Advances in Invasive Fungal Infections 2024

A special issue of Journal of Fungi (ISSN 2309-608X). This special issue belongs to the section "Fungal Pathogenesis and Disease Control".

Deadline for manuscript submissions: closed (15 April 2025) | Viewed by 9638

Special Issue Editors


E-Mail Website
Guest Editor
MiraVista Diagnost, 4705 Decatur Blvd., Indianapolis, IN 46241, USA
Interests: invasive fungal infections; emerging mycoses; resistant fungi; antifungals

E-Mail Website
Guest Editor
Transplant Infectious Diseases at IU Health Indiana University, Indianapolis, IN, USA
Interests: resistant fungi; antifungals; fungal epidemiology; fungal diagnostics

Special Issue Information

Dear Colleagues,

Invasive fungal infections are an increasing public health concern. The burden of invasive fungal infections has increased in part due to the expansion of the at-risk population. Many factors may increase the risk for developing invasive fungal infections, including waning immunity through immunosuppression, ageing, and the persistence of uncontrolled HIV infection. Furthermore, the rapid emergence of antifungal resistance compounds the limited access to diagnostics and appropriate therapies.

In 2022, the WHO published the first fungal priority pathogens list, which prioritized fungal pathogens that can cause invasive fungal infections, for which drug resistance and other treatment and management challenges exist.

During the past decade, there have been numerous advances in the epidemiology of invasive fungal infections, mechanisms of resistance, diagnostics, and treatment. These include, but are not limited to, the development of new antifungal classes and newer formulations of older antifungals.

In this Special Issue of the Journal of Fungi, we will focus on the most recent advances and developments in the field of invasive fungal infections.

Dr. L. Joseph Wheat
Dr. Nicolas Barros
Guest Editors

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Keywords

  • invasive fungal infections
  • emerging mycoses
  • resistant fungi
  • antifungals
  • fungal epidemiology
  • fungal diagnostics

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Published Papers (5 papers)

