EPIDEMIOLOGY
It is clear that substantial difference exists between members of the C. neoformans species complex and members of the C. gattii species complex and that this difference might have originated with continental drift since the breakup of the super continent Pangea (Casadevall et al.
2017). Although C. neoformans species complex isolates occur more commonly in immunosuppressed humans than isolates of the C. gattii species complex (Chen et al. 2014), each can cause disease in apparently immunocompetent humans and other animals (Malik et al. 2011). Both are globally distributed, although there are important differences in their environmental associations (Mitchell et al. 2011).Worldwide, plant associations play an important role in the epidemiology of cryptococcosis (Springer et al. 2017). Members of the C. neoformans species complex tend to be widespread throughout the environment and although plant associations are documented throughout the world, in Australia the strongest environmental magnifier is dried/aged avian guano, especially when conditions are protected from light (Staib 1962a). This is likely because of the abundant nitrogen as a substrate for growth (Staib 1964).
Within this group, C. neoformans VNI is most prevalent in Australia among both human and companion animal patients (dogs, cats, ferrets), whereas VNII is rarer and associated with higher morbidity. In immunocompromised humans there is a strong association with isolates from the C. neoformans species complex. In companion animals the consensus view is that the association with immune status is weak and that C. neoformans appears to act as a primary pathogen predominantly (Malik et al. 2011). However, there is some suggestion of an association with retroviral status in cats, with an increased likelihood of severe disease in cats infected by feline leukaemia virus or feline immunodeficiency virus (Trivedi et al.
2011). In Australian wildlife, although the possibility cannot be completely excluded, there are no data linking an immunocompromised state and cryptococcosis caused by C. neoformans species complex, and in koalas (Phascolarctos cinereus) there is not an established association with koala retrovirus infection.The C. gattii species complex is more important as a pathogen of Australian wildlife; C. gattii VGI is the most geographically widespread member of this species complex in Australia (Chen et al. 2014) and it is by far the most commonly documented cause of cryptococcosis in Australian wildlife (Krockenberger et al. 2005). This is most likely because of the strong association of VGI with Eucalyptus spp. trees (Ellis and Pfeiffer 1990) (Table 25.2). A strong association has been demonstrated between C. gattii VGI genotypes isolated from koalas from the Liverpool Plains of NSW and the genotypes isolated from Eucalyptus spp. tree hollows from within their home ranges (Kan et al. 2022). In groups of animals held in managed care, this means that careful selection and management of eucalypt browse and tree hollow material are critical. Although it is difficult to detect Cryptococcus entering zoo enclosures on eucalypt browse (used for a large number of zoo species), koalas typically amplify C. gattii species complex in the environment, leading to contamination of eucalypt browse once placed within their enclosures (Krockenberger et al. 2002a; Krocken- berger et al. 2002b). The mechanism by which koalas amplify the organism in the environment is unknown; however, re-use of eucalypt browse from koala enclosures has been associated with cryptococcosis in a variety of marsupial species in some institutions. Highest risk seems to be in institutions where there is known frequent heavy koala nasal colonisation. In this setting, the browse exiting the enclosures is usually moderately to heavily contaminated with C. gattii species complex and should not be used in other exhibits.
The evidence is somewhat circumstantial as to whether re-used koala browse increases the frequency of cases or whether are other sources of the fungus involved; however, the frequency of cases in one institution was reduced by taking this approach. The management decision to not re-use browse should be made taking into account specific institutional factors.Careful thought concerning the ‘furniture’ in animal enclosures is also encouraged, including the nature of surfaces and the frequency with which they are decontaminated with biocides. High prevalence of Subclinical
Table 25.2. Eucalypt-Cryptococcus gattii species complex associations
| Scientific name | Common name | Cryptococcus gattii association | Distribution |
| Eucalyptus Camaldulensis | River redgum | C. gattii VGI | Australia - widespread |
| E. tereticornis | Forest redgum | C. gattii VGI | Eastern Australia |
| E. blakelyi | Blakely's redgum | C. gattii VGI | Eastern Australia - NSW |
| Angophora costata | Smooth-barked apple | C. gattii VGI1 | Eastern Australia |
| A. floribunda | Rough-barked apple | C. gattii VGI3 | Eastern Australia - NSW |
| E. microcorys | Tallowwood | C. gattii VGI1 | Eastern Australia |
| E. grandis | Flooded gum | C. gattii VGI1 | Eastern Australia |
| Syncarpia glomulifera | Turpentine gum | C. gattii VGI1 | Eastern Australia |
| E. largiflorens | Blackbox | C. gattii VGI1 | Murray-Darling River system |
| E. rudis | Flooded gum | C. gattii VGI1 | Western Australia |
| E. gomphocephala | Tuart | C. gattii VGI | Western Australia |
| E. robusta | Swamp mahogany | C. gattii VGI3 | Eastern Australia |
| E. populnea | Poplar box | C. gattii VGI3 | Eastern Australia - NSW |
| E. pilularis | Blackbutt | C. gattii VGI3 | South-eastern Australia |
| Melaleuca spp. | Paperbark | C. gattii VGI3 | Australia - widespread |
| E. albens | White box | C. gattii VGI3 | Eastern Australia (inland of Great Dividing Range) |
| E. melliodora | Yellow box | C. gattii VGI4 | Eastern Australia (inland of Great Dividing Range) |
| E. microcarpa | Grey box | C. gattii VGI4 | Eastern Australia (inland of Great Dividing Range) |
| Myoporum platycarpum | Sugarwood | C. gattii VGI2 | Southern Australia |
| E. socialis | Pointed mallee | C. gattii VGI2 | Inland Australia - widespread |
| E. tetradonta | Darwin stringybark | C. gattii VGII2 | Northern Australia |
| E. miniata | Darwin woollybutt | C. gattii VGII2 | Northern Australia |
| M. rephiophylla | Swamp paperbark | C. gattii VGII2 | South-western Australia |
| Corymbia terminalis | Bloodwood | C. gattii VGII2 | Northern Australia |
| C. calophylla | Marri | C. gattii VGII2 | Western Australia |
| C. bella | Ghost gum | C. gattii VGII2 | Northern Australia |
| Erythrophleum chlorostachys | Ironwood | C. gattii VGII2 | Northern Australia |
| 1M Krockenberger, unpublished; 2N Saul, | unpublished; 3Schmertmann etal. 2019b; 4A Kan, | unpublished |
and clinical cryptococcosis in koalas has been reduced in several institutions through long-term frequent furniture surface decontamination. When placing trees containing hollows as part of any habitat, it is prudent to culture for Cryptococcus spp. before placement and avoid their use if positive, particularly red gum species.
C. gatti VGII associated disease typically occurs in WA and NT, where it is endemic. An outbreak of clinical cryptococcosis associated with C. gatti VGII occurred in managed koalas in northern Qld, a nonendemic area, following translocation of an individual koala from WA supporting the notion that koalas can translocate the organism into new environments (Schmertmann et al. 2019a). More recently, Multi-Locus Sequence Typing of Cryptococcus spp. isolates colonising zoo koalas in Japan, demonstrated that koalas were able to transport, establish and spread C. gatti in areas where it was not previously present (Omura et al. 2024).
3.