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Cryptococcus, a genus of yeast-like fungi, is the etiologic agent of cryptococcosis. Until recently, cryptococcal strains were separated into two species, Cryptococcus neoformans and Cryptococcus gattii, both of which can cause cryptococcosis in humans. The two varieties of C. neoformansgrubii and neoformans—correlate with serotypes A and D, respectively. C. gattii, although not divided into varieties, also is antigenically diverse, encompassing serotypes B and C. However, genome sequencing studies have now revealed tremendous diversity among isolates previously assigned to each species, leading to the proposal that each of the prior species classifications includes numerous new species. Hence, C. neoformans and C. gattii are now considered as species complexes. However, for clinical purposes, these species complexes cause indistinguishable disease referred to as cryptococcosis. Consequently, this chapter will continue to use the nomenclature C. neoformans and C. gattii with the understanding that these terms refer to species complexes.


Cryptococcosis was first described in the 1890s but remained relatively rare until the mid-twentieth century, when advances in diagnosis and increases in the number of immunosuppressed individuals markedly raised its reported prevalence. Although serologic evidence of cryptococcal infection is common among immunocompetent individuals, cryptococcal disease (cryptococcosis) is relatively rare in the absence of impaired immunity. Individuals at high risk for disease due to C. neoformans include patients with hematologic malignancies, recipients of solid-organ transplants who require ongoing immunosuppressive therapy, persons whose medical conditions necessitate glucocorticoid therapy, and patients with advanced HIV infection and CD4+ T lymphocyte counts of <200/μL. In contrast, C. gattii–related disease is not associated with specific immune deficits and often occurs in immunocompetent individuals.

Cryptococcal infection is acquired from the environment. C. neoformans and C. gattii species complexes inhabit different ecologic niches. C. neoformans is frequently found in soils contaminated with avian excreta and can easily be recovered from shaded and humid soils contaminated with pigeon droppings. In contrast, C. gattii is not found in bird feces. Instead, it inhabits a variety of arboreal species, including several types of eucalyptus tree. C. neoformans strains are found throughout the world; however, var. grubii (serotype A) strains are far more common than var. neoformans (serotype D) strains among both clinical and environmental isolates. The geographic distribution of C. gattii was thought to be largely limited to tropical regions until an outbreak of cryptococcosis caused by a new serotype B strain began in Vancouver in 1999. This outbreak has extended into the United States, and C. gattii infections are being encountered increasingly in several states in the Pacific Northwest.

The global burden of cryptococcosis was estimated in 2012 at ~1 million cases, with >600,000 deaths annually, although the prevalence of this disease has declined since then with the greater availability of antiretroviral therapy (ART) for HIV. Thus cryptococci are important human pathogens. Since the onset of the HIV pandemic in the early ...

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