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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.
Note: According to the College of American Pathologists (CAP, IMM.41840), cerebrospinal fluid (CSF) samples submitted for initial diagnosis which test positive by the lateral flow assay should also be submitted for routine fungal culture. Fungal cultures are not required for CSF samples which are submitted to monitor Cryptococcus antigen titers during treatment.
Monitoring Cryptococcus antigen titers in cerebrospinal fluid
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)
CSF specimens submitted for initial diagnosis, which test positive by the lateral flow assay, should also be submitted for routine fungal culture. Culture can aid to differentiate between the 2 common Cryptococcus species causing disease (Cryptococcus neoformans and Cryptococcus gattii) and can be used for antifungal susceptibility testing, if necessary. CSF specimens submitted to monitor antigen levels during treatment do not need to be cultured.
A traumatic lumbar puncture and contamination of the cerebrospinal fluid (CSF) specimen with serum may lead to a positive Cryptococcus antigen result from CSF in patients without neuroinvasive cryptococcosis.
Cryptococcus antigen titers acquired by the lateral flow assay 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.
A negative result does not preclude diagnosis of cryptococcosis, particularly if only a single specimen has been tested and the patient shows symptoms consistent with cryptococcosis.
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.
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. 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