NON-TUBERCULOUS MYCOBACTERIOSIS
1.1 Aetiology
There are over 150 species of NTM, 17 of which have been documented as causing infection in Australian mammals (Table 22.3). NTM are often split into two groups based on their rate of in vitro growth: ‘slow-growing mycobacteria’ (SGM) or ‘rapidly-growing mycobacteria’ (RGM).
The rate of in vitro growth is not necessarily relevant to the rate of clinical progression, but this categorisation may be relevant to treatment because RGM are noted for their unpredictable resistance to conventional anti-tuberculosis drugs (see section 1.6). In some cases, if molecular diagnostics are not available, laboratories may only be able to classify a NTM as either slow-growing or rapidly-growing.1.2 Epidemiology
NTM are environmental organisms, found widely and ubiquitously in soil, food, dust and both natural and treated drinking water (Ashford et al. 2001). Infection is opportunistic and occurs following exposure via ingestion, inhalation or inoculation of a wound. There is also
Table 22.1. Comparison of tuberculous and non-tuberculous mycobacteriosis in Australian mammals
| Non-tuberculous | Tuberculous | |
| Frequency in Australian mammals | Relatively common | Rare |
| Zoonotic potential | Low, primarily immunosuppressed people at risk | Serious |
| Transmission | Host-environment-host or host-vector-host | Host-to-host or host-fomite-host |
| Reservoir | Environment | Host species |
| Notifiable animal disease in Australia | Mycobacterium avium subsp. paratuberculosis, M. avium subsp. avium only | M. bovis only [M. tuberculosis in humans is notifiable] |
| Lesion distribution | Cutaneous, respiratory, osseous or disseminated | Usually respiratory and lymph node involvement, can become disseminated |
| Disease severity | Moderate to serious. Visceral or systemic infections are usually serious and difficult to treat, dermal disease less so | Serious. Likely to require euthanasia for individual and population welfare, and in some cases to mitigate risk of transfer to in-contact humans, other animals including livestock |
| Prognosis | Generally poor. Moderate for dermal lesions | Poor to grave |
some evidence that insect vector transmission is possible (Fischer et al. 2004; Mee et al. 2024). Any degree of immune compromise, including physiological stress, is likely to predispose an animal to mycobacteriosis.
NTM generally move from host to environment to host. Infected hosts shed mycobacteria into the environment, increasing the environmental load. Increased soil organic matter and moisture, such as may be found in zoo or rehabilitation enclosures, are likely to aid further replication and accumulation of NTM in the environment.
Most cases of mycobacteriosis in Australian mammals have been reported from animals in managed care. Based on these, there is a suggestion of possible species susceptibility to mycobacteriosis (Table 22.4).
Table 22.2. Important mycobacterial diseases in Australian mammals
| Mycobacterial species | Susceptible Australian mammal species | Common disease manifestation | Known geographical location |
| Non-tuberculous | |||
| Mycobacterium avium subsp. avium (MAA) and M. intracellulare | Macropods, dasyurids, native rodents, numbat (Myrmecobius fasciatus), potoroids, gliders1 | Disseminated mycobacteriosis | Australia, animals in managed care overseas |
| M. ulcerans | Possums, long-footed potoroo (Potorous longipes), koala (Phascolarctos cinereus)2 | Ulcerative dermatitis | South-eastern Vic., Australia |
| M. fortuitum complex | Dasyurids3 | Pyogranulomatous dermatitis and panniculitis | Australia (predominantly NSW), animals in managed care overseas |
| Tuberculous | |||
| M. pinnipedii (Chapter 45) | Australian sea-lion (Neophoca cinerea), longnosed fur seal (Arctophoca forsteri), Australian fur seal (Arctocephalus pusillus), Antarctic fur seal (A. gazelle) and Subantarctic fur seal (A. tropicalis)4 | Respiratory and lymphatic tuberculosis | Southern Hemisphere |
| M. bovis | Common brush-tailed possum (Trichosurus vulpecula)5 | Respiratory and lymphatic tuberculosis | NZ |
1Hime and Jones 1972; Potkay 1977; Gaynor etal. 1990; Vitali and Monaghan 2008; Vogelnest and Portas 2008; Michael and Sangster 2010; Robveille etal. 2015; ARWH 2018; 2Mitchell etal.
1987; Fowler and Mitchell 2002; O'Brien etal. 2014; ARWH 2018; Ban etal. 2020; 3Raymond etal. 2000; ARWH 2018; eWHIS 2018; 4Cousins etal. 2003; Barnes etal. 2008; 5Nugent etal. 2013
1.3 Clinical disease
Non-tuberculous mycobacteriosis has a multitude of potential presentations in Australian mammals and lesions can occur in virtually any tissue (Vogelnest 2015).
