Clinical Manifestations of Cryptococcus gattii Infection: Determinants of Neurological Sequelae and Death.
Chen, Sharon C-A. 1,2,3; Slavin, Monica A. 6; Heath, Christopher H. 8; Playford, E. Geoffrey 11; Byth, Karen 3; Marriott, Deborah 4; Kidd, Sarah E. 12; Bak, Narin 13; Currie, Bart 14; Hajkowicz, Krispin 14; Korman, Tony M. 7; McBride, William J. H. 15; Meyer, Wieland 1,2,5; Murray, Ronan 9,10; Sorrell, Tania C. 1,2,3; on behalf of the Australia and New Zealand Mycoses Interest Group (ANZMIG)-Cryptococcus Studya
[Article]
Clinical Infectious Diseases.
55(6):789-798, September 15, 2012.
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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.
(C) Copyright Oxford University Press 2012.
