FRIDAY 20 OCTOBER 2023
09:00
ECMM council meeting
Room: MC3
09:00
Educational Workshop Support by an educational grant from Pfizer Inc.
please see more information on: https://www.timm2023.org/sponsored-symposia/
Room: MC2
Plenary Session 1 - Candida: Translation from Research to Clinical Impact
Chairs: Martin Hoenigl & Anna Skiada
Room: Banqueting hall
12:30
PS 1.1 ECMM Candida III
Martin Hoenigl, Austria, FECCM
Martin Hoenigl, M.D., Assoc. Prof., FECMM is holding an appointment as Associate Professor for Translational Mycology at the Division of Infectious Diseases, Medical University of Graz, Austria. He has obtained his venia docendi in internal medicine in 2012, and is author to over 290 pub med listed publications in the field of infectious diseases, the majority in leading authorships (i.e. first or last author; ORCiD: 0000-0002-1653-2824). Dr. Hoenigl has particular expertise in conducting research on clinical mycology, including fungal diagnostics and pharmacology of antifungal drugs and correlation with clinical findings, as well as virology with a focus on HIV and respiratory viruses. He is the current president of the European Confederation of Medical Mycology (ECMM), and the Vice Chair of the EHA Infections in Hematology SWG. Dr. Hoenigl serves since 2015 as an associate editor for the journal Mycoses and as a Deputy Editor for Mycopathologia and Open Forum Infectious Diseases. Dr. Hoenigl has been awarded with the Researcher of the year 2011 award at the Medical University of Graz, with the Research Promotion award 2014, the highest award of the German Speaking mMartin Hoenigl, M.D., Assoc. Prof., FECMM is holding an appointment as Associate Professor for Translational Mycology at the Division of Infectious Diseases, Medical University of Graz, Austria. He has obtained his venia docendi in internal medicine in 2012, and is author to over 290 pub med listed publications in the field of infectious diseases, the majority in leading authorships (i.e. first or last author; ORCiD: 0000-0002-1653-2824). Dr. Hoenigl has particular expertise in conducting research on clinical mycology, including fungal diagnostics and pharmacology of antifungal drugs and correlation with clinical findings, as well as virology with a focus on HIV and respiratory viruses. He is the current president of the European Confederation of Medical Mycology (ECMM), and the Vice Chair of the EHA Infections in Hematology SWG. Dr. Hoenigl serves since 2015 as an associate editor for the journal Mycoses and as a Deputy Editor for Mycopathologia and Open Forum Infectious Diseases. Dr. Hoenigl has been awarded with the Researcher of the year 2011 award at the Medical University of Graz, with the Research Promotion award 2014, the highest award of the German Speaking mycological society, and with the ID Week Diagnostic award in 2018.
Martin Hoenigl
12:50
PS 1.2 Structure of the fungal cell wall immune epitope: the origins of immunity
Neil Gow, United Kingdom, FECCM
Biograpy
Professor Neil Gow is Deputy Vice-Chancellor for Research and Impact and Professor of Microbiology at the University of Exeter. He oversees a total research portfolio of £500 million and leads the research vision and strategy for the University. His lab is within the MRC Centre for Medical Mycology – one of the largest groupings in the field with more than 120 researchers. His research speciality is the study of the biology and immunology of fungi and in particular he is interested in the fungal cell wall as a target for antifungal drugs and of the immune system. He was Director of a Wellcome Trust Strategic Award in Medical Mycology and Fungal Immunology and a former Co-Director, MRC Centre for Medical Mycology, that has relocated to Exeter. He is a Fellow of the Royal Society, the Academy of Medical Sciences, Royal Society of Edinburgh and American Academy of Microbiology and has acted as President of four major international societies of mycology and microbiology.
Title: Structure of the fungal cell wall immune epitope: the origins of immunity
Neil A.R. Gow
Department of Biosciences, University of Exeter
Objectives:
For a fungus, there may nothing as biologically variable and highly regulated as its cell wall. This makes the wall intellectually and methodologically challenging to study, but worth the effort because they have the potential to reveal novel targets for antifungal drugs and the mechanisms that are important for immune recognition. Differences and adaptations to the cell wall composition can serve to resist chemotherapy and create a moving target for efficient immune recognition.
Methods and materials:
We have used a variety of microscopic, forward and reverse genetic and immunological tools to generate a new spatially accurate model of the cell wall and to explore how dynamic changes in the wall influence drug efficacy and immune surveillance. We also have screened a haploid library of C. albicans mutants with immune pattern recognition receptors (PRRs) to define the sub set of fungal genes that assemble and regulate immune epitopes.
Results:
Our molecular and cellular studies show that the cell has a mechanism to maintain wall robustness within physiological limits and has enabled the components of the wall to be defined with spatial precision. We also have demonstrated that immune relevant epitopes can be diffuse or clustered, superficial or buried in the cell wall and they changed during batch culture and between yeast, hypha and other cellular morphologies. Unbiased screening of a haploid mutant library has revealed gene sets for both predicted (e.g. cell wall glycosylation) and novel processes (I’ll reveal these in my talk) that are important for the assembly of the cell wall immune epitope.
Conclusion:
These experiments demonstrate that the fungal cell surface is ordered, complex and dynamically changing, requiring immune recognition to mobilise the concerted action of multiple receptors operating singly and in combination. My presentation will focus on work that demonstrates that describes recent advances that have generated a scaler and dynamic model of the cell wall that illuminates mechanisms of immune recognition and cell wall homeostasis.
Reference: Gow, N.A.R. & Lenardon, M.D. (2022). Architecture the dynamic fungal cell wall. Nature Reviews Microbiology https://doi.org/10.1038/s41579-022-00796-9. PMID 36266346
Neil Gow
13:45
Parallel Symposia 1-4
Symposium 1: WHO
Chairs: Ana Alastruey & Hatim Sati
Room: Banqueting hall
13:45
S01.1 WHO fungal list FECMM
Ana Alastruey - Izquierdo, Spain, FECMM
Biography
Ana Alastruey-Izquierdo is a research scientist at the Mycology Reference Laboratory of Spain where she leads the mould unit. She chairs the technical expert group of the Fungal priority Pathogens list by WHO, is the chair of the Fungal Infection Study group from ESCMID (EFISG), president of the Spanish Society for Mycology (AEM), fellow and board member of ECMM and member of the Scientific Advisory Board of the Joint Program Initiative on Antimicrobial Resistance (JPIAMR). Her main area of interest are Identification and early diagnosis of invasive fungal infections, antifungal susceptibility testing and surveillance and characterization on antifungal resistance. She has published more than 150 peer reviewed articles in scientific journals including several guidelines for diagnosis and treatment of fungal infections.
