Submit to JoF Review for JoF Propose a Special Issue

Journal Menu

Journal Browser

► Journal Browser

Fungal Biomarkers

Special Issue Editors
Special Issue Information
Keywords
Published Papers

A special issue of Journal of Fungi (ISSN 2309-608X).

Deadline for manuscript submissions: closed (31 January 2021) | Viewed by 33445

Share This Special Issue

Special Issue Editor

Dr. Juergen Prattes

E-Mail Website
Guest Editor

Medizinische Universität Graz, Graz, Austria
Interests: biomarkers; fungal infections; sepsis; ICU infections

Special Issue Information

Dear Colleagues,

Invasive fungal infections (IFIs) are a devastating disease in immunocompromised patients. Early and reliable diagnosis and subsequent rapid initiation of appropriate antifungal therapy has been shown to improve survival significantly. However, IFIs progress rapidly and are difficult to diagnose, especially at early stages. Culture-based approaches are important for the detection of fungal species and resistance testing, but they are limited by low sensitivities and long turnaround time. Significant advances to the field were brought about by the introduction of non-cultural diagnostic tests for aspergillosis in blood and bronchoalveolar lavage fluid, including Aspergillus IgG antibody tests (for chronic pulmonary aspergillosis), galactomannan antigen testing, molecular-based diagnostic approaches, and 1,3-ß-D-glucan testing in patients at risk. A complicating factor is the fact that performance of these tests may vary not only by fungal disease stage and type, but also by risk group (e.g., neutropenic patients versus non-neutropenic patients, neonates versus adults, anti-mold prophylaxis versus no anti-mold prophylaxis).

This Special Issue will welcome the following manuscript types: original research articles, case reports, reviews, mini-reviews, and clinical trial protocols.

Dr. Juergen Prattes
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Fungi is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

invasive fungal infections
yeast
molds
biomarkers
diagnosis
antigen tests
molecular tests

Published Papers (11 papers)

Download All Papers

Research

Jump to: Review, Other

9 pages, 1664 KiB

Open AccessArticle

Seroprevalence of Aspergillus-Specific IgG Antibody among Mozambican Tuberculosis Patients

by Helmut J. F. Salzer, Isabel Massango, Nilesh Bhatt, Emelva Machonisse, Maja Reimann, Sven Heldt, Christoph Lange, Michael Hoelscher, Celso Khosa and Andrea Rachow

J. Fungi 2021, 7(8), 595; https://doi.org/10.3390/jof7080595 - 23 Jul 2021

Cited by 7 | Viewed by 1894

Abstract

Background: Chronic pulmonary aspergillosis (CPA) is a life-threatening sequel in patients with pulmonary tuberculosis (PTB). Aspergillus-specific IgG antibody is a useful diagnostic biomarker supporting CPA diagnosis, especially in countries with limited health recourses. Methods: We conducted a prospective pilot study to assess the seroprevalence of Aspergillus-specific IgG antibodies among 61 Mozambican tuberculosis patients before, during, and after the end of TB treatment. Aspergillus-specific IgG antibody levels were measured using the ImmunoCAP^®. Results: In this study, 3 out of 21 HIV-negative PTB patients had a positive Aspergillus-specific IgG antibody level before, during, and after the end of TB treatment. Antibody levels were 41.1, 45.5, and 174 mg/L at end of treatment (EOT), respectively. Additionally, two HIV-negative PTB patients with negative Aspergillus-specific IgG antibody levels at baseline became seropositive at EOT (41.9 and 158 mg/L, respectively). Interestingly, none of the HIV-positive PTB patients (40/61) had a positive Aspergillus-specific IgG antibody level at any time, neither at baseline nor at EOT. Probable CPA was diagnosed in one HIV-negative patient (5%; 1/20). Conclusion: Seroprevalence of Aspergillus-specific IgG antibody may differ between HIV-negative and HIV-positive Mozambican PTB patients. Future studies evaluating post-tuberculosis lung disease should integrate CPA as a life-threatening sequel to PTB. Full article

(This article belongs to the Special Issue Fungal Biomarkers)

► Show Figures

Figure 1

13 pages, 1320 KiB

Open AccessArticle

Performance, Correlation and Kinetic Profile of Circulating Serum Fungal Biomarkers of Invasive Aspergillosis in High-Risk Patients with Hematologic Malignancies

by Maria Siopi, Stamatis Karakatsanis, Christoforos Roumpakis, Konstantinos Korantanis, Elina Eldeik, Helen Sambatakou, Nikolaos V. Sipsas, Panagiotis Tsirigotis, Maria Pagoni and Joseph Meletiadis

