SATURDAY 21 OCTOBER 2023

Biography
David B. Corry is Professor of Pathology & Immunology and Medicine; Vice Chair for Immunology, Department of Pathology & Immunology at Baylor College of Medicine in Houston, Texas, and Chief of the Section of Allergy & Immunology at the Michael E. DeBakey VA Medical Center. Dr. Corry further holds the Fulbright Endowed Chair in Pathology. He received his M.D. degree from the University of Texas Southwestern Medical School and after residency training in Internal Medicine at Duke University Medical Center, he completed his clinical training in Pulmonary and Critical Care Medicine at the University of California at San Francisco. He joined the faculty at Baylor College of Medicine in 1999. The primary objectives of Dr. Corry’s research are to discover the fundamental immune and environmental causes of chronic human inflammatory diseases to improve the diagnosis, prognosis, and therapy of these often profoundly disabling conditions. His current research is focused on the role that common environmental fungi play in airway diseases such as asthma and sinusitis and chronic degenerative brain diseases such as Alzheimer’s Disease. Additional research interests include microRNAs that control immune function and mechanisms of organic smoke-induced lung injury.

Abstract
Chronic degenerative brain diseases (CDBD) such as Alzheimer’s Disease (AD) are the most common causes of dementia and the leading causes of death in the US elderly.  Despite their medical and societal importance, virtually nothing is known about the underlying causes of any of these devastating disorders. Our studies over the past several years increasingly suggest that the common human fungal pathogen, Candida albicans, may play a central role in the neurodegeneration that is central to the pathogenesis of all CDBDs.  We have shown that bloodborne C. albicans enters the mouse brain causing cerebral mycosis that involves the production of granuloma- and senile-plaque like lesions. Mechanistically, we have found that microglia-expressed CD11b (Mac-1) recognizes the secreted peptide toxin, candidalysin, and is critical for eliciting microglial antifungal activity. We have further shown that C. albicans secreted aspartic proteinases (Saps), especially Sap2, are alone sufficient to convert amyloid precursor protein into amyloid beta (Ab) peptides, the sine qua non biochemical feature of the AD brain.  Recently, we discovered that oral gavage of C. albicans in mice leads to long-term gut colonization and dissemination of the fungus to diverse organs including the brain, which in turn leads to altered behavior and memory loss. Notably in this context, C. albicans is recovered from the mouse brain growing coordinately with gut-derived Staphylococcus spp. This polymicrobial (fungal + bacterial) biofilm cerebritis is remarkably like the polymicrobial cerebritis that has previously been found in the human brain with CDBD using immunohistochemical and RNA-seq based approaches.  Our recent studies further demonstrate that the dominant organism cultured from the human brain is a C. albicans-based polymicrobial biofilm that also includes a diversity of gut-derived bacteria. This chronic, apparently life-long fungal-based infection induces in mice altered behavior, especially enhanced anxiety, memory loss, and in the retina loss of synapses, deposition of Ab peptides, tauopathy, and microglial and astrocyte activation, all of which are features of Alzheimer’s Disease.  We therefore hypothesize that C. albicans in the gut induces chronic, unresolvable polymicrobial cerebritis that over many years results in neuropathology, brain inflammation, and altered behavior that culminate in a variety of CDBDs.  Further testing of this hypothesis will clarify the pathophysiology of AD and related diseases and suggest future therapeutic approaches.

Biography

Iliyan Iliev is an Immunologist and an Associate Professor at the Department of Medicine and the Jill Roberts Institute for Research in IBD at Weill Cornell Medical College, Cornell University, New York.
Dr. Iliev’s pioneering research on the gut mycobiota defined the role of commensal fungi in innate mucosal and protective humoral immunity and provided the first evidence for mycobiota involvement in the pathophysiology of Inflammatory Bowel Disease (IBD). The laboratory develops and applies translational, experimental and computational approaches to study the role of immunity and mycobiota early and later in life, upon therapeutic interventions and during conditions, such as inflammatory bowel disease, allergy, gastrointestinal cancers and immunodeficiencies, where fungi contribute to pathologies. Current effort in the laboratory, focused on the gut-bran axis and cancer, explores the unique neuro-modulatory and cancer-immunity modulating properties of fungi.
Dr. Iliev is a Burroughs Wellcome Fund PATH Investigator, Irma T. Hirschl Scholar, Kenneth Rainin Foundation Innovator, CIFAR Fungal Kingdom: Threats and Opportunities Fellow and Cancer Research Institute Lloyd J. Old STAR Fellow.

Abstract

Barrier surfaces harbor a community of microorganisms that span microbial kingdoms, including bacteria and fungi. Interactions between the microbiota and the host are becoming recognized to play ever-expanding roles in physiology. Here we will discuss recent findings on the involvement of gut fungi in host immunity and gastrointestinal cancers. We will delve into the mechanisms through which fungi influence these processes, leading to the alteration of immune outcomes and disease states.

Biography Johan Maertens

Johan Maertens is currently associate professor of Haematology at the University Hospitals Leuven, Campus Gasthuisberg Leuven, Belgium. He is a member of numerous professional societies, including the International Immunocompromised Host Society, the International Society of Human and Animal Mycology, the Multinational Association of Supportive Care in Cancer, the American Society of Hematology, the European Haematology Association, and a member of European Group for Blood and Marrow Transplantation (EBMT). He is a past-chair of the Infectious Diseases group of the European Organization for Research and Treatment of Cancer (EORTC) and a founding member and the current chair of the European Conference on Infections in Leukaemia (ECIL) group. He is a fellow of the European Confederation of Medical Mycology (ECMM).

His major professional interest is fungal and viral infections in patients with haematological disorders, development of new management approaches to invasive aspergillosis, non-invasive diagnosis of opportunistic respiratory infections, and non-myeloablative and haplo-identical allogeneic stem cell transplantation. Dr Maertens has published over 450 articles and book chapters on antifungal management and diagnosis in several prestigious journals. He is a co-editor of the book “Diagnosis of Fungal Infections.” He served as a reviewer for many journals and is a member of numerous national and international advisory boards.

Biography Gordon Ramage
Gordon graduated from Edinburgh University with a B.Sc. (Hons) in Medical Microbiology in 1996. He then received a Ph.D. from the Queen’s University of Belfast in prosthetic joint infection in 1999. He subsequently undertook two postdoctoral research positions over a 4 year period (2000-2003), focusing on fungal and bacterial biofilm infections at the University of Texas Health Science Center at San Antonio (USA) and the University of Calgary (Canada). In 2004 he returned to the UK and was appointed as a Lecturer in Microbiology at Glasgow Caledonian University prior to taking up a position of Senior Lecturer in Microbiology at the University of Glasgow Dental School in 2007. Gordon has been the head of Biological and Medical Sciences and the lead for the Infection and Immunity Research Group since 2009. Gordon received his Personal Chair in 2012 and was promoted to Professor of Medical Microbiology. His a Fellow of Royal College of Pathoologists (FRCPath), and is currently the Chair of the European Society for Clinical Microbiology and Infectious Disease (ESCMID) Study Group for Biofilms (ESGB) and a Fellow of the European Confederation of Medical Mycology (FECMM). He is an honorary member of the British Society for Medical Mycology (BSMM) and acts as a consultant and key opinion leader for a number of commercial partners.

Biography Francoise Botterel
MD, PhD, Professor in Parasitology-Mycology,
Head of Mycology – Parasitology Unit, Hôpital Henri Mondor, Creteil.
President of the French Society of Medical Mycology
Vice-dean for Pedagogy in University Paris Est Creteil, France
Head of Research Unit 7380 DYNAMYC, UPEC – ENVA – ANSES: Dynamics of microbial interactions within the respiratory microbiota: consequences on colonization, infection,
therapeutics and resistance to anti-infectious drugs in humans and animals.
Research themes: mixed biofilm between Aspergillus fumigatus and Stenotrophomonas maltophilia and interactions with bronchial epithelial cells, fungal and bacterial respiratory microbiota, Cystic Fibrosis
Members of the ECMM/ISHAM Working groups on Fungal respiratory infections in Cystic Fibrosis (Fri-CF) and Scedosporium / Lomentospora infections (SLI),
Member of ESCMID Study Group for Biofilms (ESGB)
Member of ESCMID Study Group for host and microbiota interaction (ESGHAMI)

Modelling interkingdom biofilm interactions to develop new antimicrobial strategies
Biofilms associated with human disease are often polymicrobial, comprised of a complex consortia of bacteria, fungi, viruses and protozoa. These interkingdom biofilms are often overlooked, especially given the reductionist approach to drug discovery and bioprospecting. Our group have sought to remedy this by carefully constructing and developing polymicrobial interkingdom biofilms of bacteria and fungi, using microbiome studies as a blueprint, to create robust and reproducible biofilm models representative of the oral cavity, respiratory tract, wounds and recurrent vulvovaginal candidiasis. This presentation will demonstrate that Candida albicans is a keystone component of several biofilm diseases, and that understanding its role in polymicrobial biofilms is important for improving our clinical management of these diseases. We will outline several of our key studies that have led from the bench to chairside, and also supported the development of new broad spectrum antimicrobial agents, including the application of nanoparticles and chitosan as anti-biofilm agents.

