e.g. Ziehl-Nielsen (ZN) staining. The sensitivity is variable, however, as the number of bacteria within macrophages varies depending on the mycobacterial species and on the host’s immune response to infection (Gunn-Moore, 2010). A negative cytology result does not rule out mycobacterial infection (Gunn-Moore et al., 2013). If cytology suggests granulomatous inflammation, a biopsy for histology should be obtained, as well as samples for culture and PCR if mycobacterial infection is suspected (e.g. granulomatous inflammation with or without ZN-positive staining).

 

Histology

 

Histology is useful for the diagnosis of mycobacterial infections. It allows the assessment of the inflammatory pattern, which can vary depending on the mycobacterial species involved (pyogranulomatous or granulomatous inflammation, presence of granulation tissue and/or mixed inflammatory response, necrosis, panniculitis), and allows acid-fast staining such as with ZN (Kipar et al., 2003; Gunn-Moore et al., 2011b) (Fig. 6). However, sometimes only a few bacteria are present and they are not detected by ZN staining (particularly with infections of M. microti and some NTM rapid-growing species), although culture or PCR may still give a positive result in such cases (Gunn-Moore et al., 2011b; Gunn-Moore et al., 2013). Bacterial morphology and staining do not allow the identification of the mycobacterial species. If mycobacterial infection is suspected, it is mandatory to keep fresh biopsy samples frozen without formalin for subsequent culture and PCR (Gunn-Moore, 2010); formalin can affect PCR sensitivity and prevents subsequent culture from the sample, so it is imperative that samples are kept frozen without preservative in case culture and/or PCR are needed after the histology results have been obtained.

 

Fig. 6. Large numbers of acid-fast bacteria as shown using the Ziehl–Neelsen stain (courtesy of Richard Malik, University of Sydney Veterinary School)

Fig. 6. Large numbers of acid-fast bacteria as shown using the Ziehl–Neelsen stain (courtesy of Richard Malik, University of Sydney Veterinary School)

 

Culture

 

A positive culture from a fresh tissue sample or fine needle aspirates is useful to confirm mycobacterial infection and to identify the species involved, which has implications for treatment, prognosis and assessment of zoonotic risk. Culture is the gold standard method of diagnosis for the mycobacteria species that can be  grown in culture, such as the TBC species and some NTM species. However, culture needs to be done in a specialised laboratory under containment. Many mycobacterial species need a long time to grow in culture (2 to 3 months) or even fail to grow (Malik et al., 2000; Gunn-Moore et al., 2011a; Gunn-Moore et al., 2013). It is important to contact a specialised laboratory to ask for the correct procedures and requirements for sample submission. In feline leprosy and some forms of NTM infection, cultures are always negative, even when ZN staining has been positive (Gunn-Moore et al., 2011b). Due to these limitations, it is advisable to simultaneously submit fresh samples for PCR.

 

Polymerase chain reaction (PCR)

 

PCR (followed by sequencing, if available) is  the recommended test for the rapid diagnosis  of mycobacterial infections (Kipar et al., 2003; Biet et al., 2005; Rüfenacht et al., 2011). It allows confirmation of the diagnosis and species identification more rapidly than any other procedure and is especially useful for species that cannot be grown in culture. The availability of PCR testing can be limited, depending on the commercial diagnostic laboratories in the area; otherwise samples should be submitted to an official national human laboratory for mycobacterial diagnosis. Fresh tissue samples are preferred for PCR testing, but frozen tissue samples, fine-needle aspirates (stained), cytology slides and formalin-fixed paraffin-embedded tissues have also been used to generate positive results if fresh tissue is not available (Reppas et al., 2013).

 

Interferon-gamma release assay (IGRA)

 

This test is currently commercially available mainly in the UK, although samples can be submitted from abroad. Interferon-gamma testing is useful for the diagnosis of TB complex group infections and can reduce the lag time between clinical presentation and diagnosis. The test is based on specific mycobacterial proteins being used to stimulate the cat’s heparinised peripheral mononuclear cells (PBMCs). If the cat has been previously infected with the mycobacterial organism containing these peptides, IFN-γ is released by the PBMCs and detected by the IGRA. As well as being quicker, it is also cheaper than culture, PCR and sequencing and can be performed using a blood sample. The assay has been validated for diagnostic use in cats with good sensitivity (around 90%) reported to diagnose TBC infections (O’Halloran and Gunn-Moore, 2017; O’Halloran et al., 2018). In addition, it allows discrimination between M. bovis, M. microti and M. avium infection. IGRA can be positive in clinically healthy cats, meaning that the cat has been exposed to the mycobacteria, so results should be interpreted together with the clinical signs (Rhodes et al., 2008; Fenton et al., 2010; O’Halloran et al., 2018; O’Halloran et al., 2020). Although very helpful, IGRA is not yet regarded as a gold standard method for the definitive diagnosis of mycobacterial infection, compared to a positive culture or PCR (with sequencing if needed). The test may also be useful for monitoring treatment and validation testing for this is underway (O’Halloran and Gunn-Moore, 2017)