The most common forms of disease presentation are, broadly, visceral or disseminated cutaneous, pulmonary or osseous.1.3.1 Visceral or disseminated disease
Species with documented visceral or disseminated NTM disease include macropods, dasyurids, koala, feathertailed gliders (Acrobates spp.), short-beaked echidna (Tachyglossus aculeatus), bandicoots, native rodents and common bottle-nosed dolphin (Tursiops truncatus) (Hime and Jones 1972; Schoon et al. 1993; Whittington 1993; Burns et al. 1994; Bush et al. 1995; Phelan 1996; Cleland et al. 2004; Middleton 2008; Vogelnest and Portas 2008; Wunschmann et al. 2008; Ladds 2009; Michael and Sangster 2010; Clayton et al. 2012; Hulst et al. 2015; Rob- veille et al. 2015, ARWH 2018).
Clinical signs are varied, fairly unpredictable, often non-specific and present late in the course of infection. These may include weight loss, dyspnoea, lameness, skin lesions, abscesses, neurological signs and blindness (Ott Joslin 1990; Durham et al. 1996; Montali et al. 1998; Vogelnest and Portas 2008; Vogelnest 2015). Osseous infection is most common in macropods (Mann et al. 1982; Vogelnest and Portas 2008; Ladds 2009; Robveille et al. 2015). Prognosis in all cases of visceral and disseminated NTM is poor (Vogelnest 2015).
1.3.2 Cutaneous disease
Cutaneous NTM has been reported in possums, koalas, dasyurids, macropods, numbats, dolphins and pinnipeds (Mitchell et al. 1987; Gaynor et al. 1990; Raymond et al. 2000; Wunschmann et al. 2008; Reppas et al. 2010; O’Brien et al. 2014; ARWH 2018; eWHIS 2018) (see Chapter 12). Progression to lymphadenitis and/or disseminated disease can occur (McOrist et al. 1985; O’Brien et al. 2014; ARWH 2018 case nos: 2644.1, 10676.1, 11543.1).
The most frequently reported aetiological agents are species in the M. fortuitum complex and M. ulcerans (Table 22.3) and appear to cause geographical and species-specific patterns of disease.
Mycobacterium ulcerans causes ulcerative dermatitis, primarily in possums and koalas in south and south-east Vic.
Lesions typically occur on the face, tail or limbs (Mitchell et al. 1987; O’Brien et al. 2014; WHA 2024; see Chapters 12 and 37). M. ulcerans was also found in a foot lesion of a black rat (Rattus rattus) trapped in an area where there were concurrent confirmed cases in possums (eWHIS 2018). In people, M. ulcerans causes an ulcerative dermatitis known as ‘Buruli ulcers’ (see Chapter 16). Infection is understood to occur from environmental exposure. Possum faeces appears to increase the environmental burden and infection risk (Vandelannoote et al. 2023). Vector transmission by mosquito is also possible (Mee et al. 2024), and there is a single known case of direct zoonotic transmission via a possum bite (Xu et al. 2022).The M. fortuitum-complex species produce abscessing or plaque-forming dermatitis, cellulitis or panniculitis (or a combination thereof) in dasyurids. Lesions generally occur on the ventrum, axillae or inguina and may be focal or multifocal, dermal, SC or hypodermal, nodular or plaque like, ulcerated or non-ulcerated and may feature draining sinus tracts (Raymond et al. 2000; Reppas et al. 2010; ARWH 2018 case nos: 4942.1, 7874.1, 8307.1, 8321.2,
8372.3, 9299.1-4, 9576.2.3, 9588.1, 10378.1, 11543.1, 10676.1; eWHIS 2018). In Tasmanian devils (Sarcophilus harrisii), superficially the lesions may resemble flea allergy dermatitis or fight injuries (B Bryant pers. comm.).
Other NTM reported to cause cutaneous disease in Australian mammals include M. chitae, M. abscessus, M. asiaticum, M. gordonae and M. scrofulcaeum (Pritchard 1995; Raymond et al. 2000; O’Brien et al. 2014; ARWH 2018 case no. 4592.1).
1.4 Pathology
The pathology of visceral or disseminated disease is highly variable. Lesions may occur in virtually any tissue and lesions can be nodular or diffuse, well or poorly demarcated, and produce discrete lesions or generalised organomegaly (Ladds 2009). Given the notable variability in the gross pathological appearance, NTM infection should be suspected in any animal with evidence of chronic disease and gross pathology with an appearance suggestive of a chronic inflammatory process, such as fibrous or caseous lesions, organomegaly or tissue necrosis.
