Clinical manifestations of Cryptococcus gattii infection: determinants of neurological sequelae and death

Chen, Sharon C-A., Slavin, Monica A., Heath, Christopher H., Playford, E. Geoffrey, Byth, Karen, Marriott, Deborah, Kidd, Sarah E., Bak, Narin, Currie, Bart, Hajkowicz, Krispin, Korman, Tony M., McBride, William J.H., Meyer, Wieland, Murray, Ronan, and Sorrell, Tania C. (2012) Clinical manifestations of Cryptococcus gattii infection: determinants of neurological sequelae and death. Clinical Infectious Diseases, 55 (6). pp. 789-798.

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Abstract

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 10⁶ 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.

Item ID: 23637
Item Type: Article (Refereed Research - C1)
ISSN: 1537-6591
Date Deposited: 10 Oct 2012 05:25
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1108 Medical Microbiology > 110802 Medical Infection Agents (incl Prions) @ 33%
11 MEDICAL AND HEALTH SCIENCES > 1109 Neurosciences > 110902 Cellular Nervous System @ 34%
11 MEDICAL AND HEALTH SCIENCES > 1103 Clinical Sciences > 110309 Infectious Diseases @ 33%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920109 Infectious Diseases @ 50%
92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920111 Nervous System and Disorders @ 50%
Citation Count from Web of Science Web of Science 2
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