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Cryptococcosis is an invasive fungal infection caused by Cryptococcus neoformans or Cryptococcus gattii. Cryptococcus neoformans has been isolated from several sites in nature, particularly weathered pigeon droppings. Cryptococcus gatti was previously only associated with tropical and subtropical regions, however, more recently this organism has also been found to be endemic in British Columbia and among the Pacific Northwest United States, and is associated with several different trees species.
Infection is usually acquired via the pulmonary route. Patients are often unaware of any exposure history. Approximately half of the patients with symptomatic disease have a predisposing immunosuppressive condition such as AIDS, steroid therapy, lymphoma, or sarcoidosis. Symptoms may include fever, headache, dizziness, ataxia, somnolence, and cough. While the majority of Cryptococcus neoformans infections occur in immunocompromised patient populations, Cryptococcus gattii is has a higher predilection for infection of healthy hosts.(1,2)
In addition to the lungs, cryptococcal infections frequently involve the central nervous system (CNS), particularly in patients infected with HIV. Mortality among patients with CNS cryptococcosis may approach 25% despite antibiotic therapy. Untreated CNS cryptococcosis is invariably fatal. Disseminated disease may affect any organ system and usually occurs in immunosuppressed individuals.
Monitoring Cryptococcus antigen titers in serum
Aiding in the diagnosis of cryptococcosis
The presence of cryptococcal antigen in any body fluid (serum or cerebrospinal fluid: CSF) is indicative of cryptococcosis.
Disseminated infection is usually accompanied by a positive serum test.
Declining titers may indicate regression of infection. However, monitoring titers to cryptococcal antigen should not be used as a test of cure or to guide treatment decisions. Low-level titers may persist for extended periods of time following appropriate therapy and resolution of infection.(3,4)
Cryptococcus antigen titers acquired by the lateral flow assay (LFA) may be higher than titers achieved by other Cryptococcus antigen assays. Titers acquired by different assay methods are not interchangeable.
Cryptococcus antigen titers should be followed using the same assay.
A positive result is indicative of cryptococcosis, however all test results should be reviewed in light of other clinical findings.
Testing should not be performed as a screening procedure for the general populations and should only be performed when clinical evidence suggests the diagnosis of cryptococcal disease.
Testing hemolyzed serum samples may lead to false-negative results due to the high background color on the LFA strip.
Although rare, extremely high concentrations of cryptococcal antigen can result in weak test lines and in extreme instances, yield negative test results.
This assay has not been evaluated for cross-reactivity in patients with trichosporonosis.
1. Speed B, Dunt D: Clinical and host differences between infections with the two varieties of Cryptococcus neoformans. Clin Infect Dis 1995;21(1):28-34
2. Chen S, Sorrell T, Nimmo G, et al: Epidemiology and host- and variety-dependent characteristics of infection due to Cryptococcus neoformans in Australia and New Zealand. Australasian Cyrptococcoal Study Group. Clin Infect Dis 2000;31(2):499-505
3. Lu H, Zhou Y, Yin Y, et al: Cryptococcal antigen test revisited: significance for cryptococcal meningitis therapy monitoring in a tertiary Chinese hospital. J Clin Microbiol 2005 June;43(6):2989-2990
4. Perfect JR, Dismukes WE, Dromer F, et al: Clinical practice guidelines for the management of cryptococcal disease: 2010 update by the Infectious Diseases Society of America. Clin Infect Dis 2010;50:291-322
5. Binnicker MJ, Jespersen DJ, Bestrom JE, Rollins LO: A comparison of four assays for detection of cryptococcal antigen. Clin Vaccine Immunol 2012 Dec;19(12):1988-1990
6. Warren NG, Hazen KC: Candida, Cryptococcus, and other yeasts of medical importance. In Manual of Clinical Microbiology. Seventh edition. Edited by PR Murray. Washington DC. ASM Press, 1999, pp 1184-1199