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Article ; Online: Fungal Infections Other Than Invasive Aspergillosis in COVID-19 Patients

Kerri Basile / Catriona Halliday / Jen Kok / Sharon C-A. Chen

Journal of Fungi, Vol 8, Iss 58, p

2022 Volume 58

Abstract: Invasive fungal disease (IFD) associated with Coronavirus Disease 2019 (COVID-19) has focussed predominantly on invasive pulmonary aspergillosis. However, increasingly emergent are non- Aspergillus fungal infections including candidiasis, mucormycosis, ... ...

Abstract	Invasive fungal disease (IFD) associated with Coronavirus Disease 2019 (COVID-19) has focussed predominantly on invasive pulmonary aspergillosis. However, increasingly emergent are non- Aspergillus fungal infections including candidiasis, mucormycosis, pneumocystosis, cryptococcosis, and endemic mycoses. These infections are associated with poor outcomes, and their management is challenged by delayed diagnosis due to similarities of presentation to aspergillosis or to non-specific features in already critically ill patients. There has been a variability in the incidence of different IFDs often related to heterogeneity in patient populations, diagnostic protocols, and definitions used to classify IFD. Here, we summarise and address knowledge gaps related to the epidemiology, risks, diagnosis, and management of COVID-19-associated fungal infections other than aspergillosis.
Keywords	COVID-19 ; SARS-CoV-2 ; fungal infections ; non- Aspergillus fungi ; Biology (General) ; QH301-705.5
Subject code	610
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Development of a Real-Time PCR Assay to Identify and Distinguish between Cryptococcus neoformans and Cryptococcus gattii Species Complexes

Enoch Tay / Sharon C-A. Chen / Wendy Green / Ronald Lopez / Catriona L. Halliday

Journal of Fungi, Vol 8, Iss 462, p

2022 Volume 462

Abstract: Cryptococcus neoformans and Cryptococcus gattii are the principle causative agents of cryptococcosis. Differences in epidemiological and clinical features, and also treatment, mean it is important for diagnostic laboratories to distinguish between the ... ...

Abstract	Cryptococcus neoformans and Cryptococcus gattii are the principle causative agents of cryptococcosis. Differences in epidemiological and clinical features, and also treatment, mean it is important for diagnostic laboratories to distinguish between the two species. Molecular methods are potentially more rapid than culture and cryptococcal antigen (CRAG) detection; however, commercial PCR-based assays that target Cryptococcus do not distinguish between species. Here, we developed a real-time PCR assay targeting the multicopy mitochondrial cytochrome b ( cyt b ) gene to detect C. neoformans and C. gattii in clinical specimens. Assay performance was compared with culture, histopathology, CRAG and panfungal PCR/DNA sequencing. The cyt b -directed assay accurately detected and identified all eight C. neoformans / gattii genotypes. High-resolution melt curve analysis unambiguously discriminated between the two species. Overall, assay sensitivity (96.4%) compared favorably with panfungal PCR (76.9%) and culture (14.5%); assay specificity was 100%. Of 25 fresh frozen paraffin embedded (FFPE) specimens, assay sensitivity was 96% (76% for panfungal PCR; 68% for histopathology). The Cryptococcus -specific PCR is a rapid (~4 h) sensitive method to diagnose (or exclude) cryptococcosis and differentiate between the two major species. It is suitable for use on diverse clinical specimens and may be the preferred molecular method for FFPE specimens where clinical suspicion of cryptococcosis is high.
Keywords	Cryptococcus neoformans ; Cryptococcus gattii ; Cryptococcus PCR ; diagnosis of cryptococcosis ; Biology (General) ; QH301-705.5
Subject code	610
Language	English
Publishing date	2022-04-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Scedosporium and Lomentospora Infections

Sharon C.-A. Chen / Catriona L. Halliday / Martin Hoenigl / Oliver A. Cornely / Wieland Meyer

Journal of Fungi, Vol 7, Iss 23, p

Contemporary Microbiological Tools for the Diagnosis of Invasive Disease

2021 Volume 23

Abstract: Scedosporium / Lomentospora fungi are increasingly recognized pathogens. As these fungi are resistant to many antifungal agents, early diagnosis is essential for initiating targeted drug therapy. Here, we review the microbiological tools for the ... ...

