{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T00:56:57Z","timestamp":1784336217497,"version":"3.55.0"},"update-to":[{"DOI":"10.1371\/journal.pntd.0011162","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2023,3,16]],"date-time":"2023-03-16T00:00:00Z","timestamp":1678924800000}}],"reference-count":33,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2023,3,6]],"date-time":"2023-03-06T00:00:00Z","timestamp":1678060800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p><jats:italic>Cryptococcus gattii<\/jats:italic> is a globally endemic pathogen causing disease in apparently immune-competent hosts. We describe a 22-year cohort study from Australia\u2019s Northern Territory to evaluate trends in epidemiology and management, and outcome predictors.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>A retrospective cohort study of all <jats:italic>C<\/jats:italic>. <jats:italic>gattii<\/jats:italic> infections at the northern Australian referral hospital 1996\u20132018 was conducted. Cases were defined as confirmed (culture-positive) or probable. Demographic, clinical and outcome data were extracted from medical records.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>45 individuals with <jats:italic>C<\/jats:italic>. <jats:italic>gattii<\/jats:italic> 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 <jats:italic>C<\/jats:italic>. <jats:italic>gattii<\/jats:italic>. 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\u2013715). 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 &lt;40 years, brain cryptococcomas, high cerebrospinal fluid pressure, and serum cryptococcal antigen titre &gt;1:512.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p><jats:italic>C<\/jats:italic>. <jats:italic>gattii<\/jats:italic> 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 <jats:italic>C<\/jats:italic>. <jats:italic>gattii<\/jats:italic> infection appears to increase the likelihood of durable cure and likely reduces the required duration of antifungal therapy.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pntd.0011162","type":"journal-article","created":{"date-parts":[[2023,3,6]],"date-time":"2023-03-06T18:36:36Z","timestamp":1678127796000},"page":"e0011162","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":7,"title":["Epidemiology, management and outcomes of Cryptococcus gattii infections: A 22-year cohort"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3899-8956","authenticated-orcid":true,"given":"Jennifer A.","family":"O\u2019Hern","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian","family":"Koenen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonja","family":"Janson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krispin M.","family":"Hajkowicz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iain K.","family":"Robertson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah E.","family":"Kidd","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert W.","family":"Baird","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven YC","family":"Tong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua S.","family":"Davis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phillip","family":"Carson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bart J.","family":"Currie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna P.","family":"Ralph","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,3,6]]},"reference":[{"issue":"4","key":"pntd.0011162.ref001","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1093\/cid\/cit341","article-title":"Antifungal therapy and management of complications of cryptococcosis due to Cryptococcus gattii","volume":"57","author":"SC Chen","year":"2013","journal-title":"Clin Infect Dis"},{"issue":"4","key":"pntd.0011162.ref002","doi-asserted-by":"crossref","first-page":"980","DOI":"10.1128\/CMR.00126-13","article-title":"Cryptococcus gattii infections","volume":"27","author":"SC Chen","year":"2014","journal-title":"Clin Microbiol Rev"},{"issue":"3","key":"pntd.0011162.ref003","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1086\/649858","article-title":"Clinical practice guidelines for the management of cryptococcal disease: 2010 update by the infectious diseases society of america","volume":"50","author":"JR Perfect","year":"2010","journal-title":"Clin Infect Dis"},{"issue":"6","key":"pntd.0011162.ref004","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1093\/cid\/cis529","article-title":"Clinical manifestations of Cryptococcus gattii infection: determinants of neurological sequelae and death","volume":"55","author":"SC Chen","year":"2012","journal-title":"Clin Infect Dis"},{"issue":"8","key":"pntd.0011162.ref005","doi-asserted-by":"crossref","first-page":"3865","DOI":"10.1128\/JCM.42.8.3865-3868.2004","article-title":"Cryptococcus infection in tropical Australia","volume":"42","author":"A Jenney","year":"2004","journal-title":"J Clin Microbiol"},{"issue":"6","key":"pntd.0011162.ref006","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1111\/j.1445-5994.1993.tb04726.x","article-title":"Cryptococcus neoformans in tropical northern Australia: predominantly variant gattii with good outcomes.","volume":"23","author":"D Fisher","year":"1993","journal-title":"Aust N Z J Med"},{"key":"pntd.0011162.ref007","unstructured":"Informed Decisions. 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