This test may be ordered for the early diagnosis of infections caused by Cryptococcus neoformans. It is usually appropriate for immunocompromised patients presenting with clinical signs of meningitis. Testing is most sensitive when testing CSF for cryptococcal meningitis. Testing serum has a lower sensitivity for confirmation of infection at other sites. Determination of antigen titer (testing twofold serial dilutions of the specimen) is recommended for positive CSF specimens to monitor response to treatment.
Method:
There are several formats for commercially available cryptococcal antigen tests, most commonly latex agglutination assays. In these assays, latex particles are coated with polyclonal or monoclonal antibodies against C. neoformans antigens.
Agglutination at dilutions of 1:8 or greater indicates active disease. Approximately 95% of patients with cryptococcal meningitis are detectable by cryptococcal antigen testing of the CSF.
The sensitivity for CSF is 93 " “100%, and for serum, it is 83 " “97%. Specificity for both specimen types is typically >95%.
Turnaround time: <24 hours
Interpretation
Expected results: Negative.
Positive results: Cryptococcal infection very likely. Positive results should be confirmed by culture.
Negative results: Cryptococcal infection unlikely. Use fungal culture to definitively rule out cryptococcal infection.
Limitations
False-negative reactions may occur, especially due to a prozone effect in serum samples. (Pronase treatment of serum samples decreases the incidence of the prozone phenomenon.) Some isolates from profoundly immunocompromised patients may produce very little polysaccharide capsular material, resulting in false-negative tests.
There are several sources of false-positive reactions. Positive reactions caused by rheumatoid factor (RF) may be reduced by pretreatment of the specimen with pronase, EDTA, or reducing agents. The syneresis fluid from agar media can cause false-positive results; an aliquot of the specimen for cryptococcal antigen testing should be removed before medium inoculation. Finally, several uncommon pathogens, including Trichosporon beigelii and Capnocytophaga canimorsus, can cause false-positive cryptococcal agglutination reactions.
Common pitfalls:
Positive cryptococcal antigen titers should be confirmed by culture to document active infection and rule out false-positive reactions. Some infected patients may have very low antigen titers. All specimens submitted for cryptococcal antigen testing should be accompanied by cultures of spinal fluid, blood, or other potentially infected material for fungal isolation.
Other Considerations
Antigen titers are usually higher in patients with AIDS compared to those seen in HIV-negative patients with cryptococcal infection. In patients with AIDS, baseline CSF antigen titers <1:2,048 are associated with improved prognosis. Antigen titers should fall with effective antifungal therapy. Steady or increasing cryptococcal antigen titers, even with sterilization of cultures, are an indication of likely treatment failure and recurrence of infection.