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Definition and Etiology

Cryptococcus, a genus of yeast-like fungi, is the etiologic agent of cryptococcosis. There are two species, C. neoformans and C. gattii, each of which can cause cryptococcosis in humans. C. neoformans occurs in two varieties known as grubii and neoformans, which correlate with serotypes A and D, respectively. C. gattii has not been divided into varieties but is also antigenically diverse, consisting of serotypes B and C. 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. The spectrum of disease caused by Cryptococcus species consists predominantly of meningoencephalitis and pneumonia, but skin and soft tissue infections also occur. Serologic studies have shown that, although evidence for cryptococcal infection is common among immunocompetent individuals, cryptococcal disease (cryptococcosis) is relatively rare in the absence of impaired immunity. Individuals at high risk for cryptococcosis include patients with hematologicmalignancies, 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.

Since the onset of the HIVpandemic in the early 1980s, the overwhelming majority of cryptococcosis cases have occurred in patients with AIDS (Chap. 189). To understand 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 York City—a figure far exceeding that for all cases of bacterial meningitis. With the advent of effective antiretroviral therapy, the incidence of AIDS-related cryptococcosis has been sharply reduced among treated individuals; however, the disease remains distressingly common in regions where antiretroviral therapy is not readily available, such as Africa and Asia, where up to one-third of patients with AIDS have cryptococcosis. The global burden of cryptococcosis was recently estimated at ~1 million cases, with >600,000 deaths annually. Thus cryptococci are major human pathogens.

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 ...

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