Biology, Immunology, Epidemiology, and Therapy of Fungal Infections: A Themed Issue Dedicated to Professor David A. Stevens

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 (31 December 2023) | Viewed by 31588

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University Hospital Necker for Sick Children, Paris, France
Interests: fungal infection; epidemiology and therapy

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Guest Editor
Infectious Diseases Research Laboratory, California Institute for Medical Research, San Jose, CA, USA
Interests: fungal infections; molecular epidemiology of the mycoses

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Guest Editor
Medical Mycology Research Center, Chiba University, Chiba, Japan
Interests: fungal infection; aspergillosis; basidiomycosis; antifungal resistance
Reference Unit for Parasitic and Fungal Infections, Department of Infectious Diseases, National Institute of Health, Av. Padre Cruz, 1649-016 Lisbon, Portugal
Interests: fungal infections diagnosis; Aspergillus; fungi; infectious diseases; fungal epidemiology and public health; antifungal resistance; molecular biology
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Special Issue Information

Dear Colleagues,

David A. Stevens, MD is Professor (Emeritus) of Medicine, Stanford University Medical School, and was Chief of an affiliated teaching hospital’s Infectious Diseases service, Hospital Epidemiologist, and Co-Director, Microbiology Laboratory, for 42 years. He has been President of the California Institute for Medical Research (CIMR), San Jose for 29 of the past 31 years, Principal Investigator of its Infectious Disease Research Laboratory (named and dedicated to him in 2022) engaged in laboratory and clinical research with fellows, students, graduate students for 50 years, and Director of its Clinical Laboratories. His group studies the biology, pathogenesis, immunology, epidemiology and therapy of fungal infections. He is an author of >750 full articles, editorials and book chapters, and an approximately equal number of abstracts. A recent computerized index indicated his publications have been cited >50,000 times. Fifteen of his former trainees are full professors in the faculty of professional schools, and others are at other ranks of the professoriate, clinical faculty, hospital chiefs of infectious diseases, directors of clinical microbiology laboratories, full-time laboratory researchers at national laboratories or research institutes, or clinicians. His publications include the discoveries of six new microbes, one of which was named after him by Korean scientists, owing to his efforts in study of the genus, and another named by him for CIMR, where the microbe was discovered. His honors include election to the American Society for Clinical Investigation in 1981, receipt of the Rhoda Benham Medal from the Medical Mycology Society of the Americas 1999, the 2006 recipient in Paris of the Lucille Georg Medal from the International Society for Human and Animal Mycology, the 2006 recipient of the Charles E. Smith Memorial Award from the Coccidioidomycosis Study Group, and election to these fellowships: American College of Physicians, Infectious Diseases Society of America (IDSA), and American Academy of Microbiology. He was a Project Leader in the NIAID Mycoses Study Group (National Institutes of Health multicenter clinical trials group) 1990-2000; Chair of the committee writing the first Practice Guidelines on Aspergillosis for IDSA, and later served on this committee as well as the committee writing the Practice Guidelines on Coccidioidomycosis; Chair of the Mycology Div., Amer. Soc. for Microbiology (a position also held by three of his former fellows); and Director of the NIH Fogarty International Training Grant at Stanford. He is a Co-Organizer of the biennial Advances Against Aspergillosis and Mucormycosis international meetings. His early accomplishments (while a resident) include describing a new disease (leukemia with Burkitt lymphoma cells); senior author (while a fellow) of the first controlled trial of the systemic use of an antiviral; and showing the importance of interferon in arresting progression of a viral disease. The text of a seminal review article co-authored on viral infections in non-congenital forms of immunodeficiency was later used when others were searching for a name for a new disease, namely acquired immune deficiency disease (AIDS). In mycology, he studied and introduced the first systemically useful azole antifungal, miconazole, at a time when therapy for this emerging area of infections was extremely limited, leading to the development of a dominant class of the antifungals. This led to his paper, the first on the initial oral agent of this class, on ketoconazole. His lab established a scientific base for inoculum-independent susceptibility testing of antifungals in vitro, and first demonstrated the utility of fluconazole in prophylaxis of the immunocompromised; the clinical utility of cyclodextrin for delivery of water-insoluble azoles; and that lifelong azole therapy was required for coccidioidal meningitis. His team reported the first case of azole-resistant Aspergillus (which has now become an international concern); and with his colleagues, the only randomized therapeutic trial in coccidioidomycosis, and the first clinical trial of a vaccine for coccidioidomycosis. His were many of the first reports of side effects of azoles, and of cytochrome P450 interactions of azoles with other drugs; perhaps the most important was the demonstration of blockade of host steroidal hormone synthesis, since this also led to the use of azoles as endocrinologic tools. His other studies first revealed the anti-Aspergillus activity of the echinocandins, showed the power of combined inhibition of cell wall glucan and chitin synthesis, and the “paradoxical effect” of echinocandins (losing inhibition at higher concentrations). His study was the first randomized trial of therapy in allergic bronchopulmonary aspergillosis—the first demonstration that an antimicrobial could ameliorate an allergic disease. He and his team introduced categorization of mycoses for entry into clinical trials, and an outcome scoring system, which became known as “the NIAID Mycoses Study Group criteria”, eventually evolving into the now canonical EORTC/MSG criteria. Publications include the role of cytokines in defense against mycoses, studies of how host hormones directly modulate fungal pathogen activity, and, in molecular epidemiology, molecular diagnostic methods and gene expression in fungal biologic processes. His lab developed many animal models of mycoses. A current focus in his laboratory is the nature of the interactions between prominent microbes affecting the course of airway disease in cystic fibrosis.

