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      The aetiology and clinical characteristics of cryptococcal infections in Far North Queensland, tropical Australia

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          Abstract

          Cryptococcal infections are an important cause of morbidity and mortality in tropical Australia. This retrospective audit was conducted to characterise the aetiology, temporospatial epidemiology, and clinical course of 49 cryptococcal infections in Far North Queensland between 1 January 1999 and 31 December 2019. Cryptococcus gattii was identified in 15/32 (47%) in whom it was possible to speciate the organism. Among these 15 patients, 13 (87%) had a rural residential address, 10 (67%) were Indigenous Australians and 11 (73%) presented during the May-November dry season. When compared to the 17 patients with Cryptococcus neoformans infection, patients with C. gattii were less likely to be immunocompromised (0/15 versus 8/17 (47%), p = 0.003). Neurosurgery was necessary in 5/15 C. gattii cases and 3/17 (18%) C. neoformans cases (p = 0.42). Outcomes were generally good with 42/49 (86%) cases—and 14/15 (93%) with C. gattii infection—surviving to hospital discharge. These positive outcomes are likely to be explained by the development of standardised treatment guidelines during the study period, low rates of comorbidity in the patients with C. gattii infection and access to liposomal amphotericin and neurosurgical support in the well-resourced Australian healthcare system.

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          A new method of classifying prognostic comorbidity in longitudinal studies: Development and validation

          The objective of this study was to develop a prospectively applicable method for classifying comorbid conditions which might alter the risk of mortality for use in longitudinal studies. A weighted index that takes into account the number and the seriousness of comorbid disease was developed in a cohort of 559 medical patients. The 1-yr mortality rates for the different scores were: "0", 12% (181); "1-2", 26% (225); "3-4", 52% (71); and "greater than or equal to 5", 85% (82). The index was tested for its ability to predict risk of death from comorbid disease in the second cohort of 685 patients during a 10-yr follow-up. The percent of patients who died of comorbid disease for the different scores were: "0", 8% (588); "1", 25% (54); "2", 48% (25); "greater than or equal to 3", 59% (18). With each increased level of the comorbidity index, there were stepwise increases in the cumulative mortality attributable to comorbid disease (log rank chi 2 = 165; p less than 0.0001). In this longer follow-up, age was also a predictor of mortality (p less than 0.001). The new index performed similarly to a previous system devised by Kaplan and Feinstein. The method of classifying comorbidity provides a simple, readily applicable and valid method of estimating risk of death from comorbid disease for use in longitudinal studies. Further work in larger populations is still required to refine the approach because the number of patients with any given condition in this study was relatively small.
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            A wilcoxon-type test for trend

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              Epidemiology and host- and variety-dependent characteristics of infection due to Cryptococcus neoformans in Australia and New Zealand. Australasian Cryptococcal Study Group.

              A prospective population-based study was conducted in Australia and New Zealand during 1994-1997 to elucidate the epidemiology of cryptococcosis due to Cryptococcus neoformans var. neoformans (CNVN) and C. neoformans var. gattii (CNVG) and to relate clinical manifestations to host immune status and cryptococcal variety. The mean annual incidence per 10(6) population was 6.6 in Australia and 2.2 in New Zealand. Of 312 episodes, CNVN caused 265 (85%; 98% of the episodes in immunocompromised hosts) and CNVG caused 47 (15%; 44% of the episodes in immunocompetent hosts). The incidence of AIDS-associated cases in Australia declined annually (P<.001). Aborigines in rural or semirural locations (P<.001) and immunocompetent males (P<.001) were at increased risk of CNVG infection. Cryptococcomas in lung or brain were more common in immunocompetent hosts (P< or =.03) in whom there was an association only between lung cryptococcomas and CNVG. An AIDS-associated genetic profile of CNVN serotype A was confirmed by random amplification of polymorphic DNA analysis. Resistance to antifungal drugs was uncommon. The epidemiology of CNVN infection has changed substantially. Clinical manifestations of disease are influenced more strongly by host immune status than by cryptococcal variety.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: InvestigationRole: SupervisionRole: Writing – review & editing
                Role: Data curationRole: Writing – review & editing
                Role: Data curationRole: Writing – review & editing
                Role: Data curationRole: Writing – review & editing
                Role: Data curationRole: Writing – review & editing
                Role: Writing – review & editing
                Role: ConceptualizationRole: InvestigationRole: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: SupervisionRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS One
                plos
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                30 March 2022
                2022
                : 17
                : 3
                : e0265739
                Affiliations
                [1 ] Department of Medicine, Cairns Hospital, Cairns, Australia
                [2 ] School of Medicine, University of Queensland, Brisbane, Australia
                [3 ] Kirby Institute, University of New South Wales, Sydney, Australia
                University of Michigan Health System, UNITED STATES
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                https://orcid.org/0000-0002-1423-3839
                Article
                PONE-D-21-37969
                10.1371/journal.pone.0265739
                8966997
                35353860
                b236fc74-fbf6-497f-a39e-64073bdced74
                © 2022 Sim 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.

                History
                : 30 November 2021
                : 7 March 2022
                Page count
                Figures: 7, Tables: 3, Pages: 15
                Funding
                The authors received no specific funding for this work.
                Categories
                Research Article
                Biology and Life Sciences
                Organisms
                Eukaryota
                Fungi
                Cryptococcus
                Cryptococcus Gattii
                Biology and Life Sciences
                Microbiology
                Medical Microbiology
                Microbial Pathogens
                Fungal Pathogens
                Cryptococcus Gattii
                Medicine and Health Sciences
                Pathology and Laboratory Medicine
                Pathogens
                Microbial Pathogens
                Fungal Pathogens
                Cryptococcus Gattii
                Biology and Life Sciences
                Mycology
                Fungal Pathogens
                Cryptococcus Gattii
                Biology and Life Sciences
                Organisms
                Eukaryota
                Fungi
                Cryptococcus
                Cryptococcus Neoformans
                Biology and Life Sciences
                Microbiology
                Medical Microbiology
                Microbial Pathogens
                Fungal Pathogens
                Cryptococcus Neoformans
                Medicine and Health Sciences
                Pathology and Laboratory Medicine
                Pathogens
                Microbial Pathogens
                Fungal Pathogens
                Cryptococcus Neoformans
                Biology and Life Sciences
                Mycology
                Fungal Pathogens
                Cryptococcus Neoformans
                Medicine and Health Sciences
                Medical Conditions
                Infectious Diseases
                Respiratory Infections
                Medicine and Health Sciences
                Medical Conditions
                Respiratory Disorders
                Respiratory Infections
                Medicine and Health Sciences
                Pulmonology
                Respiratory Disorders
                Respiratory Infections
                Medicine and Health Sciences
                Pharmacology
                Drugs
                Antimicrobials
                Antifungals
                Amphotericin
                Biology and Life Sciences
                Microbiology
                Microbial Control
                Antimicrobials
                Antifungals
                Amphotericin
                Biology and Life Sciences
                Mycology
                Antifungals
                Amphotericin
                Biology and Life Sciences
                Anatomy
                Nervous System
                Central Nervous System
                Medicine and Health Sciences
                Anatomy
                Nervous System
                Central Nervous System
                Biology and Life Sciences
                Organisms
                Eukaryota
                Fungi
                Cryptococcus
                People and Places
                Geographical Locations
                Oceania
                Australia
                People and places
                Population groupings
                Ethnicities
                Indigenous Australian people
                Custom metadata
                All relevant data are within the paper and its Supporting Information files.

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