Microscopically, NTM lesions feature granulomatous or pyogranulomatous inflammation often accompanied by necrosis (Plate 22.1). Acid-fast stains such as Ziehl- Nielsen (ZN) will generally reveal the presence of intral- esional acid-fast bacteria (AFB) (Plate 22.2).
1.5 Diagnosis
Definitive diagnosis requires confirmation of the presence of AFB and culture and molecular characterisation for speciation. Signalment, animal species and clinical
Table 22.3. Non-tuberculous mycobacteria causing infection in Australian mammals
| Mycobacterial species | Disease types reported | |
| Slow-growing mycobacteria | ||
| Mycobacterium avium subsp. avium (MAA) | • Most common cause Ofvisceral or disseminated (non-cutaneous) mycobacteriosis, accounting for 59% of all collected cases,la^c cutaneous lesions rareld • Marsupials, particularly macropods, are susceptible. Of 46 known cases, 32 were macropods, 7 dasyurids, 3 gliders, 2 rodents, 1 bat and 1 numbat (Myrmecobius fasciatus)u~β | Disseminated (n = 23),la pulmonary (n = 8),lb osseous (n = 8),lc cutaneous (n = 2),ld unknown (n = 2)le |
| M. avium subsp. paratuberculosis | ■ Rare cause Ofenteritis and lymphadenitis in macropods grazing on farms with infected livestock (Johne's disease)23 • Risk of infection to macropods grazing with infected livestock is approximately 1%2b • Excretion of large numbers of organisms is rare in macropods that do become infected. Macropods are therefore unlikely to be a reservoir of infection and control efforts should focus on the livestock (e.g. vaccinating sheep), rather than co-grazing macropods2c | Disseminated only (n = 2)2a |
| M. IntraceIIuIare | • Closely related to M. avium, exclusively causes non-cutaneous mycobacteriosis • Reported in 11 macropods, 5 rodents, 3 dasyurids, 1 numbat3 | Disseminated (n = 8),3a pulmonary (n = 7),3b osseous (n = 4)3c |
| M. ulcerans | • Important cause of ulcerative dermatitis in several possum species (n = 28), the koala (Phascolarctos cinereus) (n = 13) and the long-footed potoroo (Potorous Iongipes) (n = 1). • Endemic in limited but growing areas of south-east Vic. Human cases also occur in Qld, NSW and NT. • Extension from cutaneous to disseminated infection in 4 eastern ring-tailed possums (Pseudocheirus peregrinus) and 1 koala.4 | Cutaneous only (n = 46)4 |
| M. Smegmatis | • Not generally considered pathogenic, though has been found associated with cutaneous lesions in 3 spotted-tailed quolls (Dasyurus maculatus)5a and 3 cases of disseminated disease in western grey kangaroos (Macropus fulginosus)5b | Disseminated (n = 2),5b cutaneous (n = 3)5a |
| M. gordonae and M. Scrofulcaeum | ■ Co-infection in 4 koalas with M. u/cerans-associated ulcerative dermatitis6 | Cutaneous only (n = 4)6 |
| M. genavense | • Fastidious organism frequently associated with infection in birds in managed care • Found in a case of sudden death of a free-ranging tammar wallaby (Notamacropus eugenii) in SA. The nature and location of the lesions are unknown11 | Unknown (n = 1)11 |
| Rapidly-growing mycobacteria | ||
| M. fortuitum complex | • Group of soil-associated species, several which have been linked to cutaneous and disseminated mycobacteriosis in Australian mammals7a^c'11 • M. fortuitum, M. senegalense, M. mageritense, M. alvei and unspecified M. fortuitum-comp∖e? organisms have been associated with pyogranulomatous dermatitis, cellulitis and panniculitis in dasyurids, specifically Tasmanian devils (Sarcophilus harrisii) and spotted-tailed quolls7a • In 2 Tasmanian devils, cutaneous infection progressed to disseminated disease76 • Has also been associated with disseminated disease in 2 long-nosed potoroos (P. tridactylus) and 1 spinifex hopping mouse (Notomys alexis)7c | Disseminated (n = 3),7c cutaneous (n = 8)7a,11 |
352 CurrentTherapyin MecIicineofAustraIian Mammals
| Mycobacterial species | Disease types reported | |