Abstract	Scedosporium / Lomentospora fungi are increasingly recognized pathogens. As these fungi are resistant to many antifungal agents, early diagnosis is essential for initiating targeted drug therapy. Here, we review the microbiological tools for the detection and diagnosis of invasive scedosporiosis and lomentosporiosis. Of over 10 species, Lomentospora prolificans , Scedosporium apiospermum , S. boydii and S. aurantiacum cause the majority of infections. Definitive diagnosis relies on one or more of visualization, isolation or detection of the fungus from clinical specimens by microscopy techniques, culture and molecular methods such as panfungal PCR or genus-/species-specific multiplex PCR. For isolation from respiratory tract specimens, selective media have shown improved isolation rates. Species identification is achieved by macroscopic and microscopic examination of colonies, but species should be confirmed by ITS with or without β-tubulin gene sequencing or other molecular methods. Matrix-assisted laser desorption ionization-time of flight mass spectrometry databases are improving but may need supplementation by in-house spectra for species identification. Reference broth microdilution methods is preferred for antifungal susceptibility testing. Next-generation sequencing technologies have good potential for characterization of these pathogens. Diagnosis of Scedosporium / Lomentospora infections relies on multiple approaches encompassing both phenotypic- and molecular-based methods.
Keywords	Scedosporium ; Lomentospora prolificans ; culture ; histopathology ; PCR-based diagnosis ; MALDI-TOF MS ; Biology (General) ; QH301-705.5
Subject code	610
Language	English
Publishing date	2021-01-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Pulmonary Cryptococcosis

Annaleise R. Howard-Jones / Rebecca Sparks / David Pham / Catriona Halliday / Justin Beardsley / Sharon C.-A. Chen

Journal of Fungi, Vol 8, Iss 1156, p

2022 Volume 1156

Abstract: Pulmonary cryptococcosis describes an invasive lung mycosis caused by Cryptococcus neoformans or Cryptococcus gattii complex. It is often a high-consequence disease in both immunocompromised and immunocompetent populations, and may be misdiagnosed as ... ...

Abstract	Pulmonary cryptococcosis describes an invasive lung mycosis caused by Cryptococcus neoformans or Cryptococcus gattii complex. It is often a high-consequence disease in both immunocompromised and immunocompetent populations, and may be misdiagnosed as pulmonary malignancy, leading to a delay in therapy. Epidemiology follows that of cryptococcal meningoencephalitis, with C. gattii infection more common in certain geographic regions. Diagnostic tools include histopathology, microscopy and culture, and the detection of cryptococcal polysaccharide antigen or Cryptococcus -derived nucleic acids. All patients with lung cryptococcosis should have a lumbar puncture and cerebral imaging to exclude central nervous system disease. Radiology is key, both as an adjunct to laboratory testing and as the initial means of detection in asymptomatic patients or those with non-specific symptoms. Pulmonary cryptococcomas (single or multiple) may also be associated with disseminated disease and/or cryptococcal meningitis, requiring prolonged treatment regimens. Optimal management for severe disease requires extended induction (amphotericin B and flucytosine) and consolidation therapy (fluconazole) with close clinical monitoring. Susceptibility testing is of value for epidemiology and in regions where relatively high minimum inhibitory concentrations to azoles (particularly fluconazole) have been noted. Novel diagnostic tools and therapeutic agents promise to improve the detection and treatment of cryptococcosis, particularly in low-income settings where the disease burden is high.
Keywords	cryptococcosis ; diagnosis ; antifungal agents ; immunosuppression ; Biology (General) ; QH301-705.5
Subject code	610
Language	English
Publishing date	2022-10-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Assessing Differences between Clinical Isolates of Aspergillus fumigatus from Cases of Proven Invasive Aspergillosis and Colonizing Isolates with Respect to Phenotype (Virulence in Tenebrio molitor Larvae) and Genotype

Sam El-Kamand / Martina Steiner / Carl Ramirez / Catriona Halliday / Sharon C.-A. Chen / Alexie Papanicolaou / Charles Oliver Morton

Pathogens, Vol 11, Iss 428, p

2022 Volume 428

Abstract: The fungus Aspergillus fumigatus , the cause of invasive aspergillosis (IA), is a serious risk to transplant patients and those with respiratory diseases. Host immune suppression is considered the most important factor for the development of IA. Less is ... ...