Ana Alastruey-Izquierdo
14:05
S01.2 WHO fungal essential diagnostic list
David Denning, United Kingdom, FECMM
Biography
David Denning is an internationally recognised retired clinician with expertise in fungal diseases and Professor of Infectious Diseases in Global Health at The University of Manchester. He was the founding Director of the UK’s National Aspergillosis Centre in Manchester (2009-2020), the world’s only such centre. David was Chief Executive of GAFFI from its inception in 2013 until early 2023, part-time. David Denning has published more than 700 papers, books and book chapters and lectures worldwide. His writings have been cited over 95,000 times and he has successfully lead many major international collaborative science, diagnostic and treatment projects and clinical guidelines, with subsequent publication in Nature, the New England Journal of Medicine and the Lancet.
Abstract
The WHO model list of essential diagnostics (EDL) was first issued in 2018, and is now in its third iteration, with substantial updates in 2021. It is an indispensable resource for the development of national essential diagnostics lists in countries, enabling them to prioritise procurement for their populations, according to different demographic factors such as HIV/AIDS burden, fungal disease endemicity (ie Histoplasma), and levels of care (ie intensive care, transplantation etc. GAFFI, in collaboration with a number of leading medical mycology societies worldwide, continues to advocate universal access of key fungal diagnostics. The WHO EDL now includes direct microscopy, fungal culture, blood cultures, histopathology to include fungal stains, cryptococcal, Histoplasma and Aspergillus antigen, Aspergillus IgG antibody and Pneumocystis jirovecii PCR. The introduction of highly sensitive, highly specific rapid diagnostics assays presents a transformational opportunity for countries with systemic healthcare delivery challenges. The availability of low cost, quick turnaround diagnostics, maximises the chances of patient survival from fungal disease, but clinical suspicion is critical to request fungal testing appropriately, and fast response times from the laboratory.
Resources: https://gaffi.org/where/neglected-fungal-diseases/ www.aspergillus.org.uk
David Denning
14:25
S01.3 WHO Essential Medicine List
Arunaloke Chakrabarti, India, FECMM
Biography
Arunaloke Chakrabarti is Director of the Doodhadhari Burfani Hospital in Haridwar, India. He is also the Ex-Head and Professor of the Department of Medical Microbiology of the Postgraduate Institute of Medical Education and Research (PGIMER) in Chandigarh, India, where he was also in charge of the Center of Advance Research in Medical Mycology, World Health Organization Collaborating Center for Reference and Research of Fungi of Medical Importance, and the National Culture Collection of Pathogenic Fungi. He is Past President of the International Society for Human and Animal Mycology (ISHAM).He is Chairman of the Fungal Infection Study Forum and international adviser of the Leading International Fungal Education, an international nongovernmental organization
Summary
Essential medicine list (EML)
Arunaloke Chakrabarti
Doodhadhari Burfani Hospital & Research Institute, Haridwar, India
The rate of invasive fungal infections is on the rise globally with high mortality. The rise is manifold higher in low- and middle-income countries due compromise in healthcare, environmental contamination and favorable geographical niches. However, the management of invasive fungal infections in those countries is a complex problem due to lack of rapid and accurate diagnosis of invasive fungal infection, inadequacies of diagnostic mycology laboratories and treatment resources. The limited classes of antifungals, non-availability of all preparations and poor affordability of antifungal agents are additional challenges in those resource limiting environment. The advocacy for implementation of WHO essential medicine list (EML) of antifungal agents in those countries may improve the scenario, but majority of antifungals were not included in WHO EML. The Global Action Fund for Fungal infections (GAFFI), established in 2013, played important role by providing public voice for the current and future patients with fungal diseases. One of their key goals is access to antifungal therapy for everyone with fungal disease, as outlined in the 10-years roadmap ’95-95 by 2025’. Due to the advocacy of GAFFI and some of the experts in this field amphotericin B and 5 fluorocytosine were included in EML in 2013; itraconazole, voriconazole, and natamycin in 2017; and echinocandins in 2021. Though there is some improvement in availability of antifungal across globe after those inclusions, several gaps remain in global antifungal map. Further advocacy, advocacy, and advocacy by national and international societies may improve the scenario in near future.
References
- Chakrabarti A, Patel AK, Soman R, Todi S. Overcoming clinical challenges in the management of invasive fungal infections in low and middle-income countries (LMIC). Expert Rev Anti-Infective Ther 2023; org/10.1080/14787210.2023.2257895
- Kneale M, Bartholomew JS, Davies E, Denning DW. Global access to antifungal therapy and its variable cost. J Antimicrob Chemother 2016; 71: 3599-3606
- https://urldefense.com/v3/__https:/gaffi.org/antifungal-drug-maps/__;!!PDiH4ENfjr2_Jw!GHfy6BBk7JUdrccD2eYwNy7VNVZ0e56EOlIWHcv6J9UsBps0fmBumyH34dGfoDJMsYLgUtnS_hIch0gK9vUVZu1wX29OTA$
- https://gaffi.org/antifungal-drug-maps/
https://www.who.int/publications/i/item/WHO-MHP-HPS-EML-2023.02
Arunaloke Chakrabarti
14:45
S01.4 FPPL: WHO Actions to fight fungal infections
Hatim Sati, Switzerland
Symposium 2 Antifungal prophylaxis - View on high-risk populations
Chairs: Ola Blennow & Dionysios Neofytos
Room: Skalkotas hall
13:45
S02.1 Antifungal prophylaxis in haematology - what's new?
Jannik Stemler, Germany
Biography
Dr. Jannik Stemler is a fifth-year resident in internal medicine at the University Hospital of Cologne. His clinical specialization focuses on patients with haematological malignancies, infectious diseases and intensive care. At the same time, he is a physician-scientist and is active in clinical research on COVID-19, pharmacovigilance and drug-drug interactions of anti-neoplastic drugs and anti-infectives, and the epidemiology of invasive fungal diseases as well as an investigator in phase II and III clinical trials on novel anti-infectives. He has published over 30 peer-reviewed articles and is a member of several societies in the field of haematology and infectious diseases.
Abstract
Patients with haematological malignancies (HM) are at high risk to develop invasive fungal disease (IFD) with high morbidity and attributable mortality. The strong recommendation to administer antifungal prophylaxis in patients with HM with long-lasting neutropenia, i.e. <500 cells/μL for >7 days remains unchanged. Posaconazole remains the drug of choice for mould-active prophylaxis in these patients. Novel treatment options in HM, such as CAR-T-cell treatment or novel targeted therapies for AML were considered, however, data are insufficient to give general recommendations for routine antifungal prophylaxis in these patients. Major changes regarding specific recommendations are the now moderate instead of mild support for the recommendations of isavuconazole and voriconazole. Furthermore, published evidence on micafungin allows recommending with moderate strength for its use in HM. Furthermore, non-pharmaceutical measures regarding prophylaxis of IFD should be considered, comprising the use of HEPA filters, smoking, measures during construction work and neutropenic diets.
The impact of antifungal prophylaxis with triazoles on drug-drug interactions with novel targeted therapies that are metabolized via cytochrome p450 where triazoles inhibit CYP3A4/5 may be higher than expected. It is recommended to reduce the dose of venetoclax when used concomitantly with strong CYP3A4 inhibiting antifungals. Furthermore, data on prophylactic use of novel antifungal agents like rezafungin or ibrexafungerp may become available soon. Currently there is no evidence to support their use in a prophylactic setting in clinical practice.