| M. chelonae | • Caused cutaneous disease in a Tasmanian devil8a and a northern quoll (D. hallucatus);8b disseminated disease in a short-beaked echidna (Tachyglossus aculeatus),8c a brush-tailed phascogale (Phascogale tapoatafa) 8d and a common bottle-nosed dolphin (Tursiops truncatus)8β ■ A numbat was diagnosed with a combined M. chelonae-abscessus and M. Intracellulare infection before the two former organisms could be taxonomically separated8f • Most commonly associated with freshwater, soil and reptiles | Disseminated (n = 4),8c^f cutaneous (n = 2)8a'b |
| M. abscessus | • Isolated from a case of mycobacterial pneumonia in a common bottle-nosed dolphin9a • A case of dual MAA and M. abscessus infection reported in a brush-tailed phascogale9b | Disseminated only (n = 2)9a,b |
| M. asiaticum | • A case Ofcutaneous mycobacteriosis in a red kangaroo (Osphranter rufus)κ | Cutaneous only (n = 1)1° |
| M. chitae | ■ A case Ofcutaneous mycobacteriosis in a spotted-tailed quoll5a | Cutaneous disease only (n = 1)5a |
| M. arupense | • Soil-associated mycobacterium isolated from hepatic abscesses in a free-ranging western brush wallaby (N. Irma) and a black-footed rock wallaby (Petrogale lateralis) in managed care, both from WA11 | Disseminated only (n = 2)11 |
1aVogeInest and Portas 2008; Robveille etal. 2015; ARWH 2018 case nos 476.1,1651.1, 2548.1, 3572.1,4125.1,4592.1, 5085.1,6369.1; 1bBush etal. 1995; Vogelnest and Portas 2008; ARWH 2018 case nos: 4138.1,4166.2, 5423.2, 5423.3; 1cVogeInest and Portas 2008; 1dLadds 2009; 1eNAHIS 2009; 2aCIeIand etal. 2010; 2bAbbott 2002; 2cWHA 2017a; 3aThomas 1987; Vogelnest and Portas 2008; ARWH 2018 case nos: 3230.1,4166.1,4166.3, 4861.1, 9555.1; 3bPeet and Dickson 1982; Richardson and Read 1986; Burns etal. 1994; 3cPheIan 1996; Vogelnest and Portas 2008; Michael and Sangster 2010; ARWH 2018 case nos: 4196.1, 4281.1,4520.3, 9568.1; 4MitcheII etal. 1984; McOrist etal. 1985, Fowlerand Mitchell 2002; O'Brien etal. 2014; ARWH 2018 case no. 12209.1; 5aRaymond etal. 2000; 5bVogeInest and Portas 2008; ARWH 2018 case no. 4630.1; 6MitcheII etal. 1984; 7aRaymond etal. 2000; Reppas etal. 2010; ARWH 2018 case nos: 8321.2,10378.1,11543.1,10676.1, 9299.1-4, 9588.1; 7bARWH 2018 case nos: 10676.1,11543.1; 7cARWH 2018 case nos: 4588.1, 8343.1, 8800.1; 8aARWH 2018 case no. 9576.2; 8bARWH 2018 case no. 4942.1; 8cARWH 2018 case no. 10611.1; 8dARWH 2018 case no. 5423.1; 8eWunschmann etal. 2008; 8fGaynor etal. 1990; 9aCIayton etal. 2012; 9bARWH 2018 case no. 4138.1; 10Ladds 2009; 11eWHIS 2018
22 - Mycobacteriosis 353
Table 22.4. Susceptibility of Australian mammals to non-tuberculous mycobacteriosis by taxa (susceptibility inferred by number of cases reported and may not represent true susceptibility)
| Highly susceptible | Macropods, especially potoroids, dasyurids |
| Moderately susceptible | Koala (Phascolarctos cinereus), possums, dolphins |
| Rare reports | Short-beaked echidna (Tachyglossus aculeatus), numbat (Myrmecobius fasciatus), gliders, bandicoots, pinnipeds, whales, native rodents |
| No reported cases | Platypus (Ornithorhynchus anatinus), wombats, greater bilby (Macrotis lagotis), bats, dingo (Canis familiaris),* dugong (Dugong dugon)** |
| *Specific cases in dingo not reported; however, the dingo likely has the same potential for disease as domestic dogs (i.e. moderately susceptible). | |
**None reported in the dugong, though several reports in manatees (Trichechus spp.).
presentation may provide an index of suspicion of mycobacteriosis. Serological tests have limited value in the diagnosis of mycobacteriosis, particularly in marsupials (Buddle and Young 2000; Vogelnest and Portas 2008). Diagnostic imaging (conventional radiography, computed tomography, magnetic resonance imaging, ultrasonography) may be a useful diagnostic aid and can be used to guide fine needle aspiration or biopsies (Hulst et al. 2015).