Abstract	The fungus Aspergillus fumigatus , the cause of invasive aspergillosis (IA), is a serious risk to transplant patients and those with respiratory diseases. Host immune suppression is considered the most important factor for the development of IA. Less is known about the importance of fungal virulence in the development of IA including the significance of variation between isolates. In this study, isolates of A. fumigatus from cases diagnosed as having proven IA or colonisation (no evidence of IA) were compared in assays to measure isolate virulence. These assays included the measurement of radial growth and protease production on agar, sensitivity to UV light and oxidative stressors, and virulence in Tenebrio molitor (mealworm) larvae. These assays did not reveal obvious differences in virulence between the two groups of isolates; this provided the impetus to conduct genomic analysis. Whole genome sequencing and analysis did not allow grouping into coloniser or IA isolates. However, focused analysis of single nucleotide polymorphisms revealed variation in three putative genes: AFUA_5G09420 ( ccg-8 ), AFUA_4G00330, and AFUA_4G00350. These are known to be responsive to azole exposure, and ccg-8 deletion leads to azole hypersensitivity in other fungi. A. fumigatus virulence is challenging, but the findings of this study indicate that further research into the response to oxidative stress and azole exposure are required to understand the development of IA.
Keywords	Aspergillus fumigatus ; virulence ; pathogenesis ; mealworm ; Tenebrio molitor ; aspergillosis ; Medicine ; R
Subject code	610
Language	English
Publishing date	2022-03-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Central Nervous System Cryptococcal Infections in Non-HIV Infected Patients

Justin Beardsley / Tania C. Sorrell / Sharon C.-A. Chen

Journal of Fungi, Vol 5, Iss 3, p

2019 Volume 71

Abstract: Central nervous system (CNS) cryptococcosis in non-HIV infected patients affects solid organ transplant (SOT) recipients, patients with malignancy, rheumatic disorders, other immunosuppressive conditions and immunocompetent hosts. More recently described ...

Abstract	Central nervous system (CNS) cryptococcosis in non-HIV infected patients affects solid organ transplant (SOT) recipients, patients with malignancy, rheumatic disorders, other immunosuppressive conditions and immunocompetent hosts. More recently described risks include the use of newer biologicals and recreational intravenous drug use. Disease is caused by Cryptococcus neoformans and Cryptococcus gattii species complex; C. gattii is endemic in several geographic regions and has caused outbreaks in North America. Major virulence determinants are the polysaccharide capsule, melanin and several ‘invasins’. Cryptococcal plb1, laccase and urease are essential for dissemination from lung to CNS and crossing the blood–brain barrier. Meningo-encephalitis is common but intracerebral infection or hydrocephalus also occur, and are relatively frequent in C. gattii infection. Complications include neurologic deficits, raised intracranial pressure (ICP) and disseminated disease. Diagnosis relies on culture, phenotypic identification methods, and cryptococcal antigen detection. Molecular methods can assist. Preferred induction antifungal therapy is a lipid amphotericin B formulation (amphotericin B deoxycholate may be used in non-transplant patients) plus 5-flucytosine for 2–6 weeks depending on host type followed by consolidation/maintenance therapy with fluconazole for 12 months or longer. Control of raised ICP is essential. Clinicians should be vigilant for immune reconstitution inflammatory syndrome.
Keywords	Cryptococcosis ; Cryptococcus neoformans ; Cryptococcus gattii ; central nervous system ; meningo-encephalitis ; cerebral infection ; HIV-negative patients ; epidemiology ; antifungal therapy ; Biology (General) ; QH301-705.5
Subject code	610
Language	English
Publishing date	2019-08-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Epidemiology, Modern Diagnostics, and the Management of Mucorales Infections