Laurence Millon
Laurence Millon is a Professor of Parasitology and Medical Mycology at the Medicine School- Franche-Comte University, UMR Chrono-Environnement (UMR 6249 – CNRS), Besançon – France.
She has been Head of the Parasitology and Mycology Department, University Hospital of Besancon since 2008 and Head of the National Reference Center Echinococcosis (mandate 2012-2016, 2017-2022 and 2023-2028). She has coordinated of 9 national / international research projects in the last 10 years. Its main area of expertise are in the field of epidemiology, diagnosis, and prevention of fungal and parasitological diseases (with a core expertise in invasive fungal infections and Echinococcosis), and she is highly experienced in molecular and immunogical techniques.
She is the author of 180 articles in Peer Review journal including 70 in the last five years and 20 invited conferences in the last five years

Biography Alessio Mesini
After graduating in medicine I obtained my specialization in infectious diseases at the Genoa school directed by Professor Claudio Viscoli. During this time I became interested in fungal infections and pediatric infectious diseases.
Always under the guidance of Professor Viscoli, I obtained my PhD focusing my research activity mainly on Candida infections and bacterial and fungal infections in critically ill pediatric patients.
I currently work in the Infectious Diseases department at Istituto Giannina Gaslini, directed by Doctor Elio Castagnola where I’m the ID consultant of pediatric and neonatal Intensive Care Unit and I mainly deal with infections in critically ill and immunocompromised patients.

Biography Charalampos Antachopoulos

Dr Charalampos Antachopoulos studied Medicine at the University of Athens, Greece. He was trained in Pediatrics in the United Kingdom as well as in “Aghia Sophia” Children’s hospital, Athens, and became member of the Royal College of Paediatrics and Child Health (UK) in 2001. He then pursued a fellowship in Pediatric Infectious Diseases at the Children’s National Medical Center, Washington DC and the Immunocompromised Host Section of Pediatric Oncology Branch of the National Cancer Institute in Bethesda, Maryland, USA. His research projects at the National Cancer Institute focused on the optimization of assessment of metabolic activity of filamentous fungi (mainly the Mucormycetes and Aspergillus), for rapid susceptility testing of these moulds as well as for studying host immune responses against these organisms. He currently works as a Professor of Pediatrics – Infectious Diseases at the 3rd Department of Pediatrics, Aristotle University, Hippokration Hospital of Thessaloniki, Greece. His current scientific interests include fungal and nosocomial infections, pediatric and adolescent immunization, as well as the use of newer antimicrobial agents in Pediatrics. He has co-authored more than 90 papers and chapters in international journals and textbooks. He is a member of the Editorial Board of Medical Mycology Case Reports.

Abstract

Candidiasis of the central nervous system (CNS) is a serious and potentially devastating form of invasive candidiasis, most commonly affecting premature neonates as well as children with primary immunodeficiencies, such as CARD9 deficiency. Other predisposing factors include cancer, immunosuppressive treatment, human immunodeficiency virus (HIV) infection, prolonged parenteral nutrition or broad spectrum antimicrobial administration, neurosurgical procedures, abdominal surgery and the presence of medical devices such as central venous catheter.

Signs and symptoms of CNS candidiasis may be non-specific, including fever, irritability, lethargy, seizures, apnea and vomiting. Timely diagnosis requires a high degree of clinical suspicion together with appropriate cerebrospinal fluid (CSF) studies (culture, molecular / antigen detection methods). Candida albicans is the species most frequently implicated, but non-Candida species, such as Candida parapsilosis, Candida tropicalis etc. may also be isolated. The clinical course of CNS candidiasis is more severe in premature neonates. In this patient population Candida meningoencephalitis has considerable mortality and may be complicated by cerebral thromboses, abscesses, hydrocephalus, periventricular leucomalacia, calcifications, and long-term neurological sequelae, such as cerebral palsy, psychomotor retardation, blindness or deafness.

Antifungal agents that may be used for the treatment of CNS candidiasis include amphotericin B formulations, fluconazole, flucytosine and high-dose micafungin. A favorable outcome, however, may be difficult to be achieved in the presence of severe immune compromise, biofilm formation (as in patients with ventriculoperitoneal CSF shunt) or a Candida isolate resistant to the above mentioned agents. In these challenging cases a more comprehensive treatment approach should be discussed and implemented, including discontinuation of immunosuppressive agents or adjunctive immunotherapy, removal of infected shunts and even intraventricular administration of antifungal agents. Depending on the case, a close collaboration between the patient’s treating physicians, infectious disease / mycology, oncology, immunology and neurosurgery teams may be needed to optimize treatment and outcome of CNS candidiasis.

Biography Marisa Miceli
Dr. Marisa Miceli is a Professor in the Division of Infectious Diseases at the University of Michigan Medical School. She specializes in Medical Mycology and Transplant Infectious Diseases.
Dr. Miceli is active in both direct patient care and clinical research. Her scholarly work focuses on addressing unmet needs in the diagnosis of invasive fungal infections and in the treatment of patients with these diseases. Dr. Miceli is the Principal Investigator for several clinical trials for the study of novel antifungal agents. Dr. Miceli teaches and mentors Infectious Diseases Fellows and Internal Medicine Residents in the field of transplant Infectious diseases and medical mycology.
Dr Miceli has published more than 70 manuscripts in peer-reviewed journals, including Clinical Infectious Diseases, The Lancet Infectious Diseases, Infectious Disease Clinics of North America, Mycoses, and Transplant Infectious Diseases. She also has published 8 book chapters. She reviews for more than 15 journals and is an Editorial Board Member for Mycopathologia and Journal of Fungi. Dr. Miceli serves in the Board of Directors of the Mycoses Study Group Education and Research Consortium and in the Council of the International Immunocompromised Host Society. She is a Fellow of the American College of Physicians, the Infectious Diseases Society of America and the European Confederation of Medical Mycology.

Biography Diamantis Kofteridis
Dr Diamantis Kofteridis is an Internal Medicine and Infectious Diseases specialist, Professor of Internal Medicine & Infectious Diseases at the University of Crete, Greece, Head of the Department of Internal Medicine and Infectious Diseases unit, as well as Head of the Infection Control Committee and Antimicrobial Stewardship Team of the University Hospital of Heraklion. Dr Kofteridis is a researcher and has organized several research projects with the University of Crete. The result of his work is 174 original articles in peer-reviewed medical journals. His main medical interests include infections in immunocompromized hosts, in patients with diabetes mellitus, in health-care associated infections, antibiotic policies and studies on genetic factors predisposing to infections and their severity.

Antifungal Stewardship
Abstract Diamantis P Kofteridis

Invasive fungal infections (IFIs) are associated with high mortality, particularly in immunocompromised and critically ill patients. The prescribing of antifungal agents to treat and prevent IFIs is associated with high rates of adverse drug reactions, significant drug–drug interactions, emergence of antifungal resistance and substantial economic burden on the health system, as antifungals are among the costliest antimicrobial agents. Nearly 3% of all hospital admissions and 7.7% of intensive care unit admissions in the United States are associated with the prescription of systemic antifungals while, 30%–50% of antifungal prescriptions are inappropriate. Therefore, as the population at risk of IFIs continues to grow, there is a need for hospitals to implement antifungal stewardship programmes. Antifungal stewardship refers to coordinated interventions designed to  improve and measure the appropriate use of antifungals by promoting optimal antifungal drug regimen, dose, duration of therapy and route of administration. Published studies on the impact of antifungal stewardship interventions have shown improved antifungal utilization without adversely affecting patient outcomes.

Biography
Nelesh Govender, FECMM is a medical mycologist and epidemiologist based in South Africa. His work spans public health surveillance, clinical trials and reference laboratory diagnostics.

