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Article: Developments in Fungal Serology.

White, P Lewis

2023 , Page(s) 1–12

Abstract: Purpose of review: The true incidence of fungal disease is hampered by conventionally poor diagnostic tests, limited access to advanced diagnostics, and limited surveillance. The availability of serological testing has been available for over two ... ...

Abstract	Purpose of review: The true incidence of fungal disease is hampered by conventionally poor diagnostic tests, limited access to advanced diagnostics, and limited surveillance. The availability of serological testing has been available for over two decades and generally underpins the modern diagnosis of the most common forms of fungal disease. This review will focus on technical developments of serological tests for the diagnosis of fungal disease, describing advances in clinical performance when available. Recent findings: Despite their longevity, technical, clinical, and performance limitations remain, and tests specific for fungal pathogens outside the main pathogens are lacking. The availability of LFA and automated systems, capable of running multiple different tests, represents significant developments, but clinical performance data is variable and limited. Summary: Fungal serology has significantly advanced the diagnosis of the main fungal infections, with LFA availability increasing accessibility to testing. Combination testing has the potential to overcome performance limitations.
Language	English
Publishing date	2023-04-13
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2391647-3
ISSN	1936-377X ; 1936-3761
ISSN (online)	1936-377X
ISSN	1936-3761
DOI	10.1007/s12281-023-00462-4
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Zs.A 6602: Show issues

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Article ; Online: Diagnosis of invasive fungal disease in coronavirus disease 2019: approaches and pitfalls.

White, P Lewis

Current opinion in infectious diseases

2021 Volume 34, Issue 6, Page(s) 573–580

Abstract: Purpose of review: This review will comment on the current knowledge for the diagnosis of the main causes of COVID-19-associated invasive fungal disease (IFD); it will discuss the optimal strategies and limitations and wherever available, will describe ... ...

Abstract	Purpose of review: This review will comment on the current knowledge for the diagnosis of the main causes of COVID-19-associated invasive fungal disease (IFD); it will discuss the optimal strategies and limitations and wherever available, will describe international recommendations. Recent findings: A range of secondary IFDs complicating COVID-19 infection have been described and while COVID-19-associated pulmonary aspergillosis was predicted, the presentation of significant numbers of COVID-19-associated candidosis and COVID-19-associated mucormycosis was somewhat unexpected. Given the range of IFDs and prolonged duration of risk, diagnostic strategies need to involve multiple tests for detecting and differentiating various causes of IFD. Although performance data for a range of tests to diagnose COVID-19-associated pulmonary aspergillosis is emerging, the performance of tests to diagnose other IFD is unknown or based on pre-COVID performance data. Summary: Because of the vast numbers of COVID-19 infections, IFD in COVID-19 critical-care patients represents a significant burden of disease, even if incidences are less than 5%. Optimal diagnosis of COVID-19-associated IFD requires a strategic approach. The pandemic has highlighted the potential impact of IFD outside of the typical high-risk clinical cohorts, given the ever-increasing population at risk of IFD and enhanced surveillance of fungal infections is required.
MeSH term(s)	COVID-19 ; Humans ; Invasive Fungal Infections/diagnosis ; Mucormycosis ; Mycoses ; SARS-CoV-2
Language	English
Publishing date	2021-11-08
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	645085-4
ISSN	1473-6527 ; 1535-3877 ; 0951-7375 ; 1355-834X
ISSN (online)	1473-6527 ; 1535-3877
ISSN	0951-7375 ; 1355-834X
DOI	10.1097/QCO.0000000000000791
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Zs.A 2462: Show issues

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Article ; Online: Polymerase Chain Reaction of Plasma and Bronchoalveolar Lavage Fluid for Diagnosing Invasive Aspergillosis.

White, P Lewis / Donnelly, J Peter

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

2023 Volume 77, Issue 9, Page(s) 1291–1293

MeSH term(s)	Humans ; Bronchoalveolar Lavage Fluid ; Aspergillosis/diagnosis ; Aspergillus/genetics ; Mannans/blood ; Polymerase Chain Reaction ; Cell-Free Nucleic Acids
Chemical Substances	galactomannan (11078-30-1) ; Mannans ; Cell-Free Nucleic Acids
Language	English
Publishing date	2023-07-14
Publishing country	United States
Document type	Editorial ; Comment
ZDB-ID	1099781-7
ISSN	1537-6591 ; 1058-4838
ISSN (online)	1537-6591
ISSN	1058-4838
DOI	10.1093/cid/ciad421
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Article ; Online: Incorporating the Detection of Single Nucleotide Polymorphisms Associated With Invasive Aspergillosis Into the Clinic.

