Test Code SLFAT Cryptococcus Antigen Titer, Lateral Flow Assay, Serum
Useful For
Monitoring Cryptococcus antigen titers in serum
Aiding in the diagnosis of cryptococcosis
This test should not be used as a test of cure or to guide treatment decisions.
Disease States
- Cryptococcosis
Reporting Name
Cryptococcus Ag Titer, LFA, SSpecimen Type
SerumSpecimen Required
Collection Container/Tube:
Preferred: Serum gel
Acceptable: Red top
Submission Container/Tube: Plastic vial
Specimen Volume: 0.5 mL
Collection Instructions: Centrifuge and aliquot serum into a plastic vial
Specimen Minimum Volume
0.3 mL
Specimen Stability Information
Specimen Type | Temperature | Time | Special Container |
---|---|---|---|
Serum | Refrigerated (preferred) | 14 days | |
Frozen | 14 days |
Reject Due To
Gross hemolysis | Reject |
Gross lipemia | Reject |
Clinical Information
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 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.
Reference Values
Negative
Reference values apply to all ages.
Interpretation
The presence of cryptococcal antigen in any body fluid (serum or cerebrospinal fluid) 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)
Cautions
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 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.
Supportive Data
End-point titers between the IMMY Cryptococcus antigen lateral flow assay (LFA) and the Meridian latex agglutination test were compared for 10 samples positive for Cryptococcus antigen. While the overall qualitative correlation was good, these data indicate that the end-point titer achieved by the IMMY LFA was at least 2-fold higher than that achieved by the Meridian latex agglutination assay in 8 of 10 (80%) serum samples (Table).(5) Therefore, Cryptococcus antigen titers should be monitored by using the same method on serially collected samples; titers acquired by different methods are not interchangeable.
Table. Reciprocal endpoint titer
Serum sample |
Meridian latex agglutination |
IMMY LFA |
1 |
256 |
160 |
2 |
8 |
10 |
3 |
16 |
80 |
4 |
1024 |
2560 |
5 |
Negative* |
10 |
6 |
8 |
20 |
7 |
2 |
10 |
8 |
4 |
10 |
9 |
64 |
160 |
10 |
8 |
20 |
*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.
Clinical Reference
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. 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
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 Feb 1;50(3):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: Murray PR, ed. Manual of Clinical Microbiology. 7th ed. ASM Press; 1999: 1184-1199
Method Description
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-cryptococcal antigen monoclonal antibodies and gold-conjugated control antibodies deposited on the test membrane. If cryptococcal antigen is present in the specimen, it binds to the gold-conjugated, anti-cryptococcal antigen antibodies. This complex wicks up the membrane and interacts with the test line, which has immobilized anti-cryptococcal 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)
Day(s) Performed
Monday through Sunday
Report Available
Same day/1 to 2 daysSpecimen Retention Time
14 daysPerforming Laboratory
Mayo Clinic Laboratories in RochesterTest Classification
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.CPT Code Information
87899
LOINC Code Information
Test ID | Test Order Name | Order LOINC Value |
---|---|---|
SLFAT | Cryptococcus Ag Titer, LFA, S | 9818-6 |
Result ID | Test Result Name | Result LOINC Value |
---|---|---|
62077 | Cryptococcus Ag Titer, LFA, S | 9818-6 |
Method Name
Lateral Flow Assay (LFA)
Forms
If not ordering electronically, complete, print, and send Infectious Disease Serology Test Request (T916) with the specimen.