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Research

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13 pages, 3912 KiB  
Article
Novel Monoclonal Antibodies 1D2 and 4E4 Against Aspergillus Glycoprotein Antigens Detect Early Invasive Aspergillosis in Mice
by Xihua Lian, Amy Scott-Thomas, John G. Lewis, Madhav Bhatia and Stephen T. Chambers
J. Fungi 2024, 10(12), 832; https://doi.org/10.3390/jof10120832 - 2 Dec 2024
Viewed by 886
Abstract
Due to the high morbidity and mortality rates of invasive aspergillosis (IA) and the importance of early IA detection for successful treatment and subsequent outcome, this study aimed to determine a time course of detectable antigen in a mouse model of IA and [...] Read more.
Due to the high morbidity and mortality rates of invasive aspergillosis (IA) and the importance of early IA detection for successful treatment and subsequent outcome, this study aimed to determine a time course of detectable antigen in a mouse model of IA and correlate it with tissue invasion by using two novel monoclonal antibodies, 1D2 and 4E4, that can be used to detect the Aspergillus-derived glycoproteins. Immunocompromised mice were randomly divided into five groups: uninfected control, and inoculation with conidia from Aspergillus fumigatus, Aspergillus flavus, Aspergillus niger, and Aspergillus terreus. Conidia (2 × 106 cells/mL) were administered intravenously via tail vein injection. Three mice from each group were euthanised at each time point (6 h, 12 h, 18 h, 24 h, and 48 h) after inoculation. Urine and blood were collected for analysis using a double-sandwich ELISA using 1D2 and 4E4. Liver, spleen, and kidney tissues were harvested for tissue staining. The levels of liver injury in the IA mice progressively increased with time after inoculation with Aspergillus conidia. Following inoculation with A. fumigatus, swollen conidia were identified in the spleen, as well as antigens in blood after 18 h. Hyphae were detected in the spleen, liver, and kidney after 48 h. For A. flavus, the antibodies detected hyphae in the liver and spleen as well as circulating antigens in blood samples 48 h after inoculation. Tissue injury was observed in the mice inoculated with A. terreus and A. niger, but there was no evidence of fungal invasion or antigens in the blood. Antigens were not detectable in mouse urine but could be detected in glomeruli of the kidney by immunofluorescence. In conclusion, the mAb-based antigen detection double-sandwich ELISA results were consistent with the IHC results in this study. Novel monoclonal antibodies 1D2 and 4E4 can serve as tools for the early identification of IA in mice infected by A. fumigatus and A. flavus. This study also suggests the potential usefulness of this approach in human disease. Full article
(This article belongs to the Special Issue Advances in Invasive Fungal Infections 2024)
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14 pages, 1227 KiB  
Article
The Rising Threat of Mucormycosis: Oman’s Experience Before and During the COVID-19 Pandemic
by Amina Al-Jardani, Adil Al-Wahaibi, Azza Al Rashdi, Bram Spruijtenburg, Noora AlBulushi, R. Sandhya Rani, Hanan AlKindi, Fatma Al-Yaquobi, Bader Al-Rawahi, Asma AlBalushi, Saleh Al Azri, Jacques F. Meis, Iman AlBuloshi, Seif Al-Abri, Ahmed Al-Harrasi, Abdullah M. S. Al-Hatmi and Amal Al Maani
J. Fungi 2024, 10(11), 796; https://doi.org/10.3390/jof10110796 - 15 Nov 2024
Cited by 2 | Viewed by 1122
Abstract
Mucormycosis is a rare, severe fungal infection mainly affecting immunocompromised individuals. Because of limited data on its epidemiology in Oman, we present this national, multicentric, retrospective review that includes all cases of proven mucormycosis between 2006 and 2022 in Oman. There were 51 [...] Read more.
Mucormycosis is a rare, severe fungal infection mainly affecting immunocompromised individuals. Because of limited data on its epidemiology in Oman, we present this national, multicentric, retrospective review that includes all cases of proven mucormycosis between 2006 and 2022 in Oman. There were 51 cases of mucormycosis reported in Oman. The annual incidence of mucormycosis was 0.38–0.69 cases per million population before COVID-19. During the pandemic, the incidence rose significantly to 1.76 in 2020, 5.31 in 2021, then decreased to 0.87 per million population in 2022. Diabetes was observed in 82.4% (n = 42) of the cases, COVID-19 in 47.1% (n = 24), and other chronic diseases in 72.6%. The use of steroids was reported in 33.3% (n = 17) and many patients (64.7%, n = 33) had multiple risk factors. The overall mortality rate was 41.2% (n = 21) and most deaths occurred within a month of diagnosis. Mortality rate among patients diagnosed with COVID-19 was 58.3% (14/24). Survival analysis showed a statistically significant association between COVID-19 status and patient survival (p = 0.024). Annual incidence of mucormycosis in Oman rose during the pandemic. This study highlights the epidemiological features of mucormycosis and emphasizes the importance of its inclusion in the national notifiable communicable diseases priority list as well as the importance of enhancing diagnostic capacities to detect and improve patient outcomes. Full article
(This article belongs to the Special Issue Advances in Invasive Fungal Infections 2024)
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14 pages, 893 KiB  
Article
A Phase I/IIa Prospective, Randomized, Open-Label Study on the Safety and Efficacy of Nebulized Liposomal Amphotericin for Invasive Pulmonary Aspergillosis
by Jesús Fortún, Elia Gómez-García de la Pedrosa, Alberto Martínez-Lorca, Patricia Paredes, Pilar Martín-Dávila, Alicia Gómez-López, María José Buitrago, Javier López-Jiménez, Francesca Gioia, Rosa Escudero, Maria Elena Alvarez-Alvarez, Cruz Soriano, Javier Moreno-García, Diana San Miguel, Noelia Vicente and Santiago Moreno
J. Fungi 2024, 10(3), 191; https://doi.org/10.3390/jof10030191 - 1 Mar 2024
Cited by 5 | Viewed by 2364
Abstract
Although nebulized liposomal amphotericin B (NLAB) is being used in invasive pulmonary aspergillosis (IPA) prophylaxis, no clinical trial has shown its efficacy as a therapeutic strategy. NAIFI is the inaugural randomized, controlled clinical trial designed to examine the safety and effectiveness of NLAB [...] Read more.
