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Cryptococcal Antigen

Cryptococcal Antigen Detection, Cryptococcus, Crypto, C. neoformans

Test Codes

EPIC: LAB7790

Department

Microbiology

Specimen Collection Criteria

Collect one of the following specimen types:

• CSF: 1.0 mL in a sterile collection container. (Minimum: 0.5 mL)
• Blood: One plain Red-top tube. (Minimum: 3.0 mL)

All initial requests for CSF Cryptococcal Antigen must have a Fungal Culture ordered on the same specimen. If a Fungal Culture is not ordered with a CSF Cryptococcal Antigen on a patient without a prior positive CSF Cryptococcal antigen, the Microbiology Laboratory will automatically add a Fungus Culture.

CSF specimens submitted for monitoring antigen titers following an initial positive do not require a Fungal Culture.

Transport specimen to the Laboratory immediately after collection.

Physician Office/Draw Specimen Preparation

• CSF: Maintain specimen at room temperature (20-26°C or 68-78.8°F) and arrange for STAT transportation to the Laboratory. Courier Services can be contacted for a STAT pickup at 1-800-551-0488. (Minimum CSF: 0.5 mL)
  
  
• Red-top tube: Let specimen clot for 30-60 minutes then immediately centrifuge to separate serum from cells. Transfer serum to a plastic transport tube and refrigerate (2-8°C or 36-46°F). (Minimum Serum: 0.5 mL)

Preparation for Courier Transport

Transport: CSF in a sterile collection container, at room temperature (20-26°C or 68-78.8°F), and/or serum, refrigerated (2-8°C or 36-46°F). If ordering a Cryptococcal antigen with a CSF culture or Fungal culture, do not refrigerate the specimen.

Rejection Criteria

• Hemolyzed specimens.
• Specimens with a volume of less than 0.5 mL.
• CSF specimens that are clotted or grossly bloody.
• Serum Separator (SST) tubes.

Storage

Specimen Stability for Testing:

CSF
Room Temperature (20-26°C or 68-78.8°F): 24 hours
Refrigerated (2-8°C or 36-46°F): 72 hours. If ordering a Cryptococcal Antigen with a CSF culture or Fungal culture, do not refrigerate the specimen.
Frozen (-20°C/-4°F or below): Unacceptable

Serum
Room Temperature (20-26°C or 68-78.8°F): 24 hours
Refrigerated (2-8°C or 36-46°F): 72 hours
Frozen (-20°C/-4°F or below): Unacceptable

Specimen Storage in Department Prior to Disposal:

CSF: Refrigerated (2-8°C or 36-46°F): 30 days
Serum: Refrigerated (2-8°C or 36-46°F): 7 days 

Laboratory

Royal Oak Microbiology Laboratory

Performed

Sunday – Saturday, 24 hours a day.
STAT results available within 1 hour of receipt in the Royal Oak Microbiology Laboratory.
Routine results available within 12 hours.

Reference Range

Negative.

Test Methodology

Lateral Flow Assay

Interpretation

• If a physician suspects a cryptococcal infection due to clinical symptoms and a specimen gives a negative result, they should contact the Microbiology Lab to discuss and ask for a dilution to be performed.
• Assay results must be evaluated in conjunction with other clinical and diagnostic findings. Trichosporon beigelii has been shown to produce a cross-reactive polysaccharide antigen.
• Unencapsulated and weakly encapsulated strains can lead to false-negative results.
• Some persons with AIDS retain the CPS (cryptococcal polysaccharide) antigen for long periods of time. This is not due to active multiplication of the yeast. In these instances, subsequent specimen titration may assist the original laboratory findings concerning the prognosis of the disease.
• Persons with AIDS have shown serum antigen titer ranges from 1:2 to 1:32,678. The magnitude of the titer does not appear to correlate with the severity of infection but has been judged useful in the diagnosis of patients with widespread neurologic cryptococcal infection. However, titers greater than 1:10,000 in persons with AIDS are associated with 100% mortality.

Clinical Utility

The cryptococcal antigen test is a qualitative/semi-quantitative rapid test to detect the polysaccharide antigen associated with Cryptococcus neoformans infection.

Clinical Disease

• Initial cryptococcal infection begins by inhalation of the fungus into the lungs, usually followed by hematogenous spread to the brain and meninges. Involvement of the skin, bones, and joints may be seen. Cryptococcus neoformans is often cultured from the urine of patients with disseminated infections. In patients without human immunodeficiency virus infection, cryptococcosis, particularly cryptococcal meningitis, is usually seen in association with underlying conditions such as lupus erythematosus, sarcoidosis, leukemia, lymphomas, and Cushing's syndrome.
  
  
• Cryptococcosis is one of the defining diseases associated with AIDS. Patients with cryptococcosis and serologic evidence of human immunodeficiency virus infections are considered to have AIDS. In nearly 45% of AIDS patients, cryptococcosis was reported as the first AIDS-defining illness. Because none of the presenting signs or symptoms of cryptococcal meningitis (such as headache, fever, and malaise) are sufficiently characteristic to distinguish it from other infections that occur in patients with AIDS, determining cryptococcal antigen titers and culturing blood and cerebrospinal fluid are useful in making a diagnosis (1).

Epidemiology

Cryptococcus neoformans has been most frequently associated with aged pigeon (and other bird) droppings and soils contaminated with these droppings. The organism is usually not found in fresh droppings but is most evident in bird excreta that have accumulated over long periods on window ledges, vacant buildings, and other roosting sites.

Incubation Period

The incubation period, although not well defined, is probably a few weeks from the time of exposure (1).

Transmission

Acquisition is by inhalation of particles containing the organism. The fungus is not transmitted from person to person. Cryptococcus infects 5% to 10% of adults with AIDS but is less common in HIV-infected children (1).

Reference

1. Howell, S., K. Hazen, M.E. Brandt. 2015. Candida, Cryptococcus, and Other Yeasts of Medical Importance. Jorgensen, J.H., et al. (eds.). Manual of Clinical Microbiology 11^th edition. ASM Press. Washington, D.C.

CPT Codes

86403

Contacts

Last Updated

8/26/2025