Cryptococcus gattii infection in Australia 2000-2007

We participated in a major national study of Cryptococcus gattii infection in Australia coordinated by Dr Sharon Chen and the Australian and New Zealand Mycoses Interest Group (ANZMIG), a special interest group (SIG) of the Australasian Society for Infectious Diseases (ASID).

Journal Articles
Antifungal therapy and management of complications of cryptococcosis due to Cryptococcus gattii,
Chen SC. Korman TM. Slavin MA. Marriott D. Byth K. Bak N. Currie BJ. Hajkowicz K. Heath CH. Kidd SE. McBride WJH. Meyer W. Murray R. Playford EG. Sorrell TC. on behalf of the Australia and New Zealand Mycoses Interest Group (ANZMIG)-Cryptococcus Study.
Clin Infect Dis. 2013 May 22. [Epub ahead of print]
PMID: 23697747 [PubMed – as supplied by publisher]
Background. We describe antifungal therapy and management of complications due to Cryptococcus gattii (CG) infection in 86 Australian patients followed for at least 12 months.
Methods. Patient data from culture-confirmed cases (2000-2007) were recorded at diagnosis, 6 weeks, 6 months and 12 months. Clinical, laboratory and treatment variables associated with raised intracranial pressure (ICP) and immune reconstitution syndrome (IRIS) syndrome were determined.
Results. Seven of 10 patients with lung infection received amphotericin B (AMB) induction therapy (6 with 5-flucytosine [5-FC], median 2 weeks); median duration of therapy including azole eradication therapy was 41 weeks, with a complete/partial clinical response in 78%. For neurological disease, 88% of patients received AMB, 78% with 5-FC, for a median 6 weeks. The median total course was 18 months. Nine receiving fluconazole induction therapy were re-induced with AMB plus 5-FC for clinical failure. Raised ICP (31 patients) was associated with initial abnormal neurology, and neurological sequelae and/or death at 12 months (both P=.02); cerebrospinal fluid drains/shunts were placed in 58% of cases and in 64% of 22 patients with hydrocephalus. IRIS developed 2-12 months after starting antifungals in 8 patients, who presented with new/enlarging brain lesions. Risk factors included female sex, brain involvement at presentation and higher median CD4 counts (all P<.05); corticosteroids reduced cryptococcoma-associated edema.
Conclusions. Induction AMB plus 5-FC is indicated for CG neurological cryptococcosis (6 weeks) and when localized to lung (2 weeks). Shunting was often required to control raised ICP. IRIS presents with cerebral manifestations.

Clinical manifestations of Cryptococcus gattii infection: determinants of neurological sequelae and death.
Chen SC. Slavin MA. Heath CH. Playford EG. Byth K. Marriott D. Kidd SE. Bak N. Currie B. Hajkowicz K. Korman TM. McBride WJH. Meyer W. Murray R. Sorrell TC. on behalf of the Australia and New Zealand Mycoses Interest Group (ANZMIG)-Cryptococcus Study.
Clin Infect Dis. 2012 Sep;55(6):789-98. Epub 2012 Jun 5.
PMID:22670042 [PubMed – in process]
Background. Longer-term morbidity and outcomes of Cryptococcus gattii (CG) 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 CG cases from 2000-2007 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 CG infection incidence was 0.61/106 population. Sixty-two of 86 (72%) patients had no immunocompromise; 6 of 24 immunocompromised hosts had idiopathic CD4 lymphopenia and 1, HIV/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%, respectively. Complications in CNS disease included raised intracranial pressure (42%), hydrocephalus (30%), neurological deficits (27%; 6% developed during therapy) and immune reconstitution-like syndrome (11%). Geometric mean serum cryptococcal antigen (CRAG) titres in CNS disease were 563.9 (vs. 149.3 in isolated lung infection). Patient immunocompromise was associated with increased mortality risk. Initial cerebrospinal fluid CRAG titre of ≥256 predicted death and/or neurological sequelae (P = .05).
Conclusions. Neurological CG disease predominates in Australian endemic setting. Lumbar puncture and cerebral imaging, especially if serum CRAG titres are ≥512, are essential. Long-term follow up is required to detect late neurological complications. Immune system evaluation is important since host immunocompromise is associated with reduced survival.

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