 

Treatment

 

Treatment of mycobacterial infections is generally challenging. There have been no prospective, controlled clinical trials, and recommendations are based on case reports or retrospective studies. Good outcomes have been reported after identification of the mycobacterial species and treatment with a long (several months) course of an appropriate antibiotic combination (Gunn-Moore, 2010). Surgery is indicated when local skin lesions can be removed; more diffuse lesions can be treated with surgical debridement and subsequent antibiotic treatment (Baral et al., 2006; Elsner et al., 2008; Horne and Kunkle, 2009).

 

Before starting mycobacterial treatment, four important issues must be considered:

  • Firstly, the zoonotic risk (particularly for the TB complex group including M. microti, but also for MAC) must be discussed with the owner (Emmanuel et al., 2007; Gunn-Moore, 2010), especially, but not only, if the owner is immunocompromised or if there are very young or old people in the household. In such cases, treatment of the cat might not be recommended, and euthanasia might be considered as an option.
  •  

  • Secondly, confirmation (by culture or PCR) of the mycobacterial species might take time; in this case, the zoonotic risk (especially in the case of M. tuberculosis (which is very rare in cats) or M. bovis (more commonly encountered in cats) can be unacceptable, and inappropriate initial antibiotic selection can lead to the development of mycobacterial resistance (Masur, 1993; Gunn-Moore, 2010; Gunn-Moore et al., 2011b; Gunn-Moore et al., 2013).
  •  

  • Thirdly, treatment requires several months of an antibiotic combination regime; compliance, adverse effects and financial issues must be discussed with the owners.
  •  

  • Fourthly, a final diagnosis should always be based on culture and/or PCR tests, but in some situations the clinical context and IGRA can be helpful to indicate the mycobacteria species involved and to evaluate the zoonotic risk and guide initial treatment. For example, in non-TB endemic areas, cats with mycobacterial infection will be less of a zoonotic risk, especially if the lesions are cutaneous with no evidence of systemic infection, and cats with diffuse panniculitis due to rapidly growing mycobacteria species pose less of a zoonotic risk.

 

Tuberculosis complex group and NTM group

 

For the tuberculosis complex and non-tuberculous mycobacteria (NTM) groups, double or triple therapy is currently recommended: rifampicin (10 to 15 mg/kg q24h) plus a fluoroquinolone (marbofloxacin 2 mg/kg q24h; or pradofloxacin 3 to 5 mg/kg q24h) plus a macrolide (clarithromycin125 mg/cat q24h or 7 to 15 mg/kg q24h; or azithromycin 5 to 15 mg/kg q24h) for 6 to 9 months. Ideally, the three drugs (triple therapy) should be administered during an initial phase for 2 months, followed by two of the drugs (dual therapy) for 4 to 7 months (Baral et al., 2006; Gunn-Moore et al., 2011a) (EBM grade III) (Gunn-Moore et al., 1996; Gunn-Moore, 2010).

 

The newer fluoroquinolones (moxifloxacin and pradofloxacin) might be more effective than older ones (Malik et al., 2002; Horne and Kunkle, 2009). Unpublished clinical experience suggests that pradofloxacin is a good choice; in confirmed localised disease, pradofloxacin could be a good initial treatment pending species confirmation (Smith et al., 2009) (EBM grade IV), but multiple antibiotic therapy is often indicated for mycobacterial treatment pending confirmation of diagnosis to avoid resistance developing (see below).

 

Recently alternative treatment courses to the original course of triple therapy for two months and then dual therapy for 4 to 7 months have been suggested. The alternatives comprise either triple therapy for 3 months alone or triple therapy given for 2-3 months beyond resolution of clinical signs or beyond static thoracic imaging abnormalities. The latter alternative course typically comprises 4 to 6 months of treatment in total and has been described as unpublished observations for the treatment of TB in cats (Major et al., 2018; O’Halloran and Gunn-Moore, 2019;). However, follow up information on this protocol is not yet available. The rationale for this treatment protocol is based on recommendations from human medicine where at least 3 or 4 antibiotics are given in combination to reduce the development of multi-drug resistant mycobacteria.

