Clinical manifestations of Cryptococcus gattii infection: determinants of neurological sequelae and death.
BACKGROUND
Longer-term morbidity and outcomes of Cryptococcus gattii infection are not described. We analyzed clinical, microbiological, and outcome data in Australian patients followed for 12 months, to identify prognostic determinants.


METHODS
Culture-confirmed C. gattii cases from 2000 to 2007 were retrospectively evaluated. Clinical, microbiological, radiological, and outcome data were recorded at diagnosis and at 6 weeks, 6 months, and 12 months. Clinical and laboratory variables associated with mortality and with death and/or neurological sequelae were determined.


RESULTS
Annual C. gattii infection incidence was 0.61 per 10(6) population. Sixty-two of 86 (72%) patients had no immunocompromise; 6 of 24 immunocompromised hosts had idiopathic CD4 lymphopenia, and 1 had human immunodeficiency virus/AIDS. Clinical and microbiological characteristics of infection were similar in immunocompromised and healthy hosts. Isolated lung, combined lung and central nervous system (CNS), and CNS only disease was reported in 12%, 51% and 34% of the cases, respectively. Complications in CNS disease included raised intracranial pressure (42%), hydrocephalus (30%), neurological deficits (27%; 6% developed during therapy) and immune reconstitutionlike syndrome (11%). Geometric mean serum cryptococcal antigen (CRAG) titers in CNS disease were 563.9 (vs 149.3 in isolated lung infection). Patient immunocompromise was associated with increased mortality risk. An initial cerebrospinal fluid CRAG titer of ≥256 predicted death and/or neurological sequelae (P = .05).


CONCLUSIONS
Neurological C. gattii disease predominates in the Australian endemic setting. Lumbar puncture and cerebral imaging, especially if serum CRAG titers are ≥512, are essential. Long-term follow up is required to detect late neurological complications. Immune system evaluation is important because host immunocompromise is associated with reduced survival.
Centre for Infectious Diseases and Microbiology, Westmead Millennium Institute, Sydney, Australia. sharon.chen@swahs.health.nsw.gov.au
Sharon C-A
SC
Chen
Monica A
MA
Slavin
Christopher H
CH
Heath
E Geoffrey
EG
Playford
Karen
K
Byth
Deborah
D
Marriott
Sarah E
SE
Kidd
Narin
N
Bak
Bart
B
Currie
Krispin
K
Hajkowicz
Tony M
TM
Korman
William J H
WJ
McBride
Wieland
W
Meyer
Ronan
R
Murray
Tania C
TC
Sorrell
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001315:Australia / Q000453:epidemiology; D002555:Cerebrospinal Fluid / Q000469:parasitology; D054022:Cerebrum / Q000000981:diagnostic imaging; D056285:Cryptococcus gattii / Q000472:pathogenicity*; D006801:Humans; D008297:Male; D016919:Meningitis, Cryptococcal / Q000175:diagnosis / Q000453:epidemiology / Q000401:mortality* / Q000473:pathology*; D008875:Middle Aged; D011379:Prognosis; D011859:Radiography; D012189:Retrospective Studies; D012307:Risk Factors; D013129:Spinal Puncture; D016896:Treatment Outcome; D055815:Young Adult