Difficulty in diagnosing chronic meningitis caused by capsule-deficient Cryptococcus neoformans

We report a case of chronic meningitis due to capsule-deficient Cryptococcus neoformans which could not be diagnosed by routine morphological and immunological cerebrospinal fluid (CSF) examination. Repeated CSF examination and culture did not disclose the fungal body, and the cryptococcal antigen tests were always negative. Culture of ventricular fluid showed non-encapsulated cultured cells which were stained positively by indirect immunofluorescence using diluted sera from another patient diagnosed with cryptococcal meningitis. Inoculation of dispersed colonies into mice resulted in encapsulated C neoformans. It is important to suspect capsule-deficient C neoformans when the conventional diagnostic approaches fail to identify the organism or antigens.