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Aiding in the diagnosis of pulmonary cryptococcosis
Cryptococcosis is an invasive fungal infection caused by Cryptococcus neoformans. The organism has been isolated from several sites in nature, particularly weathered pigeon droppings.
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.
In addition to the lungs, cryptococcal infections frequently involve the central nervous system (CNS), particularly in patients infected with HIV. Mortality in 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.
The presence of cryptococcal antigen in any body fluid is indicative of cryptococcosis.
Higher titers appear to correlate with more severe infections. Declining titers in serum may indicate regression of infection or response to therapy. However, monitoring titers to cryptococcal antigen should not be used as a test of cure, as low level titers may persist for extended periods of time following appropriate therapy and the resolution of infection.
In addition to testing for cryptococcal antigen, patients with presumed pulmonary disease due to Cryptococcus neoformans should have respiratory specimens (eg, bronchoalveolar lavage fluid) submitted for routine smear and fungal culture.
A negative result does not preclude the diagnosis of cryptococcosis, particularly if only a single specimen has been tested and the patient shows symptoms consistent with cryptococcosis.
Patients having trichosporonosis may yield false-positive results.
Rheumatoid factor may produce false-positive results.
Thirty analyte-negative pleural fluid specimens were spiked with a positive control specimen (purified cryptococcal antigen derived from a culture isolate of Cryptococcus neoformans to yield a desired endpoint titer of 1:16 (10 specimens), 1:64 (10 specimens) or 1:512 (10 specimens). These samples were then tested by the Cryptococcal Antigen Latex Agglutination System (CALAS; Meridian Bioscience, Cincinnati, OH) and all specimens yielded the expected endpoint titer (one, 2-fold serial dilution).
To assess analytical specificity, analyte-negative pleural fluid specimens were spiked with material (eg, clinical specimen or control material) positive for Histoplasma (n=6), Blastomyces (n=1), or Aspergillus antigen (n=16). These specimens were then tested by the CALAS antigen assay and all (23/23) were negative.
Hazen KC, Howell,SA: Candida, Cryptococcus, and other Yeasts of Medical Importance. In Manual of Clinical Microbiology. Ninth edition. Edited by PR Murray. Washington, DC, ASM Press, 2007, pp 1762-1788.