Cryptococcus Neoformans

BackgroundThe organism C neoformans is an encapsulated yeast; its environmental niche has not been completely defined, although outbreaks of disease have been associated in particular with pigeon roosts and other large contaminated sites. There are two varieties of C neoformans, distinguished by antigenic differences in the outer capsule of the organism: serotypes A and D (C neoformans var neoformans, the most common strain) and serotypes B and C (C neoformans var gatti). Cryptococcus neoformans var neoformans is the principal pathogen in patients with AIDS. Cryptococcus neoformans var gatti, which is found predominantly in Australia, Asia, and Southern California, has only rarely been implicated to cause disease in this population.
Antigenic specificity of the capsular polysaccharides define the four different serotypes of C. neoformans; A, B, C and D. C. neoformans variety neoformans includes serotypes A and D while C. neoformans var. gattii are associated with serotypes B and C. Worldwide, most Cryptococcal infections in immunocompromised patients, including HIV infected patients, are due to C. neoformans var. neoformans, serotype A. In a smaller number of immunocompromised patients, infecton is caused by C. neoformans var. neoformans, Serotype D. For unknown reasons, HIV infected patients and other immunosuppressed patients are rarely infected with the variety gattii. Patients infected with C. neoformans var. gattii are usually immunocompetent, respond slowly to treatment, and are at risk for developing intracerebral mass lesions (cryptococcomas).
Cryptococcus neoformans reproduces by budding and forms round yeast-like cells 3-6 micrometers in diameter. Within the host and in certain culture media, a large polysaccharide capsule surrounds each cell. Cryptococcus neoformans forms smooth, convex, yellow or tan colonies on solid media at 20 to 37 degrees Celsius. The identification of this fungus is based on its microscopic appearance, biochemical tests, and its ability to grow at 37 degrees Celsius. Most nonpathogenic strains of Cryptococcus do not grow at 37 degree Celsius. In addition, C. neoformans does not assimilate lactose and nitrates or produce pseudomycelia on cornmeal or rice-Tween agar. Most strains of C. neoformans can use creatinine as a nitrogen source, which may partially explain the growth of the organism in creatinine rich avian feces. Another useful biochemical characteristic of C. neoformans that distinguishes it from non-pathogenic strains is its ability to produce melanin. The fungal enzyme phenol oxidase acts on certain substrates like dihydroxyphenylalanine and caffeic acid to produce melanin.
Cryptococcus neoformans is an encapsulated yeast that was first described in an 1894 paper presented to the Greifswald Medical Society by Busse, a pathologist. Busse isolated the yeast from the tibia of a 31 year old woman, noted its resistance to sodium hydroxide, and published the case that same year. The following year Buschke, a surgeon, reported the same isolate from the same patient. Thus, the early eponym of Busse-Buschke\'s disease. This one case served not only to identify a new yeast, but also to prove its pathogenic potential.
The exact pathogenesis of infection is still unclear. Pulmonary involvement is a common early event, and the organism is consequently assumed to gain access to the host via the respiratory route. In the absence of normal T-cell function, it then disseminates widely throughout the body, but especially to the central nervous system. Thus, most AIDS patients infected with C neoformans develop meningitis, although acute cryptococcal infection of almost every other organ has been described. Since the initial reports, the diverse spectrum of host responses to cryptococcal infection has become apparent. The spectrum ranges from harmless colonization of the airways and asymptomatic infection of laboratory workers resulting in a positive skin test to meningitis or disseminated disease. Although virulence for animals and possibly humans varies among strains of cryptococci, virulence probably plays a relatively small part in determining the outcome of an infection. The crucial factor appears to be the immune status of the host. The most serious infections usually occur in individuals with defective cell mediated immunity, such as the Acquired Immunodeficiency Syndrome (AIDS), organ transplantation, reticuloendothelial malignancy, corticosteroid treatment (but not neutropenia or immunoglobulin deficiency) and sarcoidosis. With the global emergence of AIDS, the incidence of cryptococcosis is increasing and now represents a major life threatening fungal infection in these patients. In the United States, 7% to 15% of patients with AIDS develop cryptococcal infectious. However, in some parts of sub-Saharan Africa coinfection with HIV