CRYPTOCOCCUS, ANTIGEN, CEREBROSPINAL FLUID (CSF)/SERUM

Test Code: CRAG

Test Indications:
The Cryptococcal Antigen Lateral Flow Assay (CrAG LFA, IMMY, Norman, Oklahoma) may be used as an aid in the diagnosis of cryptococcosis. The test should only be performed when clinical evidence suggests the diagnosis of cryptococcal disease. Culture should always be ordered together with the CrAg LFA test.
Cryptococcosis is an invasive fungal infection caused by the Cryptococcus neoformans and Cryptococcus gattii species complex. While C. neoformans is distributed world-wide, C. gatti is mainly endemic in tropical and subtropical regions, in Southern Australia, and in the pacific northwest (British Columbia and US).
Cryptococcus infection usually occurs via the respiratory route. While the majority of C. neoformans infections occur in immunocompromised patients (steroid therapy, lymphoma, AIDS, sarcoidosis), C. gattii also infects healthy hosts. From the lungs, Cryptococcus frequently spreads to the central nervous system causing CNS cryptococcosis, which is associated with high mortality despite appropriate antibiotic therapy. Disseminated disease may affect any organ system and usually occurs in immunosuppressed individuals. Skin lesions can occur as either localized infections or as a result of disseminated disease.

Test limitations:
- Sensitivity and specificity of the test are excellent. However, false-positive reactions may rarely occur in cases of invasive trichosporonosis, and in patients with high levels of human anti-mouse antibodies.
- Prozone effects have caused false negative test results when cryptococcal antigen titers are very high. Contact the laboratory to request repeat testing of a 1:10 diluted sample, if the test was negative but suspicion for cryptococcal infection remains high.

Recommendations:
Monitoring serum or CSF titers to cryptococcal antigen should not be used as a test of cure or to guide treatment decisions, as variable titers may persist for extended periods of time following appropriate therapy and the resolution of infection.
Early meningitis can present with negative CSF studies and positive CrAg in blood only. Thus, serum CrAg testing should always be performed in an immunocompromised individual with an unknown central nervous system (CNS) disorder. Serum CrAg is positive in both meningeal and non-meningeal cryptococcal infections and may be present weeks to months before symptom onset.
Samples and requisitions must be labeled/completed in accordance with the Shared Health Specimen Acceptance Policy.
Accurate patient identification must be made prior to sample collection. Patient identification should be done in accordance with the site policy.

Patient Preparation Instructions:
CSF collection:
- Sample must be acquired using aseptic technique.
- Follow protocols outlined by your health care facility for this sample type.
- Submit the second or third tube collected for microbiologic examination.

For Blood: Serum Tube(s), with or without barrier gel - Full Tube Collection
Sterile Tube (for CSF only)

_SH Microbiology - Provincial Requisition (R250-10-06)

Negative.
Test result interpretation:
- If a test result is positive a serum titer will be performed and reported.
- A CrAg LFA titer of ≥1:10 is suggestive of infection.
- A CrAg lFA titre of ≤1:5 has an increased chance of being a false (+) reaction. Careful evaluation of the patient and repeat CrAg LFA testing may be indicated.
In a patient with HIV, when serum CrAg LFA titers are >1:160, disseminated disease becomes increasingly more likely, and when CrAg LFA titers are >1:640, disseminated and/or CNS involvement should be assumed, regardless of CSF test results.

Weekdays

FLUID (E.G., CEREBROSPINAL FLUID [CSF]/BONE MARROW), CULTURE, AEROBIC BACTERIA - (CSF)

Specimen Handling:
Samples can be stored for ≤24 hrs at room temperature. If required, serum (after transfer to a clean tube) or CSF can be stored for up to a week at 2-8°C or at ≤ -20°C if longer storage is required.