Abstract

Candida auris was detected as a healthcare-associated pathogen in South Africa in 2014. However, a retrospective review of a culture collection from national surveillance for candidaemia in 2009-10 showed that earlier cases had been missed owing to species misidentification. A second cycle of national surveillance in 2016-2017 revealed that C. auris caused >10% of cases of candidaemia in South Africa, with most (86%) cases detected in the Gauteng Province. During 2019-21, the proportion attributable to C. auris increased even further to 25% (of 12,959 national cases of candidaemia), with a concomitant reduction in cases caused by C. parapsilosis. This may suggest a concerning replacement of multidrug-resistant C. auris in an ecological healthcare niche previously occupied by azole-resistant C. parapsilosis. An epidemiological shift was also observed with an expanding number of acute healthcare facilities reporting C. auris outside the Gauteng Province epicentre and large persistent healthcare-associated infection outbreaks in neonatal units, particularly in the under-resourced South African public health sector. The epidemiological situation in other African countries is not as well documented but a new fungal surveillance initiative spanning ten Southern African countries may help to clarify this. Wastewater surveillance, widely rolled out for SARS-CoV-2 testing, may also be a useful method to document the spread and endemicity of C. auris in resource-limited settings. Clade III appears to have originated in Africa and still dominates in South Africa, but in recent years, clade mixing (I, III and IV) has been increasingly documented in hospitals across Africa.

Biography
Dr. Ostrosky-Zeichner received his medical degree from Universidad Nacional Autonoma de Mexico, completed his internal medicine residency at Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, and his infectious diseases fellowship at the University of Texas Health Science Center at Houston/MD Anderson Cancer Center combined program. He is currently a Professor of Medicine and Epidemiology and the Memorial Hermann Endowed Chair at the University of Texas Health Science Center at Houston, where he is appointed as the vice chairman of Medicine for Healthcare Quality and the Division Chief at the Division of Infectious Diseases. He also serves as the Chief Epidemiology Officer for the Memorial Hermann Healthcare System. He has consulted for the FDA and the CDC. He has published over 200 peer-reviewed articles and actively pursues translational and clinical research in medical mycology, transplant infectious diseases, healthcare epidemiology, and antimicrobial stewardship.

Summary
Candida auris is the first Candida species to be considered a public health threat, due to its ability to spread within healthcare settings and its antifungal resistance. Most C. auris isolates are resistant to azoles and some can be resistant to echinocandins or azoles. Clinician can also encounter isolates that are multi-drug-resistant (two classes) or extreme-drug-resistant (three or more classes). This lecture will focus on the epidemiology of drug resistance in C. auris and new developments in treatment, including the emergence of novel antifungals.

Biography

Anuradha Chowdhary is Director Professor, Medical Mycology & In charge of National Reference Laboratory of Antimicrobial Resistance in Fungal Pathogens, Department of Microbiology at the Vallabhbhai Patel Chest Institute, University of Delhi, India. She received her medical degree in 1992 and MD (Microbiology) degree in 1996 from University of Delhi (Lady Hardinge Medical College), India and PhD, from Faculty of Medical Sciences, Radboud University Medical Center, Netherlands and had a post-doctoral fellowship from Mycotic Disease Branch, Centres for Disease Control (CDC), Atlanta, USA. Dr Chowdhary’s research interests include molecular ecology and population genetics of pathogenic fungi and antifungal drug resistance. She is currently working on Candida auris, drug resistant dermatophytosis and rare yeast infections. She is an elected fellow of numerous professional societies, including the American Academy of Microbiology, Canadian Institute for Advance Research, International Society of Antimicrobial Agents & Chemotherapy, the European Confederation of Medical Mycology, the Royal College of Pathologists, and the Infectious Diseases Society of America.

She has held editorial positions at several scientific journals including Editor in mBio, Chief Editor of Fungal pathogenesis specialty section in Frontiers in Cellular and Infection Microbiology, Editor in FEMS Pathogens and Disease, Editor PLOS Pathogen, Associate Editor of Mycoses, Fungal genetics & Biology, Review Editor of Medical Mycology, member editorial board of Journal of Clinical Microbiology, and the Journal of Hospital Infection. She has published >200 scientific papers in the peer reviewed journals.

Abstract

Candida auris is a nosocomial health risk, with widespread outbreaks occurring in hospitals worldwide. Since the first reported case of a C. auris infection in 2009 from Japan, these infections are now being reported from more than 40 countries, with mortality rates between 30-60%. Most importantly, C. auris is the first fungal pathogen showing pronounced drug resistance to all known antifungal classes, including azoles, amphotericin B (AmB) and echinocandins. In just over a decade since its discovery, C. auris has rapidly emerged as a significant nosocomial pathogen across the globe. Unlike other pathogenic Candida spp, C. auris is not a commensal yeast that colonises the mucosal surfaces and the gastrointestinal tract. However, C. auris displays an unique tropism for skin and shows persistent colonization of human skin and abiotic surfaces in healthcare environments facilitating the inter- and intrahospital clonal transmission causing outbreaks in healthcare facilitiesThe simultaneous emergence of genetically unrelated clades of this fungal pathogen in six continents and its recent isolation from the natural wetland environment hints towards an important factor of that environment probably play in the orginal emergence and development of antifungal resistance. Importantly, climate change and steady rise in global temperature are suggested as important factors in the emergence of C. auris. The climatological factors may have contributed to the evolution of C. auris into a thermotolerant organism that led to the expansion of C. auris into the human populatio. Outside the hospital settings, C. auris has been isolated from the surface of stored apples, tidal marshes, hypersaline environments and recently from wastewater suggesting that this yeast can survive in harsh conditions. Also, the recent observation of C. auris isolation from the skin of the ear canal of dogs unfolds a perspective that this yeast may have association with animals. A key factor in the recent emergence of antifungal resistance in C. auris populations, is increased use of azole antifungals in agriculture and clinical practice The mystery of its origin has just only started unlocking as evidence for several environmental niches of C. auris outside the hospital settings has emerged suggesting that transmission and emergence of C. auris is multifaceted warranting one health approach for its containment.

Biography
I am a medical microbiologist specializing in antimicrobials, fungal diagnostics and pathogenesis, molecular epidemiology, and genomics. I am a board-certified clinical laboratory director with experience directing laboratories at the New York State and the State of California Health Departments. I am the Chief Microbiology, Molecular Biology, Virology/ Professor of Pathology, Microbiology, and Immunology at Westchester Medical Center/ New York Medical College, Valhalla, NY. My laboratory was among the first to apply molecular epidemiology tools to study the occurrence, distribution, and impact of primary and opportunistic pathogens in the United States. We developed new tools to highlight the event of fungal diseases outside of known endemic areas. We have a long track record in antifungal test standardization, including several rapid and sensitive methods for susceptibility testing of antifungals alone and in combination. My team was among the first to validate CLIA-compliant genome methods for clinical laboratories and to use deep sequencing to understand infectious disease dynamics. I have actively promoted the adaptation of quality management systems for developing and validating new technologies by the clinical laboratories. Lastly, as the Editor-in-Chief of Mycopathologia, I strive to promote high-quality science on fungal diseases and pathogenic fungi.

Biography
Associate professor in medical mycology at Paris University and Hospital Saint-Louis in Paris, France. Researcher at Institut Pasteur. Interested about Aspergillus fumigatus, innate immunity, antifungal resistance and molecular diagnostic tests.

Humoral immunity against Aspergillus fumigatus
Sarah Dellière and Vishukumar Aimaniand

Humoral immunity against A. fumigatus has often been overshadowed by cellular immunity. A simple Pubmed database search since 2000 comparing [aspergillus AND humoral immunity] and [aspergillus AND cellular immunity] finds a mean number of publications per year of 2.5 and 13.1 respectively. Furthermore, most research involving humoral immune response and A. fumigatus has been done using humoral immune components from the serum to study such interaction. However, A. fumigatus is an inhaled pathogen and interacts first with alveolar fluid immune component. Our group recently showed that when conidia are opsonized with bronchoalveolar lavage fluid or serum followed by shotgun proteomic analysis of the conidial bound proteins, proteins identified vary greatly. Unsurprisingly surfactant proteins are only present in BAL opsonized conidial extract, whereas complement proteins C2, MBL, factor I, MASP-1 and MASP-2 were only found in serum opsonized conidial extract. Furthermore, these differentially opsonized conidia elicited distinct cytokine responses from hMDM This was the first study to shed light on lung-specific innate response against A. fumigatus. Consequently, many unknows remain and the existing data may need to be rediscussed. Therefore, the aims of this work and presentation are to discuss how we identified major players of humoral immunity against A. fumigatus in bronchoalveolar lavage fluid of patients infected by A. fumigatus and to understand how we studied the interaction of these major players with A. fumigatus at molecular level and their impact on the immune response in vitro. Short and long-term perspectives are to identify candidate host markers of aspergillosis, new evidence to understand host-pathogen interaction and eventually new leads to develop alternative therapeutic strategy.

Biography
Lore Vanderbeke is working as an Infectious diseases resident at the University Hospitals of Leuven. She obtained her PhD in Medical Mycology in 2022, on the topic of viral-associated pulmonary aspergillosis in the ICU.

Pathogenesis and pathology of respiratory viral and fungal coinfections
Lore Vanderbeke MD PhD

Invasive pulmonary aspergillosis (IPA) is increasingly recognized in patients admitted to intensive care departments with severe viral infections, supporting the establishment of severe influenza and COVID-19 as important risk factors for IPA development. However debate on the clinical relevance of the diagnosis is often supported by limited evidence of gold-standard pathology-proof of disease.

