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Cryptococcosis is a sporadic, cosmopolitan mycotic disease caused by the yeastlike fungus Cryptococcus neoformans and its variant, Cryptococcus neoformans gattii.Cryptococcus species reproduce by budding and vary from 4 to 20 μm in diameter. The fungus is surrounded by a mucopolysaccharide capsule that aids in its identification in body fluids and tissues. Of the more than 30 species in the genus Cryptococcus, C neoformans and C gattii are the pathogenic yeasts of cryptococcosis. Both species cause similar clinical manifestations, primarily in the lung and central nervous system. C neoformans is most responsible for infection in immunocompromised individuals and occurs worldwide. C gattii more commonly infects immunocompetent hosts. C gattii was originally thought to be limited to tropical and subtropical regions, but a recent outbreak of C gattii on Vancouver Island in Canada demonstrated a wider distribution.1


Cryptococcosis is an opportunistic infection and occurs primarily in patients with impaired cell-mediated immunity. Susceptibility to the disease is markedly increased in those with T cell–immune dysfunction. Cryptococcosis has been described in children with AIDS, acute lymphoblastic leukemia, hyper IgM and IgE syndromes, Bruton agammaglobulinemia, as well as in children receiving prolonged corticosteroid therapy.2 Before the use of highly active antiretroviral therapy (HAART), cryptococcal infection was a major cause of morbidity and mortality in adult patients with advanced HIV, infecting up to 10% of individuals with AIDS. In contrast, children infrequently develop cryptococcal disease, and prevalence rates in children with AIDS are reported to be around 1%.3,4 Interestingly, serologic studies from urban areas in the United States have shown that healthy asymptomatic children have high titers to cryptococcal polysaccharide.5 In the past decade, the incidence of cryptococcosis in patients with HIV/AIDS has significantly decreased due to the use of aggressive antiretroviral therapy.6 However, due to increasing numbers of solid-organ transplants and the use of immunosuppressive agents, the number of cases of cryptococcosis in immunocompromised, non-HIV patients continues to be high. It is currently the third-most common invasive fungal infection behind infections with Candida and Aspergillus in solid-organ transplant recipients.7 Cryptococcal basidiospores can be found in soil and in avian excrement. The organism can withstand prolonged drying and can persist in the soil for long periods of time. Pigeons are a frequent source, but cases have been linked to other birds, including starlings. The birds themselves are probably not infected, but their excreta serve as an excellent culture medium for the organism. Human disease is believed to be initiated by inhalation of cryptococcal cells, although infection via the gastrointestinal tract and direct inoculation into tissues can also be mechanisms of infection. The initial host response is thought to be through cell-mediated immunity, and similar to infection with Mycobacterium tuberculosis, the organism may stay dormant for long periods of time, only becoming active when there is a decline in the host’s immune system.


Clinical Manifestations


After cryptococcal cells are inhaled, they localize in the ...

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