Cryptococcal antigen screen and titer by LFA

Test Mnemonic


CPT Codes

  • 87899 - QTY (1)




  • Antigen Detection, Cryptococcus
  • CAD
  • Cerebrospinal fluid
  • Cryptococcus
  • CSF fungal
  • serum, Cryptococcus

Performing Laboratory

Cleveland Clinic Laboratories

Specimen Requirements

Volume Type Container Collect Temperature Transport Temperature Special Instructions
1 mLCerebrospinal fluid (CSF)Sterile container  Sterile technique should be used to collect specimen to decrease contamination issues. FUNCSF order is suggested in recovering Cryptococcus from clinical specimen with consistently low titers and in cases where susceptibility testing may be indicated.
1 mLSerumSST (Gold)  Serum should be separated as soon as possible after collection by centrifuging. Grossly hemolysed samples may cause false positive results and will be rejected.

Minimum Specimen Requirements

Volume Type Container Collect Temperature Transport Temperature Special Instructions
0.1 mL     


Environmental Condition Description
RefrigeratedSerum separated from clot: 1 week; Serum not separated from clot: 72 hours; CSF: 72 hours
FrozenSerum: Indefinitely; CSF: Indefinitely

Days Performed

Sun - Sat

Turnaround Time

1 day


Name Description
Line Immunoassay (INNO-LIA) 

Reference Range

Cryptococcal antigen
Sex Age From Age To Type Range Range Unit
~      Negative 

Special Info

The Cryptococcal antigen lateral flow assay is a dipstick immunochromatographic assay. The test utilizes specimen wicking up the membrane to interact with capture gold-conjugated anti-CrAG antibodies. The antibody-antigen complex continues to wick up the membrane and interact with test line which has the immobilized anti-CrAg monoclonal antibodies. The antibody-antigen complex forms a visible line at the "test line". In order to report a test positive, a visible line is also needed at the "control line" which ensures proper migration of the specimen through the membrane. Thus, positive test results will create two lines (test and control), negative test results will only form one line (control). Test may result as invalid if a control line does not develop. Semi-quantitative titration procedures are employed with an initial positive or if there is an extremely faint line to rule out false negative results from high titer specimens (hook effect/postzone) If Cryptococcal Antigen Detection is positive, a titer will be performed at an additional charge with CPT code 87899 applied. If Cryptococcal Antigen Detection is positive, fungal culture will be reflexed.

Clinical Info

Cryptococcus species are typically acquired by the pulmonary route and have a predilection for CNS infections. CSF is the specimen of choice for detection of cryptococcal meningitis in adults. Cryptococcus antigen test on serum and CSF specimens is a rapid and sensitive diagnostic method for detection of Cryptococcal 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 resolution of infection

Clinical Limitation

Testing is limited CSF and serum specimens only. CSF specimens submitted for initial diagnosis that test positive by the lateral flow assay, should also be submitted for routine fungal culture. Culture can aid in differentiating between the 2 common Cryptococcus species causing disease (Cryptococcus neoformans and Cryptococcus gattii) and can be used for antifungal susceptibility testing, if necessary. CAD test should not be used as a screening procedure for the general population. This test should not be used as a test of cure or to guide treatment decisions. Bloody lumbar puncture and/or contamination of the cerebrospinal fluid (CSF) specimen with serum, other yeast infections such as Trichosporon may lead to a positive Cryptococcus antigen result. CAD titers can be utilised to monitor therapy but titers acquired by different assays are not interchangeable; titers acquired by lateral flow assay may be higher than other antigen assays such as agglutination tests. Extremely high concentrations of cryptococcal antigen can result in negative CAD results. If high burden is suspected, sample may be diluted to resolve false negative. Please call the lab/medical director in such instances.

Clinical Reference

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 "Westblade et. al. Larone’s Medically Important Fungi, 7th edition, ASM press, Washington DC., 2024. Leber et al., Clinical Microbiology Procedures Handbook, 5th edition, ASM press, Washington, DC. 2023. Carroll, et al. Manual of Clinical Microbiology, 13th Edition, Volume 3, ASM Press, Washington, DC. 2024. "