Mycobacterioses (tuberculosis, non-tuberculous mycobacterial infections, leprosy)

edited October 21, 2015

 

 

The Mycobacterioses in cats guidelines that the present article is updating were published in J Feline Med Surg 2013; 15: 591-597;1 mycobacterial infections are important in humans and animals, with an increasing awareness in recent years.

 

 

Synopsis

 

An unsual cluster of M bovis infection in cats was recently reported from the UK. Cat-to-cat transmission was suspected, and two humans became infected.2 Also nosocomial infection was reported in a cluster of cases which had attended a veterinary practice in Ireland.3

 

For diagnostic purposes, the PCR is recommended; it should ideally be performed on fresh tissue samples, but fixed stained smears and formalin-fixed paraffin-embedded tissues can be used with good sensitivity.4

 

The zoonotic risk has to be considered when planning therapeutic measures.1 It is aggravated by the fact that confirmation of the mycobacterial species takes time, and antibiotic therapy requires several months. Therefore, euthanasia rather than treatment should be considered as a sensible course of action, in view of the public health implications and the prognostic uncertainties of treatment.

 

For the tuberculosis complex and non-tuberculous mycobacteria (NTM) groups, double or triple therapy is currently recommended: rifampicin -10 to15 mg/kg q24h – plus a quinolone (marbofloxacine – 2 mg/kg q24h – or pradofloxacin – 3 to 5 mg/kg q24h) plus a macrolide (clarithromycin – 125 mg/cat q24h or 7 to 15 mg/kg q24h – or azythromycin – 5 to 15 mg/kg q24h) for 6 to 9 months. Ideally, the three drugs should be administered during an initial phase of 2 months, followed by two of the drugs for 4 to 7 months.5,6 (EBM grade III)

 

The newer fluoroquinolones (moxifloxacin and pradofloxacin) might be more effective than the older ones.7,8 Unpublished clinical experience suggests that pradofloxacin is a good choice; in localised disease, pradofloxacin would be a good initial treatment pending species confirmation.9 (EBM grade IV)

 

Treatment of NTM infections is ideally based on culture and susceptibility tests for each case, as different mycobacterial species or strains may have different antibiotic sensitivity. However, this is not always possible, as specific culture systems are unavailable or results take too long.

 

Disseminated M avium-intracellulare complex (MAC) infections usually respond poorly to treatment, and old generation quinolones are not very effective.10,11,12 The recommended first choice treatment is clarithromycin with clofazimine – 4 to 8 mg/kg q24h – or rifampicin or doxycycline – 5 to 10 mg/kg q12h – based on the few cases reported with good outcomes.13,14,15 (EBM grade IV) Limited clinical experiences with pradofloxacin suggests that it is more effective than the older fluoroquinolones.9

 

Most cats with feline leprosy can be cured by surgery (small lesions), and treatment with combinations of rifampicin, clofazimine, clarithromycin and pradofloxacin for several months.16,17 (EBM grade IV) Spontaneous remission has been documented in one cat.18

 

Keeping the cat indoors and avoiding contact with wild rodents are the only measures for preventing mycobacterial infection.

 

 

The 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.6,19 In a recent cluster of feline cases of M bovis infection in the South West of England, two persons became infected after having been in contact with the cats.2 The Public Health Agency in England then changed the risk level of transmission from negligible to low (www.hpa.org.uk/webc/HPAwebFile/HPAweb_C/1317140243205).

 

Euthanasia or treatment of cats with confirmed M bovis 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 suggested 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 tuberculosis, M microti and M avium).

 

 

References

 

1 Lloret A, Hartmann K, Pennisi MG, Gruffydd-Jones T, Addie D, Bélak S, et al. Mycobacteriosis in cats. ABCD guidelines on prevention and management. J Feline Med Surg 2013; 15: 591-597.

 

2 Roberts T, O’Connor C, Nuñez-Garcia J, de la Rua-Domenech R and Smith NH. Unusual cluster of Mycobacterium bovis infection in cats. Vet Rec 2014; 174(13): 326.

