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INTRODUCTION

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Cryptococcosis is a sporadic mycotic disease caused by the yeast-like fungi Cryptococcus neoformans and Cryptococcus gattii. The incidence of disease with these organisms has increased in the past few decades due to the increased number of individuals living with immunosuppressed conditions.

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PATHOGENESIS AND EPIDEMIOLOGY

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Cryptococcus species reproduce by budding and vary from 4 to 20 μm in diameter. The fungus is surrounded by a mucopolysaccharide capsule, which aids in its identification in body fluids and tissues. 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 of C neoformans, but cases have been linked to other birds, including starlings. The birds themselves are likely not infected, but their excreta serve as excellent culture medium for the organism. C gattii is commonly associated with eucalyptus tree species and less commonly with several other trees native of tropical, subtropical, and temperate climates. Human disease is initiated by inhalation of cryptococcal cells, although infection via the gastrointestinal tract and direct inoculation into tissues can also be mechanisms of infection. After cryptococcal cells are inhaled, they localize in the pulmonary parenchyma and may cause an isolated pneumonitis or disseminate hematogenously to any organ of the body.

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Of the more than 30 species in the genus Cryptococcus, C neoformans and C gattii are commonly known to be pathogenic to humans. Recently, Cryptococcus laurentii has been associated with cases of keratitis, endophthalmitis, cutaneous infection, lung abscess, peritonitis, meningitis, and fungemia. C neoformans is responsible for approximately 95% of cryptococcal infections, affecting mostly immunocompromised individuals, and occurs worldwide. C gattii more commonly infects immunocompetent hosts and was originally thought to be limited to tropical and subtropical regions. However, since the outbreak of C gattii in Vancouver, British Columbia, in 1999, the Pacific Northwest region of the United States has been increasingly affected by C gattii, and sporadic cases have been reported in other regions of the country. Interestingly, serologic studies from urban areas in the United States have shown that healthy asymptomatic children have high titers to cryptococcal polysaccharide.

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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 acquired immunodeficiency syndrome (AIDS), acute lymphoblastic leukemia, hyper-IgM and -IgE syndromes, and X-linked agammaglobulinemia, as well as in children receiving prolonged corticosteroid therapy. Before the use of highly active antiretroviral therapy (HAART), cryptococcal infection was a major cause of morbidity and mortality in adult patients with advanced human immunodeficiency virus (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%. Over the past 2 decades, the incidence of cryptococcosis ...

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