 

Treatment of NTM infections is ideally based on individual culture and sensitivity tests, as different mycobacterial species or strains can have different antibiotic sensitivity (Munro et al., 2021). However, this is not always possible, as specific culture systems are unavailable or results take too long.

 

Surgical debridement or excision are needed in some skin cases along with the multiple antibiotic therapy.

 

In some cats, an oesophageal feeding tube is needed to allow prolonged and intensive drug administration (Gunn-Moore, 2010).  Reformulations of drugs (e.g. rifampicin and azithromycin) into one capsule are available from some manufacturers to allow for easier dosing. Alternatively, tablets can be combined into a single gelatine capsule. Adverse effects (cutaneous, hepatic) are not uncommon, and in some cats treatment must be discontinued (Gunn-Moore, 2010). Short courses of antibiotic and/or monotherapy (e.g. quinolones or beta-lactams) have been associated with clinical responses and remissions, but also with a high risk of relapse, which can be followed by systemic spread and possible mycobacterial antibiotic resistance (Gunn-Moore et al., 2011b). It is therefore recommended to always start complete multiple antibiotic treatment whilst awaiting diagnosis confirmation and species identification.

 

MAC infections

 

Disseminated MAC infections usually respond poorly to treatment, and old generation fluoroquinolones are not very effective (Jordan et al., 1994; Burthe et al., 2008; Gunn-Moore et al., 2013). The recommended first choice treatment is clarithromycin (dose given above) with clofazimine (4 to 8 mg/kg q24h) or rifampicin (dose given above) or doxycycline (5 mg/kg q12h or 10 mg/kg q24h), based on the few cases reported with good outcomes (Kaufman et al., 1995; Aranaz et al., 1996; Malik et al., 2000; Biet et al., 2005; Sieber-Ruckstuhl et al., 2007) (EBM grade IV). Limited clinical experience with pradofloxacin suggests that it is more effective than the older fluoroquinolones (Smith et al., 2009) although resistance to fluoroquinolones and aminoglycosides was found to be common among M. avium isolates (Munro et al., 2021).

 

Feline leprosy

 

Most cats with leprosy due to M lepraemurium can be cured by surgery (small lesions) together with combinations of rifampicin, clofazimine and clarithromycin for several months (Greene and Gunn-Moore, 2006; Horne and Kunkle, 2009). Spontaneous remission has been documented in one cat (Roccabianca et al., 1996).

 

Prevention

 

Keeping a cat indoors and avoiding contact with wild rodents are the only measures for preventing mycobacterial infection. Based on recent M. bovis infection in UK associated with commercial raw food contamination, feeding raw diets should be avoided.

 

Prognosis

 

Prognosis must be considered guarded in general but depends on the mycobacterial species and the extent and severity of the disease. Disseminated infections (TBC, MAC and ‘Candidatus M. lepraefelis’ species) are associated with a poorer prognosis (Gunn-Moore et al., 1996; Barry et al., 2002; De Lorenzi and Solano-Gallego, 2009; Smith et al., 2009; De Groot et al., 2010; Rivière et al., 2011). Localised skin disease due to NTM, M. microti infections and leprosy can have a good prognosis if treated properly (Baral et al., 2006; Horne and Kunkle, 2009; Gunn-Moore et al., 2011b).

 

Zoonotic risk

 

All members of the TBC complex are potentially zoonotic, including M. microti. However, the risk of transmission from cats (and dogs) to humans is low, as cats are spillover hosts (Biet et al., 2005; Baral et al., 2006; Couto and Artacho, 2007).

 

An unusual cluster of M. bovis infection in cats was reported from the UK in 2012 to 2013. Cat-to-cat transmission was suspected, and zoonotic infection of two humans was documented (O’Connor et al., 2019). Similarly, cat-to-human transmission was suspected in Texas, USA (Ramdas et al., 2015).

 

After documented evidence of cat-to-human transmission, the risk of spread of M. bovis from cats to their human contacts was increased from negligible to very low (Human Animal Infections and Risk Surveillance (HAIRS) Group, 2014). Cats with clinical signs compatible with disseminated disease are believed to pose the greatest risk to humans, most likely by ingestion from a contaminated environment, following handling of discharges from exudative tuberculous lesions, or by aerosols from cats with respiratory signs or aerosol-generating procedures.