Sampling for microbiological or microscopic assessment can be performed using any method appropriate to the case and lesion location, including: tracheobronchial lavage, pus sampling, fine needle aspiration, impression smears or tissue biopsy. Some samples (respiratory secretions, skin lesions) may be contaminated with environmental AFB, leading to a false-positive result.
If AFB are seen microscopically via cytological or histological examination from a lesion utilising an acid-fast stain such as ZN, then culture and/or PCR will be required to confirm the mycobacterial species. Knowing the NTM species involved based on PCR may help inform antibiotic selection (in lieu of culture and susceptibility testing), and/or may be epidemiologically significant and is therefore recommended. Speciation should always be pursued whenever tuberculous mycobacteriosis cannot be excluded.
If the animal dies or is euthanased a necropsy should be performed (see section 3).
1.6 Treatment
In general, visceral and disseminated non-tuberculous mycobacteriosis carries a poor prognosis. Documented successful treatment and recovery is rare and prolonged treatment is likely to be required (Table 22.5). In comparison, cutaneous mycobacteriosis can be amenable to treatment. Resolution of lesions in all cases requires prolonged antimicrobial therapy, which should be initiated as soon as AFB are detected in lesions. Antibiotic choice should be based on culture and susceptibility results where possible, as resistance is unpredictable, particularly in RGM. Most cases of cutaneous mycobacteriosis are caused by RGM, though a few cases of SGM have also been documented (Table 22.3). In general, SGM are considered more reliably susceptible to specific anti-tuberculosis drugs, whereas RGM are more likely to be resistant to anti-tuberculosis drugs and susceptible to broad-spectrum antibiotics (Ashford et al. 2001).
1.6.1 Treatment of cutaneous mycobacteriosis
Cutaneous mycobacteriosis has been successfully treated in Tasmanian devils, quolls, tree-kangaroos, and numbats (Table 22.5). If lesions are discrete and amenable to resection then surgical debulking or debriding can be used in combination with antibiosis. Although there has been a report that cutaneous lesions in tree-kangaroos have been treated and cured by surgical resection alone (Ott Joslin 1990), it is still recommended that surgical resection is accompanied by prolonged antimicrobial treatment to minimise the risk of recurrence.
Various drugs and treatment protocols have been used (see Appendix 4 and Table 22.5).
1.7 Prevention and control
Control of the disease is challenging because many NTM are ubiquitous in the environment and antemortem testing of subclinically shedding animals is poorly developed, unreliable and difficult to interpret. Where possible, consider isolating animals with known active lesions from cohabited enclosures for at least 4 wk after treatment is initiated to avoid potential shedding into the substrate of enclosures. Substrate changes or treatments may aid in reduction of the environmental burden of NTM and should be considered, particularly if there are repeated cases within a cohort or particular enclosure.
Table 22.5. Documented successful chemotherapeutic treatment of cutaneous mycobacteriosis in Australian mammals
| Species | Treatment regimen |
| Tasmanian devil (Sarcophilus harrisii) | Enrofloxacin 5-10 mg/kg sid PO or 50 mg sid PO, ideally for 80 d following clinical resolution allowing clearance of NTM residing in macrophages1,2 Drug combinations may be considered in recalcitrant cases (e.g. doxycycline 50 mg sid PO for 10 d, followed by moxifloxacin 75 mg sid PO for 20 d)2 Drug-resistance to clarithromycin, doxycycline, trimethoprim/sulfamethoxazole and imipenem were commonly encountered in various M. fortuitum-complex isolates2 Surgical biopsy, histopathology, and culture should be repeated if lesions fail to resolve and at the end of treatment to confirm clearance of infection May be preferable to treat animals in enclosures with impermeable, readily cleaned and disinfected substrate to minimise possibility of environmental contamination from lesions1 |
| Numbat (Myrmecobius fasciatus) | Amikacin 7.5 mg/kg bid IM for 6 d with repeat 10-d course 6 wk later4 |
| Spotted-tailed quoll (Dasyurus maculatus) | Amikacin 3 mg/kg bid, enrofloxacin 2.5 mg/kg and rifabutin 20 mg/kg sid (precise regimen not described) for 3-16 wk. In most cases lesions were surgically debrided before medical treatment; 8 animals treated, 2 remained free from further NTM disease until their deaths5,6 |
| 1B Bryant and L Vogelnest pers. comm.; 2ARWH 2018; 3Reppas etal. 2010; 4Gaynor etal. 1990; 5Raymond etal. 2000; 6Holz 2008 | |
2.