The Journal of Fungi is pleased to announce a Special Issue honoring David A. Stevens for his outstanding contributions to medical mycology. The submissions can be on any topic relevant to medical mycology.

Prof. Dr. Bertrand Dupont
Prof. Dr. Karl V. Clemons
Prof. Dr. Roderick J. Hay
Prof. Dr. Katsuhiko Kamei
Dr. Raquel Sabino
Guest Editors

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Keywords

  • biology
  • pathogenesis
  • immunology
  • epidemiology
  • therapy

Published Papers (16 papers)

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Research

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10 pages, 1146 KiB  
Article
Antifungal Resistance and Genotyping of Clinical Candida parapsilosis Complex in Japan
by Hazim O. Khalifa, Akira Watanabe and Katsuhiko Kamei
J. Fungi 2024, 10(1), 4; https://doi.org/10.3390/jof10010004 - 20 Dec 2023
Viewed by 980
Abstract
Non-albicans Candida infections have recently gained worldwide attention due to their intrinsic resistance to different antifungal agents and the limited therapeutic options for treating them. Although the Candida parapsilosis complex is reported to be the second or third most prevalent Candida spp., little [...] Read more.
Non-albicans Candida infections have recently gained worldwide attention due to their intrinsic resistance to different antifungal agents and the limited therapeutic options for treating them. Although the Candida parapsilosis complex is reported to be the second or third most prevalent Candida spp., little information is available on the prevalence of antifungal resistance along with genotyping of the C. parapsilosis complex. In this study, we aimed to evaluate the prevalence of antifungal resistance, the genetic basis of such resistance, and the genotyping of C. parapsilosis complex isolates that were recovered from hospitalized patients in Japan from 2005 to 2019. Our results indicated that, with the exception of one single C. metapsilosis isolate that was dose-dependently susceptible to fluconazole, all other isolates were susceptible or showed wild phenotypes to all tested antifungals, including azoles, echinocandins, amphotericin B, and flucytosine. Molecular analyses for azole and echinocandin resistance via evaluating ERG11 mutation and FKS1 hotspot one (HS1) and hotspot two (HS2) mutations, respectively, confirmed the phenotypic results. Genotyping of our isolates confirmed that they belong to 53 different but closely related genotypes, with a similarity percentage of up to 90%. Our results are of significant concern, since understanding the genetic basis of echinocandin resistance in the C. parapsilosis complex as well their genotyping is essential for directing targeted therapy, identifying probable infection sources, and developing strategies for overcoming epidemic spread. Full article
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16 pages, 899 KiB  
Article
Epidemiology of Coccidioidomycosis in the Veterans Health Administration, 2013–2022
by Cynthia Lucero-Obusan, Rishi Deka, Patricia Schirmer, Gina Oda and Mark Holodniy
J. Fungi 2023, 9(7), 731; https://doi.org/10.3390/jof9070731 - 06 Jul 2023
Cited by 1 | Viewed by 1465
Abstract
We describe the epidemiology of coccidioidomycosis among a national cohort of Veterans. Using electronic health record data from adults tested for coccidioidomycosis between 1 January 2013 and 31 December 2022, we analyzed differences in baseline demographics (age, sex, race/ethnicity, birth country, comorbidities, residence, [...] Read more.
We describe the epidemiology of coccidioidomycosis among a national cohort of Veterans. Using electronic health record data from adults tested for coccidioidomycosis between 1 January 2013 and 31 December 2022, we analyzed differences in baseline demographics (age, sex, race/ethnicity, birth country, comorbidities, residence, and Charlson Comorbidity Index score) between 4204 coccidioidomycosis-test-positive and 63,322 test-negative Veterans. Log-binomial regression models with adjusted risk ratios (aRRs) were used to evaluate risk factors associated with coccidioidomycosis including dissemination, hospitalization, and mortality. Case counts and incidence rates were highest in select counties in Arizona and California where Coccidioides is endemic. Coccidioidomycosis-positive Veterans were younger, more likely to be male, and Philippine-born. The risk factors most highly associated with being coccidioidomycosis-positive included Native Hawaiian/Pacific Islander (aRR 1.068 [95%CI: 1.039–1.098]), Asian (aRR 1.060 [95%CI: 1.037–1.083]), Black (aRR 1.029 [95%CI: 1.022–1.036]), American Indian/Alaska Native (aRR 1.026 [95%CI: 1.004–1.048]) race, and Hispanic/Latino ethnicity (aRR 1.021 [95%CI: 1.013–1.028]). Black race (aRR: 1.058 [95%CI: 1.037–1.081]) and Hispanic/Latino ethnicity (aRR 1.018 [95%CI: 1.0003–1.036]) were also associated with disseminated coccidioidomycosis, strengthening the evidence for the association of coccidioidomycosis, including severe infections, with specific racial and ethnic groups. There were no statistically significant differences in hospitalization within 45 days of testing or 30-day all-cause mortality. Improving our understanding of coccidioidomycosis risk factors is important for targeted prevention strategies and to reduce delays in diagnosis and ineffective treatment. Full article