David Pham / Annaleise R. Howard-Jones / Rebecca Sparks / Maurizio Stefani / Varsha Sivalingam / Catriona L. Halliday / Justin Beardsley / Sharon C.-A. Chen

Journal of Fungi, Vol 9, Iss 659, p

2023 Volume 659

Abstract: Mucormycosis is an uncommon, yet deadly invasive fungal infection caused by the Mucorales moulds. These pathogens are a WHO-assigned high-priority pathogen group, as mucormycosis incidence is increasing, and there is unacceptably high mortality with ... ...

Abstract	Mucormycosis is an uncommon, yet deadly invasive fungal infection caused by the Mucorales moulds. These pathogens are a WHO-assigned high-priority pathogen group, as mucormycosis incidence is increasing, and there is unacceptably high mortality with current antifungal therapies. Current diagnostic methods have inadequate sensitivity and specificity and may have issues with accessibility or turnaround time. Patients with diabetes mellitus and immune compromise are predisposed to infection with these environmental fungi, but COVID-19 has established itself as a new risk factor. Mucorales also cause healthcare-associated outbreaks, and clusters associated with natural disasters have also been identified. Robust epidemiological surveillance into burden of disease, at-risk populations, and emerging pathogens is required. Emerging serological and molecular techniques may offer a faster route to diagnosis, while newly developed antifungal agents show promise in preliminary studies. Equitable access to these emerging diagnostic techniques and antifungal therapies will be key in identifying and treating mucormycosis, as delayed initiation of therapy is associated with higher mortality.
Keywords	mucormycosis ; Mucorales ; epidemiology ; DNA sequencing ; diagnostics ; antifungal agents ; Biology (General) ; QH301-705.5
Subject code	610
Language	English
Publishing date	2023-06-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Colliding Epidemics and the Rise of Cryptococcosis

Christina C. Chang / Sharon C.-A. Chen

Journal of Fungi, Vol 2, Iss 1, Pp 1-

2015

Abstract: Discovered more than 100 years ago as a human pathogen, the Cryptococcus neoformans–Cryptococcus gattii (C. neoformans–C. gattii) complex has seen a large global resurgence in its association with clinical disease in the last 30 years. First isolated in ... ...

Abstract	Discovered more than 100 years ago as a human pathogen, the Cryptococcus neoformans–Cryptococcus gattii (C. neoformans–C. gattii) complex has seen a large global resurgence in its association with clinical disease in the last 30 years. First isolated in fermenting peach juice, and identified as a human pathogen in 1894 in a patient with bone lesions, this environmental pathogen has now found niches in soil, trees, birds, and domestic pets. Cryptococcosis is well recognized as an opportunistic infection and was first noted to be associated with reticuloendothelial cancers in the 1950s. Since then, advances in transplant immunology, medical science and surgical techniques have led to increasing numbers of solid organ transplantations (SOT) and hematological stem cell transplantations being performed, and the use of biological immunotherapeutics in increasingly high-risk and older individuals, have contributed to the further rise in cryptococcosis. Globally, however, the major driver for revivification of cryptococcosis is undoubtedly the HIV epidemic, particularly in Sub-Saharan Africa where access to care and antiretroviral therapy remains limited and advanced immunodeficiency, poverty and malnutrition remains the norm. As a zoonotic disease, environmental outbreaks of both human and animal cryptococcosis have been reported, possibly driven by climate change. This is best exemplified by the resurgence of C. gattii infection in Vancouver Island, Canada, and the Pacific Northwest of the United States since 1999. Here we describe how the colliding epidemics of HIV, transplantation and immunologics, climate change and migration have contributed to the rise of cryptococcosis.
Keywords	cryptococcosis ; epidemiology ; history ; HIV ; transplantation ; outbreaks ; Biology (General) ; QH301-705.5
Subject code	333
Language	English
Publishing date	2015-12-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Growth and protease secretion of Scedosporium aurantiacum under conditions of hypoxia

Han, Zhiping / Helena Nevalainen / Liisa Kautto / Sharon C.-A. Chen / Wieland Meyer

Microbiological research. 2018 Nov., v. 216

2018

Abstract: One of the micro-environmental stresses that fungal pathogens, such as Scedosporium aurantiacum, colonising human lungs encounter in vivo is hypoxia, or deficiency of oxygen. In this work, we studied the impacts of a hypoxic micro-environment (oxygen ... ...

