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

• Published in: PLoS neglected tropical diseases Vol. 17; no. 3; p. e0011162
• Main Authors: O'Hern, Jennifer A, Koenen, Adrian, Janson, Sonja, Hajkowicz, Krispin M, Robertson, Iain K, Kidd, Sarah E, Baird, Robert W, Tong, Steven Yc, Davis, Joshua S, Carson, Phillip, Currie, Bart J, Ralph, Anna P
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.03.2023; Public Library of Science (PLoS)
• Subjects: Adult; Antifungal Agents - therapeutic use; Antigens; Australian aborigines; Biology and Life Sciences; Care and treatment; Central nervous system; Cerebrospinal fluid; Cohort Studies; Cohorts; Complications; Cryptococcal infections; Cryptococcosis - drug therapy; Cryptococcosis - epidemiology; Cryptococcus gattii; Data collection; Distribution; End-stage renal disease; Epidemiology; Ethics; Fluid pressure; Fungal infections; Fungi; Fungicides; Health aspects; Health services; HIV; Hospitals; Human immunodeficiency virus; Humans; Immune reconstitution; Induction therapy; Infections; Infectious diseases; Inflammation; Kidney diseases; Lung diseases; Lungs; Medical records; Medical research; Medicine and Health Sciences; Mortality; Native peoples; Northern Territory; Pathogens; Patient outcomes; Patients; Population; Retrospective Studies; Serum; Surgery; Surgical operations; Survival; Therapy; Thorax; Tropical diseases; Northern Territory; Australia; United States > US
• ISSN: 1935-2735; 1935-2727; 1935-2735
• DOI: 10.1371/journal.pntd.0011162

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. 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. 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. 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.