J. Fungi 2021, 7(3), 211; https://doi.org/10.3390/jof7030211 - 13 Mar 2021

Cited by 4 | Viewed by 1893

Abstract

As conventional microbiological documentation of invasive aspergillosis (IA) is difficult to obtain, serum fungal biomarkers are important adjunctive diagnostic tools. Positivity rates and the kinetic profiles of galactomannan (GM), 1,3-β-D-glucan (BDG) and Aspergillus DNA (PCR) were studied in high-risk patients with hematologic malignancies. GM, BDG and PCR data from serial serum specimens (n = 240) from 93 adult hematology patients with probable (n = 8), possible (n = 25) and no (n = 60) IA were retrospectively analyzed. Positivity rates and sensitivity/specificity/positive/negative predictive values (NPV) of each fungal biomarker alone and in combination were estimated. The three markers were compared head-to-head and correlated with various biochemical, demographic and patient characteristics. The positivity rates for patients with probable/possible/no IA were 88%/8%/0% for GM (X² = 55, p < 0.001), 62%/46%/35% for BDG (X² = 2.5, p = 0.29), 62%/33%/27% for PCR (X² = 3.9, p = 0.15), 50%/4%/0% for GM + BDG and GM + PCR (X² = 31, p < 0.001), 50%/8%/22% for BDG + PCR (X² = 6.5, p = 0.038) and 38%/4%/0% for GM + BDG + PCR (X² = 21, p < 0.001). Higher agreement (76%) and negative correlation (r_s = −0.47, p = 0.0017) was found between GM index and PCR Ct values. The sensitivity and NPV was 45–55% and 90–92% when biomarkers assessed alone and increased to 75–90% and 93–97%, respectively when combined. Weak significant correlations were found between GM, PCR and BDG results with renal/liver function markers (r = 0.11–0.57) with most GM+ and PCR+ samples found in the first and second week of clinical assessment, respectively and BDG later on. Different positivity rates, time profiles and performances were found for the three biomarkers advocating the combination of GM with PCR for the early diagnosis of IA, whereas the high NPV of combined biomarkerscould help excluding IA. Full article

(This article belongs to the Special Issue Fungal Biomarkers)

► Show Figures

Figure 1

9 pages, 1355 KiB

Open AccessCommunication

Performance of Existing Definitions and Tests for the Diagnosis of Invasive Fungal Diseases other than Invasive Candidiasis and Invasive Aspergillosis in Critically Ill, Adult Patients: A Systematic Review with Qualitative Evidence Synthesis

by Daniele R. Giacobbe, Andrea Cortegiani, Ilias Karaiskos, Toine Mercier, Sofia Tejada, Maddalena Peghin, Cecilia Grecchi, Chiara Rebuffi, Erika Asperges, Valentina Zuccaro, Luigia Scudeller, Matteo Bassetti and the FUNDICU investigators

J. Fungi 2021, 7(3), 176; https://doi.org/10.3390/jof7030176 - 28 Feb 2021

Cited by 4 | Viewed by 2962

Abstract

The Fungal Infections Definitions in Intensive Care Unit (ICU) patients (FUNDICU) project aims to provide standard sets of definitions for invasive fungal diseases (IFDs) in critically ill, adult patients, including invasive aspergillosis (IA), invasive candidiasis (IC), Pneumocystis jirovecii pneumonia (PJP), and other non-IA, non-IC IFDs. The first step of the project was the conduction of separated systematic reviews of the characteristics and applicability to critically ill, adult patients outside classical populations at risk (hematology patients, solid organ transplant recipients) of available definitions and diagnostic tests for IFDs. We report here the results of two systematic reviews exploring the performance of available definitions and tests, for PJP and for other non-IA, non-IC IFDs. Starting from 2585 and 4584 records for PJP and other IFDs, respectively, 89 and 61 studies were deemed as eligible for full-text evaluation. However, only two studies for PJP and no studies for other IFDs met the FUNDICU protocol criteria for inclusion in qualitative synthesis. Currently, there is no sufficient solid data for directly evaluating the performance of existing definitions and laboratory tests for the diagnosis of PJP and other non-IA, non-IC IFDs in critically ill adult patients outside classical populations at risk. Full article

(This article belongs to the Special Issue Fungal Biomarkers)

