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

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dc.contributor.authorO’hern, J.A.
dc.contributor.authorKoenen, A.
dc.contributor.authorJanson, S.
dc.contributor.authorHajkowicz, K.M.
dc.contributor.authorRobertson, I.K.
dc.contributor.authorKidd, S.E.
dc.contributor.authorBaird, R.W.
dc.contributor.authorTong, S.Y.C.
dc.contributor.authorDavis, J.S.
dc.contributor.authorCarson, P.
dc.contributor.authorCurrie, B.J.
dc.contributor.authorRalph, A.P.
dc.contributor.editorNosanchuk, J.
dc.date.issued2023
dc.description.abstractBackground Cryptococcus gattii is a globally endemic pathogen causing disease in apparently immunecompetent 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.
dc.description.statementofresponsibilityJennifer A. O,'Hern, Adrian Koenen, Sonja Janson, Krispin M. Hajkowicz, Iain K. Robertson, Sarah E. Kidd, Robert W. Baird, Steven YC Tong, Joshua S. Davis, Phillip Carson, Bart J. Currie, Anna P. Ralph
dc.identifier.citationPLoS Neglected Tropical Diseases, 2023; 17(3):e0011162-1-e0011162-20
dc.identifier.doi10.1371/journal.pntd.0011162
dc.identifier.issn1935-2727
dc.identifier.issn1935-2727
dc.identifier.orcidKidd, S.E. [0000-0002-5957-4178]
dc.identifier.urihttps://hdl.handle.net/2440/141438
dc.language.isoen
dc.publisherPublic Library of Science (PLoS)
dc.rights© 2023 O’Hern et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
dc.source.urihttps://doi.org/10.1371/journal.pntd.0011162
dc.subjectAdult
dc.subjectAntifungal Agents
dc.subjectCohort Studies
dc.subjectCryptococcosis
dc.subjectCryptococcus gattii
dc.subjectHumans
dc.subjectNorthern Territory
dc.subjectRetrospective Studies
dc.subject.meshHumans
dc.subject.meshCryptococcosis
dc.subject.meshAntifungal Agents
dc.subject.meshRetrospective Studies
dc.subject.meshCohort Studies
dc.subject.meshAdult
dc.subject.meshNorthern Territory
dc.subject.meshCryptococcus gattii
dc.titleEpidemiology, management and outcomes of Cryptococcus gattii infections: A 22-year cohort
dc.typeJournal article
pubs.publication-statusPublished

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