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9 pages, 857 KiB  
Communication
Novel Antifungals and Aspergillus Section Terrei with Potpourri Susceptibility Profiles to Conventional Antifungals
by Roya Vahedi-Shahandashti, Jos Houbraken, Mike Birch and Cornelia Lass-Flörl
J. Fungi 2023, 9(6), 649; https://doi.org/10.3390/jof9060649 - 06 Jun 2023
Cited by 1 | Viewed by 1066
Abstract
The epidemiology of invasive fungal infections (IFIs) is currently changing, driven by aggressive immunosuppressive therapy, leading to an expanded spectrum of patients at risk of IFIs. Aspergillosis is a leading cause of IFIs, which usually affects immunocompromised patients. There are a limited number [...] Read more.
The epidemiology of invasive fungal infections (IFIs) is currently changing, driven by aggressive immunosuppressive therapy, leading to an expanded spectrum of patients at risk of IFIs. Aspergillosis is a leading cause of IFIs, which usually affects immunocompromised patients. There are a limited number of antifungal medications available for treating IFIs, and their effectiveness is often hindered by rising resistance rates and practical limitations. Consequently, new antifungals, especially those with novel mechanisms of action, are increasingly required. This study assessed the activity of four novel antifungal agents with different mechanisms of activity, namely, manogepix, rezafungin, ibrexafungerp, and olorofim, against 100 isolates of Aspergillus section Terrei, containing amphotericin-B (AmB)-wildtype/non-wildtype and azole-susceptible/-resistant strains, according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) method. In general, all tested agents showed potent and consistent activity against the tested isolates, exhibiting geometric mean (GM) and minimum effective concentration (MEC)/minimum inhibitory concentration (MIC) ranges, respectively, as follows: manogepix (0.048 mg/L, 0.032–0.5 mg/L), rezafungin (0.020 mg/L, 0.016–0.5 mg/L), ibrexafungerp (0.071 mg/L, 0.032–2 mg/L), and olorofim (0.008 mg/L, 0.008–0.032 mg/L). In terms of MIC90/MEC90, olorofim had the lowest values (0.008 mg/L), followed by rezafungin (0.032 mg/L), manogepix (0.125 mg/L), and ibrexafungerp (0.25 mg/L). All the antifungals tested demonstrated promising in vitro activity against Aspergillus section Terrei, including A. terreus as well as azole-resistant and AmB-non-wildtype cryptic species. Full article
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14 pages, 3246 KiB  
Article
Comparison of Multi-locus Genotypes Detected in Aspergillus fumigatus Isolated from COVID Associated Pulmonary Aspergillosis (CAPA) and from Other Clinical and Environmental Sources
by Susana Morais, Cristina Toscano, Helena Simões, Dina Carpinteiro, Carla Viegas, Cristina Veríssimo and Raquel Sabino
J. Fungi 2023, 9(3), 298; https://doi.org/10.3390/jof9030298 - 24 Feb 2023
Cited by 1 | Viewed by 1466
Abstract
Background: Aspergillus fumigatus is a saprophytic fungus, ubiquitous in the environment and responsible for causing infections, some of them severe invasive infections. The high morbidity and mortality, together with the increasing burden of triazole-resistant isolates and the emergence of new risk groups, namely [...] Read more.
Background: Aspergillus fumigatus is a saprophytic fungus, ubiquitous in the environment and responsible for causing infections, some of them severe invasive infections. The high morbidity and mortality, together with the increasing burden of triazole-resistant isolates and the emergence of new risk groups, namely COVID-19 patients, have raised a crescent awareness of the need to better comprehend the dynamics of this fungus. The understanding of the epidemiology of this fungus, especially of CAPA isolates, allows a better understanding of the interactions of the fungus in the environment and the human body. Methods: In the present study, the M3 markers of the STRAf assay were used as a robust typing technique to understand the connection between CAPA isolates and isolates from different sources (environmental and clinical-human and animal). Results: Of 100 viable isolates that were analyzed, 85 genotypes were found, 77 of which were unique. Some isolates from different sources presented the same genotype. Microsatellite genotypes obtained from A. fumigatus isolates from COVID+ patients were all unique, not being found in any other isolates of the present study or even in other isolates deposited in a worldwide database; these same isolates were heterogeneously distributed among the other isolates. Conclusions: Isolates from CAPA patients revealed high heterogeneity of multi-locus genotypes. A genotype more commonly associated with COVID-19 infections does not appear to exist. Full article