Jannik Stemler
14:05
S02.2 Invasive fungal disease in solid organ transplantation - prophylactic and diagnostic strategies
Shahid Husain, Canada, FECMM
Biography
Dr. Shahid Husain completed his Internal Medicine residency from Cook County Hospital and his three-year Infectious Diseases Fellowship from the University of Pittsburgh Medical Center (UPMC) with specialized training in Transplant Infectious Diseases. He completed his Masters in Clinical Trials from the University of Pittsburgh. He remained at UPMC as faculty and joined the University of Toronto in 2008.
Dr. Husain is an internationally recognized expert in the field of Transplant Infectious Diseases, as well as serving as Chairman of the Infectious Diseases Council of the International Society of Heart and Lung Transplantation. He is actively involved in the Canadian Society of Transplantation and currently serves as Chair of Transplant Infectious Diseases group. Shahid is an active contributor in the development of guidelines for the management of infections in solid organ transplant recipients on the behest of the American Thoracic Society and American Society of Transplantation.
Dr. Husain’s research has focused on the risk factors and outcomes of infections in solid organ transplant recipients. He has a particular interest in antibiotic stewardship of immunocompromised hosts. His funded clinical research is directed towards the evaluation of diagnostic tests for early diagnosis of invasive aspergillosis, development of appropriate antiviral, anti-bacterial and antifungal prophylactic strategies in immunocompromised hosts. He has been funded through the National Institute of Health, Canadian Institute of Health Research and the Center for Disease Control.
To date, Dr. Husain has published more than 200 peers reviewed publications and has authored more than seven book chapters. He also serves as a reviewer in various journals. Dr. Husain is passionate about teaching the future generation of transplant physicians and in 2009 he established the world’s largest structured Transplant Infectious Diseases Fellowship program. Currently, he serves as the Director of Research for the Ajmera Transplant Centre at Toronto General Hospital, University Health Network.
Shahid Husain
14:25
S02.3 The ventilated patient - is there a role for antifungal prophylaxis?
Jürgen Prattes, Austria, FECMM
Biography
Juergen Prattes, M.D., has received his medical degree from the Medical University in Graz, Austria in 2013 and has since been working at the Section of Infectious Diseases and Tropical Medicine of the Department of Internal Medicine at the Medical University of Graz, Austria. Following medical school, Dr. Prattes also completed a post-doctoral research fellowship at the Medical University in Graz. He has obtained his venia docendi in 2018 in internal medicine. Infectious diseases biomarker research, with special focus on fungal biomarkers, is one of his main research interests, where he authored numerous publications and gave numerous lectures in national and international conferences. Besides patient care and research, Dr. Prattes is dedicated to train undergraduate and post-graduate students in infectious diseases.
He currently holds the position of the president of the Austrian Society of Medical Mycology (ÖGMM), is a member of the German speaking Mycological Society (DMykG), of the Fungal Infection Study Group of the European Society of Clinical Microbiology and Infectious Diseases (EFISG), of the SWG Infections in Hematology of the European Hematology Association (EHA) and of the Infection Study Group of the German Society for Hematology and Oncology (AGIHO). He has been serving as reviewer for numerous international scientific journals and serves as deputy editor for Mycoses. Dr. Prattes is recipient of many national and international awards such as TIMM – ECMM Young Investigators Travel Award in 2017 and 2015, the ID Week Trainee Award in 2016, the ICAAC/ICC 2015 Infectious Disease Fellows Grant in 2015 and the Researcher of the Year at the Medical University of Graz in 2018.
Juergen Prattes
14:45
S02.4 Invasive Aspergillosis and Aspergillus Colonization in Lung Transplant Recipients (LTRs) in a Large Contemporary Cohort (abstract)
Remsha Nadeem, USA
Objectives: Invasive aspergillosis (IA) is a significant concern for lung transplant recipients (LTRs). Understanding current factors associated with the development of IA is crucial for effective prevention and management strategies. This retrospective cohort study aimed to assess the contemporary risk factors for the development of IA in LTRs overall and separately for those with pre (preAC)- and post-transplant Aspergillus colonization (postAC).
Methods & Materials: The study included all LTRs who underwent lung transplantation at Toronto General Hospital between January 2010 and December 2019, targeted approach is used for antifungal prophylaxis: pre-emptive treatment is only given in the presence of specific risk factors. The participants were followed for one year after transplantation, and diagnosis of IA was established as per ISHLT criteria. Multivariable and univariable logistic regression models were used to evaluate the impact of various factors on the development of IA overall and for LTRs with pre- and postAC separately.
Results: Among the 1358 LTRs, 451 (33%) received preemptive antifungal prophylaxis. 81 LTRs (5.96%) were diagnosed with IA in the first-year post-LT. At IA diagnosis 55/81 (68%) respiratory fungal cultures were positive: Most prevalent were Aspergillus fumigatus (65%, 36/55), followed by A. niger (9%, 5/55) , A. flavus (5%, 3/55), A. terreus (4%, 2/55), A. versicolor (2/55), and A. species (13%, 7/55). The median time from transplantation to IA was 100 days (IQR 58-186). In the multivariable analysis (Table A), infection with a respiratory virus (OR 1.94, p=0.028), statin use (OR 0.51, p=0.018), preAC (OR 3.78, p=0.002), postAC (OR 10.10 p=0.000), and pre-emptive fungal treatment post-transplantation (OR 0.14, p<0.001), were identified as factors associated with development of IA in contrast to ATG use (OR 1.23 p=0.60).
A total of 408 participants (30%) had any fungal colonization. 99 patients (7%) had documented preAC, at a median of 74 days (IQR 183-16.5) before transplant. 71/99 (71%) received pre-emptive antifungal treatment. 11/99 (11%) were diagnosed with IA post-transplant. In the univariate analysis (Table B), the following factors were associated with IA occurrence: CMV viremia (OR 3.95, p=0.040) and postAC (OR 9.64, p=0.005) but not pre-emptive antifungal treatment (OR 0.65, p=0.53).
346 patients (25%) had documented postAC, that occurred at a median of 80 days after transplant (IQR 1-184). 193/346 (56%) received pre-emptive antifungal treatment. In this group 53/346 (15%) were diagnosed with IA within one year post-transplant. In the multivariate analysis pre-transplant aspergillus colonization (OR 3.94, p=0.008) and pre-emptive antifungal treatment (OR 0.15, p<0.001) were associated with IA occurrence. At one year post-transplant 25% of LTRs with IA (20/81) were deceased compared with 12% in LTRs without IA (149/1277, p=0.001).
Conclusion: In this contemporary cohort involving >1300 LTRs IA incidence was <6%. Pre- and postAC were the most important risk factor for the development of IA. Factors associated with IA differed in the presence of pre- or post-transplant Aspergillus Colonization. Highlighting the potential benefits of tailored targeted interventions to mitigate the risk of IA and associated outcomes in lung transplant recipients.
