O'Hern JA

Koenen, Adrian

Janson, Sonja

Hajkowicz KM

Robertson IK

Kidd SE

Baird, Robert

Tong SYC

Davis JS

Carson P

Currie, Bart

Ralph, Anna

2023-03-06

BACKGROUND: Cryptococcus gattii is a globally endemic pathogen causing disease in apparently immune-competent hosts. We describe a 22-year cohort study from Australia's Northern Territory to evaluate trends in epidemiology and management, and outcome predictors. METHODS: A retrospective cohort study of all C. gattii infections at the northern Australian referral hospital 1996-2018 was conducted. Cases were defined as confirmed (culture-positive) or probable. Demographic, clinical and outcome data were extracted from medical records. RESULTS: 45 individuals with C. gattii infection were included: 44 Aboriginal Australians; 35 with confirmed infection; none HIV positive out of 38 tested. Multifocal disease (pulmonary and central nervous system) occurred in 20/45 (44%). Nine people (20%) died within 12 months of diagnosis, five attributed directly to C. gattii. Significant residual disability was evident in 4/36 (11%) survivors. Predictors of mortality included: treatment before the year 2002 (4/11 versus 1/34); interruption to induction therapy (2/8 versus 3/37) and end-stage kidney disease (2/5 versus 3/40). Prolonged antifungal therapy was the standard approach in this cohort, with median treatment duration being 425 days (IQR 166-715). Ten individuals had adjunctive lung resection surgery for large pulmonary cryptococcomas (median diameter 6cm [range 2.2-10cm], versus 2.8cm [1.2-9cm] in those managed non-operatively). One died post-operatively, and 7 had thoracic surgical complications, but ultimately 9/10 (90%) treated surgically were cured compared with 10/15 (67%) who did not have lung surgery. Four patients were diagnosed with immune reconstitution inflammatory syndrome which was associated with age <40 years, brain cryptococcomas, high cerebrospinal fluid pressure, and serum cryptococcal antigen titre >1:512. CONCLUSION: C. gattii infection remains a challenging condition but treatment outcomes have significantly improved over 2 decades, with eradication of infection the norm. Adjunctive surgery for the management of bulky pulmonary C. gattii infection appears to increase the likelihood of durable cure and likely reduces the required duration of antifungal therapy.

Department of Infectious Diseases, Royal Darwin Hospital, Darwin, Australia.

Department of General Surgery, Royal Darwin Hospital, Darwin, Australia.

Royal Brisbane and Women's Hospital, Brisbane, Australia.

College of Health and Medicine, University of Tasmania, Launceston, Tasmania, Australia.

National Mycology Reference Centre, SA Pathology, Adelaide, Australia.

Territory Pathology, Department of Health, Darwin, Australia.

Menzies School of Health Research, Charles Darwin University, Darwin, Australia.

PLoS Negl Trop Dis . 2023 Mar 6;17(3):e0011162. doi: 10.1371/journal.pntd.0011162. eCollection 2023 Mar.

0000-0003-3899-8956

https://pubmed.ncbi.nlm.nih.gov/36877729/?otool=iaurydwlib

https://hdl.handle.net/10137/12412

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Epidemiology, management and outcomes of Cryptococcus gattii infections: A 22-year cohort.

Journal Article

Publication