 

3 Murray A, Dineen A, Kelly P, McGoey K, Madigan G, Nighallchoir E, et al. Nosocomial spread of Mycobacterium bovis in domestic cats. J Fel Med Surg 2014; 17: 173-180.

 

4 Reppas G, Fyfe J, Foster S, Smits B, Martin P, Jardine J, et al. Detection and identification of mycobacteria in fixed stained smears and formalin-fixed paraffin-embedded tissues using PCR. J Small Anim Pract 2013; 54(12): 638-646.

 

5 Gunn-Moore DA, Jenkins PA and Lucke VM. Feline tuberculosis: a literature review and discussion of 19 cases caused by an unusual mycobacterial variant. Vet Rec 1996; 138: 53-58.

 

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

 

7 Govendir M, Hansen T, Kimble B, Norris JM, Baral RM, Wigney DI, et al. Susceptibility of rapidly growing mycobacteria isolated from cats and dogs, to ciprofloxacin, enrofloxacin and moxifloxacin. Vet Microbiol 2011a; 147(1-2): 113-118.

 

8 Govendir M, Norris JM, Hansen T, Wigney DI, Muscatello G, Trott DJ, et al. Susceptibility of rapidly growing mycobacteria and Nocardia isolates from cats and dogs to pradofloxacin. Vet Microbiol 2011b; 153(3-4): 240-245.

 

9 Gunn-Moore DA. Feline mycobacterial infections. Vet J 2014; 201(2): 230-238.

 

10 Rivière D, Pringet JL, Etievant M, Jechoux A, Lanore D, Raymond-Letron I, et al. Disseminated Mycobacterium avium subespecies infection in a cat. J Feline Med Surg 2011; 13:125-128.

 

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

 

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

 

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

 

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

 

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

 

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

 

17 Horne KS and Kunkle GA. 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 2009; 11: 627-632.

 

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

 

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

 

 

Bacterial properties

 

Mycobacteria are intracellular, acid-fast, slow-growing bacilliform bacteria, highly resistant to environmental conditions.1,2 Mycobacterial taxonomy is complex and many species can infect the cat and induce different clinical presentations. Different classifications have made in the past based on features and ability to growth in culture as well as biochemical properties.2 The use of molecular techniques has led to taxonomic changes, and some species have been or will be classified into different groups.2

 

For practical purposes, we will here classify mycobacteria on the basis of their biologic behaviour, including aspects of clinical presentation, diagnosis and culture, their response to treatment and on zoonotic aspects.

 

 

Tuberculosis (TBC) complex group

 

M. tuberculosis (mainly infecting humans and dogs, rarely cats and other species), M. bovis (infecting cattle, dogs and cats) and M. microti (infecting small rodents like voles, shrews and cats). These bacteria can be grown only in specific culture media. Tuberculosis in cats is a systemic disease with disseminated internal lesions3,4, but infections with M microti may also present with localized or disseminated cutaneous disease.5

 

 

Non-tuberculous mycobacteria (NTM) group

 

This group includes a large number of slow-growing species like M. mageritense, M. genavese and M. malmoense and rapidly-growing species like M. fortuitum, M. chelonae-abscessus, M. avium, M. smegmatis, M. flavescens, the M. avium-intracellulare complex (MAC) amongst others. NTM infections in cats are typically subcutaneous (local or disseminated), rarely progressing to systemic disease.6 However, MAC infections, which in some classifications are included within the TBC complex group, are frequently sytemic.3,7

 

 

Feline leprosy

 

The M. lepraemurium and several other species cannot be grown in culture. Infection in cats is restricted to the skin where it produces mainly localized and rarely disseminated cutaneous nodules.8

 

 

Epidemiology

 

The 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 published. In recent years, more cases have been recognised, probably meaning that the infection has been under-diagnosed earlier.7,9,10 A recent survey (2009) from diagnostic laboratories in the UK evaluating tissue samples with an histological diagnosis of mycobacterial infection showed a significant incidence of around 1%.11

 