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12 pages, 290 KiB  
Article
Yeast Bloodstream Infections in the COVID-19 Patient: A Multicenter Italian Study (FiCoV Study)
by Anna Prigitano, Elisabetta Blasi, Maria Calabrò, Caterina Cavanna, Maria Cornetta, Claudio Farina, Anna Grancini, Patrizia Innocenti, Giuliana Lo Cascio, Lucia Nicola, Laura Trovato, Massimo Cogliati, Maria Carmela Esposto, Anna Maria Tortorano, Luisa Romanò and on behalf of the FiCoV Study Group
J. Fungi 2023, 9(2), 277; https://doi.org/10.3390/jof9020277 - 20 Feb 2023
Cited by 4 | Viewed by 1978
Abstract
Fungemia is a co-infection contributing to the worsening of the critically ill COVID-19 patient. The multicenter Italian observational study FiCoV aims to estimate the frequency of yeast bloodstream infections (BSIs), to describe the factors associated with yeast BSIs in COVID-19 patients hospitalized in [...] Read more.
Fungemia is a co-infection contributing to the worsening of the critically ill COVID-19 patient. The multicenter Italian observational study FiCoV aims to estimate the frequency of yeast bloodstream infections (BSIs), to describe the factors associated with yeast BSIs in COVID-19 patients hospitalized in 10 hospitals, and to analyze the antifungal susceptibility profiles of the yeasts isolated from blood cultures. The study included all hospitalized adult COVID-19 patients with a yeast BSI; anonymous data was collected from each patient and data about antifungal susceptibility was collected. Yeast BSI occurred in 1.06% of patients, from 0.14% to 3.39% among the 10 participating centers. Patients were mainly admitted to intensive or sub-intensive care units (68.6%), over 60 years of age (73%), with a mean and median time from the hospitalization to fungemia of 29 and 22 days, respectively. Regarding risk factors for fungemia, most patients received corticosteroid therapy during hospitalization (61.8%) and had a comorbidity (25.3% diabetes, 11.5% chronic respiratory disorder, 9.5% cancer, 6% haematological malignancies, 1.4% organ transplantation). Antifungal therapy was administered to 75.6% of patients, mostly echinocandins (64.5%). The fatality rate observed in COVID-19 patients with yeast BSI was significantly higher than that of COVID-19 patients without yeast BSI (45.5% versus 30.5%). Candida parapsilosis (49.8%) and C. albicans (35.2%) were the most fungal species isolated; 72% of C. parapsilosis strains were fluconazole-resistant (range 0–93.2% among the centers). The FiCoV study highlights a high prevalence of Candida BSIs in critically ill COVID-19 patients, especially hospitalized in an intensive care unit, a high fatality rate associated with the fungal co-infection, and the worrying spread of azole-resistant C. parapsilosis. Full article
7 pages, 283 KiB  
Article
Initial Results of the International Efforts in Screening New Agents against Candida auris
by Vanice Rodrigues Poester, Lívia Silveira Munhoz, Jéssica Louise Benelli, Aryse Martins Melo, Abdullah M. S. Al-Hatmi, David J. Larwood, Marife Martinez, David A. Stevens and Melissa Orzechowski Xavier
J. Fungi 2022, 8(8), 771; https://doi.org/10.3390/jof8080771 - 25 Jul 2022
Cited by 2 | Viewed by 1544
Abstract
Background: Candida auris is an emergent fungal pathogen and a global concern, mostly due to its resistance to many currently available antifungal drugs. Objective: Thus, in response to this challenge, we evaluated the in vitro activity of potential new drugs, diphenyl diselenide (PhSe) [...] Read more.
Background: Candida auris is an emergent fungal pathogen and a global concern, mostly due to its resistance to many currently available antifungal drugs. Objective: Thus, in response to this challenge, we evaluated the in vitro activity of potential new drugs, diphenyl diselenide (PhSe)2 and nikkomycin Z (nikZ), alone and in association with currently available antifungals (azoles, echinocandins, and polyenes) against Candida auris. Methods: Clinical isolates of C. auris were tested in vitro. (PhSe)2 and nikZ activities were tested alone and in combination with amphotericin B, fluconazole, or the echinocandins, micafungin and caspofungin. Results: (PhSe)2 alone was unable to inhibit C. auris, and antagonism or indifferent effects were observed in the combination of this compound with the antifungals tested. NikZ appeared not active alone either, but frequently acted cooperatively with conventional antifungals. Conclusion: Our data show that (PhSe)2 appears to not have a good potential to be a candidate in the development of new drugs to treat C. auris, but that nikZ is worthy of further study. Full article