White, P Lewis / Price, Jessica S

Frontiers in cellular and infection microbiology

2022 Volume 12, Page(s) 860779

Abstract: Exposure to fungi is inevitable, yet only a small number of patients with significant clinical risk develop invasive aspergillosis (IA). While timing of exposure in relation to immune status, environmental and occupational factors will influence the ... ...

Abstract	Exposure to fungi is inevitable, yet only a small number of patients with significant clinical risk develop invasive aspergillosis (IA). While timing of exposure in relation to immune status, environmental and occupational factors will influence the probability of developing IA, factors specific to the individual will likely play a role and variation in the host's genetic code associated with the immunological response to fungi have been linked to increased risk of developing IA. Screening for SNPs in genes significantly associated with IA (e.g. Pentraxin-3, Toll-like receptor 4, Dectin-1, DC-SIGN) could form part of the clinical work-up on admission or post allogeneic stem cell transplantation, to complement fungal biomarker screening. Through the combination of clinical and genetic risk with mycological evidence, we are approaching a time when we should be able to accurately predict the risk of IA in the haematology patient, using predictive modelling to stratifying each individual's management. Understanding the host and their immune responses to infection through genomics, transcriptomics and metabolomics/proteomics is critical to achieving how we manage the individual's risk of IA, underpinning personalized medicine. This review will investigate what is known about the genetic risk associated with developing IA, primarily in haematology patients and whether these strategies are ready to be incorporated into routine clinical practice, and if not what are the remaining hurdles to implementation.
MeSH term(s)	Aspergillosis/diagnosis ; Aspergillosis/genetics ; Genetic Predisposition to Disease/etiology ; Hematopoietic Stem Cell Transplantation/adverse effects ; Humans ; Invasive Fungal Infections/diagnosis ; Invasive Fungal Infections/genetics ; Polymorphism, Single Nucleotide
Language	English
Publishing date	2022-04-12
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2619676-1
ISSN	2235-2988 ; 2235-2988
ISSN (online)	2235-2988
ISSN	2235-2988
DOI	10.3389/fcimb.2022.860779
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Article ; Online: Recent advances and novel approaches in laboratory-based diagnostic mycology.

White, P Lewis

Medical mycology

2019 Volume 57, Issue Supplement_3, Page(s) S259–S266

Abstract: The field of diagnostic mycology represents much more than culture and microscopy and is rapidly embracing novel techniques and strategies to help overcome the limitations of conventional approaches. Commercial molecular assays increase the applicability ...

Abstract	The field of diagnostic mycology represents much more than culture and microscopy and is rapidly embracing novel techniques and strategies to help overcome the limitations of conventional approaches. Commercial molecular assays increase the applicability of PCR testing and may identify markers of antifungal resistance, which are of great clinical concern. Lateral flow assays simplify testing and turn-around time, with potential for point of care testing, while proximity ligation assays embrace the sensitivity of molecular testing with the specificity of antibody detection. The first evidence of patient risk stratification is being described and together with the era of next generation sequencing represents an exciting time in mycology.
MeSH term(s)	Clinical Laboratory Techniques/trends ; Humans ; Mycology/trends ; Mycoses/diagnosis
Language	English
Publishing date	2019-07-10
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1421796-x
ISSN	1460-2709 ; 1369-3786
ISSN (online)	1460-2709
ISSN	1369-3786
DOI	10.1093/mmy/myy159
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Zs.A 520: Show issues

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Article ; Online: Age difference of patients with and without invasive aspergillosis: a systematic review and meta-analysis.

Shekhova, Elena / Salazar, Fabián / Da Silva Dantas, Alessandra / Chakraborty, Tanmoy / Wooding, Eva L / White, P Lewis / Warris, Adilia

BMC infectious diseases

2024 Volume 24, Issue 1, Page(s) 220

Abstract: Background: Invasive Aspergillosis (IA) is a life-threatening fungal disease with significant mortality rates. Timely diagnosis and treatment greatly enhance patient outcomes. This study aimed to explore the association between patient age and the ... ...

Abstract	Background: Invasive Aspergillosis (IA) is a life-threatening fungal disease with significant mortality rates. Timely diagnosis and treatment greatly enhance patient outcomes. This study aimed to explore the association between patient age and the development of IA, as well as the potential implications for risk stratification strategies. Methods: We searched National Center for Biotechnology Information (NCBI) databases for publications until October 2023 containing age characteristics of patients with and without IA. A random-effects model with the application of inverse-variance weighting was used to pool reported estimates from each study, and meta-regression and subgroup analyses were utilized to assess sources of heterogeneity. Results: A systematic review was conducted, resulting in the inclusion of 55 retrospective observational studies with a total of 13,983 patients. Meta-analysis revealed that, on average, patients with IA were approximately two and a half years older (95% Confidence Interval [CI] 1.84-3.31 years; I Conclusions: Further research, such as individual patient data meta-analysis, is necessary to better understand the potential relationship between increasing age and the likelihood of IA. Improved risk stratification strategies based on patient age could potentially enhance the early detection and treatment of IA, ultimately improving patient outcomes.
MeSH term(s)	Humans ; Retrospective Studies ; Aspergillosis/diagnosis ; Aspergillosis/drug therapy ; Invasive Fungal Infections/diagnosis ; Databases, Factual ; Probability
Language	English
Publishing date	2024-02-19
Publishing country	England
Document type	Meta-Analysis ; Systematic Review ; Journal Article
ZDB-ID	2041550-3
ISSN	1471-2334 ; 1471-2334
ISSN (online)	1471-2334
ISSN	1471-2334
DOI	10.1186/s12879-024-09109-2
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Article ; Online: Evaluation of the Performance of the Associates of Cape Cod STAT Assay for the Diagnosis of Invasive Fungal Disease in Critical-Care Patients with COVID-19.