Symposium 3 Fungal respiratory infections in Cystic Fibrosis
Chairs: Timoleon-Achilleas Vyzantiadis & Raquel Sabino
Room: MC3
13:45
S03.1 Towards international guidelines for fungal detection in CF
Sean Zhang, United States
Biography
Dr. Sean Zhang is an Associate Professor of Pathology at the Johns Hopkins University School of Medicine and Medical Director of Medical Mycology Laboratory at the Johns Hopkins Hospital. He is American Board-certified in Medical Microbiology (ABMM) with expertise in fungal diagnostics. Dr. Zhang’s research focuses on identifying fungal pathogens from FFPE (Formalin-Fixed Paraffin-Embedded) tissue blocks, fungal antigen assays, host-driven response assays, multiplex PCR, next-generation sequencing, identification and characterization of new emerging fungal pathogens, the role of fungal pathogens in cystic fibrosis patients, and antifungal drug resistance. He has authored over 100 publications. Dr. Zhang is the Executive Editor of Medical Mycology, an Editorial Board Member of the Clinical Microbiology Reviews. He is a Section Editor (Mycology) for the Manual of Clinical Microbiology (13th Edition). He serves as an advisor to the Clinical and Laboratory Standards Institute (CLSI) Antifungal Susceptibility Testing subcommittee, a member of American Society of Microbiology (ASM) Laboratory Practice Subcommittee, and a member of the College of American Pathologist (CAP) Microbiology Committee. He is also a co-founding chair of Fungal Diagnostics Laboratory Consortium (FDLC) in the USA/Canada.
Towards international guidelines for fungal detection in CF
The importance of Aspergillus and other fungi as lung pathogens in CF is becoming increasingly recognized. However, the true prevalence of these fungi in CF and their roles on impacting the disease are not well defined, largely due to lack of standardized optimal laboratory approach for CF fungal culture. A variety of factors are considered to contribute to fungal detection by culture in CF. These include sample type (expectorated sputa vs throat swabs), sample process (mucolytic or sonication), sample inoculum volume, selection of fungal culture media, incubation conditions and duration. In this talk, current data on supporting laboratory practice for optimal recovery fungi from respiratory samples in CF will be reviewed and discussed. In addition, non-culture-based methods, including galactomannan detection, serum beta-D-glucan detection, Aspergillus serology, Aspergillus PCR, and next generation sequencing, will be described for their potentials to improve and enhance fungal detection in CF.
Sean Zhang
14:05
S03.2 Rasamsonia argillacea species complex in cystic fibrosis
Andrew Borman, United Kingdom, FECMM
Biography
Professor Andy Borman is the Deputy Director of Public Health England’s UK National Mycology Reference Laboratory since 2003 and also an Honorary Professor at the College of Life and Environmental Sciences, University of Exeter, UK. His research interests include the epidemiology of emerging fungal pathogens and neglected tropical diseases caused by filamentous fungi, the diagnosis and management of fungal infections, the molecular and proteomic identification of pathogenic fungi, fungi associated with cystic fibrosis, and fungal taxonomy, phylogenetics and nomenclature.
Educated at the Universities of Manchester (B.Sc.) and Cambridge (Ph.D), Andy has published over 160 peer-reviewed papers and book chapters. He serves as a reviewer for a wide range of scientific journals, was previously on the editorial boards of the Journal of Clinical Microbiology and Mycopathologia and is a current editor for Medical Mycology and Journal of Fungi.
He is a member of the ASM and the BSMM, a fellow of the ECMM and several working groups of the International Society of Human and Animal Mycology (ISHAM). He also served as co-convenor for the ISHAM working group on “Fungal respiratory infections in cystic fibrosis” from 2009-2017.
Rasamsonia argillacea species complex in cystic fibrosis
Prof. Andrew M Borman.
UK National Mycology Reference laboratory, UK Health Security Agency, Southmead Hospital, Bristol BS10 5NB and Medical Research Council Centre for Medical Mycology (MRC CMM), University of Exeter, Exeter EX4 4QD, United Kingdom.
Species within the Rasamsonia argillacea complex are recognised colonisers of the airways of patients with cystic fibrosis and have been reported to cause fatal disseminated infections in CF patients post lung transplantation and also in patients with chronic granulomatous disease. Members of the complex are associated with high minimum inhibitory concentrations with the triazole antifungal agents, particularly voriconazole and posaconazole, whereas the echinocandin class of antifungals appear to retain clinically relevant activity against these organisms. Here we review the evidence for the ability of the organism to persist in CF lungs, the clinical impact of colonisation with R. argillacea complex on CF lung function and the most appropriate treatment regimens for eradication of the organism in colonised patients and the treatment of invasive/disseminated infections.
Andrew Borman
14:25
S03.3 Updates on Scedosporium and Lomentospora species
Michaela Lackner, Austria, FECMM
Biography
Michaela Lackner is University Professor for Experimental Mycology at the Institute of Hygiene and Medical Microbiology (HMM) at the Medical University of Innsbruck (MUI), Innsbruck. Austria that is an ECMM Excellent Center. Since 2017, she heads the Mycological Research Group at the HMM. She completed both her Master and her PhD in natural sciences with distinction at the University of Innsbruck (LFU) in 2007 and 2010, respectively. Since 2007, she has a strong interest in fungal pathogens, particularly in the development of novel diagnostic tools and in understanding antifungal azole resistance mechanisms. She is FECMM member, ECFS fungal pathogens working group co-coordinator, member of the FPCRI expert board – leading the clinical translational working party on Mucorales, convenor of the ECMM-ISHAM working group on Pseudallescheria/Scedosporium infections and the ISHAM working group of ISHAM Working Group Nomenclature of Clinical Fungi. Lackner has authored more than 100 publications in peer-reviewed articles and is involved in the training of medical and science graduates and undergraduates in Social Medicine, Hygiene and Medical Microbiology.
Michaela Lackner
14:45
S03.4 Differential transcriptomic response dynamics of primary human macrophages to Scedosporium apiospermum infection compared to Aspergillus fumigatus (abstract)
Hélène Guegan, France
Objectives
Scedosporium is the second most prevalent airway colonization fungal agent after Aspergillus in cystic fibrosis. Long-term bacterial and fungal airway colonization in CF patients contribute to maintain a chronic inflammation, through the release of various damage- associated molecular patterns, which may be involved in lung injury. We hypothesized that disparities in terms of cell wall structure and conidia morphology between both fungi, may affect interactions with host innate cells, that may ultimately affect fungal survival within the host.
The objectives of this study were i) to perform the first comparative transcriptomic analysis of human macrophages challenged with S. apiospermum (Sap) or A. fumigatus (Afu) conidia, at two distinct time points, i.e. 4 h and 12h, ii) to measure the inflammatory cytokine response and iii) to assess the survival of Sap and Afu conidia after macrophage challenge.