With our histological investigation of viral-associated pulmonary aspergillosis (VAPA) based on autopsy review, we identified tissue-based proof of invasive fungal disease frequently and with similar histological pattern amongst critically ill influenza and COVID-19 cases. The archetypical manifestation of aspergillosis upon autopsy was one of impeded fungal growth within alveoli and bronchi(oli), a finding explanatory for the bronchoalveolar galactomannan sensitivity. This fungal presence was reminiscent of the autopsy findings in graft-versus-host disease patients or animals immunosuppressed with corticosteroids, where pulmonary inflammatory damage is more excessive than fungal load. Overall, our findings highlight the invasive nature of IPA in both viral contexts.

The susceptibility of critically ill viral pneumonia patients to invasive aspergillosis is currently understudied, yet several pathophysiological explanations have been proposed. Viral-induced necrosis of respiratory epithelium may provide a port-of-entry for Aspergillus to become invasive. Besides barrier disruption, influenza and COVID-19 both cause a specific viral-induced host inflammatory response, with a disbalanced hyperinflammatory myeloid immune response and lymphopenia as common features. This likely affects antifungal host responses, as has been shown already in a recent transcriptomic study of broncho-alveolar lavage samples of viral and viral-fungal co-infected patients.  Additionally, immunomodulatory treatments and possibly genetic variation in host immune susceptibility to IPA could be linked to VAPA; all of which require further study.

The importance of a balanced immune response is evident, both in viral pneumonia as in aspergillosis setting. The host immune reactions truly act as a ‘double-edged’ sword, with suppressed immune reactions leading to pathogen invasion and/or persistence while immune hyperactivation contributes to tissue damage and worsening disease. Our autopsy data reinforce this bipolar inflammatory function, with different Aspergillus growth patterns associated with different immune status. Importantly, hyperinflammation and immune paralysis can co-exist, and it is key to identify biomarkers that allow timely, appropriate interventions aimed at rebalancing the dysregulated immune responses. Indeed, the lack of data showing benefit of antifungal treatment on VAPA patient outcome likely indicates a need for additional host-directed therapeutic modifications. Unraveling the intricate interplay of the different host immune players and influences of microbiome, genetics and metabolomics as well as viral and fungal factors, will eventually lead to guidance of host-directed immunomodulatory therapies and individualized antifungal prophylaxis.

Biography

Laurence Delhaes (MD, PhD)
For several years, I have been working on Aspergillus and Scedosporium models, as well as on clinical trials focused on fungal risks in chronic pulmonary diseases such as asthma and cystic fibrosis (CF). Our major objective was to establish reliable prevalence of fungal colonization or infection, and clinical relevance of moulds isolated from respiratory tract of patients with chronic respiratory diseases. To be able to compare data from one centre or country to another, We (I and my research group) developed a consensual standardized protocol for current mycological analysis, through both a national and an internatial studies I coordinated.
More recently we acquired expertise on mycobiome analysis and high-throughput genomics, and joined in 2016 Inserm U-1045 (P Berger’s Team) to develop molecular and cellular analysis of mycobiome impact on cell remodelling in chronic pulmonary diseases. Currently, we are etting up the deployment of clinical trials combined with the mycobiome-microbiome analysis of lung samples of asthmatic or CF patients, and with in-vitro experiments based on an ALI or bronchial epithelial, plus microbial coinfections of in-vitro cultures of cells.
Professor (PU-PH) Head of Parasitology-Mycology Department at Hospital of Bordeaux University; In charge of the research axis: “Lung inflammatory chronic diseases and mycobiome” (U1045); Head of the CNR (National Reference Centre) of chronic aspergillosis; Co-cordinator of the PGTB (Genome transcriptome platform of Bordeaux)

Abstract

Until recently (2010), the lower pulmonary tract was considered sterile, however the advance of high-throughput sequencing techniques has revealed a bacterial, viral and/or fungal polymicrobial flora composing the lung microbiome, even in healthy subjects. Lung microbiota is now recognized as important component of the respiratory tract. Although data is still limited, particularly concerning the respiratory mycobiome and the virome, links have already been demonstrated between this microbiota and numerous chronic respiratory diseases (asthma, COPD or CF).

On the whole, the respiratory microbiome is thought to play a key role in both the genesis and evolution of these chronic respiratory diseases, and is undeniably a new area of research that several teams are currently exploring. Even if questions remain open, studies carried out show the role of this microbiome (especially regarding the mycobiome) in the evolution of the chronic respiratory diseases, its interactions with the host response and also with the external environment, in particular with the microbial exposome.

After outlining the methodological advances brought about by high-throughput sequencing, we will discuss these new concepts of microbiome and mycobiome, and data of respiratory microbiome, in particular by addressing the notions of dysbiosis, inter-kingdom networks (or interactome) and their modeling in the context of chronic respiratory diseases.

Biography
Research Associate at the University of Manchester. Currently based at the NIHR Centre for Precision Approaches to Combating Antimicrobial Resistance (C-PACA) at Manchester University NHS Foundation Trust. Gained a PhD in molecular microbiology studying Campylobacter N-glycosylation systems. Previous postdoctoral experience includes mycobiome and amplicon sequencing-based diagnostics for fungal infection. Current research interests include mycobiome, microbiome and NGS diagnostics for infection and antimicrobial resistance.

Summary
Covid-associated pulmonary aspergillosis (CAPA) is a life-threatening complication in patients with severe COVID-19. Previously, acute respiratory distress syndrome in patients with COVID-19 has been associated with lung fungal dysbiosis, evidenced by reduced microbial diversity and Candida colonisation. Increased fungal burden in the lungs of critically ill COVID-19 patients is linked to prolonged mechanical ventilation and increased mortality. However, specific mycobiome signatures associated with severe COVID-19 in the context of survival and antifungal drug prophylaxis have not yet been determined and such knowledge could have an important impact on treatment. This study aimed to understand the composition of the respiratory mycobiome in critically ill COVID-19 patients with and without CAPA, the impact of antifungal use and its role in patient outcome. We performed a multi-national study of 39 COVID-19 patients in intensive care units (ICU) with and without CAPA. Respiratory mycobiome was profiled using ITS1 sequencing and Aspergillus fumigatus burden was further validated using qPCR. Fungal communities were investigated using alpha diversity, beta diversity, taxa prevalence and taxa abundances. Respiratory mycobiomes were dominated by Candida and Aspergillus. There was no significant association with corticosteroid use or CAPA diagnosis and respiratory fungal communities. Increased A. fumigatus burden was associated with mortality. The use of antifungals at ICU admission was associated with an absence of A. fumigatus. Our findings suggest that systemic antifungal treatment at ICU admission may be protective against A. fumigatus-associated mortality in CAPA.

Biography

I am currently an Associate Professor (MCU-PH) in Parasitology-Mycology at Université Paris-Est Créteil and a hospital practitioner at Hôpital Henri Mondor, Assistance Publique des Hôpitaux de Paris. I specialize in microbiology, mycology, parasitology, epidemiology, and metagenomics. I completed my PhD on the emergence and dissemination of resistant microorganisms (bacteria and fungi) within the commensal flora in an Amerindian population of French Guiana. In my current research team (Dynamyc team), I am focusing primarily on studying the interactions between bacteria and fungi in the respiratory microbiota of patients (both human and animal) with chronic respiratory diseases. I am also working on the use of tools such as shotgun metagenomics for the diagnosis of fungal and parasitic infections in humans.

abstract

Cystic fibrosis (CF) is a genetic disorder characterized by chronic microbial colonization and inflammation of the respiratory tract, leading to pulmonary exacerbations (PEx) and progressive lung damage. While the bacterial component of the lung microbiota has been extensively studied in CF, the mycobiome remains understudied. However, its importance as a contributor to CF pathophysiology has been increasingly highlighted over past years. In this presentation, we aim to provide an overview of the current state of knowledge concerning the mycobiome and the interplay between bacterial and fungal microorganisms in CF patients.

Different studies have shown that the mycobiome in CF lungs is a dynamic entity, with a lower diversity and abundance compared to the bacterial microbiome. It is now well recognized that the progression of the lung damage is associated with a decrease in diversity of the fungal taxa in parallel with the bacterial taxa. Some fungi, such as Aspergillus or Scedosporium/Pseudallescheria have a proven involvement in PEx, while the role of others, such as Candida or Malassezia, remains unclear. Recent studies focusing on intra and inter-kingdom correlations between fungal and bacterial taxa have shown various co-occurrence or co-exclusion patterns. The biologic and pathophysiologic relevance of these interactions still needs to be further studied, as they might significantly influence the disease progression. Also, the mycobiome-host interaction in CF is complex, involving immune responses and the formation of biofilms. It is increasingly recognized that fungal presence could modulate the immune system, contributing to the chronic inflammation characteristic of CF. Furthermore, the ability of some fungi to form biofilms with bacterial pathogens reinforces the hypothesis of inter-kingdom interplay that may impact antimicrobial resistance and therapeutic strategies. Finally, with the recent advent of CFTR modulator therapies, our understanding of the pulmonary microbiome and mycobiome in CF patients is about to be turned upside down and new studies on the subject are expected.

