Laboratory diagnosis

Clinical diagnosis is confirmed by cultures from the blood, CSF, or other clinically relevant fluids or tissue. However, early diagnosis is suggested by direct observation of C. neoformans in the CSF by India ink staining (Fig. 84-3B)41 Similarly, detection of cryptococcal antigen in either serum or CSF can provide a rapid diagnosis with greater than 95% sensitivity and specificity and appears to correlate with fungal burden.41 A positive serum antigen test of greater than 1:4 strongly suggests cryptococcal infection, and greater than or equal to 1:8 is indicative of active disease. Antigen titers in serum are positive in 99% of patients with cryptococcal meningitis and typically exceed titers of 1:2,048 in patients with AIDS. 1 However, the time course of cryptococcal antigen elimination is unknown, and a positive test result can persist for many years. Changes in the CSF cryptococcal antigen titers have limited value in the monitoring of drug therapy for cryptococcal meningitis, although it is expected that a decrease should be seen after two or more weeks of antifungal therapy.41

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