Methods
All experiments were performed with conidia harvested from 9 day-cultures of the wild-type 14462 Scedosporium apiospermum strain (Sap) and the wild-type Af 293 Aspergillus fumigatus strain. Macrophages derived from human peripheral blood mononuclear cells (PBMCs). RNA sequencing was performed from macrophage lysates obtained after 4h and 12h infection at 37°C with Sap or Afu conidia (MOI 10:1), and from uninfected macrophages. Bioinformatics analysis was conducted to identify differentially expressed genes (DEGs), comparing Sap-infected vs uninfected cells, Afu-infected vs uninfected cells and Sap-infected vs Afu-infected cells, at 4h and 12h (Ιlog2fold-changeΙ>1). Cytokines were measured in culture supernatants after 12h infection at 37°C with Sap or Afu, using a 13plex-bead-based immunoassay LEGENDplex® multi-analyte flow assay (BioLegend). After co-incubation at 37°C for 6h, the killing macrophage of Af and Sap conidia by macrophages was determined by cytometry assay after propidium iodide staining.
Results
Sap triggered the activation of several pro-inflammatory pathways, which were similar to the pathways activated by Afu. At 4h post-infection, a total of 15 pathways involved in inflammatory processes were differentially expressed in Sap-infected macrophages (FDR of 4.10-2 to 7.10-13), of which 12 were concomitantly enriched in Afu-infected macrophages (FDR of 4.10-2 to 0), independently of the sense of variation. The four more strongly dysregulated pathways were signaling pathways associated with TNF, IL-17, NF-kappa B, and actors of cytokine-cytokine receptor interactions, commonly described during antifungal response. Interestingly, Sap triggered a stronger and earlier activation of pro-inflammatory pathways, as revealed by the three-fold higher number of over-expressed DEGs at 4h by Sap, compared to Afu (671 vs 200). Sap infection also triggered a higher release of IL-6, IL-1β, TNF-α, IL-23, IL-10 (p<0.001) and IFN-α2 (p<0.05) in culture supernatants, which supported transcriptomic data. If the rate of infected macrophages was similar at 4h between both fungi, the killing of Sap conidia was higher than Afu conidia after 6h co-incubation (46.6% vs 34.5%, p<0.05), reflecting a lower ability of Sap to survive macrophage antifungal mechanisms.
Conclusion
- apiospermum tailored a stronger and quicker inflammatory macrophage response, which could mediate a facilitated clearance, compared to A. fumigatus. An excessive inflammatory response could be deleterious for the host in the long term, especially in the specific context of cystic fibrosis.
Symposium 4a Fungal infections in paediatrics: challenges & practices
Chairs: Valentina Arsić Arsenijević & Emmanuel Roilides
Room: MC2
13:45
S04.1a Fungal diagnostics in paediatrics: challenges in usage
Elio Castagnola, Italy
Biography
Born in Setri Levante (Italy) on January 26th 1961, medical degree in 1986 at Univeristy of Genoa, degree in Infectious Diseases, in Paediatrics, and PhD in Immunology, Vaccines and Organ Transplant, training in Microbiology, Infectious Diseases and Infections in Transplant. At present Chief of the Infectious Diseases Unit and Chief of the Department of Pediatric Medical Sciences at Istituto Giannina Gaslini Children’s Hospital, Genoa –Italy. Dealing with infections in pediatric leukaemia, solid tumours, and hematopoietic stem cell transplant, with special attention to bacterial and fungal invasive diseases for more than 35 years. In the last 10 years the scientific and clinical interest expanded to infection in preterm/low birth weight neonates and in patients with cystic fibrosis and more recently to application of pharmacokinetic/pharmacodynamic studies for treatment of bacterial and fungal invasive infections in paediatrics.
Elio Castagnola
14:05
S04.2a Clinical pharmacology of antifungal agents in paediatric patients
Andreas Groll, Germany, FECMM
Biography
Dr Andreas H Groll is Professor of Paediatrics, Head of the Infectious Disease Research Programme and Deputy Director of the Department of Haematology/Oncology at the University Children’s Hospital in Münster, Germany. Dr.Groll’s research interests include infectious complications in the immunocompromised host, particularly invasive fungal infections, the pharmacokinetics and pharmacodynamics of antimicrobial agents, and the design and conduct of clinical research studies. He is a member of several international medical societies, on the editorial board of several international journals and has published more than 300 scientific articles thus far. He is regularly engaged in patient care as Attending Physician of the inpatient and outpatient service and the haematopoietic stem cell transplant program.
Andreas Groll
14:25
S04.3a Usage of antifungal agents in Paediatric patients versus adults: knowledge and gaps
Emmanuel Roilides, Greece, FECMM
Biography
Emmanuel Roilides, MD, PhD is Professor of Paediatrics-Infectious Diseases in Aristotle University School of Medicine at Hippokration General Hospital in Thessaloniki, Greece. He is Fellow of European Confederation of Medical Mycology as well as of European Society of Clinical Microbiology and Infectious Diseases, member of the Steering Committee of European Paediatric Mycology Network (EPMyN). His research focuses on serious infections in neonates and children. He is the author of >680 peer reviewed articles and book chapters with >15000 citations. He has been co-ordinator or partner in several multicentre or multinational studies. He leads the national hub of conect4children, a European network of pediatric centers of excellence for clinical studies.
Emmanuel Roilides
14:45
S04.4a Characterisation of Candida species isolated from the skin of admitted neonates at a regional South African hospital (abstract)
Tshiama Miriam Mwamba, South Africa
Objectives: Microorganisms that colonise the gastrointestinal tract, mucous membranes, skin, monitoring devices, and indwelling lines of admitted neonates are implicated in healthcare-associated invasive infections. Approximately 7%-28% of neonates with a low birth weight (< 1500 g) and Candida colonisation develop invasive candidiasis. We aimed to determine the prevalence of Candida species colonising the skin of neonates admitted to an 83-bed neonatal unit of a regional hospital in South Africa and to characterise these cultured fungal pathogens.
Materials and methods: Admitted neonates were enrolled into the study between 25 October 2021 and 30 April 2022. At enrolment and every 48-96 hours throughout the duration of the hospital stay, skin samples were collected from around the umbilicus, axilla and the groin area using flocked swabs. These were immediately placed in Amies transport medium and transported to the mycology reference laboratory. Candida species were isolated in culture using selective media. Antifungal susceptibility testing was performed for Candida auris and C. parapsilosis isolates using commercial methods (Sensititre YeastOne, Thermo Fisher Scientific and Etest, bioMerieux); CLSI and tentative CDC breakpoints were applied.
