Test Id : SLFA

If result is positive, Cryptococcus titer will be performed at an additional charge.

Collection Container/Tube:

Preferred: Serum gel

Acceptable: Red top

Submission Container/Tube: Plastic vial

Specimen Volume: 1 mL

Collection Instructions: Centrifuge and aliquot serum into a plastic vial.

If not ordering electronically, complete, print, and send Infectious Disease Serology Test Request (T916) with the specimen.

0.5 mL

Aiding in the diagnosis of cryptococcosis

This test should not be used as a test of cure or to guide treatment decisions.

This test should not be used as a screening procedure for the general populations.

If result is positive, Cryptococcus titer will be performed at an additional charge.

Cryptococcosis is an invasive fungal infection caused by Cryptococcus neoformans or Cryptococcus gattii. C neoformans has been isolated from several sites in nature, particularly weathered pigeon droppings. C gattii was previously only associated with tropical and subtropical regions. More recently, however, this organism has been found to be endemic in British Columbia and the Pacific Northwestern United States and is associated with several different tree 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 C neoformans infections occur in immunocompromised patient populations, C gattii is has a higher predilection for infection of healthy individuals.(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.

Negative

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 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. Low-level titers may persist for extended periods of time following appropriate therapy and the resolution of infection.(3)

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.

There were 634 serum specimens (632 prospective and 2 archived) tested in a blinded fashion by the IMMY Cryptococcus antigen lateral flow assay (LFA), the Meridian latex agglutination (Meridian Bioscience Inc) assay, and the Meridian Cryptococcus antigen enzyme immunoassay (EIA) within a 24-hour period. Specimens with discordant results after initial testing were repeated by both assays during the same freeze/thaw cycle. The results are summarized in Table 1 and Table 2 below:

Table 1: Comparison of the IMMY LFA to the Meridian latex agglutination assay

*This sample showed 1+ reactivity by the Meridian latex agglutination assay upon screening but was interpreted as negative according to the package insert requirement for 2+ reactivity.

Sensitivity: 100% (9/9); 95% CI: 65.5%-100%

Specificity: 99.8% (624/625); 95% CI: 99.0%-99.9%

Overall Percent Agreement: 99.8% (633/634); 95% CI: 99.0%-99.9%

Table 2: Comparison of the IMMY LFA to the Meridian Cryptococcus antigen EIA

*These 5 samples were positive by the Meridian latex agglutination assay

Sensitivity: 100% (5/5); CI: 51.7%-100%

Specificity: 99.2% (624/629); CI: 98.1%-99.7%

Overall Percent Agreement: 99.2% (629/634); CI: 98.1%-99.7%

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 Cryptococcal Study Group. Clin Infect Dis. 2000 Aug;31(2):499-505. doi: 10.1086/313992

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 Feb 1;50(3):291-322

4. Warren NG, Hazen KC: Candida, Cryptococcus, and other yeasts of medical importance. In: Murray PR, ed. Manual of Clinical Microbiology. 7th ed. ASM Press; 1999:1184-1199

5. Lu H, Zhou Y, Yin Y, Pan X, Weng X : Cryptococcal antigen test revisited: significance for cryptococcal meningitis therapy monitoring in a tertiary Chinese hospital. J Clin Microbiol. 2005 June;43(6):2989-2990

6. Perfect JR: Cryptococcosis (Cryptococcus neoformans and Cryptococcus gattii). In: Bennett JE, Dolin R, Blaser MJ, eds. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases. 9th ed. Elsevier; 2020:3146-3161

The Cryptococcus antigen (CrAg) lateral flow assay is a sandwich immunochromatographic assay. Specimens and diluent are added to a test tube and the lateral flow device is added. The test uses specimen wicking to capture gold-conjugated, anti-Cryptococcus antigen monoclonal antibodies and gold-conjugated control antibodies deposited on the test membrane. If Cryptococcus antigen is present in the specimen, it binds to the gold-conjugated, anti-Cryptococcus antigen antibodies. This complex wicks up the membrane and interacts with the test line, which has immobilized anti-Cryptococcus antigen monoclonal antibodies. The antigen-antibody complex forms a sandwich at the test line causing a visible line to form. A valid test shows a visible line at the control line. Positive test results create 2 lines (control and specimen) while negative results form only the control line.(Package insert: CrAg Lateral Flow Assay. IMMY; Rev 06/27/2019)

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This test has been cleared, approved, or is exempt by the US Food and Drug Administration and is used per manufacturer's instructions. Performance characteristics were verified by Mayo Clinic in a manner consistent with CLIA requirements.

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