Data on the prevalence of the different mycobacterial species are also lacking. However, a recent retrospective study from the UK evaluating 339 cases of mycobacterial disease in cats found that 53% could not be identified through culture, 19% were M. microti, 15% M. bovis, 7% MAC and 6% non-tuberculous mycobacteria.5 Most cats with mycobacterial infections have an outdoor lifestyle5,8, living in a non-urban area seems to increase the risk.10 Adult tomcats seem to be predisposed to develop disease3,5 , as are Siamese and Abyssinian breeds.5,7,12

 

 

Tuberculosis complex group

 

M. microti infection is mainly related to direct contact with small rodents like voles and mice.13 M. tuberculosis infection is rare in cats, probably due to their natural resistance.14 M. tuberculosis and M. bovis are directly transmitted to cats by ingestion of milk from infected cattle and by direct or environmental contact with badgers (M. bovis).15

 

 

Non-tuberculous mycobacteria group

The main risk here is wound contamination by mycobacteria present in the environment, soil, water and decaying vegetation.6,9,16

 

 

Feline leprosy

The main risk comes from direct contact or rodent bites, or from wound contamination by mycobacteria present in soil or on plants.8,17 

 

 

Pathogenesis

 

Mycobacteria infect the macrophage and induce granulomatous and pyogranulomatous inflammatory responses in the organs involved.18 The mycobacterial species, route of infection and immune responses determine the extent, location and severity of the lesions.

 

 

Tuberculosis complex group

 

The primary site of infection by M. tuberculosis and M. bovis may be the alimentary tract, the lungs or skin.2,15 From these sites dissemination and systemic infection may occur. Only rarely, the infection is primarily systemic.

 

In M. microti infection, the portal of entry is the skin, in locations commonly affected by wild rodent bites (the face and legs).5

 

 

Non-tuberculous mycobacteria group

 

Primary site of infection is the skin, mainly traumatic or surgical wounds contaminated with mycobacteria.6,9 Some fast growing mycobacteria show a predilection to replicate in lipid-rich tissues, like the ventral abdominal and inguinal areas, particularly after a surgical wound contamination. (Fig. 1) Also a lipoid pneumonia case caused by mycobacterial infection has been reported.19 Dissemination from the skin and systemic infections are not common for bacteria of this group, with the exception of M. avium complex infections which are easily disseminated. 7, 11, 20-22

 

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)

 

Feline leprosy

 

Primary site of infection is the skin, with localised subcutaneous granulomas, and less commonly disseminated skin granulomas.8

 

 

Clinical presentation

 

Most mycobacterial infections occur in immunocompetent animals.3,5 Cases in cats with primary or acquired immunodeficiency, and associated with retrovirus infection have been reported, with disseminated MAC infections and atypical mycobacterial infection.23,24 One case has been documented of an atypical mycobacterial infection in a cat with an idiopathic CD4+ lymphopaenia.25 Two cases (MAC disseminated infection and mycobacterial osteomyelitis) have been reported after renal transplantation and long-term immunosuppressive therapy with cyclosporine.26,27

 

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)

 

Cutaneous forms

 

M. microti, the NTM complex 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.5,6,8,9,10 (Figs. 2, 3, 4) Common locations are the facial area, extremities, tail base, perineum, ventral thorax and abdomen. Lesions maybe solitary or multiple.5,9 Multiple skin lesions may result from local spread or haematogenous dissemination. Local or generalised lymphadenopathy is present in about half of the cases and may be the only clinical sign (especially submandibular and praescapular).

Fig. 4a. Subcutaneous nodules in lepra (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. 4b. 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)

 

Visceral (digestive or respiratory) or systemic forms

 

The TB complex and MAC species are the most common mycobacteria producing visceral or systemic lesions.3,20-23 NTM infections rarely produce disseminated disease.19 Common clinical signs and abnormalities are digestive (weight loss, mesenteric lymphadenopathy) or respiratory (pneumonia, hilar lymphadenopathy, pneumothorax, pleural or perdicardial effusions) which can be accompanied by signs of systemic dissemination like fever, ocular signs, splenomegaly, hepatomegaly, generalised lymphadenopathy, bone lesions and CNS signs.4,7,12, 20-22,27

 

 

Diagnosis

 

Diagnosis may be difficult, especially when skin lesions are absent. It is based on a clinical suspicion when the presentation is indicative and other diseases are ruled out. In these cases, appropriate samples should be obtained for cytology and/or histology (including acid-fast staining), culture and PCR.