Results: There were 1297 newborn admissions to the neonatal unit during the study period, 102 (7.9%) of whom were enrolled into this study. The median weight of all 102 neonates was 2660 g (interquartile range [IQR], 1840-3300 g), and 41% (42/102) had a gestational age of <37 weeks. The median duration of admission was four days (IQR, 2 – 10 days). A total of 265 skin swabs were collected from 93 of the neonates for the Candida colonisation study. Candida colonisation was detected in 92 skin swabs from 42/93 (45%) neonates. C. parapsilosis was the most common Candida species (70%, 64/92) followed by C. auris (20%, 18/92), C. albicans (10%, 9/92), and C. krusei (1%, 1/92). Fourteen of the 42 neonates (33%) were colonised with Candida within 24 hours of birth. The odds of colonisation by Candida spp was higher among neonates admitted for >72 hours (34/42) compared to neonates admitted for <72 hours (1/13) (OR = 0.02, 95% CI, 0.00-0.18; p<0.001); no such association was found with gestational age or mode of delivery. Six of the 12 neonates who died were co-colonised with ESKAPE bacterial organisms and Candida. Most C. parapsilosis (70%, 45/64) and C. auris (94%, 17/18) isolates were resistant to fluconazole (MIC ≥ 8 µg/mL and ≥32 µg/mL respectively), and 28% (5/18) of C. auris isolates were considered resistant to amphotericin B (MIC of ≥2 µg/mL). We identified five neonates whose first isolates of C. parapsilosis were susceptible to voriconazole and fluconazole, but whose subsequent C. parapsilosis isolates were resistant to both azoles.
Conclusions: Neonates with a hospital admission ≥72 hours were more likely to be colonised with Candida. In this neonatal unit with intermittently-reported clusters of candidaemia, C. parapsilosis was the most common colonizing species, followed by C. auris. Understanding the prevalence, distribution and susceptibility of Candida colonizing isolates in a unit can help guide infection prevention measures, and empiric treatment options for neonates with suspected invasive Candida infection.
Symposium 4b selected abstracts
Chairs: Aneke Chioma & Georgia Vrioni
Room: MC3.4
13:45
S04.1b Molecular epidemiology of invasive infection due to Trichosporon spp.: increasing of trichosporonosis and emerging of new species in France (abstract)
Marie Desnos-Ollivier, France
Objectives:
Trichosporon species are basidiomycetous yeast-like considered as emerging pathogen. Fungemia due to Trichosporon have increased in recent years in many countries (Taiwan, France, Italy, Spain, USA, Turkey, Brazil). Trichosporon fungemia is frequently associated with haematological malignancies, neutropenia, intensive care units (ICU), skin lesions and frequently reported in the pediatric population. Some horizontal transmission were also documented maybe due to the fact that some species are found on inanimate surfaces. Many species among the Trichosporon genus are involved in human infections but T. asahii remains the leading species in invasive infection. Recently, molecular analyses reclassified Trichosporon species in different genera. Epidemiological data based on multicentric survey associated with molecular identification remain relatively rare.
Materials & Methods:
Here we report clinical data of 68 episodes of Trichosporon invasive infections based on a national active surveillance program (RESSIF). Thirty three French hospital reported all their cases of invasive infection between January 2012 and December 2022. All isolates were identified by using IGS1 and whole genome sequecencing. The episodes involving Trichosporon together with other genus such as Candida, Aspergillus, Pneumocystis were considered as mixed infections and were excluded from this analysis (n=13).
Results:
The 68 episodes were due to 10 different species. Of these, 3 species respectively closely related to T. inkin, T. faecale or T. coremiiforme have not been previously described. Trichosporon asahii corresponds to the major species involved (n=36) and 5 different IGS haplotypes were identified ; haplotype 1 was the most frequent (16/36) as in most countries. Surprisingly, the second most frequent species was closely related to T. inkin (Trichosporon cf. inkin, n=19) and has yet to be described. Of note, two of the 10 spceies were in the genus Cutaneotrichosporon and one in Apiotrichum. Overall, there was a trend towards an increase in the number of cases of invasive Trichosporon infection over time in France.
Most isolates were involved in fungemia (n=51) ; 62% of patients were male, the mean age was 45 years and 19% of the patients were less than 15 year-old. The main associated factors were ICU (42%), haematological malignancies (32%) and recent surgery (27%). Pre-exposition to antifungal agents was also frequent (43%) as the presence of foreign devices (77%). Global mortality rate was high (49%). When comparing the characteristics of patients infected with the two major species (T. asahii and T. cf. inkin) T. asahii was significantly associated in fungemia (p=0.049), while T. cf. inkin was more frequently associated with recent surgery (p=0.021) and organ transplant (p=0.011).
Conclusions:
Our data confirm the trend of increasing cases of invasive infections due to Trichosporon species and unfortunatly a high mortality rate. The use of molecular data allowed us to 10 distinct species of which 3 do not seem to be described yet. Moreover, among these new species, T. cf. inkin ranked second in frequency and was associated with organ transplant and recent surgery. Trichosporon asahii remained the leading species with 5 different IGS haplotypes involved in invasive trichosporonosis in France.
13:55
S04.2b Polymorphisms in genes encoding (1,3)-β-D-glucan release components in Pneumocystis jirovecii (abstract)
Yohann Le Govic, France
Objectives: Serum 1,3-β-D-glucan (BG) testing is increasingly used to guide the management of suspected Pneumocystis pneumonia (PCP). It may be useful as a non-invasive adjuvant tool for PCP diagnosis in patients infected with the human immunodeficiency virus (HIV). Contrastingly, sensitivity is lower among non-HIV patients who develop PCP, especially those suffering from hematological malignancy or solid cancer. Our aim was to assess whether molecular mechanisms could be involved in this reduced sensitivity. For this purpose, we assessed the polymorphism of two genes implicated in BG release from the fungal cell wall: bgl2 and ace2, encoding a β-1,3 endoglucanase and its transcription factor, respectively.
Materials & Methods: This retrospective, monocentric, non-interventional study (July 2014 – December 2021) aimed at sequencing ace2 and bgl2 genes of Pneumocystis jirovecii isolates obtained from PCP patients who underwent a diagnostic bronchoalveolar lavage (BAL), and for whom a BG result was available. The patients were divided into two groups according to the BG level (positive vs. negative). Sanger sequencing of the two target genes was performed on P. jirovecii DNA from BAL samples. Single nucleotide polymorphisms (SNPs) were then identified by sequence alignment with reference genomes, and their frequency has been compared between the two groups of patients. Finally, the genomic sequences were translated into amino acid sequences to assess the impact of SNPs on the corresponding protein.
Results: A total of 22 BAL samples from 21 patients (8 HIV and 13 non-VIH) were analyzed. Among these samples, eight were associated with a negative level of BG, of which seven were collected from non-HIV patients. Both target genes were amplified in 20/22 (91%) samples. Sequence analysis revealed significant polymorphism, with eight SNPs identified for each locus, resulting in four missense mutations. However, these mutations corresponded to poorly conserved residues among phylogenetically related fungi, and were identified regardless of the BG level. Therefore, they do not seem to be responsible for the lower sensitivity of BG assay. Conversely, an absence of amplification of at least one of the two genes was observed for two non-HIV patients, both presenting a negative level of BG. This suggests the existence of deleterious genomic changes that might have hampered the target amplification by PCR and also the release of BG.
Conclusions: This study provides the first evidence of potential involvement of the genetic polymorphism of P. jirovecii in false-negative BG results. Moreover, the apparent lack of imputability of some missense mutations suggests that host factors may also affect BG detection, but this issue deserves further investigations.