 

As an example, Public Health England in the UK now advises that all close contacts of household companion animals with confirmed M. bovis infections should be assessed by a public health professional and receive guidance on how best zoonotic transmission can be minimised. In addition, as part of an enhanced surveillance system in England and Wales, newly diagnosed human patients with M. bovis infection are asked explicitly about contact with pets with suspected or confirmed M. bovis disease (O’Connor et al., 2019). Similar follow-up likely exists in other countries.

 

In summary, M. bovis disease in companion animals, particularly cats with severe systemic features including exudative lesions, can have to be regarded as posing a significant public health risk. Cats with clinical signs of disseminated disease are the greatest risk to humans by ingestion from a contaminated environment and/or by aerosols from cats.

 

Euthanasia or treatment of cats with confirmed M. bovis or M. tuberculosis infection should be a consensus decision between the owner and the veterinarian, but due to the risk of cat to human transmission and antimicrobial resistance, euthanasia has been proposed by some authorities and experts (http://www.bva.co.uk/News-campaigns-and-policy/Newsroom/News-releases/Updated-statement-on-TB-in-cats/ 2014). Similarly, euthanasia might be considered after infection with any of the other potential zoonotic species (M. microti and M. avium).

 

In the recently published outbreaks in cats that might have been infected following the consumption of contaminated raw food, no transmission to owners was observed. However, there is concern about the potential risk of infection to owners by them handling contaminated raw food during meal preparation, as well as home environment contamination by M. bovis faecal shedding by the cats.    

 

MAC species, particularly subsp hominissuis, are potentially transmissible from cat to humans, but so far there have been no reports of human cases caused by cat infection (Biet et al., 2005).

 

There is a single published report from Australia of a human mycobacterial infection, a case of Mycobacterium marinum (in the NTM group) local skin infection, acquired from a cat after a scratch (Phan and Relic, 2010).

 

The use of gloves is strongly recommended when treating cats with any suspected mycobacterial infections and/or when taking and processing biopsy samples. In TB-endemic areas, veterinarians and technicians handling cats with compatible lesions should use gloves, facial filtration particle masks and protective clothing. Infections are most likely to be spread (to humans and other susceptible hosts) via discharges from skin wounds or via the respiratory tract if this system is involved (e.g. coughing, collection of bronchoalveolar lavage samples, intubation). The effectiveness of disinfectants against mycobacterial species should be checked as some (e.g. chlorhexidine) are not mycobacteriocidal. A country’s regulation should be consulted to determine if any health authorities must be notified if mycobacterial disease (e.g. due to M. tuberculosis or M. bovis) is confirmed.

 

Acknowledgement

 

ABCD Europe gratefully acknowledges the support of Boehringer Ingelheim (the founding sponsor of the ABCD) and Virbac.

 

References

 

Alander-Damsten YK, Brander EE, Paulin LG (2003): Panniculitis, due to Mycobacterium smegmatis, in two Finnish cats. J Feline Med Surg 5, 19-26.

 

Albini S, Mueller S, Bornand V, et al (2007): Cutaneous atypical mycobacteriosis due to Mycobacterium massiliense in a cat. Schweiz Arch Tierheilkd 149, 553-558.

 

Aranaz A, Liébana E, Pickering X, Novoa C, Mateos A, Domínguez L (1996): Use of polymerase chain reaction in the diagnosis of tuberculosis in cats and dogs. Vet Rec 138, 276-280.

 

Attig F, Barth SA, Kohlbach M, Baumgärtner W, Lehmbecker A (2019): Unusual Manifestation of a Mycobacterium Bovis SB0950 Infection in a Domestic Cat. J Comp Pathol 172, 1-4.

 

Baral RM, Metcalfe SS, Krockenberger MB, Catt MJ, Barrs VR, McWhirter C, Hutson CA, Wigney DI, Martin P, Chen SC, Mitchell DH, Malik R (2006): Disseminated Mycobacterium avium infection in young cats: over-representation of Abyssinian cats. J Feline Med Surg 8, 23-44.

 

Barry M, Taylor J, Woods JP (2002): Disseminated Mycobacterium avium in a cat. Can Vet J 43, 369-371.

 

Bennet AD, Lalor S, Schwarz T, Gunn-Moore DA (2011): Radiographic findings in cats with mycobacterial infections. J Feline Med Surg 13, 776-780.