Biography

I am a Associate Professor of Infectious Diseases (MED/17) in the Department of Molecular Medicine at the University of of Padua. I earned my Doctor of Pharmacy (Pharm.D.) degree from the University of Kansas, followed by post-graduate clinical residency training at Barnes-Jewish Hospital in St. Louis, Missouri. I then completed an infectious diseases research fellowship at the University of Iowa in Iowa City, Iowa with a focus on antifungal pharmacology.
I have over 20 years experience in laboratory and clinical research of antimicrobial pharmacokinetics and pharmacodynamics in immunocompromised hosts. My current research focuses on the development of prognostic risk models and decision support tools for the diagnosis and treatment of fungal infections and multi-drug resistant bacteria. I also serve as a Senior PK/PD Editor for the Journal of Antimicrobial Chemotherapy- the official journal of the British Society for Antimicrobial Chemotherapy.

Abstract

Therapeutic drug monitoring (TDM) is recommended for most triazole antifungals of highly variable pharmacokinetics and frequent drug interactions. However, TDM is still not commonly performed in many institutions, and a recent multicentre trial failed to show a clinical benefit of voriconazole TDM. Similar to recent TDM studies for antibacterials and immunosuppressants, the idea of a “therapeutic range” for triazole antifungals may limit the interpretation of measured drug concentrations and diminish the anticipated clinical benefit of dosage individualisation to patients by using oversimplified pharmacodynamic models. Alternative approaches to serum concentration-controlled dosing, such as target concentration intervention (TCI) incorporate a single drug concentration target instead of a therapeutic range, PK/PD models to estimate individual patient parameters, and model-informed dosage recommendations to improve individualise dosing. TCI approaches and other alternative strategies for antifungal therapy individualization are discussed.

Biography
Roger is associate professor in clinical pharmacology of anti-infectives and board member of the Radboudumc CWZ Center of Expertise in Mycology. He is responsible for the translational pharmacological research on antifungal drugs. His work involves three domains ranging from in vitro and animal research to trials in humans with strong national and international collaborations. Roger’s research involves the pharmacological research in special patient populations (paediatrics, ICU, obese, patients with Viral Associated Fungal Infections) and PK-PD behaviour of (novel) antifungal drugs and factors that impact this.

Biography
A United States Military Academy (USMA – West Point) graduate and Officer in the United States Army Medical Service Corps. I am currently serving as a Microbiologist at the Walter Reed Army Institute of Research (WRAIR) in Silver Spring, Maryland, USA. My educational and research experiences are
centered on molecular epidemiology of infectious diseases, public health, and global and cultural humanities. I have diverse research backgrounds to include transmission dynamics of malaria infections and NHP malaria models, bacterial antimicrobial resistance global surveillance, and bacterial and fungal infections of traumatic wounds. Previous military assignments include leading combat medics in medical evacuation and treatment, overseeing patient affairs and accountability (deployed and local), and managing hospital administration programs at Brooke Army Medical Center. I am nearing completion of a Master Certificate in Medical Education from the Uniformed Services University of Health Sciences (USUHS). I have previously completed graduate level courses in Global Health from the Humanitarian and Conflict Response Institute at The University of Manchester, Manchester, UK as well as course completion of the Military Tropical Medicine Course at USUHS. With a focus on global infectious
diseases, my knowledge and skills can be applied in military relevant research solving problems for Soldiers forward deployed in global and austere environments.

Fungal Infections of Combat Wounds: Burden, Epidemiology, and Mycology
Ashleigh N. Roberds¹, Alexander G. Bobrov¹, Thomas J. Walsh^2,3

¹ Wound Infections Department, Bacterial Diseases Branch, Center for Infectious Diseases Research, Walter Reed Army Institute of Research, Silver Spring, MD, USA
² Center for Innovative Therapeutics and Diagnostics, Richmond, VA, USA
³ Departments of Medicine and Microbiology & Immunology, University of Maryland School of Medicine, Baltimore, MD, USA

 Presentation/Lecture Abstract

Over the last two decades, invasive fungal wound infections (IFWIs) have reemerged as an important cause of mortality and increased morbidity in military personnel. Historically, mycotic infections acquired in combat operations were reported throughout the Vietnam War and were associated with a high prevalence of burn wounds. While modern combat-related IFIs are initially associated with severe traumatic events, including extremity amputation and extensive blood loss, persistent primary infection or secondary fungal invasion of exposed soft-tissue further complicates wound management and can lead to deep tissue necrosis, long hospitalizations, extensive surgeries, and more severe amputation. Studies of combat-related IFWIs among U.S. military personnel in Operation Enduring Freedom (Afghanistan) showed incidence rates of approximately 7% followed by mortality rates as high as 8%. Similarly, IFWIs were also present in UK service personnel returning from Afghanistan and are currently emerging with the Ukraine conflict. Mucorales species (spp.) are often incriminated in combat-related necrotizing wound infections and have a high incidence of angioinvasion. Mucorales spp. are opportunistic pathogens that thrive in patients with immune system imbalances, an unfortunate phenomenon seen in patients following a traumatic injury. Additionally, these species are found in fertile and temperate soils, explaining the previously described association between combat IFWIs and heavy environmental wound contamination. The risk of current and future IFWIs may be further complicated by the inadequacy of current antifungal agents, a paucity of new compounds, and emerging global antifungal drug resistance. During this presentation, we will synthesize the global burden and epidemiology of combat-related fungal infections, and also the basic mycology of incriminated fungi that cause IFWIs and are a significant threat for wounded service member.

Biography
Dr Riina Richardson is an academic clinician with the University of Manchester and Manchester University NHS Foundation Trust. She is the Head of Service and a Consultant for the NHS Mycology Reference Centre Manchester and a member of the Infectious Diseases team, and a PI at the University of Manchester. She has a special interest in antifungal stewardship as well as acute invasive and chronic mucosal candidosis. She has expertise in the management of a spectrum of other mycoses including fungal sinusitis and skin infections in compromised patients. To date she has published a total of over 170 peer-reviewed articles and books or book chapters and has an h-index of 45.

Biography
Thomas J. Walsh, MD, PhD (hon), FIDSA, FAAM, FECMM, serves as Founding Director of the Center for Innovative Therapeutics and Diagnostics, the Henry Schueler Foundation Scholar in Mucormycosis, Adjunct Professor of Pathology of Johns Hopkins University School of Medicine, and Adjunct Professor of Medicine, Microbiology and Immunology of the University of Maryland School of Medicine, as well as Visiting Professor in Infectious Diseases and Medical Mycology, Aristotle University School of Medicine, and Visiting Professor, National and Kapodistrian University of Athens School of Medicine. Following graduation from Johns Hopkins University School of Medicine, and completing 10 years of post-doctoral training, leading to board certification in Medicine, Infectious Diseases, and Oncology, Dr. Walsh became the Chief of the Immunocompromised Host Section in the Pediatric Oncology Branch at the National Cancer Institute, where he founded a translational and clinical research program dedicated to the pharmacotherapeutics, immunopharmacology, and molecular detection of invasive fungal diseases in immunocompromised pediatric and adult patients. He was then recruited to serve as Professor of Medicine, Pediatrics, Microbiology & Immunology and the Founding Director of the first Weill Cornell/New York Presbyterian Hospital Transplantation-Oncology Infectious Diseases Program. As the author of more than 1,100 publications and investigator for more than 100 clinical studies, he and his colleagues have laid translational research foundations for major advances in diagnosis, host defenses, treatment, and prevention of invasive mycoses in immunocompromised pediatric and adult patients. Dr. Walsh has mentored more than 200 physicians, and scientists, and taught Medical Mycology, Pharmacology, and Immunology to more than medical 8,000 medical students. Finally, he has devoted his life to caring for pediatric and adult patients with severe life-threatening fungal diseases worldwide (www.missionfromtheheart.org).