Review

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24 pages, 2187 KiB  
Review
Interplay of Cytokines and Chemokines in Aspergillosis
by Jata Shankar, Raman Thakur, Karl V. Clemons and David A. Stevens
J. Fungi 2024, 10(4), 251; https://doi.org/10.3390/jof10040251 - 27 Mar 2024
Viewed by 794
Abstract
Aspergillosis is a fungal infection caused by various species of Aspergillus, most notably A. fumigatus. This fungus causes a spectrum of diseases, including allergic bronchopulmonary aspergillosis, aspergilloma, chronic pulmonary aspergillosis, and invasive aspergillosis. The clinical manifestations and severity of aspergillosis can [...] Read more.
Aspergillosis is a fungal infection caused by various species of Aspergillus, most notably A. fumigatus. This fungus causes a spectrum of diseases, including allergic bronchopulmonary aspergillosis, aspergilloma, chronic pulmonary aspergillosis, and invasive aspergillosis. The clinical manifestations and severity of aspergillosis can vary depending on individual immune status and the specific species of Aspergillus involved. The recognition of Aspergillus involves pathogen-associated molecular patterns (PAMPs) such as glucan, galactomannan, mannose, and conidial surface proteins. These are recognized by the pathogen recognition receptors present on immune cells such as Toll-like receptors (TLR-1,2,3,4, etc.) and C-type lectins (Dectin-1 and Dectin-2). We discuss the roles of cytokines and pathogen recognition in aspergillosis from both the perspective of human and experimental infection. Several cytokines and chemokines have been implicated in the immune response to Aspergillus infection, including interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), CCR4, CCR17, and other interleukins. For example, allergic bronchopulmonary aspergillosis (ABPA) is characterized by Th2 and Th9 cell-type immunity and involves interleukin (IL)-4, IL-5, IL-13, and IL-10. In contrast, it has been observed that invasive aspergillosis involves Th1 and Th17 cell-type immunity via IFN-γ, IL-1, IL-6, and IL-17. These cytokines activate various immune cells and stimulate the production of other immune molecules, such as antimicrobial peptides and reactive oxygen species, which aid in the clearance of the fungal pathogen. Moreover, they help to initiate and coordinate the immune response, recruit immune cells to the site of infection, and promote clearance of the fungus. Insight into the host response from both human and animal studies may aid in understanding the immune response in aspergillosis, possibly leading to harnessing the power of cytokines or cytokine (receptor) antagonists and transforming them into precise immunotherapeutic strategies. This could advance personalized medicine. Full article
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11 pages, 673 KiB  
Review
Anticytokine Autoantibodies and Fungal Infections
by Shanthi Kappagoda and Stanley Deresinski
J. Fungi 2023, 9(8), 782; https://doi.org/10.3390/jof9080782 - 25 Jul 2023
Cited by 1 | Viewed by 1288
Abstract
Anticytokine autoantibodies (ACAAs) can cause adult onset immunodeficiencies which mimic primary immunodeficiencies and can present as refractory and severe fungal infections. This paper provides an overview of the role of innate immunity, including key cytokines, in fungal infections and then describes four clinical [...] Read more.
Anticytokine autoantibodies (ACAAs) can cause adult onset immunodeficiencies which mimic primary immunodeficiencies and can present as refractory and severe fungal infections. This paper provides an overview of the role of innate immunity, including key cytokines, in fungal infections and then describes four clinical scenarios where ACAAs are associated with severe presentations of a fungal infection: (1) Talaromyces marneffei infection and anti-interferon-γ, (2) histoplasmosis and anti-interferon-γ, (3) Cryptococcus gattii infection and anti-GM-CSF, and (4) mucocutaneous candidiasis and anti-IL-17A/F (IL-22). Testing for ACAAs and potential therapeutic options are discussed. Full article
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16 pages, 782 KiB  
Review
Mortality in ICU Patients with COVID-19-Associated Pulmonary Aspergillosis
by Anna Beltrame, David A. Stevens and Donna Haiduven
J. Fungi 2023, 9(6), 689; https://doi.org/10.3390/jof9060689 - 20 Jun 2023
Cited by 3 | Viewed by 1239
Abstract
A review of 38 studies involving 1437 COVID-19 patients admitted to intensive care units (ICUs) with pulmonary aspergillosis (CAPA) was conducted to investigate whether mortality has improved since the pandemic’s onset. The study found that the median ICU mortality was 56.8%, ranging from [...] Read more.