 

Bennie CJ, To JL, Martin PA, Govendir M (2015): In vitro interaction of some drug combinations to inhibit rapidly growing mycobacteria isolates from cats and dogs and these isolates' susceptibility to cefovecin and clofazimine. Aust Vet J 93, 40-45.

 

Biet F, Boschiroli ML, Thorel MF, Guilloteau LA (2005): Zoonotic aspects of Mycobacterium bovis and Mycobacterium avium-intracellulare complex (MAC). Vet Res 36, 411-436.

 

Broughan JM, Crawshaw TR, Downs SH, Brewer J, Clifton-Hadley  RS (2013): Mycobacterium bovis infections in domesticated non-bovine mammalian species. Part 2: A review of diagnostic methods. The Veterinary Journal 198 (2), 346-351.

 

Burthe S, Bennet M, Kipar A et al (2008): Tuberculosis (Mycobacterium microti) in wild field vole populations. Parasitology 35, 309-317.

 

Černá P, O'Halloran C, Sjatkovskaj O, Gunn-Moore DA (2019): Outbreak of tuberculosis caused by Mycobacterium bovis in a cattery of Abyssinian cats in Italy. Transbound Emerg Dis 66(1), 250-258.

 

Couto SS, Artacho CA (2007): Mycobacterium fortuitum pneumonia in a cat and the role of lipids in the pathogenesis of atypical mycobacterial infections. Vet Pathol 44, 543-546.

 

Cox A, Udenberg TJ (2020): Mycobacterium porcinum Causing Panniculitis in the Cat. Can Vet J 61(1), 39-43.

 

De Groot PH, van Ingen J, de Zwaan R, Mulder A, Boeree MJ, van Soolingen D (2010): Disseminated Mycobacterium avium subsp. avium infection in a cat, the Netherlands. Vet Microbiol 144, 527-529.

 

De Lorenzi D, Solano-Gallego L (2009): Tracheal granuloma because infection with a novel mycobacterial species in an old FIV-positive cat. J Small Anim Pract 50, 143-146.

 

Dietrich U, Arnold P, Guscetti F, Pfyffer GE, Spiess B (2003): Ocular manifestation of disseminated Mycobacterium simiae infection in a cat. J Small Anim Pract 44, 121-125.

 

Elsner L, Wayne J, O’Brien CR et al (2008): Localised Mycobacterium ulcerans infection in a cat in Australia. J Feline Med Surg 10, 407-412.

 

Elze J, Grammel L, Richter E, Aupperle H (2013): First description of Mycobacterium heckeshornense infection in a feline immunodeficiency virus-positive cat. J Feline Med Surg 15, 1141-1144.

 

Emmanuel FX, Seagar AL, Doig C, Rayner A, Claxton P, Laurenson I (2007): Human and animal infections with Mycobacterium microti, Scotland. Emerg Infect Dis 13, 1924-1927.

 

Fenton KA, Fitzgerald SD, Kaneene JB, Kruger JM, Greenwald R, Lyashchenko KP (2010): Comparison of three immunodiagnostic assays for antemortem detection of Mycobacterium bovis in domestic cats. J Vet Diagn Invest 22, 724-729.

 

Foster SF, Martin P, Davis W, Allan GS, Mitchell DH, Malik R (1999): Chronic pneumonia caused by Mycobacterium thermoresistibile in a cat. J Small Anim Pract 40, 433-438.

 

Govendir M, Hansen T, Kimble B, et al (2011a): Susceptibility of rapidly growing mycobacteria isolated from cats and dogs, to ciprofloxacin, enrofloxacin and moxifloxacin. Vet Microbiol 147, 113-118.

 

Govendir M, Norris JM, Hansen T, et al (2011b): Susceptibility of rapidly growing mycobacteria and Nocardia isolates from cats and dogs to pradofloxacin. Vet Microbiol 153, 240-245.

 

Greene CE, Gunn-Moore DA (2006): Mycobacterial infections. In: Greene CE (ed). Infectious diseases of the dog and the cat. 3rd ed. St Louis: Saunders Elsevier; 462-488.

 

Griffin A, Newton AL, Aronson LR, Brown DC, Hess RS (2003): Disseminated Mycobacterium avium complex infection following transplantation in a cat. J Am Vet Med Assoc 222, 1097-1101.

 

Gunn-Moore DA  (2010): Mycobacterial infections in cats and dogs. In: Ettinger S, Feldman E (eds). Textbook of veterinary internal medicine. 7th ed. Philadelphia: WB Saunders, 875-881.