 

Haematology and biochemistry changes are nonspecific, suggesting a chronic inflammatory condition. Hypercalcaemia due to granulomatous disease has been reported in systemic MAC7 and M. microti infections.5 Cats infected with mycobacteria may show reduced levels of vitamin D when compared to healthy cats, as it occurs in humans.28

 

Thoracic radiographic changes are variable and not specific, ranging from no abnormalities to bronchial, alveolar or interstitial nodular mixed patterns, pleural effusion and/or mediastinal and perihilar lymphadenopathy.29 (Fig. 5) Appendicular radiographs may show bone osteolytic lesions, and – less frequently – osteoproliferative changes, associated with systemic infections.27,29 Abdominal ultrasound maybe useful to find mesenteric lymphadenopathy or granulomatous lesions and as a guide to obtain fine needle aspirates.26

 

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 from granulomatous lymph nodes should always be stained for acid-fast bacteria, using e.g. the Ziehl-Nielsen (ZN) procedure. Sensitivity is variable, as the number of bacteria within macrophages varies depending on the mycobacterial species and on the host’s immune response.2 A negative cytology result does not rule out mycobacterial infection.10 If it suggests a granulomatous inflammation, a biopsy for histology must be obtained. Samples for culture and PCR should be obtained in all cases when a mycobacterial infection is suspected (granulomatous inflammation and ZN-positive staining)

 

 

Histology

 

Histology is useful to diagnose mycobacterial infections. It allows to assess the inflammatory pattern (pyogranulomatous or granulomatous) and to perform special acid-fast staining like ZN.18,30 (Fig. 6) However, only a few bacteria may be present and pass undetected by staining (M. microti and some NTM species), although culture or PCR may give a positive result.10,30 Bacterial morphology and staining do not allow identification of the mycobacterial species. If a mycobacterial infection is suspected it is mandatory to keep fresh biopsy samples frozen for further culture and PCR.2

 

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

 

Culture from a fresh tissue sample is useful to confirm mycobacterial infection and to identify the species involved, which has implications for treatment, prognosis and assessment of zoonotic risk. However, this needs to be done in a specialised laboratory, many mycobacterial species are slow-growing (2 to 3 months) or even fail to grow.5,10,15 In feline leprosy and some forms of NTM infection, cultures are always negative, even when ZN staining has been positive.30 Due to these limitations it is advisable to simultaneously submit samples for PCR.

 

 

Polymerase chain reaction (PCR)

The PCR (eventually followed by sequencing) is the recommended test for diagnosing mycobacterial infections.4,14,18 It allows confirmation of the diagnosis and species identification more rapidly than any other procedure. Availability maybe limited depending on private diagnostic laboratories in the area; otherwise samples should be submitted to an official national laboratory for mycobacterial diagnosis.

 

 

Interferon gamma test and other immunoassays

These tests are currently commercially unavailable, but they are promising for the diagnosis of TB complex group infections.31,32 A recent study evaluating cell-based interferon gamma test and serum antibody tests showed an excellent specificity and a variable, moderate sensitivity.33

 

 

Treatment

 

Treatment of mycobacterial infections is generally difficult and challenging. There are no prospective controlled clinical trials, and the recommendations are based on case reports or retrospective studies. Good outcomes have been published after identification of the mycobacterial species and treatment with a long (several months) course of an appropriate antibiotic combination.2 Surgery is indicated when local skin lesion can be removed; more diffuse lesions can be treated with surgical debridement and the cats subsequently treated with proper antibiotics.6,8,34

 

Before starting the treatment, three important issues must be addressed:

  • First, the zoonotic risk (particularly of the TB complex group including M. microti and MAC) must be discussed with the owner2,35, especially, but not only, in the case when he or she suffers from an immunodeficiency condition. In some cases we should advise against treating these cats.
  • Second, confirmation (by culture or PCR) of the mycobacterial species may take time; in this case, the zoonotic risk (in case of M. tuberculosis or M. bovis) may be unacceptable, and inappropriate initial antibiotic selection may lead to the development of mycobacterial resistance.2,10,30,36
  • Third, treatment requires several months of an antibiotics combination regime; compliance, adverse effects and financial issues must be discussed with the owners.