Pathogenesis, Preclinical Models, and Treatment of Combat Wound Mucormycosis
Alexander G. Bobrov, Rex Jeya Rajkumar Samdavid Thanapaul¹, Yonas Alamneh¹,  Venkatasivasai S. Sajja², Ashleigh N. Roberds¹, Thomas J. Walsh^3,4
¹Wound Infections Department, Walter Reed Army Institute of Research, 503 Robert Grant Avenue. Silver Spring, MD, USA
²Blast-Induced Neurotrauma Branch, Center for Military Psychiatry and Neuroscience, Walter Reed Army Institute of Research, Silver Spring, MD, USA
³Center for Innovative Therapeutics and Diagnostics, Richmond, VA, USA
⁴Departments of Medicine and Microbiology & Immunology, University of Maryland School of Medicine, Baltimore, MD, USA

Abstract
      During Operation Enduring Freedom in Afghanistan, invasive fungal infections (IFIs) were found to cause unacceptably high morbidity and mortality of wounded military personnel with blast polytrauma. Wounded soldiers with IFIs require extensive hospitalization, multiple surgeries, and often limb amputation. Mucormycosis, a prevalent military IFI, is an especially debilitating disease because it causes massive tissue necrosis, intractable non-healing wounds, and death.

There are two main lines of defense against wound mucormycosis, skin and connective tissue barriers and phagocytic immune response mostly via neutrophils. Use of conventional bombs and improvised explosive devices will continue to be one of the main mechanisms of combat injury. These injuries are characterized by extensive tissue loss, embedding of foreign material deep in the tissue, extensive blood loss and blast overpressure (BOP) exposure that adds another traumatic insult. This polytrauma also is known to cause immune dysregulation. Our group has contributed to this understanding by recently demonstrating that blast and trauma induce immunosuppression which predispose a service member to opportunistic IFIs.

To date, the majority of animal studies of mucormycosis have focused on disseminated or pulmonary models. Only a few studies have reported animal models of cutaneous mucormycosis. Immunosuppressive treatments were required for development of local infections produced by a very high inoculum of sporangiospores. We reasoned that hyphal involvement in the development of blast wound infections is underappreciated. We therefore recently developed a Galleria mellonella model of mucormycosis of Mucorales strains, in which we investigated the comparative virulence of sporangiospores and hyphae. We then utilized a unique combat-relevant blast and wound polytrauma animal model of mucormycosis that closely simulates blast injuries to soldiers on the battlefield.

Current antifungal agents used as standard of care are often ineffective in the management of combat wound associated mucormycosis. Additionally, they may have substantial toxic effects. We are therefore investigating innovative strategies in relevant animal models of combat wound-associated mucormycosis that may ultimately deliver new therapeutics to reduce mortality and morbidity of wound IFIs in injured warfighters.

Biography
Dr. Rosanne Sprute is a research associate and resident physician at the Department for Haematology, Oncology, and Infectious Diseases of the University Hospital Cologne, Germany. Her research interest focuses on opportunistic infections including invasive fungal disease in the setting of haematological malignancies and other severe immunocompromise. She is investigator in clinical trials evaluating novel drugs for infectious diseases. She is significantly involved in guideline development at national and international level and member of several scientific societies and working groups, including the ECMM, ISHAM, EHA-SWG Infections in Haematology and German Society of Haematology and Oncology Infectious Diseases Working Group.

Summary
The use of currently available antifungal drugs is limited by constraints in administration routes and tissue penetration, drug-drug interactions and toxicity. In addition, there are still too few antifungal classes in view of emerging resistances. Despite these unmet needs in the treatment and prophylaxis of invasive fungal infections the development of new antifungal drugs has been slow over the past decades. However, during the last years several repurposed drugs and drugs with new mechanisms of action have been and are investigated for use in prophylaxis and treatment. This includes both drugs in early preclinical stage and late clinical stage of development, such as fosmanogepix, MAT2203, NP339, olorofim, and opelconazole. Two new drugs, rezafungin and ibrexafungerp, have recently been FDA approved and will have their purpose mainly in the prophylaxis and treatment of Candida infections. Ibrexafungerp is representing the first approved member of a new antifungal class in two decades. These new players will change the landscape of antifungal treatment in the near future.

Biography
Egger Matthias M.D. is an intern at the Division of Infectious Diseases in Graz, Austria. He received his tertiary education at the Medical University of Graz and currently works on his doctoral thesis focusing on the lung mycobiome and fungal translocation in patients with liver cirrhosis.
He is part of the Translational Medical Mycology Research Unit, ECMM Excellence Center for Medical Mycology, Medical University of Graz, Austria with its PI Prof. Hoenigl.
His primary research interests include diagnostics of invasive fungal infections, novel antifungal agents and composition of the gut and lung mycobiome in health and disease. He is a member of the ECMM, ISHAM, ESCMID and especially of its young associations.

Biography

Ilan Schwartz (MD PhD FECMM) is an Infectious Diseases physician-researcher and Associate Professor of Medicine at Duke University. His clinical focus is in preventing and managing infections in immunocompromised hosts and his research involves emerging and endemic fungal infections. He is a co-author of multiple treatment guidelines for ECMM and IDSA. He serves on the board of directors of the Mycoses Study Group Education & Research Consortium and is an editor for Mycoses and Clinical Infectious Diseases.

Abstract

Across the field of infectious diseases, there is a movement towards shorter courses of antimicrobials for the treatment of infections. The “Shorter is Better” movement aims to minimize antimicrobial overuse by trimming antimicrobial courses to the shortest effective treatment duration. This talk will examine the rationale behind currently recommended treatment lengths for invasive candidiasis and aspergillosis and will identify clinical scenarios best suited for clinical trials to establish the shortest effective treatment duration for these serious mycoses.

Biography
Oliver Cornely is Director & Chair of Translational Research at the CECAD Institute of the University of Cologne, and Scientific Director of the Center for Clinical Trials. Clinically, he serves as Infectious Diseases Consultant at the University Hospital of
Cologne, Germany. He is board certified in internal medicine, infectious diseases, haematology, oncology, and emergency medicine, and holds degrees in medical mycology and travel medicine. Originating from an HIV/AIDS clinical research group, Dr Cornely’s research interest
centres on infections in immunocompromised hosts, including invasive fungal diseases, antimicrobial resistance, Clostridium difficile infection, and vaccine preventable infections. Oliver Cornely is immediate-past President of the European Confederation of Medical Mycology (ECMM), the roof organization of 28 national mycology societies, and did set up the ECMM Global Guideline Program, ECMM Academy (Fellows program), and ECMM Excellence Center Initiative, designating clinical and microbiological excellence centres after an international audit procedure. He is founder and chair of the Infectious Diseases Scientific Working Group of the European Hematology Association (EHA). Oliver Cornely is a member of the Council of the International Society for Human and Animal Mycology (ISHAM) and serves as Chair of the Infectious Diseases Working Party (AGIHO), a working group of the German Society for Haematology and Oncology (DGHO). He was recently elected as site spokesman for Bonn/Cologne for the German Center for Infection Research (DZIF). Oliver Cornely coordinates guidelines on invasive fungal infections and currently collaborates with mycologists from in 87 countries on tailoring management guidelines to health care settings throughout the world. He intends to intensify global networking, which he regards as paramount to improve management and care of these mostly rare
diseases. In September 2022, he was awarded the Johann-Lucas-Schönlein Medal by the German-speaking Mycological Society (Deutschsprachige Mykologische Gesellschaft e.V.). In January 2021, he founded the VACCELERATE platform, which currently includes 23
countries and 29 partner institutions for the European Commission to accelerate vaccine development against COVID-19 and future pandemic pathogens. He published over 600 peer-reviewed articles, books, book chapters, and electronic media; runs the YouTube® channel ID in Motion™, and ranks among the Top 1% most cited researchers. He is a reviewer for numerous medical scientific journals, editorial board member for Haematologica and Infectious Disease, and Editor-in-Chief of Mycoses.

Biography
Dr. Patterson’s clinical and research interests focus on the diagnosis and treatment of fungal diseases. He has been involved in developing new antifungal drugs and in clinical trials of new antifungal compounds and is funded by the NIH and industry for grants and contracts on drug and diagnostic development. He has conducted pre-clinical studies and clinical trials for invasive mycoses and received the UTHSA Presidential Distinguished Research Scholar award. He has been a co-chair or member of the IDSA Aspergillus Guideline committees. Dr. Patterson has published and lectured extensively with over 350 peer reviewed publications, chapters, books and reviews. He serves as an external consultant for the CDC for fungal meningitis outbreaks. He has served as member of the American Board of Internal Medicine, Subspecialty Committee for Infectious Diseases and is a Fellow of the American College of Physicians and the Infectious Diseases Society of America, Past-President of the Texas Infectious Disease Society, and past-President, International Immunocompromised Host Society.