 

Gunn-Moore DA, Gaunt C, Shaw DJ (2013): Incidence of mycobacterial infections in cats in Great Britain: estimate from feline tissue samples submitted to diagnostic laboratories. Transbound Emerg Dis 60(4), 338-344.

 

Gunn-Moore DA, Jenkins PA, Lucke VM (1996): Feline tuberculosis: a literature review and discussion of 19 cases caused by an unusual mycobacterial variant. Vet Rec 138, 53-82.

 

Gunn-Moore DA, McFarland SE, Brewer JI, Crawshaw TR, Clifton-Hadley RS, Kovalik M, Shaw DJ (2011a): Mycobacterial disease in cats in Great Britain: I. Culture results, geographical distribution and clinical presentation of 339. J Feline Med Surg 13, 934-944.

 

Gunn-Moore DA, McFarland SE, Schock A, Brewer JI, Crawshaw TR, Clifton-Hadley RS, Shaw DJ (2011b): Mycobacterial disease in a population of 339 cats in Great Britain: II. Histopathology of 225 cases, and treatment and outcome of 184 cases. J Feline Med Surg 13, 945-952.

 

HAIRS (Human Animal Infections and Risk Surveillance) Group (2014):  https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/457151/M_bovis_cats_Risk_Assessment_Web_FINAL.pdf; assessed 22 February 2021.

 

Horne KS, Kunkle GA (2009): Clinical outcome of cutaneous rapidly growing mycobacterial infections in cats in the south-eastern United States: a review of 10 cases (1996-2006). J Feline Med Surg 11, 627-632.

 

Hughes MS, Ball NW, Love DN, Canfield PJ, Wigney DI, Dawson D, Davis PE, Malik R (1999): Disseminated mycobacterium genavense infection in a FIV-positive cat. J Feline Med Surg 1, 23-29.

 

Jang SS, Hirsch DC (2002): Rapidly growing members of the genus Mycobacterium affecting dogs and cats. J Am Anim Hosp Assoc 38, 217-220.

 

Jordan HL, Cohn LA, Armstrong PJ (1994): Disseminated Mycobacterium avium complex infection in three Siamese cats. J Am Vet Med Assoc 204, 90-93.

 

Kaufman AC, Greene CE, Rkich PM, Weigner DD (1995): Treatment of localized Mycobacterium avium complex infection with clofazimine and doxycycline in a cat. J Am Vet Med Assoc 207, 457-459.

 

Kayanuma H, Ogihara K, Yoshida S, et al (2018): Disseminated nontuberculous mycobacterial disease in a cat caused by Mycobacterium sp. strain MFM001. Vet Microbiol 220, 90-96.

 

Kipar A, Schiller I, Baumgärtner W (2003): Immunopathological studies on feline cutaneous and (muco)cutaneous mycobacteriosis. Vet Immunol Immunopathol 91, 169-182.

 

Krajewska-Wedzina M, Dabrowska A, Augustynowicz-Kopec E, Weiner M, Szulowski K (2019): Nontuberculous mycobacterial skin disease in cat; diagnosis and treatment - Case report. Ann Agric Environ Med 26, 511-513.

 

Krug S, Himstedt V, Dorn N, Göggerle U, Rieker T (2018): Feline leprosy in a 5-month-old male cat in Germany. Tierarztl Prax Ausg K Kleintiere Heimtiere 46(4), 271-275.

 

Lalor SM, Mellanby RJ, Friend EJ, Bowlt KL, Berry J, Gunn-Moore DA (2012): Domesticated cats with active mycobacteria infections have low serum vitamin D (25(OH)D) concentrations. Transbound Emerg Dis 59, 279-281.

 

Lee SH, Go DM, Woo SH, Park HT, Kim E, Yoo HS, Kim DY (2017): Systemic Mycobacterium kansasii Infection in a Domestic Shorthair Cat. J Comp Pathol 157(2-3), 215-219.

 

Lo AJ, Goldschmidt MH, Aronson LR (2012): Osteomyelitis of the coxofemoral joint due to Mycobacterium species in a feline transplant recipient. J Feline Med Surg 14, 919-923.

 

MacWilliams PS, Whitley N, Moore F (1998): Lymphadenitis and peritonitis caused by Mycobacterium xenopi in a cat. Vet Clin Pathol 27, 50-53.

 

Madarame H, Saito M, Ogihara K, Ochiai H, Oba M, Omatsu T, Tsuyuki Y, Mizutani T (2017): Mycobacterium avium subsp. hominissuis meningoencephalitis in a cat. Vet Microbiol 204, 43-45.

