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


METHODS
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).


RESULTS
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).


CONCLUSIONS
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.
Nguyen
M Hong
MH
The University of Florida, College of Medicine, Gainesville, FL, USA. MHN5+@pitt.edu
Husain
Shahid
S
Clancy
Cornelius J
CJ
Peacock
James E
JE
Hung
Chien-Ching
CC
Kontoyiannis
Dimitrios P
DP
Morris
Arthur J
AJ
Heath
Christopher H
CH
Wagener
Marilyn
M
Yu
Victor L
VL
D018806:APACHE; D000328:Adult; D000935:Antifungal Agents / Q000627:therapeutic use; D001315:Australia / Q000453:epidemiology; D018791:CD4 Lymphocyte Count; D020314:Central Nervous System Fungal Infections / Q000150:complications / Q000276:immunology* / Q000401:mortality / Q000503:physiopathology* / Q000628:therapy; D002557:Cerebrospinal Fluid Shunts; D003453:Cryptococcosis / Q000150:complications / Q000276:immunology* / Q000401:mortality / Q000503:physiopathology* / Q000628:therapy; D003454:Cryptococcus / Q000302:isolation & purification; D015658:HIV Infections / Q000150:complications; D006801:Humans; D007121:Immunocompetence; D016867:Immunocompromised Host; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D016019:Survival Analysis; D013624:Taiwan / Q000453:epidemiology; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology
D000935:Antifungal Agents