► Show Figures

Figure 1

20 pages, 1863 KiB

Open AccessArticle

Longitudinal Evaluation of Plasma Cytokine Levels in Patients with Invasive Candidiasis

by Stefanie Wunsch, Christoph Zurl, Heimo Strohmaier, Andreas Meinitzer, Jasmin Rabensteiner, Wilfried Posch, Cornelia Lass-Flörl, Oliver Cornely, Gudrun Pregartner, Elisabeth König, Gebhard Feierl, Martin Hoenigl, Juergen Prattes, Ines Zollner-Schwetz, Thomas Valentin and Robert Krause

J. Fungi 2021, 7(2), 101; https://doi.org/10.3390/jof7020101 - 01 Feb 2021

Cited by 4 | Viewed by 1870

Abstract

Interleukin (IL) 17A plays a decisive role in anti-Candida host defense. Previous data demonstrated significantly increased IL-17A values in candidemic patients. We evaluated levels and time courses of IL-17A, and other cytokines suggested to be involved in Candida-specific immunity (IL-6, IL-8, IL-10, IL-17F, IL-22, IL-23, interferon-γ, tumor necrosis factor-α, Pentraxin-related protein 3, transforming growth factor-β) in patients with invasive candidiasis (IC) compared to bacteremic patients (Staphylococcus aureus, Escherichia coli) and healthy controls (from previous 4 days up to day 14 relative to the index culture (−4; 14)). IL-17A levels were significantly elevated in all groups compared to healthy controls. In IC, the highest IL-17A values were measured around the date of index sampling (−1; 2), compared to significantly lower levels prior and after sampling the index culture. Candidemic patients showed significantly higher IL-17A values compared to IC other than candidemia at time interval (−1; 2) and (3; 7). No significant differences in IL-17A levels could be observed for IC compared to bacteremic patients. Candidemic patients had higher IL-8, IL-10, IL-22, IFN-γ, PTX3 and TNF-α values compared to non-candidemic. Based on the limited discriminating competence between candidemia and bacteremia, IL-17A has to be considered a biomarker for blood stream infection rather than invasive Candida infection. Full article

(This article belongs to the Special Issue Fungal Biomarkers)

► Show Figures

Figure 1

12 pages, 299 KiB

Open AccessArticle

Utility of 1,3 β-d-Glucan Assay for Guidance in Antifungal Stewardship Programs for Oncologic Patients and Solid Organ Transplant Recipients

by Marina Machado, Esther Chamorro de Vega, María del Carmen Martínez-Jiménez, Carmen Guadalupe Rodríguez-González, Antonio Vena, Raquel Navarro, María Isabel Zamora-Cintas, Caroline Agnelli, María Olmedo, Alicia Galar, Jesús Guinea, Ana Fernández-Cruz, Roberto Alonso, Emilio Bouza, Patricia Muñoz and Maricela Valerio

J. Fungi 2021, 7(1), 59; https://doi.org/10.3390/jof7010059 - 17 Jan 2021

Cited by 7 | Viewed by 2970

Abstract

The implementation of 1,3 β-d-glucan (BDG) has been proposed as a diagnostic tool in antifungal stewardship programs (ASPs). We aimed to analyze the influence of serum BDG in an ASP for oncologic patients and solid organ transplant (SOT) recipients. We conducted a pre–post study. In the initial period (PRE), the ASP was based on bedside advice, and this was complemented with BDG in the post-period (POST). Performance parameters of the BDG assay were determined. Antifungal (AF) use adequacy was evaluated using a point score. Clinical outcomes and AF costs were also compared before and after the intervention. Overall, 85 patients were included in the PRE-period and 112 in the POST-period. Probable or proven fungal infections were similar in both groups (54.1% vs. 57.1%; p = 0.67). The determination of BDG contributed to improved management in 75 of 112 patients (66.9%). The AF adequacy score improved in the POST-period (mean 7.75 vs. 9.29; p < 0.001). Median days of empiric AF treatment was reduced in the POST-period (9 vs. 5 days, p = 0.04). All-cause mortality (44.7% vs. 34.8%; p = 0.16) was similar in both periods. The cost of AF treatments was reduced in the POST-period with a difference of 779.6 €/patient. Our data suggest that the use of BDG was a cost-effective strategy that contributed to safely improving the results of an ASP for SOT and oncologic patients. Full article

(This article belongs to the Special Issue Fungal Biomarkers)

8 pages, 2041 KiB

Open AccessArticle

Variable Correlation between Bronchoalveolar Lavage Fluid Fungal Load and Serum-(1,3)-β-d-Glucan in Patients with Pneumocystosis—A Multicenter ECMM Excellence Center Study

by Toine Mercier, Nesrine Aissaoui, Maud Gits-Muselli, Samia Hamane, Juergen Prattes, Harald H. Kessler, Ivana Mareković, Sanja Pleško, Jörg Steinmann, Ulrike Scharmann, Johan Maertens, Katrien Lagrou, Blandine Denis, Stéphane Bretagne and Alexandre Alanio