 

Major A, Holmes A, Warren-Smith C, Lalor S, Littler R, Schwarz T, Gunn-Moore D (2016): Computed tomographic findings in cats with mycobacterial infection. J Feline Med Surg 18(6), 510-517.

 

Malik R, Hughes MS, James G, Martin P, Wigney DI, Canfield PJ, et al (2002): Feline leprosy: two different syndromes. J Feline Med Surg 4, 43-59.

 

Malik R, Wigney DI, Dawson D et al (2000): Infection of the subcutis and skin of cats with rapidly growing mycobacteria: a review of microbiological and clinical findings. J Feline Med Surg 2, 35-48.

 

Mannion A, McCollester T, Sheh A, Shen Z, Holcombe H, Fox JG (2020): Draft Genome Sequence of a Mycobacterium porcinum Strain Isolated from a Pet Cat with Atypical Mycobacterial Panniculitis. Microbiol Resour Announc 9(11): e00006-20.

 

Masur H (1993): Recommendations on prophylaxis and therapy for disseminated Mycobacterium avium complex disease in patients infected with the human immunodeficiency virus. Public health service task force on prophylaxis and therapy for Mycobacterium avium complex. N Engl J Med 329,  898-904.

 

McIntosh DW (1982): Feline leprosy: a review of forty-four cases from Western Canada. Can Vet J 23, 291-295.

 

Meeks C, Levy JK, Crawford PC, Farina LL, Origgi F, Alleman R, Seddon OM et al (2008): Chronic disseminated Mycobacterium xenopi infection in a cat with idiopathic CD4+ lymphocytopenia. J Vet Int Med 22, 1043-1047.

 

Munro MJL, Byrne BA, Sykes JE (2021): Feline mycobacterial disease in northern California: Epidemiology, clinical features, and antimicrobial susceptibility. J Vet Intern Med 35, 273–283. doi: 10.1111/jvim.16013.

 

Murray A, Dineen A, Kelly P, McGoey K, Madigan G, NiGhallchoir E, Gunn-Moore DA (2015): Nosocomial spread of Mycobacterium bovis in domestic cats. J Feline Med Surg 17(2), 173-180.

 

Ngan N, Morris A, de Chalain T (2005): Mycobacterium fortuitum infection caused by a cat bite. N Z Med J 118, U1354.

 

Niederhäuser S, Klauser L, Bolliger J, Friedel U, Schmitt S, Ruetten M, Greene CE, Ghielmetti G (2018): First report of nodular skin lesions caused by Mycobacterium nebraskense in a 9-year-old cat. JFMS Open Rep 2018 Jul-Dec; 4(2): 2055116918792685.

 

O'Brien CR, Malik R, Globan M, Reppas G, McCowan C, Fyfe JA (2017a): Feline leprosy due to Candidatus 'Mycobacterium lepraefelis': Further clinical and molecular characterisation of eight previously reported cases and an additional 30 cases. J Feline Med Surg 19(9), 919-932.

 

O'Brien CR, Malik R, Globan M, Reppas G, McCowan C, Fyfe JA (2017b): Feline leprosy due to Mycobacterium lepraemurium. J Feline Med Surg 19(7), 737-746.

 

O'Brien CR, Malik R, Globan M, Reppas G, McCowan C, Fyfe JA (2017c): Feline leprosy due to Candidatus 'Mycobacterium tarwinense': Further clinical and molecular characterisation of 15 previously reported cases and an additional 27 cases. J Feline Med Surg 19(5), 498-512.

 

O'Connor CM, Abid M, Walsh AL, Behbod B, Roberts T, Booth LV, Thomas HL, Smith NH, Palkopoulou E, Dale J, Nunez-Garcia J, Morgan D (2019): Cat-to-Human Transmission of Mycobacterium Bovis, United Kingdom. Emerg Infect Dis 25(12), 2284-2286.

 

O'Halloran C, Ioannidi O, Reed N, Murtagh K, Dettemering E, Van Poucke S, Gale J, Vickers J, Burr P, Gascoyne-Binzi D, Howe R, Dobromylskyj M, Mitchell J, Hope J, Gunn-Moore D (2019): Tuberculosis due to Mycobacterium bovis in pet cats associated with feeding a commercial raw food diet. J Feline Med Surg 21(8), 667-681.

 

O'Halloran C, Gunn-Moore D (2017): Mycobacteria in cats: an update. In Practice 39, 399-406.

