Cryptococcus Antigen Screen with Titer, Serum
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
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.
An aid in the diagnosis of cryptococcosis
The presence of cryptococcal antigen in any body fluid (serum or cerebrospinal fluid) is indicative of cryptococcosis. Specimens that are positive by the lateral flow assay screen are automatically repeated with the same method utilizing dilutions in order to generate a titer value.
Disseminated infection is usually accompanied by a positive serum test.
Higher Cryptococcus antigen titers appear to correlate with more severe infections. 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, as low level titers may persist for extended periods of time following appropriate therapy and the resolution of infection.(3)
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
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.
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 specimens may lead to false-negative results due to the high background color on the lateral flow assay 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.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
Clinical References Provides recommendations for further in-depth reading of a clinical nature
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. 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. 2009;50:291-322
4. 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
5. 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