J. Fungi 2020, 6(4), 327; https://doi.org/10.3390/jof6040327 - 01 Dec 2020

Cited by 15 | Viewed by 2079

Abstract

Pneumocystis jirovecii pneumonia is a difficult invasive infection to diagnose. Apart from microscopy of respiratory specimens, two diagnostic tests are increasingly used including real-time quantitative PCR (qPCR) of respiratory specimens, mainly in bronchoalveolar lavage fluids (BAL), and serum β-1,3-d-glucan (BDG). It is still unclear how these two biomarkers can be used and interpreted in various patient populations. Here we analyzed retrospectively and multicentrically the correlation between BAL qPCR and serum BDG in various patient population, including mainly non-HIV patients. It appeared that a good correlation can be obtained in HIV patients and solid organ transplant recipients but no correlation can be observed in patients with hematologic malignancies, solid cancer, and systemic diseases. This observation reinforces recent data suggesting that BDG is not the best marker of PCP in non-HIV patients, with potential false positives due to other IFI or bacterial infections and false-negatives due to low fungal load and low BDG release. Full article

(This article belongs to the Special Issue Fungal Biomarkers)

► Show Figures

Figure 1

9 pages, 203 KiB

Open AccessArticle

Performance of Aspergillus Galactomannan Lateral Flow Assay on Bronchoalveolar Lavage Fluid for the Diagnosis of Invasive Pulmonary Aspergillosis

by Kathleen A. Linder, Carol A. Kauffman and Marisa H. Miceli

J. Fungi 2020, 6(4), 297; https://doi.org/10.3390/jof6040297 - 18 Nov 2020

Cited by 12 | Viewed by 2044

Abstract

Background: Several newly developed biomarker tests for invasive pulmonary aspergillosis (IPA) have been developed, including the IMMY Aspergillus galactomannan lateral flow assay (Aspergillus GM-LFA) evaluated in this study. Methods: Twenty patients with proven/probable IPA (EORTC/MSGERC criteria) were matched by age and underlying disease with 20 patients without IPA. Bronchoalveolar lavage fluid (BALF) was analyzed in duplicate using the Aspergillus GM-LFA. Results were read visually by two blinded observers, and the optical density index (ODI) was obtained digitally with a cube reader. Results: Using a cutoff of ≥0.5 ODI, the Aspergillus GM-LFA had a sensitivity of 40%, specificity of 80%, positive predictive value (PPV) of 67% and negative predictive value (NPV) of 57%. When the cutoff was increased to ≥1.0 ODI, sensitivity remained at 40%, specificity rose to 95%, PPV was 89%, and NPV was 61%. Excellent agreement was found when duplicate samples were read either visually (κ = 1) or with the cube reader (κ = 0.89). Correlation of results obtained by visual inspection and those obtained using the cube reader was excellent (κ = 0.82). Conclusion: The Aspergillus GM-LFA had poor sensitivity but excellent specificity for proven/probable IPA in BALF. The assay was easy to interpret, and there was high concordance between results obtained visually and with a cube reader. Full article

(This article belongs to the Special Issue Fungal Biomarkers)

11 pages, 879 KiB

Open AccessArticle

Comparison of β-D-Glucan and Galactomannan in Serum for Detection of Invasive Aspergillosis: Retrospective Analysis with Focus on Early Diagnosis

by Karl Dichtl, Johannes Forster, Steffen Ormanns, Heidi Horns, Sebastian Suerbaum, Ulrich Seybold and Johannes Wagener

J. Fungi 2020, 6(4), 253; https://doi.org/10.3390/jof6040253 - 28 Oct 2020

Cited by 9 | Viewed by 4352

Abstract

The early diagnosis of invasive aspergillosis (IA) relies mainly on computed tomography imaging and testing for fungal biomarkers such as galactomannan (GM). We compared an established ELISA for the detection of GM with a turbidimetric assay for detection of the panfungal biomarker β-D-glucan (BDG) for early diagnosis of IA. A total of 226 serum specimens from 47 proven and seven probable IA cases were analysed. Sensitivity was calculated for samples obtained closest to the day of IA-diagnosis (d0). Additional analyses were performed by including samples obtained during the presumed course of disease. Most IA cases involved the respiratory system (63%), and Aspergillus fumigatus was the most frequently isolated species (59%). For proven cases, sensitivity of BDG/GM analysis was 57%/40%. Including all samples dating from –6 to +1 weeks from d0 increased sensitivities to 74%/51%. Sensitivity of BDG testing was as high as or higher than GM testing for all subgroups and time intervals analysed. BDG testing was less specific (90–93%) than GM testing (99–100%). Combining BDG and GM testing resulted in sensitivity/specificity of 70%/91%. Often, BDG testing was positive before GM testing. Our study backs the use of BDG for diagnosis of suspected IA. We suggest combining BDG and GM to improve the overall sensitivity. Full article