 

O'Halloran C, Gunn-Moore D (2019): Tuberculosis in UK cats associated with a commercial raw food diet. J Feline Med Surg 21(8), 665-666.

 

O'Halloran C, McCulloch L, Rentoul L, Alexander J, Hope JC, Gunn-Moore DA (2018): Cytokine and Chemokine Concentrations as Biomarkers of Feline Mycobacteriosis. Sci Rep 23;8(1), 17314.

 

O'Halloran C, Tornqvist-Johnsen C, Woods G, Mitchell J, Reed N, Burr P, Gascoyne-Binzi D, Wegg M, Beardall S, Hope J, Gunn-Moore, D (2020): Feline tuberculosis caused by Mycobacterium bovis infection of domestic UK cats associated with feeding a commercial raw food diet. Transbound Emerg Dis 00, 1–13. doi: 10.1111/tbed.13889

 

Paharsingh I, Suepaul R, Gyan L, Hosein A, Pargass I (2020): Disseminated Mycobacterium avium subsp. hominissuis infection and ascites in an FIV-positive cat. Vet Clin Pathol 49, 465-469.

 

Pekkarinen H, Airas N, Savolainen LE, Rantala M, Kilpinen S, Miuku O, Speeti M, Karkamo V, Malkamäki S, Vaara M, Sukura A, Syrjä P (2018): Non-tuberculous Mycobacteria can Cause Disseminated Mycobacteriosis in Cats. J Comp Pathol 160, 1-9.

 

Phan TA, Relic J (2010): Sporotrichoid Mycobacterium marinum infection of the face following a cat scratch. Australas J Dermatol 51, 45-48.

 

Ramdas KE, Lyashchenko KP, Greenwald R, Robbe-Austerman S, McManis C, Waters WR (2015): Mycobacterium bovis infection in humans and cats in same household, Texas, USA, 2012. Emerg Infect Dis 21(3), 480-483.

 

Reppas G, Fyfe J, Foster S, Smits B, Martin P, Jardine J, Lam A, O'Brien C, Malik R (2013): Detection and identification of mycobacteria in fixed stained smears and formalin‐fixed paraffin‐embedded tissues using PCR. Journal of Small Animal Practice 54, 638-646.

 

Rhodes SG, Gruffydd-Jones T, Gunn-Moore DA, Jahans K (2008): Interferon-gamma test for feline tuberculosis. Vet Rec 162, 453-455.

 

Rivière D, Pringet JL, Etievant M, Jechoux A, Lanore D, Raymond-Letron I, Boucraut-Baralon C (2011): Disseminated Mycobacterium avium subspecies infection in a cat. J Feline Med Surg 13, 125-128.

 

Roccabianca P, Caniatti M, Scanziani E, Penati V (1996): Feline leprosy: spontaneous remission in a cat. J Am Anim Hosp Assoc 32, 189-193.

 

Rüfenacht S, Bögli-Stuber K, Bodmer T, Bornand Jaunin VF, Gonin Jmaa DC, Gunn-Moore DA (2011): Mycobacterium microti infection in the cat: a case report, literature review and recent clinical experience. J Feline Med Surg 13, 195-204.

 

Sieber-Ruckstuhl NS, Sessions JK, Sanchez et al (2007): Long-term cure of disseminated Mycobacterium avium infection in a cat. Vet Rec 160, 131-132.

 

Smith NH, Crawshaw T, Parry J, Birtles RJ (2009): Mycobacterium microti: more diverse than previously thought. J Clin Microbiol 47, 2551-2559.

 

Stavinohova R, O'Halloran C, Newton JR, Oliver JAC, Scurrell E, Gunn-Moore DA (2019): Feline Ocular Mycobacteriosis: Clinical Presentation, Histopathological Features, and Outcome. Vet Pathol 56(5), 749-760.

 

Suy F, Carricajo A, Grattard F, et al (2013): Infection due to Mycobacterium thermoresistibile: a case associated with an orthopedic device. J Clin Microbiol 51, 3154-3156.

 

Vishkautsan P, Reagan KL, Keel MK, Sykes JE (2016): Mycobacterial panniculitis caused by Mycobacterium thermoresistibile in a cat. J Feline Med Surg Open Reports 1–7.

 

Willemse T, Groothuis DG, Koeman JP, Beyer EG (1985): Mycobacterium thermoresistibile: extrapulmonary infection in a cat. J Clin Microbiol 21, 854-856.

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