 

Tuberculosis complex group and NTM group

Currently, double or triple therapy is recommended: rifampicin -10-15 mg/kg q24h – plus a quinolone (marbofloxacine – 2 mg/kg q24h-) plus a macrolide (clarithromycin – 125 mg/cat q24h- or azythromycin – 5-15 mg/kg q24h -) for 6 to 9 months. Ideally, the three drugs should be giving during initial phase of 2 months followed by two of the drugs for 4 to 7 months.2,3 In many cats, an oesophageal tube is needed to allow for such a long and intensive pill administration.2 Adverse effects (cutaneous, hepatic) are not uncommon, and in some cats treatment must be discontinued.2 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 relapses, which may be followed by systemic spread.30 It is recommended to always start complete treatment while waiting for the diagnosis confirmation and species identification.

 

 

MAC infections

 

Disseminated MAC infections usually respond poorly to treatment, and quinolones are not very effective.20-22 Recommended first choice is clarithromycin with clofazimine – 4-8 mg/kg q24h – or rifampicin or doxycycline – 5-10 mg/kg q12h – based on the few cases reported with good outcomes.7,37,38

 

 

Feline leprosy

 

Most cats with leprosy can be cured by surgery (small lesions) and applying combinations of rifampicin, clofazimine and clarithromycin for some months.1,8 Spontaneous remission has been documented in one cat.39

 

Keeping the cat indoors and avoiding contact with wild rodents are the only measures for preventing mycobacterial infection.

 

 

Prognosis

 

Prognosis generally must be considered guarded, but depends on the mycobacterial species and the extent and severity of the disease. Disseminated infections (TBC complex and MAC) are associated with a poor prognosis.3,9,20-23 Localised skin disease (NTM), M. microti infection and leprosy may have a good prognosis if treated properly.6,8,30

 

 

Potential 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.2,35 There is a single published report from Australia of a human mycobacterial infection, a case of M. marinum (NTM group) local skin infection acquired from a cat after a scratch.40 However, cats are at risk to become infected, if the owner is diagnosed with tuberculosis.

 

The use of gloves is strongly recommended when treating cats with suspected mycobacterial infections and/or when taking and processing biopsy samples. Country regulations need to be consulted to learn whether health authorities must be notified of the disease.

 

 

References

 

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

2 Gunn-Moore DA. Mycobacterial infections in cats and dogs. In: Ettinger S, Feldman E, eds. Textbook of veterinary internal medicine. 7th ed. Philadelphia: WB Saunders, 2010: 875-81

3 Gunn-Moore DA, Jenkins PA, Lucke VM. Feline tuberculosis: a literature review and discussion of 19 cases caused by an unusual mycobacterial variant. Vet Rec 1996; 138:53-8

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

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

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

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

8 Horne KS, Kunkle GA. 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 2009; 11: 627-32

9 Smith NH, Crawshaw T, Parry J, Birtles RJ. Mycobacterium microti: more diverse than previously thought. J Clin Microbiol 2009; 47:2551-9

10 Gunn-Moore DA, Gaunt C, Shaw DJ. Incidence of mycobacterial infections in cats in Great Britain: estimate from feline tissue samples submitted to diagnostic laboratories. Transbound Emerg Dis. Epub ahead of print 21 June 2012. DOI:10.1111/j.1865-1682.2012.01352.x.