White, P Lewis / Price, Jessica S / Backx, Matthijs

Journal of clinical microbiology

2021 Volume 59, Issue 9, Page(s) e0086921

Abstract: During the COVID-19 pandemic, there have been increasing reports of invasive fungal disease (IFD) in critical care, where rapid access to (1-3)-β-d-glucan (BDG) testing may have enhanced diagnosis. The potential benefit of rapidly accessible BDG results ... ...

Abstract	During the COVID-19 pandemic, there have been increasing reports of invasive fungal disease (IFD) in critical care, where rapid access to (1-3)-β-d-glucan (BDG) testing may have enhanced diagnosis. The potential benefit of rapidly accessible BDG results is limited by local availability of BDG testing, with low demand resulting in testing being performed in specialist centers. The recent release of the Associates of Cape Cod STAT assay provides a simple, low-throughput BDG platform, potentially increasing accessibility. During the pandemic, BDG testing using the Fungitell assay (FA) was a critical component of screening for IFD in our critical care. The performance of the STAT was retrospectively determined through a case-control study of 107 serum samples from critical-care COVID-19 patients with IFD defined according to international guidelines. The STAT demonstrated excellent qualitative (observed agreement, 97.2%; kappa, 0.94) and quantitative (Spearman's coefficient, 0.8962) agreement with the FA. Sample positivity was greater (
MeSH term(s)	COVID-19 ; Case-Control Studies ; Critical Care ; Humans ; Invasive Fungal Infections/diagnosis ; Pandemics ; Retrospective Studies ; SARS-CoV-2 ; Sensitivity and Specificity ; beta-Glucans
Chemical Substances	beta-Glucans
Language	English
Publishing date	2021-08-18
Publishing country	United States
Document type	Journal Article
ZDB-ID	390499-4
ISSN	1098-660X ; 0095-1137
ISSN (online)	1098-660X
ISSN	0095-1137
DOI	10.1128/JCM.00869-21
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Zs.A 1188: Show issues

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Article ; Online: An Evaluation of the OLM

Price, Jessica S / Fallon, Melissa / Posso, Raquel / Backx, Matthijs / White, P Lewis

Journal of fungi (Basel, Switzerland)

2023 Volume 9, Issue 11

Abstract: Background: The use of the PCR to aid in the diagnosis of : Methods: Retrospective case/control and consecutive cohort performance evaluations of the OLM : Results: After being used to test 317 patients (32 with PcP), the overall performance of ... ...

Abstract	Background: The use of the PCR to aid in the diagnosis of Methods: Retrospective case/control and consecutive cohort performance evaluations of the OLM Results: After being used to test 317 patients (32 with PcP), the overall performance of the Conclusions: The OLM
Language	English
Publishing date	2023-11-15
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2784229-0
ISSN	2309-608X ; 2309-608X
ISSN (online)	2309-608X
ISSN	2309-608X
DOI	10.3390/jof9111106
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Article ; Online: Metagenomic Next-Generation Sequencing of Plasma for Diagnosis of COVID-19-Associated Pulmonary Aspergillosis.

Hoenigl, Martin / Egger, Matthias / Price, Jessica / Krause, Robert / Prattes, Juergen / White, P Lewis

Journal of clinical microbiology

2023 Volume 61, Issue 3, Page(s) e0185922

Abstract: Timely diagnosis remains an unmet need in non-neutropenic patients at risk for aspergillosis, including those with COVID-19-associated pulmonary aspergillosis (CAPA), which in its early stages is characterized by tissue-invasive growth of the lungs with ... ...