(This article belongs to the Special Issue Fungal Biomarkers)

► Show Figures

Figure 1

Review

Jump to: Research, Other

27 pages, 410 KiB

Open AccessReview

The Evolving Landscape of Fungal Diagnostics, Current and Emerging Microbiological Approaches

by Zoe Freeman Weiss, Armando Leon and Sophia Koo

J. Fungi 2021, 7(2), 127; https://doi.org/10.3390/jof7020127 - 09 Feb 2021

Cited by 26 | Viewed by 5168

Abstract

Invasive fungal infections are increasingly recognized in immunocompromised hosts. Current diagnostic techniques are limited by low sensitivity and prolonged turnaround times. We review emerging diagnostic technologies and platforms for diagnosing the clinically invasive disease caused by Candida, Aspergillus, and Mucorales. Full article

(This article belongs to the Special Issue Fungal Biomarkers)

15 pages, 1366 KiB

Open AccessReview

Specificity Influences in (1→3)-β-d-Glucan-Supported Diagnosis of Invasive Fungal Disease

by Malcolm A. Finkelman

J. Fungi 2021, 7(1), 14; https://doi.org/10.3390/jof7010014 - 29 Dec 2020

Cited by 39 | Viewed by 4795

Abstract

(1→3)-β-glucan (BDG) testing as an adjunct in the diagnosis of invasive fungal disease (IFD) has been in use for nearly three decades. While BDG has a very high negative predictive value in this setting, diagnostic false positives may occur, limiting specificity and positive predictive value. Although results may be diagnostically false positive, they are analytically correct, due to the presence of BDG in the circulation. This review surveys the non-IFD causes of elevated circulating BDG. These are in the main, iatrogenic patient contamination through the use of BDG-containing medical devices and parenterally-delivered materials as well as translocation of intestinal luminal BDG due to mucosal barrier injury. Additionally, infection with Nocardia sp. may also contribute to elevated circulating BDG. Knowledge of the factors which may contribute to such non-IFD-related test results can improve the planning and interpretation of BDG assays and permit investigational strategies, such as serial sampling and BDG clearance evaluation, to assess the likelihood of contamination and improve patient care. Full article

(This article belongs to the Special Issue Fungal Biomarkers)

► Show Figures

Figure 1

Other

Jump to: Research, Review

7 pages, 1009 KiB

Open AccessBrief Report

Diagnostic Performance of Bronchoalveolar Lavage (1,3)-β-d-Glucan Assay for Pneumocystis jirovecii Pneumonia

by Shiwei Zhou, Kathleen A. Linder, Carol A. Kauffman, Blair J. Richards, Steve Kleiboeker and Marisa H. Miceli

J. Fungi 2020, 6(4), 200; https://doi.org/10.3390/jof6040200 - 01 Oct 2020

Cited by 3 | Viewed by 1905

Abstract

We evaluated the performance of the (1,3)-β-d-glucan (BDG) assay on bronchoalveolar lavage fluid (BALF) as a possible aid to the diagnosis of Pneumocystis jirovecii pneumonia. BALF samples from 18 patients with well-characterized proven, probable, and possible Pneumocystis pneumonia and 18 well-matched controls were tested. We found that the best test performance was observed with a cut-off value of 128 pg/mL; receiver operating characteristic/area under the curve (ROC/AUC) was 0.70 (95% CI 0.52–0.87). Sensitivity and specificity were 78% and 56%, respectively; positive predictive value was 64%, and negative predictive value was 71%. The low specificity that we noted limits the utility of BALF BDG as a diagnostic tool for Pneumocystis pneumonia. Full article

(This article belongs to the Special Issue Fungal Biomarkers)

► Show Figures

Figure 1

Journal Menu

Journal Browser

Fungal Biomarkers

Share This Special Issue

Special Issue Editor

Special Issue Information

Keywords

Published Papers (11 papers)

Research

Review

Other

Further Information

Guidelines

MDPI Initiatives

Follow MDPI