Summary
A large health care-associated infection outbreak of fungal meningitis occurred in the United States during 2012-2013 following injection of contaminated methylprednisolone. Infections due to Exserohilum rostratum occurred in 753 patients with overall mortality occurring in 8%.  Long-term outcomes were poor with persistent or worsening pain in ~70% of those with spinal/paraspinal infection or meningitis/stroke.  Cure rates at 12 months were less than 50%.  Several important lessons were learned: careful and thorough CDC investigation identified risk factors associated with infection and allowed mitigation of the outbreak.  It was also apparent that even asymptomatic patients could be infected so that preemptive evaluation for at risk patients was key. Although the etiological agent was susceptible in vitro to triazoles, including voriconazole, high doses of therapy and combination with polyenes was frequently required. Cure rates were poor despite high doses of antifungals and prolonged therapy which frequently resulted in adverse events ranging from 70-80%.  Neurosurgical intervention was important in improving outcomes.  Long-term disability and persistent pain was common.

Biography
Dr. Ostrosky-Zeichner received his medical degree from Universidad Nacional Autonoma de Mexico, completed his internal medicine residency at Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, and his infectious diseases fellowship at the University of Texas Health Science Center at Houston/MD Anderson Cancer Center combined program. He is currently a Professor of Medicine and Epidemiology and the Memorial Hermann Endowed Chair at the University of Texas Health Science Center at Houston, where he is appointed as the vice chairman of Medicine for Healthcare Quality and the Division Chief at the Division of Infectious Diseases. He also serves as the Chief Epidemiology Officer for the Memorial Hermann Healthcare System. He has consulted for the FDA and the CDC. He has published over 200 peer-reviewed articles and actively pursues translational and clinical research in medical mycology, transplant infectious diseases, healthcare epidemiology, and antimicrobial stewardship.

Summary
Candida auris is the first Candida species to be considered a public health threat, due to its ability to spread within healthcare settings and its antifungal resistance. Most C. auris isolates are resistant to azoles and some can be resistant to echinocandins or azoles. Clinician can also encounter isolates that are multi-drug-resistant (two classes) or extreme-drug-resistant (three or more classes). This lecture will focus on the epidemiology of drug resistance in C. auris and new developments in treatment, including the emergence of novel antifungals.

Biography
Agostinho Carvalho is a Principal Investigator and the Vice-Director of the Life and Health Sciences Research Institute (ICVS), University of Minho, Braga, Portugal. His research group focuses on understanding the contribution of host genetics and immunity and their crosstalk to the development of fungal diseases. Dr Carvalho’s main areas of research are the regulatory effects of interindividual genetic variation on molecular and cellular processes of antifungal immunity in the lung, and the identification of novel prognostic, diagnostic and therapeutic targets for the development of personalized medical interventions. These aims are being addressed by a multidisciplinary team that combines basic scientists and clinical experts, and that resorts to advanced cellular and animal models of disease and human patients enrolled in national and international consortia.

Biography

I am a Microbiologist-Immunologist, specialized in fungal innate immune response and inter-microbial interactions. During my graduation in Prof. Jean-Paul Latgé Unit at Institut Pasteur (Paris), I worked on pulmonary microbiota interaction between the filamentous fungi Aspergillus fumigatus and the bacteria Pseudomonas aeruginosa. Then as a postdoctoral research associate in the Dr. Thirumala-Devi Kanneganti lab at St. Jude Children’s Research Hospital (Memphis), I studied molecular mechanisms that lead to activation of inflammatory response by the innate immune system in response to Aspergillus fumigatus infection. Today I am Principal Investigator in the Research Center for Respiratory Diseases (U1100, INSERM, Tours) to pursue my work on the innate immune response against fungal pathogens.

Abstract

Invasive fungal infections are recognized as a global public health issue. Collectively, they are responsible for over a million deaths a year. Aspergillus fumigatus is one of the fungal pathogens responsible for a multitude of infections and pathologies, from the allergy to the more dramatic form of pulmonary invasive aspergillosis.

The innate immune system has developed effective anti-infectious strategies. It recognizes danger signals and engages a cellular and physiological response to maintain homeostasis. The inflammasome is one of the main mechanisms of the innate immune system, with crucial roles in fighting infection. There are several types of inflammasome; these are multimeric protein platforms that lead to inflammatory activation of caspase-1, which in turn results in proteolytic maturation of the pro-inflammatory cytokines IL-1β and IL-18. At the same time, activated caspase-1 also induces cleavage and activation of the gasdermin-D protein, which forms pores in the plasma membrane leading to lytic cell death called pyroptosis and facilitates extracellular release of IL-1β and IL-18.

Infection with A. fumigatus leads to activation of the inflammasome, which is required for host resistance to infection. We investigated the molecular mechanisms by which the host controls inflammasome activation during A. fumigatus infection, and the fungal motifs (Pathogen-Associated Molecular Patterns, PAMPs) responsible for this activation. We describe the essential role of the inflammasome in response to fungal infection.

However, today, A. fumigatus infections are described as secondary superinfections in patients with respiratory comorbidities, often resulting from chronic bacterial infections (as seen in patients with cystic fibrosis) or viral pneumonias (caused by influenza or COVID-19 infections). Currently, we are investigating the regulatory mechanisms and functions of the inflammasome, along with the associated mechanisms during fungal superinfections. Furthermore, we are exploring the potential benefits and harms of this heightened inflammatory response.

Biography

Georgios Chamilos is Professor and Head of the Clinical Microbiology Department at the Medical School of the University of Crete and an affiliated scientist with the Institute of Molecular Biology and Biotechnology (IMBB), Heraklion, Crete. He received his M.D. from the University of Athens (1996), completed his residency in Internal Medicine in Athens (2004), obtained a clinical fellowship in Infectious Diseases at UT, Houston (2006 to 2008), and carried out research in fungal pathogenesis (2004 to 2006, the MDACC, Houston, TX) and a postdoctoral research fellowship on dendritic cell immunity (2007 to 2009, Immunology Department, UT, Houston, TX). Since 2009, he is a group leader at University of Crete, Greece, and the IMBB Institute. His research interests include understanding (i) host effector mechanisms regulating inhibition of growth and killing of airborne filamentous fungi, including Aspergillus fumigatus and the Mucorales, inside the phagosome of myeloid phagocytes, (ii) pathogenetic mechanisms employed by fungal cell wall molecules to target phagosome biogenesis pathways, and (iii) molecular mechanisms of immunoparalysis of phagocytes induced by sepsis and other immunosuppressive conditions associated with development of invasive mold infections.

Abstract

Aspergillus fumigatus is a major respiratory fungal pathogen in humans. Inhaled conidia of Aspergillus are efficiently eliminated by tissue resident macrophages and circulating phagocytes on a daily basis without causing inflammation or disease. Incompletely understood immunοmetabolic defects in phagocytes in an expanding group of patients with acquired immunodeficiencies results in intracellular germination of Aspergillus conidia and development of invasive fungal disease. The mortality rates of invasive pulmonary aspergillosis approach 50% despite antifungal therapy. Therefore, it is essential to understand the physiological mechanisms of intracellular elimination of fungal conidia following phagocytosis in order to design novel therapeutic strategies. LC3-associated phagocytosis (LAP) is a specialized, non-canonical autophagy pathway, regulating killing of conidia and anti-inflammatory immune responses against Aspergillus. In my lecture I will present recent advances on understanding LAP-dependent and -independent mechanisms of host defense against Aspergillus with physiological relevance in disease pathogenesis. I will also highlight unresolved questions and important future directions in phagocyte immunity against Aspergillus.

Biography
Applied Chemist-Biotechnologist, specialised in clinical mycology and environmental research. Positioned at the Department of Environmental Health, at the Portuguese National Institute of Health Doutor Ricardo Jorge, leading sand contaminants research and the Quality Assessment Programme on sand quality. Integrated researcher at the Center for Environmental and Marine Studies (CESAM). National EMEG technical expert member for the European Bathing Water and Drinking Water Directives

Summary
The emergence of Candida auris has raised the interest of the international community of Fungi, especially in the contexts of environmental and occupational health, water management and research. In their 2021 guidelines for recreation water quality management, the World Health Organisation (WHO) discusses several fungal taxa as “of interest” in recreational water quality management. In an effort to maximize human health protection, these guidelines also include a recommendation to monitor beach sand for bacterial indicators of faecal pollution and all Fungi (indiscriminately as they represent the level of contamination, which reflects the chance of exposure of beach users to these microorganisms).

In 2022, a watch list of Fungi of interest was also published by the WHO, cementing the recommendation to monitor Fungi in national and supranational regulation. Europe recently concluded a revision of its Drinking Water Directive, with a state of play document recommending fungi to be monitored in public buildings used by immunocompromised patients, including hospitals and nursing homes.

Armed with these guidelines and directives, the world is now ready to integrate fungi in water quality regulation (drinking and bathing/recreational). However, the costs and specificity of the methodologies associated with these parameters presents a challenge for implementation. Water microbiology regulation is focused nearly exclusively on faecal indicator bacteria (depending on the area of the globe where it is enforced) and  integration of Fungi would require further training and funding. Despite governmental work on directives and guidance, non-governmental organisations are taking the lead on implementation. The blue flag programme, that awards beaches of high quality in terms of biosafety, comfort and environmental education activities, integrated sand quality in its list of criteria necessary to comply in order to earn the award, and the European Bathing Water Directive is now under review with sand part of the discussion.

