Outcomes of central nervous system cryptococcosis vary with host immune function: Results from a multi-center, prospective study

Abstract

Central nervous system (CNS) cryptococcosis is most commonly encountered among HIV-infected and other immunosuppressed hosts but is less well-characterized among non-immunosuppressed patients. We conducted a three year, prospective, observational study to compare the clinical manifestations and outcome of CNS cryptococcosis in three patient populations: HIV-infected patients (n=54), HIV-negative immunosuppressed patients (n=21), and non-immunosuppressed patients (n=11). Time from initial symptoms to presentation did not differ between the groups. HIV-infected patients were significantly more likely to present with fevers (p<0.0001), but were less likely to have abnormal mental status, CNS mass lesions and pulmonary involvement (p=0.001, 0.01 and 0.03, respectively). The clinical manifestations among HIV-negative immunosuppressed patients were generally intermediate to the other groups. Overall, acuity of illness was worse among non-immunosuppressed patients, as measured by APACHE II scores (p=0.02). Intracranial pressure was higher in HIV-infected and non-immunosuppressed patients than immunosuppressed patients (p=0.008 and 0.01, respectively). Repeated lumbar punctures were more common among HIV-infected patients (p=0.01). There was a trend toward more frequent placement of permanent CNS shunts among non-HIV patients (p=0.05). The mortality rate was greatest for non-immunosuppressed patients (p=0.04). CNS cryptococcosis in non-immunosuppressed patients was associated with poorer prognosis. Our findings suggest that host immune responses may contribute to pathogenesis of CNS cryptococcosis, with more intact immune function associated with increased CNS-related morbidity and overall mortality.