14:05
S04.3b Candida albicans presence induces metabolic reprogramming and molecular alterations of MB16F10 melanoma cells leading to a more aggressive phenotype (abstract)
Aitziber Antoran, Spain
Objectives:
Candida albicans is an opportunistic fungus that is part of the human microbiota, populating body sites such as oral cavity and gut. There, C. albicans presence has been related with tumor promotion and progression. However, in the skin, where C. albicans is also commonly found, its association with the aggressive cancer melanoma has not yet been studied. Therefore, the aim of this work was to study the effect of C. albicans presence on melanoma cells both in vitro and in vivo.
Materials & Methods:
For this purpose, melanoma cells were exposed to C. albicans and its effect on cell migration, adhesion to endothelial cells and proliferation was measured in vitro. In addition, to deepen into molecular mechanisms activated, a transcriptomic analysis was performed using RNA-seq. These results were then confirmed by RT-qPCR for gene expression analysis and Extracellular Acidification Rate (ECAR) assays. Moreover, to study further the routes, specific inhibitors of the pathways in which overexpressed genes appeared in the transcriptomic study were used, analyzing their effect on VEGF production by ELISA and endothelial cell migration promotion.
Furthermore, in vivo assays were performed in C57BL/6 mice. For that, melanoma cells were stimulated with C. albicans and intrasplenically inoculated into mice. After two weeks, livers were extracted and the number of metastatic foci was counted and affected areas measured.
Results:
First, migration and adhesion assays demonstrated that C. albicans is able to enhance both processes in melanoma cells, but no effect was observed on cell proliferation. Moreover, the transcriptomic analysis revealed an increase in the expression of various genes related to the Warburg effect (Hk2, Eno2) and cancer progression (Vegfa, Jun, Cfos, …) after the contact with the fungus. The induction of the expression of some of these genes (Hk2, Eno2, Cfos), the Warburg effect and the production of VEGF after C. albicans contact with melanoma cells were confirmed by RT-qPCR, ECAR assays and ELISA analysis, respectively. Moreover, the inhibition of the MAPK/ERK pathway showed a reduction of VEGF release and a decrease in endothelial cell migration promotion, indicating the importance of this pathway in the signal transduction induced by C. albicans in melanoma cells. Altogether, this indicate that the contact with the fungus causes the development of a more aggressive tumor phenotype.
Finally, in vivo assays showed a significantly higher metastatic area, both micro- and macroscopically, in mice inoculated with melanoma cells stimulated with the fungus in comparison to the control.
Conclusions:
Overall, these results indicate that C. albicans promotes metabolic and molecular changes in melanoma tumor cells that could lead to increased pro-tumor and metastatic capacity.
Funding information: This research is funded by Basque Government (IT1657-22). MA, LAP and ORE have received a predoctoral grant from Basque Government (MA and ORE) or UPV/EHU (LAP).
14:15
S04.4b The role of rhizoferrin in growth and virulence of Rhizopus microspores (abstract)
Ulrike Binder, Austria
Objectives:
One essential element for all living organisms is iron. Fungi secrete siderophores to enable chelation and uptake of ferric iron. For clinically relevant mucormycetes it has been shown that a polycarboxylate siderophore, identified as rhizoferrin, is secreted. The aim of this study was to determine the role of rhizoferrin production for growth and virulence of R.microsporus by determining germination, growth, rhizoferrin production and virulence potential of rfs deletion strains in comparison to their wildtype.
Methods and Material:
To elucidate the role of rhizoferrin in virulence, we achieved disruption of rfs gene in Rhizopus microsporus by applying plasmid free CRISPR/Cas9 system and HR-mediated DNA repair. Homokaryon formation was induced by repetitive plating and confirmed by PCR and Southern Blot analysis. Growth and germination assays were carried out in various media with variable iron concentrations or inpresence of serum. Virulence potential and progression of infection was studied in Galleria mellonella larvae. Rhizoferrin production was determined by CAS assay and is currently confirmed by HPLC analysis.
Results:
Rfs deletion resulted in significantly reduced virulence potential in the Galleria mellonella infection model. Further, rfs deletion strains were unable to form hyphae within Galleria larvae and growth reduction/unability under low iron conditions was evident. Currently investigations are carried out to determine if virulence and germination can be restored in the presence of iron or xenosiderophores.
Conclusion:
Rhizoferrin production is inevitable for virulence of R.microsporus.
14:25
S04.5b Innate and adaptive immune response in subjects with CPA secondary to post-pulmonary tuberculosis lung disease (abstract)
Inderpaul Sehgal, India
Objectives: Post-tuberculosis lung disease (PTBLD) is the commonest risk factor for chronic pulmonary aspergillosis (CPA) and 14-25% of the subjects with PTBLD develop CPA. The pathogenesis and the host immune response in chronic pulmonary aspergillosis (CPA) are not well understood. Herein, we investigate the immune response in patients with post-tuberculosis pulmonary sequalae with or without chronic pulmonary aspergillosis.
Materials & Methods: We prospectively compared the innate and adaptive immune responses mounted by patients with PTBLD with or without CPA. We studied the neutrophil oxidative burst (by DHR), classic (serum C3 and C4 levels) and alternative (mannose binding lectin protein levels) complement pathway, serum immunoglobulins (IgG, IgM, and IgA), B and T lymphocyte subset in subjects with PTBLD with or without CPA.
Results: We included 111 subjects (58 CPA and 53 controls) in the current study. The mean±SD age of the study population was 42.6±15.7 years (Table 1). The cases and controls were matched for age, gender distribution and body weight.
14:35
S04.6b Comparative performances of non-invasive and invasive respiratory specimens for the molecular diagnosis of Pneumocystis jirovecii Pneumonia : the DANIPOP study. (abstract)
Cécile Garnaud, France
Incidence and morbi-mortality of Pneumocystis jirovecii Pneumonia (PCP) are increasing. As for other fungal diseases, the earlier the diagnosis, the better the prognosis. Today, its biological diagnosis relies on Pneumocystis jirovecii (Pj) detection in bronchoalveolar lavage (BAL) fluid, as the fungus lives and multiplies at the surface of type I pneumocytes. However, BAL sampling is an invasive procedure which can not always be performed urgently on hypoxemic patients. More superficial respiratory specimens, including sputa, are therefore often sampled for Pj PCR, although their diagnostic performances are not well established to date.
Objectives:
To study the diagnostic value of Pj PCR on non-invasive and/or superficial respiratory samples (oral fluids, sputa and bronchial aspirates (BA)) compared to the current gold-standard (Pj PCR on BAL).
Materials & Methods:
A monocentric case-control prospective study was conducted in the Grenoble Alpes University Hospital (France) from June 2018 to December 2022. Patients with radiological or clinical suspicion of PCP and for which a diagnostic bronchoscopy was planned were included in this study. Oral fluids, sputa and BA were sampled in addition to BAL fluids. Pj fungal load was assessed in all the respiratory samples by an in-house RT-qPCR technique targeting the Pj mtLSU gene using the BDMAX (Becton Dickinson) platform. Main clinical, radiological and biological parameters (including serum beta-D-glucans (BDG) levels) were collected for each patient. The study was approved by a French ethics committee and declared to competent authorities.