Over time, fungal parameters will be integrated into regulation but there is one more limiting factor to address. A causal relationship between exposure and pathogenesis, expressed with intrinsic infection/ailment doses per taxa, remains elusive. without such relationship, no Quantitative Microbial Risk Assessment (QMRA) can be calculated for either setting (recreational and drinking water or sand).

Biography
Prof. Arikan-Akdagli is the Director of the Department of Medical Microbiology and Head of the Mycology Laboratory of Hacettepe University Medical School, Ankara, Turkey. She received her MD and Clinical Microbiology and Infectious Diseases specialist degree from the same university and completed a research fellowship in Division of Infectious Diseases, Center for Emerging and Remerging Pathogens, Mycology Research Laboratory at University of Texas Medical School, Houston, Texas. She served as the Editor of Antimicrobial Agents and Chemotherapy (2010-2020) and Executive Committee member of European Fungal Infection Study Group (ESCMID-EFISG) (2012-2016-Treasurer, 2016-2020-Secretary). Her research and publications focus on novel antifungal drugs, antifungal susceptibility testing, antifungal resistance, and laboratory diagnosis of invasive fungal infections. Based on articles published since 2012, her expertise in antifungal agents ranks in the top 0.044% and she is recognized as an Expertscape World Expert in Antifungal Agents [expertscape.com – @Daily_Experts].

Biography
Dr Lottie Brown BSc, MSc, MBChB, is a junior doctor (ST1) and academic clinical fellow in infectious diseases at St George’s University Hospital, London, UK. She is an active member of the Fungal PCR Initiative Pneumocystis and Candida working groups. She became committed to a career in mycology early in her medical training at the University of Manchester, an international Centre of Excellence for Mycology. Her primary research interests are the diagnosis and management of superficial fungal infections, including fungal keratitis and vulvovaginal candidiasis as well as invasive fungal infections like pneumocystosis and histoplasmosis. She is also interested in neglected tropical diseases, having completed a Masters in Tropical Disease Biology at the Liverpool School of Tropical Medicine. Her early career achievements include 10 publications, 7 national prizes and 4 international presentations.

Abstract
Title: PCR on respiratory tract specimens of immunocompromised patients to diagnose Pneumocystosis (PcP): A systematic review and meta-analysis

Background
Several meta-analyses have demonstrated high performance of PCR for diagnosis of Pneumocystis jirovecii pneumonia (PcP), but it is not yet considered the diagnostic reference standard. The aim of this systematic review and meta-analysis was to identify the optimum approach to PCR diagnosis of PcP for different respiratory tract samples.

Methods
A systematic search of PubMed, Scopus, Embase and Cochrane from January 1, 1946 to June 30, 2021 was performed. Prospective studies which examined the performance of PCR on respiratory specimens for the diagnosis of proven PcP, according to European Organisation for Research and Treatment of Cancer – Mycoses Study Group Education and Research Consortium (EORTC/MSGERC), were included. The QUADAS-2 tool was used to assess risk of bias. Case-control studies were excluded. Articles were screened and summary data was extracted from reports by independent pairs of reviewers, with any discrepancies resolved by a third reviewer. A meta-analysis of the primary outcome of diagnostic performance was performed with a bivariate model. Diagnostics odds-ratio (DOR) was also calculated. Heterogeneity was evaluated by random effects meta-regression analysis. This study is registered with PROSPERO (CRD42018087812).

Results
Of the 3760 articles identified, 50 articles, including 9564 respiratory tract samples from 7742 patients at risk of PcP, were included in the analyses. Against the consensus definition of proven PcP, the sensitivity, specificity and related DOR values in the overall analysis were high. Quantitative PCR (qPCR) on bronchoalveolar lavage fluid (BALF) provided the highest pooled sensitivity at 98.6% (95% CI 96.7-99.4%), closely followed by qPCR on induced sputum (IS) (sensitivity 97.6% (93.6-99.1%)). Conventional PCR on upper respiratory tract samples provided the lowest sensitivity at 74.3% (42.6-91.9%) and the highest specificity at 96.7% (91.5-98.7%). qPCR on IS provided lowest specificity at 81.9% (71.9-88.9%). Overall diagnostic performance, as indicated by diagnostic odds ratio (DOR), was highest for conventional PCR on BALF (DOR=712 (300-1691)), followed by qPCR on BALF (DOR=589 (258-1342)), and lowest for qPCR on upper respiratory tract samples (DOR=69 (23-206)). There was no significant difference in sensitivity and specificity of PCR according to HIV status of patients enrolled in the trial.

Conclusion
In both HIV and non-HIV populations, qPCR on BALF offered the best sensitivity of all the sampling approaches for the diagnosis of PcP, while PCR on IS also provided high sensitivity. Across all sample types, conventional PCR provided higher overall diagnostic accuracy versus qPCR due to its higher specificity. The lower specificity and higher rates of qPCR “false positives” is likely due to its very high sensitivity, which allows for detection of very low fungal burdens that reflect colonisation/contamination rather than genuine infection. The technical benefits associated with qPCR (quantification of fungal burden, reduced opportunity for contamination, identification of mutations potentially associated with resistance to PcP therapy) preclude the use of conventional PCR when qPCR is an option.  There was no significant difference in sensitivity and specificity of PCR according to HIV status of patients enrolled in the trial, which is important given the evolving epidemiology of PcP, with an increase in cases in non-HIV populations.

Funding
None.

Biography
Laurence Millon is a Professor of Parasitology and Medical Mycology at the Medicine School- Franche-Comte University, UMR Chrono-Environnement (UMR 6249 – CNRS), Besançon – France.
She has been Head of the Parasitology and Mycology Department, University Hospital of Besancon since 2008 and Head of the National Reference Center Echinococcosis (mandate 2012-2016, 2017-2022 and 2023-2028). She has coordinated of 9 national / international research projects in the last 10 years. Its main area of expertise are in the field of epidemiology, diagnosis, and prevention of fungal and parasitological diseases (with a core expertise in invasive fungal infections and Echinococcosis), and she is highly experienced in molecular and immunogical techniques.
She is the author of 180 articles in Peer Review journal including 70 in the last five years and 20 invited conferences in the last five years.

Summary
Molecular techniques have provided a new understanding of the epidemiology of mucormycosis and improved the diagnosis and therapeutic management of this life-threatening disease.

PCR amplification and sequencing have been used to identify the fungus directly from the infected tissues or from bronchalveolar lavage, and they helped to accurately identify Mucorales fungi in tissue samples when the cultures were negative.  Very recently, PCR-based procedures to detect Mucorales DNA in non-invasive samples, such as plasma or serum, have proved successful in diagnosing mucormycosis early in all patients, whatever the clinical status, and these procedures are becoming essential to improving patient outcome. In the prospective Modimucor trial, the sensitivity of Mucorales PCR was  85.2%, specificity 89.8%. The first Mucorales qPCR-positive serum was observed a median of 4 days before sampling of the first mycological or histological positive specimen and a median of one day before the first imaging was performed. Negativity of Mucorales qPCR within seven days after liposomal-amphotericin B initiation was associated with an 85% lower 30-day mortality rate. Low interlaboratory variability of the Mucorales qPCR was demonstrated in a large study from the FPCRI Mucorales Laboratory group. Serum Mucorales qPCR can be performed on molecular biology platforms in most teaching hospitals due to increased availability of in-house techniques and commercial kits. Serum Mucorales qPCR is a non-invasive technique that can help to anticipate the diagnosis of mucormycosis and trigger early targeted antifungal treatment. Follow-up of the Mucorales DNA load in serum could also be helpful for therapeutic management. The possible standardization of the test and very good performance now demonstrated in a prospective multicenter study, argue for the addition of Mucorales qPCR in clinical settings and EORTC/MSGERC consensual definitions to improve the management of mucormycosis

Biography
Lewis White is consultant clinical scientist and leads the Public Health Wales Mycology Regional Reference Unit. He is a fellow of the European Confederation of Medical Mycologists and the Royal College of Pathologists, and leads the laboratory working party of the Fungal PCR initiative. Lewis is Education Secretary for the ESCMID Fungal Infection study group, Meeting Secretary for the British Society for Medical Mycology and the Vice President of the Welsh Microbiological Association. His research interests include evaluating novel fungal diagnostics and assessing diagnostic-driven and risk stratification approaches to managing invasive fungal disease, including the critically-ill COVID19 patient. He has published extensively in the field of medical mycology including international guidelines on defining and managing fungal disease.