Cryptococcus in Wildlife and Free-Living Mammals

Abstract

Cryptococcosis is typically a sporadic disease that affects a broad range of animal species globally. Disease is a consequence of infection with members of the Cryptococcus neoformans or Cryptococcus gattii species complexes. Although cryptococcosis in many domestic animals has been relatively well-characterized, free-living wildlife animal species are often neglected in the literature outside of occasional case reports. This review summarizes the clinical presentation, pathological findings and potential underlying causes of cryptococcosis in various other animals, including terrestrial wildlife species and marine mammals. The evaluation of the available literature supports the hypothesis that anatomy (particularly of the respiratory tract), behavior and environmental exposures of animals play vital roles in the outcome of host-pathogen-environment interactions resulting in different clinical scenarios. Key examples range from koalas, which exhibit primarily C. gattii species complex disease presumably due to their behavior and environmental exposure to eucalypts, to cetaceans, which show predominantly pulmonary lesions due to their unique respiratory anatomy. Understanding the factors at play in each clinical scenario is a powerful investigative tool, as wildlife species may act as disease sentinels.

Keywords: C. gattii; C. neoformans; Cryptococcus; cryptococcosis; felid; koala; marine; wildlife.

Figure 1

Historical nomenclature of C. neoformans and C. gattii species complex. * Hagen et al., 2015 [18]; ^# hybrid (Modified from Kwon-Chung et al., 2017 [3]).

Figure 2

Cryptococcosis caused by C. gattii VGI in a 12 month old female koala (A–D) presenting with severe dyspnea and tachypnea and later developing seizures. (A) Lung at low magnification. There is marked consolidation of the pulmonary parenchyma. Some large airways containing exudate are evident. (B) The lungs exhibit a diffuse marked increase in cellularity due to an inflammatory infiltrate predominantly made up of macrophages. Note the budding yeast with the large negatively staining capsule. (C) In some parts of the specimen, the negatively stained capsule around the yeast is very large and there is an associated multinucleate giant cell macrophage response. (D) The thoracic lymph node exhibits a complete loss of normal architecture and is replaced almost entirely by large aggregates of encapsulated yeast cells, with some surrounding pyogranulomatous inflammatory infiltrate in places. (E) Lung at high magnification from a young male koala that presented with dyspnea, lymphadenomegaly and multifocal skin lesions associated with cryptococcosis caused by C. gattii VGI. There was significant widespread severe lung consolidation present at necropsy, in addition to multifocal lymph node involvement and multifocal skin lesions. Note the encapsulated yeast in the multinucleate giant cell macrophage.

Figure 3

(A) Primary pulmonary cryptococcoma (yellow star) in a lateral chest radiograph from a captive cheetah. The “glassy-eyed stare” seen with peripheral blindness is evident in (C), which shows the cheetah being given a subcutaneous infusion of amphotericin B. The patient after successful therapy is shown in (B), with its carer; note the alert demeanor and normal posture.

Figure 4

Cryptococcosis in the koala. (A) Koala with sinonasal cryptococcosis undergoing a computerized tomography scan. (B) Koala with destructive cryptococcal rhinitis due to C. gattii. (C) Multifocal skin involvement over the planum nasale of a koala with C. gattii infection. (D) Lungs from a koala that died of pneumonia due to C. gattii and Bordetella bronchiseptica. (E) Koala with cryptococcal rhinosinusitis with extension to the brain. (F) Koala with cryptococcal rhinitis with ventral extension to involve the hard palate.

Figure 5

Host–pathogen–environment interactions: the wheel that steers investigation and understanding of infectious disease development. Interactions may enhance or ameliorate disease. P, pathogen; H, host defenses; E, environment; D, disease outcome (subclinical or clinical effect on the host). For any potential pathogen, the interaction of host, pathogen and the environment determine where on the disease–outcome continuum the relationship will lie. This integration of concepts gives rise to a template of questions and generates hypotheses for use in investigating wildlife disease (adapted from ideas developed by Emeritus Professor Paul Canfield).