Results:
Eighty-one patients were included in this study, among which 30 cases and 51 control patients. Main underlying diseases were hemopathies (n=44, 54.3%), solid tumors (n=11, 13.5%) and solid organ transplants (n=11, 13.5%). BA, sputa and oral fluids samples were available in 66.7% (n=20), 66.7% (n=20) and 96.7% (n=29) of the PCP cases, with respective Pj PCR positivity rates of 90.0%, 65.0% and 41.4%. Mean fungal loads in BAL, BA and sputa did not differ significantly between eachothers, but were higher than that in oral fluids (Figure 1). As expected, serum BDG levels were significantly higher in cases than in controls (502.2 vs 98.4 pg/mL, p = 0.004)
Conclusions:
To our knowledge, this is the first study comparing PCP diagnostic performances of four different respiratory specimens sampled at the same time in a single patient. BA and sputa represent an interesting alternative to BAL with comparable fungal loads and no requirement for lavage or invasive procedure, even if a negative PCR on these samples could not definitely exclude PCP.
14:45
S04.7b New insights into the interplay between certain enzymatic ergosterol biosynthesis steps and the antifungal effects of azoles in Aspergillus fumigatus (abstract)
Johannes Wagener, Ireland
Objectives
Azole antifungals are actively used to treat many fungal infections. Depending on the fungal species, azoles have fungistatic or fungicidal activities. We have previously shown that azoles induce the formation of cell wall carbohydrate patches in the pathogenic mold Aspergillus fumigatus, which contribute to the fungicidal activity. The mode of action of the azole class of antifungals relies on inhibition of the lanosterol 14α-demethylase (CYP51). In our present study we explored the relevance of several other key enzymes in the ergosterol biosynthesis pathway for growth and viability of A. fumigatus.
Methods & Material
We have constructed a set of A. fumigatus mutants in which selected enzymes of the ergosterol biosynthesis pathway can be downregulated. The mutants were subsequently analyzed by fluorescence microscopy and with drug susceptibility testing assays.
Results
Many of these enzymes turned out to be essential for viability. The lack of some enzymes appears to be compatible with viability of the mold, but results in a sterile mycelium. Interestingly, inhibition of certain enzymes affects the azole susceptibility of A. fumigatus in a manner that is different from what would be expected in yeast.
Conclusion
Our results will help to understand the antifungal activities of agents used to treat infections caused by this pathogen. They also reveal which other enzymes of the ergosterol biosynthesis pathway might represent promising targets for future antifungal treatments.
15:00
Coffee break
15:30
Sponsored Diagnostic Symposium 1
More information on https://www.timm2023.org/sponsored-symposia/
Room: Banqueting hall
16:45
Sponsored Integrated Symposium 1
More information on https://www.timm2023.org/sponsored-symposia/
Room: Banqueting hall
Opening Session
Room: Banqueting hall
18:15
Welcome address
Emmanuel Roilides & Anna Skiada
18:30
New ECMM Journal Presentation
Martin Hoenigl, Jean-Pierre Gangneux, Neil Gow, Johan Maertens and Vishnu Chaturvedi
18:35
Memorandum on Nikolai Klimko
Oliver Cornely, Germany, FECMM
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.
Oliver Cornely
18:50
The Patient Voice: Advocacy in Policy, Funding and Research
Rob Purdie, United States
Biography
With over a decade of experience fighting coccidioidal meningitis, Robert (Rob) Purdie brings a unique perspective and passion to mycology advocacy. Rob is the Patient and Program Development Coordinator at the Valley Fever Institute at Kern Medical Center and a founding member of MyCARE. He is a lifelong Bakersfield resident who was diagnosed with coccidioidomycosis in 2012. Since his diagnosis, he has been dedicated to raising awareness of the impact Valley Fever has on individuals and communities and fighting to improve outcomes for his fellow patients fighting this challenging fungal infection.
Rob has spearheaded several awareness campaigns for Valley Fever. He has shared his personal knowledge and experience with numerous media entities at the local, state, and national level as well as internationally. His efforts include bringing community awareness through events such as the Valley Fever Walk, which he has helped organize since 2016.
Rob’s legislative efforts have included involvement in multiple aspects of California Assembly Bills on Valley Fever, resulting in $8 million in budget allocations for awareness and research. Rob has continued his efforts at the federal level working with patients and stakeholders to support legislation to improve patient outcomes.
Rob has been a Sponsored Participant and Presenter at workshops hosted by the NIH and FDA, provided Patient Advocacy at a Valley Fever Roundtable in Washington DC and recently at an international roundtable on fungal infections. He coauthored an article published in Clinical Infectious Diseases (CID), a leading journal in the field of infectious diseases with a broad international readership. Rob has many additional presentations scheduled, providing a voice for patients at several research and policy symposiums and meetings in 2023.
Rob’s desire to become involved in broader advocacy efforts springs from the relationships he has built with researchers, clinicians, and stakeholders and the realization that the issues experienced by Valley Fever patients are similar to those of other patients with fungal disease. His path to addressing the broader need was provided through collaborations established under a CDC Cooperative Agreement in mycology. Through these collaborations, Rob connected with additional members of the mycology community who shared his passion and vision for improving the lives of those battling fungal diseases. We trust that with Rob’s passion and guidance, MyCARE will make a difference for patients across the mycology spectrum.
Rob Purdie
E. Drouhet lecture (ECMM)
Chairs: Martin Hoenigl & Jean-Pierre Gangneux
Room: Banqueting hall
19:00
20 years in antifungal susceptibility testing: progress and remaining challenges - E. Drouhet lecture (ECMM)
Maiken Cavling Arendrup, Denmark
Biography
Prof Maiken Cavling Arendrup (MD) is specialist in clinical microbiology. She holds PhD and Dr. Med. Sci degrees. Currently, Dr. Arendrup is Professor at the University Hospital Rigshospitalet in Copenhagen and the Head of the Mycology Unit at Statens Serum Institut, Copenhagen, where she is responsible for the fungal laboratory, which receives 13,000 routine and reference samples per year for culture, susceptibility testing, antigen- and antibody-detection, and PCR as well as for the national surveillance programmes of candidaemia and of azole resistance in Aspergillus. She is responsible for the supervision of several PhD students. Prof Arendrup was the founder of the Nordic Society of Medical Mycology (NSMM) the president since the formation of the society in 2003 until 2018. She is chair of the EUCAST Antifungal Susceptibility Testing Subcommittee Steering Committee, head of the EUCAST Development Laboratory for fungi. In 2017 she was appointed Fellow of the European Society for Clinical Microbiology and Infectious Diseases and in 2018 honouree member of the NSMM. Prof Arendrup has authored 280 publications in international journals and as book chapters. She has received two research awards. Her main research interests include the epidemiology, susceptibility, breakpoint development, diagnostics and treatment of fungal infections.
Maiken Cavling Arendrup
19:30
Welcome reception