TEST CATALOG ORDERING & RESULTS SPECIMEN HANDLING CUSTOMER SERVICE EDUCATION & INSIGHTS
Test Catalog

Test ID: PLFA    
Cryptococcus Antigen Screen, Lateral Flow Assay, Pleural Fluid

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

Diagnosis of infection with Cryptococcus species

Testing Algorithm Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

If this screen is positive, the antigen titer will be performed at an additional charge.

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 C 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; however, more recently this organism has also been found to be endemic in British Columbia, along the Pacific Northwest, and in the Southeastern United States. 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 hosts. 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 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 pleural fluid is indicative of infection with Cryptococcus species.

 

Monitoring cryptococcal antigen levels as a means to determine response to therapy is discouraged, as antigen levels may persist despite adequate treatment and disease resolution.

 

A negative result indicates lack of infection; however, rare cases of false-negative results have been reported. Fungal culture should always be ordered alongside antigen testing.

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

A negative result does not preclude diagnosis of cryptococcal infection, particularly if the patient is at risk for cryptococcosis and shows symptoms consistent with this disease.

 

False-positive results may occur in patients with trichosporonosis or infection with Capnocytophaga species.

Supportive Data

Sixty pleural fluid samples, including 30 specimens collected from patients without microbiologic testing ordered and 30 specimens spiked at various dilutions with Cryptococcus antigen (CrAg)-positive specimens, were evaluated by both the IMMY CrAg LFA and the Meridian CALAS assays. The results are summarized in Table 1.

 

Table 1. Comparison of the IMMY CrAg LFA and the Meridian CALAS assays

Meridian CALAS Result

Positive Agreement (95% CI)

Negative Agreement (95% CI)

Overall Agreement (95% CI)

Positive

Negative

81% (65.4-90.8)

100% (86.5-100)

89.5% (79.6-95.1)

IMMY LFA Result

Positive

23

7(a)

Negative

0

30

(a)Details for these 7 discordant samples are provided in Table 2. All 7 specimens were pleural fluid spiked with CrAg-positive material and were expected to be positive by both assays.

 

Table 2. Comparison of discordant specimens between the IMMY CrAg LFA and Meridian CALAS Assays

Sample

Meridian Qualitative Result

LFA Qualitative Result

LFA Quantitative Result

1

Negative

Positive

1:10

2

Negative

Positive

1:2

3

Negative

Positive

1:10

4

Negative

Positive

1:2

5

Negative

Positive

1:5

6

Negative

Positive

1:160

7

Negative

Positive

1:80

The IMMY CrAg LFA has been shown to be significantly more sensitive in both serum and CSF specimens in prior studies.(1) Our findings in pleural fluid are consistent with these previous studies.

 

The reportable range for this assay is 1:2 to 1:2560 and the reference range is negative. Cross-reactivity was not observed with specimens positive for Histoplasma capsulatum or Aspergillus species antigens.

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

1. Binnicker MJ, Jespersen DJ, Bestrom JE, Rollins LO: Comparison of four assays for the detection of cryptococcal antigen. J Clin Micro 2012;19(12):1988-1990

2. Howell SA, Hazen KC, Brandt ME: Candida, cryptococcus, and other yeast of medical importance. In Manual of Clinical Microbiology. 11th edition. Washington, DC. ASM Press, 2015, pp 1984-2014