11 Jordan HL, Cohn LA, Armstrong PJ. Disseminated Mycobacterium avium complex infection in three Siamese cats. J Am Vet Med Assoc 1994, 204: 90-3

12 Burthe S, Bennet M, Kipar A et al. Tuberculosis (Mycobacterium microti) in wild field vole populations. Parasitology 2008; 35:309-17

13 Aranaz A, Liébana E, Pickering X, Novoa C, Mateos A, Domínguez L. Use of polymerase chain reaction in the diagnosis of tuberculosis in cats and dogs. Vet Rec 1996; 138:276-80

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

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

16 Jang SS, Hirsch DC. Rapidly growing members of the genus Mycobacterium affecting dogs and cats. J Am Anim Hosp Assoc 2002; 38:217-20

17 McIntosh DW. Feline leprosy: a review of forty-four cases from Western Canada. Can Vet J 1982; 23:291-5

18 Kipar A, Schiller I, Baumgärtner W. Immunopathological studies on feline cutaneous and (muco)cutaneous mycobacteriosis. Vet Immunol Immunopathol 2003; 91: 169-82

19 Couto SS, Artacho CA. Mycobacterium fortuitum pneumonia in a cat and the role of lipids in the pathogenesis of atypical mycobacterial infections. Vet Pathol 2007; 44: 543-6

20 Rivière D, Pringet JL, Etievant M, Jechoux A, Lanore D, Raymond-Letron I, Boucraut-Baralon C. Disseminated Mycobacterium avium subespecies infection in a cat. J Feline Med Surg 2011; 13:125-8

21 Barry M, Taylor J, Woods JP. Disseminated Mycobacterium avium in a cat. Can Vet J 2002; 43: 369-71

22 de Groot PH, van Ingen J, de Zwaan R, Mulder A, Boeree MJ, van Soolingen D. Disseminated Mycobacterium avium subsp. avium infection in a cat, the Netherlands. Vet Microbiol 2010; 144: 527-9

23 De Lorenzi D, Solano-Gallego L. Tracheal granuloma because infection with a novel mycobacterial species in an old FIV- positive cat. J Small Anim Pract 2009; 50: 143-6

24 Hughes MS, Ball NW, Love DN, Canfield PJ, Wigney DI, Dawson D, Davis PE, Malik R. Disseminated mycobacterium genavense infection in a FIV-positive cat. J Feline Med Surg 1999; 1: 23-9

25 Meeks C, Levy JK, Crawford PC, Farina LL, Origgi F, Alleman R, Seddon OM et al. Chronic disseminated Mycobacterium xenopi infection in a cat with idiopathic CD4+ lymphocytopenia. J Vet Int Med 2008; 22:1043-7

26 Griffin A, Newton AL, Aronson LR, Brown DC, Hess RS. Disseminated Mycobacterium avium complex infection following transplantation in a cat. J Am Vet Med Assoc 2003; 222:1097-101

27 Lo AJ, Goldschmidt MH, Aronson LR. Osteomyelitis of the coxofemoral joint due to Mycobacterium species in a feline transplant recipient. J Feline Med Surg 2012; 14:919-23

28 Lalor SM, Mellanby RJ, Friend EJ, Bowlt KL, Berry J, Gunn-Moore DA. Domesticated cats with active mycobacteria infections have low serum vitamin D (25(OH)D) concentrations. Transbound Emerg Dis 2012; 59: 279-81

29 Bennet AD, Lalor S, Schwarz T, Gunn-Moore DA. Radiographic findings in cats with mycobacterial infections. J Feline Med Surg 2011; 13:776-80

30 Gunn-Moore DA, McFarland SE, Schock A, Brewer JI, Crawshaw TR, Clifton-Hadley RS, Shaw DJ. 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 2011; 13: 945-952

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

32 Fenton KA, Fitzgerald SD, Kaneene JB, Kruger JM, Greenwald R, Lyashchenko KP. Comparison of three immunodiagnostic assays for antemortem detection of Mycobacterium bovis in domestic cats. J Vet Diagn Invest 2010; 22:724-9

33 Rhodes SG, Gunn-Moore DA, Boschiroli ML, Schiller I, Esfandiari J, Greenwald R, Lyashchenko KP. Comparative study of IFNgamma and antibody tests for feline tuberculosis. Vet Immunol Immunopathol 2011; 144: 129-34

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

35 Xavier Emmanuel F, Seagar AL, Doig C, Rayner A, Claxton P, Laurenson I. Human and animal infections with Mycobacterium microti, Scotland. Emerg Infect Dis 2007; 13: 1924-7

36 Masur H. 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 1993; 329: 898-904

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

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