Although nebulized liposomal amphotericin B (NLAB) is being used in invasive pulmonary aspergillosis (IPA) prophylaxis, no clinical trial has shown its efficacy as a therapeutic strategy. NAIFI is the inaugural randomized, controlled clinical trial designed to examine the safety and effectiveness of NLAB (dosage: 25 mg in 6 mL, three times per week for 6 weeks) against a placebo, in the auxiliary treatment of IPA. Throughout the three-year clinical trial, thirteen patients (six NLAB, seven placebo) were included, with 61% being onco-hematological with less than 100 neutrophils/μL. There were no significant differences noted in their pre- and post-nebulization results of forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and oxygen saturation between the groups. Neither bronchospasm nor serum amphotericin B levels were reported in any patients given NLAB. 18F-Fluorodeoxyglucose positron emission tomography (FDG-PET-TC) was carried out at the baseline and after 6 weeks. A notable decrease in median SUV (standardized uptake value) was observed in NLAB patients after 6 weeks (−3.6 vs. −0.95, p: 0.039, one tail). Furthermore, a reduction in serum substance galactomannan and beta-D-Glucan was identified within NLAB recipients. NLAB is well tolerated and safe for patients with IPA. Encouraging indirect efficacy data have been derived from image monitoring or biomarkers. However, further studies involving more patients are necessary. Full article
(This article belongs to the Special Issue Advances in Invasive Fungal Infections 2024)
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10 pages, 949 KiB  
Brief Report
Evaluation of a New Automated Mono-Test for the Detection of Aspergillus Galactomannan: Comparison of Aspergillus Galactomannan Ag VirCLIA® Mono-Test with PlateliaTM Aspergillus Ag ELISA Assay
by Giuliana Lo Cascio, Valentina Lepera, Annarita Sorrentino, Domenico Caleca, Paolo Gigante, Gabriella Tocci, Alda Bazaj, Annalisa Mancini, Marina Bolzoni, Evelina Cattadori, Davide Gibellini, Chiara Gorrini, Claudio Farina, Roberta Schiavo and on behalf of the Medical Mycology Committee (CoSM)—Italian Association of Clinical Microbiology (AMCLI)
J. Fungi 2024, 10(11), 793; https://doi.org/10.3390/jof10110793 - 15 Nov 2024
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Abstract
The analytical performance of the new Aspergillus Galactomannan Ag VirCLIA® mono-test (Vircell S.L.) was compared to the Platelia™ Aspergillus Ag ELISA assay (Bio-Rad). Prospective serum and bronchoalveolar lavage (BAL) samples from patients at risk of invasive aspergillosis (IA) were tested using both [...] Read more.
The analytical performance of the new Aspergillus Galactomannan Ag VirCLIA® mono-test (Vircell S.L.) was compared to the Platelia™ Aspergillus Ag ELISA assay (Bio-Rad). Prospective serum and bronchoalveolar lavage (BAL) samples from patients at risk of invasive aspergillosis (IA) were tested using both the Aspergillus Galactomannan Ag VirCLIA® mono-test and the Platelia™ Aspergillus Ag ELISA assay. Concordance, sensitivity, specificity, and positive and negative predictive values were calculated using the manufacturer-recommended cutoff levels. Receiver operating characteristic (ROC) analysis and the Youden index were performed to determine the optimal cutoff. A total of 187 serum samples and 73 BAL samples were analyzed with both assays. The concordance between the Aspergillus Galactomannan Ag VirCLIA® mono-test and the Platelia™ Aspergillus Ag ELISA assay was 87.8%, with a Cohen’s kappa of 0.75. The sensitivity and specificity of the Aspergillus Galactomannan Ag VirCLIA® mono-test were 78.6% and 96.2%, respectively, with positive and negative predictive values of 94.8% and 83.3%. The ROC curve for the Aspergillus Galactomannan Ag VirCLIA® mono-test demonstrated an area under the curve (AUC) of 0.87, and the Youden index at the manufacturer’s established cutoff was 0.73. This new Aspergillus Galactomannan Ag VirCLIA® mono-test exhibited adequate analytical and clinical performance, showing good correlation with the Platelia™ Aspergillus Ag ELISA assay. The single-sample, semi-automated test is user-friendly, allowing small laboratories to perform the test on demand without the need for batch evaluations, providing a useful solution for timely diagnostic support for clinicians. Full article
(This article belongs to the Special Issue Advances in Invasive Fungal Infections 2024)
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19 pages, 1382 KiB  
Systematic Review
Global Epidemiology of Invasive Infections by Uncommon Candida Species: A Systematic Review
by Sandra Pinho, Isabel M. Miranda and Sofia Costa-de-Oliveira
J. Fungi 2024, 10(8), 558; https://doi.org/10.3390/jof10080558 - 7 Aug 2024
Cited by 3 | Viewed by 3057
Abstract
Emerging and uncommon Candida species have been reported as an increasing cause of invasive Candida infections (ICI). We aim to systematize the global epidemiology associated with emergent uncommon Candida species responsible for invasive infections in adult patients. A systematic review (from 1 January [...] Read more.
Emerging and uncommon Candida species have been reported as an increasing cause of invasive Candida infections (ICI). We aim to systematize the global epidemiology associated with emergent uncommon Candida species responsible for invasive infections in adult patients. A systematic review (from 1 January 2001 to 28 February 2023) regarding epidemiological, clinical, and microbiological data associated to invasive Candida infections by uncommon Candida spp. were collected. In total, 1567 publications were identified, and 36 were selected according to inclusion criteria (45 cases). The chosen studies covered: C. auris (n = 21), C. haemulonii (n = 6), C. fermentati (n = 4), C. kefyr (n = 4), C. norvegensis (n = 3), C. nivariensis (n = 3), C. bracarensis (n = 1), C. duobushaemulonii (n = 1), C. blankii (n = 1), and C. khanbhai (n = 1). Over the recent years, there has been an increase in the number of invasive infections caused by uncommon Candida spp. Asia and Europe are the continents with the most reported cases. The challenges in strain identification and antifungal susceptibility interpretation were significant. The absence of clinical breakpoints for the susceptibility profile determination for uncommon Candida spp. makes interpretation and treatment options a clinical challenge. It is crucial that we focus on new and accessible microbiology techniques to make fast and accurate diagnostics and treatments. Full article
(This article belongs to the Special Issue Advances in Invasive Fungal Infections 2024)
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