Abstract	Timely diagnosis remains an unmet need in non-neutropenic patients at risk for aspergillosis, including those with COVID-19-associated pulmonary aspergillosis (CAPA), which in its early stages is characterized by tissue-invasive growth of the lungs with limited angioinvasion. Currently available mycological tests show limited sensitivity when testing blood specimens. Metagenomic next-generation sequencing (mNGS) to detect microbial cell-free DNA (mcfDNA) in plasma might overcome some of the limitations of conventional diagnostics. A two-center cohort study involving 114 COVID-19 intensive care unit patients evaluated the performance of plasma mcfDNA sequencing for the diagnosis of CAPA. Classification of CAPA was performed using the European Confederation for Medical Mycology (ECMM)/International Society for Human and Animal Mycoses (ISHAM) criteria. A total of 218 plasma samples were collected between April 2020 and June 2021 and tested for mcfDNA (Karius test). Only 6 patients were classified as probable CAPA, and 2 were classified as possible, while 106 patients did not fulfill CAPA criteria. The Karius test detected DNA of mold pathogens in 12 samples from 8 patients, including Aspergillus fumigatus in 10 samples from 6 patients. Mold pathogen DNA was detected in 5 of 6 (83% sensitivity) cases with probable CAPA (A. fumigatus in 8 samples from 4 patients and Rhizopus microsporus in 1 sample), while the test did not detect molds in 103 of 106 (97% specificity) cases without CAPA. The Karius test showed promising performance for diagnosis of CAPA when testing plasma, being highly specific. The test detected molds in all but one patient with probable CAPA, including cases where other mycological tests from blood resulted continuously negative, outlining the need for validation in larger studies.
MeSH term(s)	COVID-19/complications ; Aspergillosis/diagnosis ; Aspergillosis/microbiology ; Humans ; Middle Aged ; Cell-Free Nucleic Acids/isolation & purification ; Male ; Female
Chemical Substances	Cell-Free Nucleic Acids
Language	English
Publishing date	2023-02-21
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	390499-4
ISSN	1098-660X ; 0095-1137
ISSN (online)	1098-660X
ISSN	0095-1137
DOI	10.1128/jcm.01859-22
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Article ; Online: Impact of the introduction of nucleic acid amplification testing on Clostridioides difficile detection and ribotype distribution in Wales.

Perry, Michael D / White, P Lewis / Morris, Trefor E

Anaerobe

2020 Volume 67, Page(s) 102313

Abstract: Objectives: To determine the impact of the 2018 introduction of nucleic acid amplification tests (NAATs) for C. difficile detection on the laboratory diagnosis of C. difficile infection (CDI), and the distribution of C. difficile ribotypes.: Methods: ...

Abstract	Objectives: To determine the impact of the 2018 introduction of nucleic acid amplification tests (NAATs) for C. difficile detection on the laboratory diagnosis of C. difficile infection (CDI), and the distribution of C. difficile ribotypes. Methods: A retrospective analysis of five years (2015-2019) of C. difficile diagnostic laboratory and PCR ribotyping test results. Results: A total of 255,104 diagnostic results, from 136,353 patients were analysed: 199,794 samples where glutamate dehydrogenase (GDH) was used as the primary screen; and 55,310 where NAATs were employed. An overall decrease in frontline positivity from 2015 to 2019 (10.3% [n = 5017] to 6% [n = 3190] - p < 0.0001) was observed, despite an increase in the number of samples tested (48,778 to 52,839). NAAT positivity was lower than GDH (p < 0.0001) for the two years where it was implemented. The variance was accounted for by increased overall C. difficile isolation and reduced toxin negative strain culture from NAAT positive samples (p < 0.0001). Ribotype distribution (6546 samples) remained stable with decreasing RT27 isolation in each year except 2017 (p < 0.0001). RT78 was associated with toxin A/B EIA positivity (p < 0.0001). Conclusions: Use of NAAT for the detection of C. difficile, as part of a 2-step algorithm, has not led to an increase in CDI laboratory diagnostic test positivity. In spite of ribotype distribution being comparable for screening in toxin A/B positive samples, there is a significantly greater correlation between NAAT positivity and culture of toxigenic strains compared to GDH.
MeSH term(s)	Bacterial Proteins/analysis ; Bacterial Toxins/analysis ; Clostridioides difficile/classification ; Clostridioides difficile/isolation & purification ; Clostridium Infections/diagnosis ; Clostridium Infections/epidemiology ; Diagnostic Tests, Routine ; Glutamate Dehydrogenase/analysis ; Humans ; Immunoassay ; Nucleic Acid Amplification Techniques ; Polymerase Chain Reaction ; Retrospective Studies ; Ribotyping/methods ; Wales/epidemiology
Chemical Substances	Bacterial Proteins ; Bacterial Toxins ; Glutamate Dehydrogenase (EC 1.4.1.2)
Language	English
Publishing date	2020-12-09
Publishing country	England
Document type	Journal Article
ZDB-ID	1237621-8
ISSN	1095-8274 ; 1075-9964
ISSN (online)	1095-8274
ISSN	1075-9964
DOI	10.1016/j.anaerobe.2020.102313
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