A review of 38 studies involving 1437 COVID-19 patients admitted to intensive care units (ICUs) with pulmonary aspergillosis (CAPA) was conducted to investigate whether mortality has improved since the pandemic’s onset. The study found that the median ICU mortality was 56.8%, ranging from 30% to 91.8%. These rates were higher for patients admitted during 2020–2021 (61.4%) compared to 2020 (52.3%), and prospective studies found higher ICU mortality (64.7%) than retrospective ones (56.4%). The studies were conducted in various countries and used different criteria to define CAPA. The percentage of patients who received antifungal therapy varied across studies. These results indicate that the mortality rate among CAPA patients is a growing concern, mainly since there has been an overall reduction in mortality among COVID-19 patients. Urgent action is needed to improve prevention and management strategies for CAPA, and additional research is needed to identify optimal treatment strategies to reduce mortality rates among these patients. This study serves as a call to action for healthcare professionals and policymakers to prioritize CAPA, a serious and potentially life-threatening complication of COVID-19. Full article
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12 pages, 1183 KiB  
Review
Invasive Aspergillosis after Renal Transplantation
by Liyanage Shamithra Madhumali Sigera and David W. Denning
J. Fungi 2023, 9(2), 255; https://doi.org/10.3390/jof9020255 - 15 Feb 2023
Cited by 8 | Viewed by 2712
Abstract
Over 95,000 renal transplantation procedures were completed in 2021. Invasive aspergillosis (IA) affects about 1 in 250 to 1 in 43 renal transplant recipients. About 50% of cases occur in the first 6 months after transplantation; the median time of onset is nearly [...] Read more.
Over 95,000 renal transplantation procedures were completed in 2021. Invasive aspergillosis (IA) affects about 1 in 250 to 1 in 43 renal transplant recipients. About 50% of cases occur in the first 6 months after transplantation; the median time of onset is nearly 3 years. Major risk factors for IA include old age, diabetes mellitus (especially if prior diabetic nephropathy), delayed graft function, acute graft rejection, chronic obstructive pulmonary disease, cytomegalovirus disease, and neutropenia. Hospital construction, demolition activities, and residential refurbishments also increase the risk. Parenchymal pulmonary infection is the most common (~75%), and bronchial, sinus, cerebral, and disseminated disease are less common. Typical pulmonary features of fever, dyspnea, cough, and hemoptysis are seen in most patients, but 20% have non-specific general features of illness. Non-specific infiltrates and pulmonary nodules are the commonest radiological features, with bilateral disease carrying a worse prognosis. Bronchoscopy for direct microscopy, fungal culture, and Aspergillus antigen are the fastest means of establishing the diagnosis; a positive serum Aspergillus antigen presages a worse outcome. Standard therapy includes voriconazole, isavuconazole, or posaconazole, with great attention necessary to assess likely drug–drug interactions. Liposomal amphotericin B and echinocandins are less effective. A reduction in or stopping immunosuppression needs careful consideration, given the overall mortality of IA in renal-transplanted patients; continuing corticosteroid after the diagnosis of IA increases mortality by 2.5 times. Surgical resection or the addition of a gamma interferon should also be considered. Full article
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10 pages, 1071 KiB  
Review
Epidemiologic Aspects of Mycetoma in Africa
by Michel Develoux
J. Fungi 2022, 8(12), 1258; https://doi.org/10.3390/jof8121258 - 29 Nov 2022
Cited by 3 | Viewed by 1934
Abstract
Mycetoma is a chronic, disabling infection caused by fungi or actinomycetes that affects the disadvantaged rural populations of arid tropical regions. The identification of etiological agents is long, difficult, and often imprecise or unsuccessful. Recently developed molecular methods can be used to identify [...] Read more.
Mycetoma is a chronic, disabling infection caused by fungi or actinomycetes that affects the disadvantaged rural populations of arid tropical regions. The identification of etiological agents is long, difficult, and often imprecise or unsuccessful. Recently developed molecular methods can be used to identify causal agents at the species level. However, diagnosis can only be implemented in specialized laboratories. For these reasons, the distribution of causal agents in endemic African countries remains approximate. It is known that the pathogenic organisms of mycetoma are present in the environment, introduced as a result of injuries or trauma. There are still unknowns concerning the natural habitats of agents and the mode of infection. A potential association between mycetoma and acacia was uncovered in Sudan, allowing the elaboration of a risk map of the country. A new hypothesis for the mode of contamination involves the intervention of an intermediate host. The first surveys in Sudanese endemic villages gave a higher prevalence than the previous estimates, indicating that the prevalence of mycetoma in endemic African countries has previously been underestimated. Full article
