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Test Catalog

Test ID: CLFAT    
Cryptococcus Antigen Titer, Lateral Flow Assay, Spinal Fluid

Useful For Suggests clinical disorders or settings where the test may be helpful

Monitoring Cryptococcus antigen titers in cerebrospinal fluid

 

Aiding in the diagnosis of cryptococcosis

 

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

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Cryptococcosis is an invasive fungal infection caused by Cryptococcus neoformans or Cryptococcus gattii. Cryptococcus neoformans has been isolated from several sites in nature, particularly weathered pigeon droppings. C gatti was previously associated with tropical and subtropical regions only, however, more recently this organism has also been found to be endemic in British Columbia and among the Pacific Northwest United States and is associated with several different trees 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.

 

Note: According to the College of American Pathologists (CAP, IMM.41840), cerebrospinal fluid (CSF) samples submitted for initial diagnosis that test positive by the lateral flow assay should also be submitted for routine fungal culture. Fungal cultures are not required for CSF samples that are submitted to monitor Cryptococcus antigen titers during treatment.

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

Negative

Interpretation Provides information to assist in interpretation of the test results

The presence of cryptococcal antigen in any body fluid (serum or cerebrospinal fluid: CSF) 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)

 

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 to differentiate between the 2 common Cryptococcus species causing disease (Cryptococcus neoformans and Cryptococcus gattii) and can be used for antifungal susceptibility testing, if necessary. CSF specimens submitted to monitor antigen levels during treatment do not need to be cultured.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

A traumatic lumbar puncture and contamination of the cerebrospinal fluid (CSF) specimen with serum may lead to a positive Cryptococcus antigen result from CSF in patients without neuroinvasive cryptococcosis.

 

Cryptococcus antigen titers acquired by the lateral flow assay 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.

 

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. 

 

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.

 

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

Endpoint titers between the IMMY lateral flow assay (LFA) and the Meridian latex agglutination test were compared for 18 cerebrospinal fluid (CSF) samples positive for Cryptococcus antigen. While the overall qualitative correlation was good, these data indicate that the endpoint titer achieved by the IMMY LFA was at least 2-fold higher than that achieved by the Meridian latex agglutination assay in 15 of 17 (88%) serum samples. (Table 1) Therefore, Cryptococcus antigen titers should be monitored by using the same method on serially-collected samples; titers acquired by different methods are not interchangeable.

 

 

Reciprocal endpoint titer by:

CSF sample

Meridian latex agglutination

IMMY LFA

1

>256

5120

2

2

80

3

128

40

4

64

640

5

2

10

6

>256

5120

7

128

40

8

>256

640

9

>256

5120

10

32

256

11

256

10,240

12

64

640

13

64

2560

14

>256

10,240

15

32

640

16

>256

10,240

17

64

2560

18

1

5

Clinical Reference Recommendations for in-depth reading of a clinical nature

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 Cyrptococcoal Study Group. Clin Infect Dis. 2000;31(2):499-505

3. Lu H, Zhou Y, Yin Y, et al: 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;50:291-322

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

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