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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, suggesting that some may be reclassified as new species. Most clinical microbiology laboratories do not routinely distinguish between C. neoformans and C. gattii or among varieties, but rather identify and report all isolates simply as C. neoformans.


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.

image Cryptococcal infection is acquired from the environment. C. neoformans and C. gattii 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 recently estimated at ~1 million cases, with >600,000 deaths annually. Thus cryptococci are important human pathogens. Since the onset of the HIV pandemic in the early 1980s, the overwhelming majority of cryptococcosis cases have occurred in patients with AIDS (Chap. 197). To comprehend the impact of HIV infection on the epidemiology of cryptococcosis, it is instructive to note that in the early 1990s there were >1000 cases of cryptococcal meningitis each year in New ...

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