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14 pages, 1224 KiB  
Review
Quantifying Deaths from Aspergillosis in HIV Positive People
by David W. Denning and Ellen Frances Morgan
J. Fungi 2022, 8(11), 1131; https://doi.org/10.3390/jof8111131 - 27 Oct 2022
Cited by 9 | Viewed by 2006
Abstract
Aspergillus spp. are ubiquitous and cause severe infections in immunocompromised patients. Less is known about its incidence and prognosis in patients with HIV/AIDS. We reviewed the mortality of invasive aspergillosis in HIV/AIDS patients. Pubmed, Embase and Medline databases were used to search for [...] Read more.
Aspergillus spp. are ubiquitous and cause severe infections in immunocompromised patients. Less is known about its incidence and prognosis in patients with HIV/AIDS. We reviewed the mortality of invasive aspergillosis in HIV/AIDS patients. Pubmed, Embase and Medline databases were used to search for articles. Studies were excluded if they contained other aspergillosis risk factors, no original or patient survival data or were not in English. From 747 articles published, 54 studies and case reports were identified following reading, published between 1985 and 2021, with 54% papers prior to 2000 reporting 853 patients from 16 countries, none from Africa. 707 (83%) patients died with an average time from diagnosis to death of 77.5 days. Postmortem diagnosis was seen in 21% of deaths recorded. A national series from France of 242 cases of invasive aspergillosis diagnosed in life recorded a 3 month mortality of 68% pre-ART, falling to 31% after introduction of ART and voriconazole. CD4 count was recorded in 39 studies and ranged from 2 to >1000 cells/mm3; only 8 patients (1.8%) had a CD4 > 100 cells/mm3. Aspergillosis occurs in patients with HIV/AIDS and associated with high mortality but its slow progression should allow diagnosis and treatment with improved outcome. Full article
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36 pages, 6409 KiB  
Review
Coccidioides Species: A Review of Basic Research: 2022
by Theo N. Kirkland, David A. Stevens, Chiung-Yu Hung, Sinem Beyhan, John W. Taylor, Lisa F. Shubitz, Sascha H. Duttke, Arash Heidari, Royce H. Johnson, Stanley C. Deresinski, Antje Lauer and Joshua Fierer
J. Fungi 2022, 8(8), 859; https://doi.org/10.3390/jof8080859 - 16 Aug 2022
Cited by 5 | Viewed by 5123
Abstract
Coccidioides immitis and posadasii are closely related fungal species that cause coccidioidomycosis. These dimorphic organisms cause disease in immunocompetent as well as immunocompromised individuals and as much as 40% of the population is infected in the endemic area. Although most infections resolve spontaneously, [...] Read more.
Coccidioides immitis and posadasii are closely related fungal species that cause coccidioidomycosis. These dimorphic organisms cause disease in immunocompetent as well as immunocompromised individuals and as much as 40% of the population is infected in the endemic area. Although most infections resolve spontaneously, the infection can be prolonged and, in some instances, fatal. Coccidioides has been studied for more than 100 years and many aspects of the organism and the disease it causes have been investigated. There are over 500 manuscripts concerning Coccidioides (excluding clinical articles) referenced in PubMed over the past 50 years, so there is a large body of evidence to review. We reviewed the most accurate and informative basic research studies of these fungi including some seminal older studies as well as an extensive review of current research. This is an attempt to gather the most important basic research studies about this fungus into one publication. To focus this review, we will discuss the mycology of the organism exclusively rather than the studies of the host response or clinical studies. We hope that this review will be a useful resource to those interested in Coccidioides and coccidioidomycosis. Full article
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16 pages, 2574 KiB  
Review
Vaccines to Prevent Coccidioidomycosis: A Gene-Deletion Mutant of Coccidioides Posadasii as a Viable Candidate for Human Trials
by John N. Galgiani, Lisa F. Shubitz, Marc J. Orbach, M. Alejandra Mandel, Daniel A. Powell, Bruce S. Klein, Edward J. Robb, Mana Ohkura, Devin J. Seka, Thomas M. Tomasiak and Thomas P. Monath
J. Fungi 2022, 8(8), 838; https://doi.org/10.3390/jof8080838 - 10 Aug 2022
Cited by 7 | Viewed by 2501
Abstract
Coccidioidomycosis is an endemic fungal infection that is reported in up to 20,000 persons per year and has an economic impact close to $1.5 billion. Natural infection virtually always confers protection from future exposure, and this suggests that a preventative vaccine strategy is [...] Read more.