Abstract	One of the micro-environmental stresses that fungal pathogens, such as Scedosporium aurantiacum, colonising human lungs encounter in vivo is hypoxia, or deficiency of oxygen. In this work, we studied the impacts of a hypoxic micro-environment (oxygen levels ≤1%) on the growth of a clinical S. aurantiacum isolate (WM 06.482; CBS 136046) and an environmental strain (S. aurantiacum WM 10.136; CBS 136049) on mucin-containing synthetic cystic fibrosis sputum medium. Additionally, profiles of secreted proteases were compared between the two isolates and protease activity was assessed using class-specific substrates and inhibitors. Overall, both isolates grew slower and produced less biomass under hypoxia compared to normoxic conditions. The pH of the medium decreased to 4.0 over the cultivation time, indicating that S. aurantiacum released acidic compounds into the medium. Accordingly, secreted proteases of the two isolates were dominated by acidic proteases, including aspartic and cysteine proteases, with optimal protease activity at pH 4.0 and 6.0 respectively. The clinical isolate produced higher aspartic and cysteine protease activities. Conversely, all serine proteases, including elastase-like, trypsin-like, chymotrypsin-like and subtilisin-like proteases had higher activities in the environmental isolate. Sequence similarities to 13 secreted proteases were identified by mass spectrometry (MS) by searching against other fungal proteases in the NCBI database. Results from MS analysis were consistent with those from activity assays. The clinical highly-virulent, and environmental low-virulence S. aurantiacum isolates responded differently to hypoxia in terms of the type of proteases secreted, which may reflect their different virulence properties.
Keywords	biomass ; cysteine proteinases ; cystic fibrosis ; databases ; enzyme activity ; fungi ; humans ; hypoxia ; lungs ; mass spectrometry ; normoxia ; oxygen ; pathogens ; pH ; Scedosporium ; secretion ; sequence homology ; serine proteinases ; virulence
Language	English
Dates of publication	2018-11
Size	p. 23-29.
Publishing place	Elsevier GmbH
Document type	Article
ZDB-ID	1189614-0
ISSN	1618-0623 ; 0944-5013
ISSN (online)	1618-0623
ISSN	0944-5013
DOI	10.1016/j.micres.2018.08.003
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Documenting elimination of co-circulating COVID-19 clusters using genomics in New South Wales, Australia

Alicia Arnott / Jenny Draper / Rebecca J. Rockett / Connie Lam / Rosemarie Sadsad / Mailie Gall / Elena Martinez / Roy Byun / Jennie Musto / Ben Marais / Sharon C.-A. Chen / Jen Kok / Dominic E. Dwyer / Vitali Sintchenko

BMC Research Notes, Vol 14, Iss 1, Pp 1-

2021 Volume 4

Abstract: Abstract Objective To adapt ‘fishplots’ to describe real-time evolution of SARS-CoV-2 genomic clusters. Results This novel analysis adapted the fishplot to depict the size and duration of circulating genomic clusters over time in New South Wales, ... ...

Abstract	Abstract Objective To adapt ‘fishplots’ to describe real-time evolution of SARS-CoV-2 genomic clusters. Results This novel analysis adapted the fishplot to depict the size and duration of circulating genomic clusters over time in New South Wales, Australia. It illuminated the effectiveness of interventions on the emergence, spread and eventual elimination of clusters and distilled genomic data into clear information to inform public health action.
Keywords	SARS-CoV-2 ; Genomic epidemiology ; Bioinformatics ; Whole genome sequencing ; Australia ; Medicine ; R ; Biology (General) ; QH301-705.5 ; Science (General) ; Q1-390
Language	English
Publishing date	2021-11-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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