Mobile Site ›
Print Friendly View

Test ID: CLFA    
Cryptococcus Antigen Screen with Titer, Spinal Fluid

Useful For Suggests clinical disorders or settings where the test may be helpful

Aids in the diagnosis of cryptococcosis

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 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 that are submitted to monitor Cryptococcus antigen titers during treatment.

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.

Negative 

Interpretation Provides information to assist in interpretation of the test results

The presence of cryptococcal antigen in any body fluid (serum or cerebrospinal fluid: CSF) is indicative of cryptococcosis. Specimens that are positive by the lateral flow assay (LFA) screen are automatically repeated by the same method utilizing dilutions in order to generate a titer value. CSF specimens submitted for initial diagnosis, which test positive by LFA, 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.

                                

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 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.

 

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.

 

Although rare, extremely high concentrations of cryptococcal antigen can result in weak test lines and in extreme instances, yield false-negative test results.

 

This assay has not been evaluated for cross-reactivity in patients with trichosporonosis.

Supportive Data

Cerebrospinal fluid (CSF) retrospective specimens (111) were tested in a blinded fashion by the IMMY Cryptococcus Antigen Lateral Flow Assay (LFA; Normon, OK) and the Meridian Latex Agglutination (Meridian Bioscience Inc, Cincinnati, OH) assay within a 24-hour period. Of these 111 specimens, 45 were also tested by the Meridian Cryptococcus Antigen EIA also within a 24-hour period. Samples with discordant results after initial testing were repeated by both assays during the same freeze/thaw cycle. The results are summarized below in Table 1 and Table 2:

 

Table 1.  Comparison of the IMMY LFA to the Meridian Latex Agglutination Assay in CSF

 

Meridian Latex Agglutination

LFA IMMY

 

Positive

Negative

Total

Positive

18

0

18

Negative

0

93

93

Total

18

93

111

Sensitivity: 100% (18/18); 95% Confidence Interval (95% CI): 81.2%-100%

Specificity: 100% (93/93); 95% CI: 96.0%-100%

Overall Percent Agreement: 100% (111/111); 95% CI: 99.0%-100%

                                                                      

Table 2.  Comparison of the IMMY LFA to the Meridian Cryptococcus Antigen EIA Assay in CSF

 

Meridian EIA

LFA IMMY

 

Positive

Negative

Total

Positive

12

0

12

Negative

0

33

33

Total

12

33

45

Sensitivity: 100% (12/12); 95% CI: 72.2%-100%

Specificity: 100% (33/33); 95% CI: 87.8%-100%

Overall Percent Agreement: 100% (45/45); 95% CI: 90.8%-100%

Clinical Reference 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. Clin Infect Dis 2010;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