Coccidioidomycosis is an endemic fungal infection that is reported in up to 20,000 persons per year and has an economic impact close to $1.5 billion. Natural infection virtually always confers protection from future exposure, and this suggests that a preventative vaccine strategy is likely to succeed. We here review progress toward that objective. There has been ongoing research to discover a coccidioidal vaccine over the past seven decades, including one phase III clinical trial, but for reasons of either efficacy or feasibility, a safe and effective vaccine has not yet been developed. This review first summarizes the past research to develop a coccidioidal vaccine. It then details the evidence that supports a live, gene-deletion vaccine candidate as suitable for further development as both a veterinary and a human clinical product. Finally, a plausible vaccine development plan is described which would be applicable to this vaccine candidate and also useful to other future candidates. The public health and economic impact of coccidioidomycosis fully justifies a public private partnership for vaccine development, and the development of a vaccine for this orphan disease will likely require some degree of public funding. Full article
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8 pages, 490 KiB  
Brief Report
Co-Occurrence of Gram-Negative Rods in Patients with Hematologic Malignancy and Sinopulmonary Mucormycosis
by Stephanie L. Egge, Sebastian Wurster, Sung-Yeon Cho, Ying Jiang, Dierdre B. Axell-House, William R. Miller and Dimitrios P. Kontoyiannis
J. Fungi 2024, 10(1), 41; https://doi.org/10.3390/jof10010041 - 04 Jan 2024
Viewed by 1234
Abstract
Both Mucorales and Gram-negative rods (GNRs) commonly infect patients with hematological malignancies (HM); however, their co-occurrence is understudied. Therefore, we retrospectively reviewed the records of 63 patients with HM and proven or probable sinopulmonary mucormycosis at MD Anderson Cancer Center (Houston, Texas) from [...] Read more.
Both Mucorales and Gram-negative rods (GNRs) commonly infect patients with hematological malignancies (HM); however, their co-occurrence is understudied. Therefore, we retrospectively reviewed the records of 63 patients with HM and proven or probable sinopulmonary mucormycosis at MD Anderson Cancer Center (Houston, Texas) from 2000–2020. Seventeen out of sixty-three reviewed patients (27.0%) had sinopulmonary co-occurrence of GNRs (most commonly Pseudomonas aeruginosa and Stenotrophomonas maltophilia) within 30 days of a positive Mucorales culture or histology demonstrating Mucorales species. Eight of seventeen co-isolations of Mucorales and GNRs were found in same-day samples. All 15 patients with GNR co-occurrence and reported antimicrobial data had received anti-Pseudomonal agents within 14 days prior to diagnosis of mucormycosis and 5/15 (33.3%) had received anti-Stenotrophomonal agents. Demographic and clinical characteristics of patients with and without GNR co-occurrence were comparable. Forty-two-day all-cause mortality was high (34.9%) and comparable in patients with (41.2%) and without (32.6%) GNR detection (p = 0.53). In summary, over a quarter of heavily immunosuppressed patients with sinopulmonary mucormycosis harbored GNRs in their respiratory tract. Although no impact on survival outcomes was seen in a background of high mortality in our relatively underpowered study, pathogenesis studies are needed to understand the mutualistic interplay of GNR and Mucorales and their influence on host responses. Full article
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12 pages, 1896 KiB  
Perspective
Severe Fungal Asthma: A Role for Biologics and Inhaled Antifungals
by Richard B. Moss
J. Fungi 2023, 9(1), 85; https://doi.org/10.3390/jof9010085 - 06 Jan 2023
Cited by 8 | Viewed by 2559 | Correction
Abstract
Allergic asthma has traditionally been treated with inhaled and systemic glucocorticosteroids. A continuum of allergic fungal airways disease associated with Aspergillus fumigatus colonization and/or atopic immune responses that encompasses fungal asthma, severe asthma with fungal sensitization and allergic bronchopulmonary aspergillosis is now recognized [...] Read more.
Allergic asthma has traditionally been treated with inhaled and systemic glucocorticosteroids. A continuum of allergic fungal airways disease associated with Aspergillus fumigatus colonization and/or atopic immune responses that encompasses fungal asthma, severe asthma with fungal sensitization and allergic bronchopulmonary aspergillosis is now recognized along a phenotypic severity spectrum of T2-high immune deviation lung disease. Oral triazoles have shown clinical, anti-inflammatory and microbiologic efficacy in this setting; in the future inhaled antifungals may improve the therapeutic index. Humanized monoclonal antibody biologic agents targeting T2-high disease also show efficacy and promise of improved control in difficult cases. Developments in these areas are highlighted in this overview. Full article
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