1 Global guideline for the diagnosis and management of the Endemic Mycoses 2 George R. Thompson III1, Thuy Le2, Ariya Chindamporn3, Carol A. Kauffman4, Ilan 3 Schwartz5, Ana Alastruey-Izquierdo6, Neil M. Ampel7, David R. Andes8, Darius Armstrong- 4 James9, Olusola Ayanlowo10, John W. Baddley11, Bridget M. Barker12, Leila Lopes Bezerra13, 5 Maria J. Buitrago6, Leili Chamani-Tabriz14, Jasper F.W. Chan15, Methee Chayakulkeeree16, 6 Oliver A. Cornely17, Cao Cunwei18, Jean-Pierre Gangneux19, Nelesh P. Govender20, Ferry Ha- 7 gen21, Mohammad T. Hedayati22, Tobias M. Hohl23, Grégory Jouvion24, Chris Kenyon25, Chris- 8 topher C. Kibbler26, Nikolaj Klimko27, David CM Kong28, Robert Krause29, Low Lee Lee30, 9 Graeme Meintjes31, Marisa H. Miceli32, Peter-Michael Rath33, Andrej Spec34, Flavio Queiroz- 10 Telles35, Ebrahim Variava36, Paul E. Verweij37, Alessandro C. Pasqualotto38 11 1 Department of Internal Medicine, Division of Infectious Diseases and the Department of 12 Medical Microbiology and Immunology, University of California-Davis Medical Center; 13 Sacramento CA, USA 95817 14 2 Division of Infectious Diseases and International Health, Duke University School of Med- 15 icine, Durham, North Carolina, USA and Oxford University Clinical Research Unit, Ho 16 Chi Minh City, Vietnam 17 3 Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, 18 Thailand 19 4 VA Ann Arbor Healthcare System and University of Michigan, Ann Arbor, Michigan 20 5 Division of Infectious Diseases, Faculty of Medicine and Dentistry, University of Alberta, 21 Edmonton, Alberta, Canada 22 6 Mycology Reference Laboratory, National Centre for Microbiology, Instituto de Salud Car- 23 los III, Madrid, Spain 24 7 Division of Infectious Diseases, Mayo Clinic in Arizona, Phoenix, AZ, USA and the Uni- 25 versity of Arizona College of Medicine, Tucson, AZ, USA 26 8 Department of Internal Medicine, Division of Infectious Diseases and the Department of 27 Medical Microbiology and Immunology, University of Wisconsin; Madison, WI, USA 28 9 Department of Infectious Diseases, Imperial College London, London, United Kingdom 29 10 Department of Medicine, Faculty of Clinical Sciences, University of Lagos, Lagos, Nige- 30 ria. 31 11 University of Maryland, School of Medicine, Baltimore, MD, United States 32 12 Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ, United 33 States 1 34 13 Lab. Cellular Mycology and Proteomics, Rio de Janeiro State University (UERJ), Rio de 35 Janeiro, Brazil 36 14 Infectious Diseases Unit, Department of Internal medicine, Saudi German Hospital Dubai, 37 Dubai, UAE 38 15 State Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, De- 39 partment of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong 40 Kong, Pokfulam, Hong Kong Special Administrative Region, China 41 16 Division of Infectious Diseases and Tropical Medicine, Department of Medicine, Faculty 42 of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand. 43 17 University Hospital of Cologne, Department I of Internal Medicine, Excellence Center for 44 Medical Mycology (ECMM), Cologne, Germany; and University of Cologne, Cologne Ex- 45 cellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Co- 46 logne, Germany 47 18 The Department of Dermatology and Venereology, The First Affiliated Hospital of Guangxi 48 Medical University, Nanning, Guangxi, People's Republic of China 49 19 Univ Rennes, CHU Rennes, Inserm, IRSET (Institut de recherche en santé environnement 50 et travail)-UMR_S 1085, Rennes, France. 51 20 National Institute for Communicable Diseases, a Division of the National Health Laboratory 52 Service and University of the Witwatersrand, Johannesburg, South Africa 53 21 Westerdijk Fungal Biodiversity Institute, Utrecht, The Netherlands; Department of Medical 54 Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands; and Labora- 55 tory of Medical Mycology, Jining No. 1 People's Hospital, Jining, Shandong, People's Re- 56 public of China. 57 22 Invasive Fungi Research Center/ Department of Medical mycology, School of medicine, 58 Mazandaran University of Medical Sciences, Sari, Iran. 59 23 Infectious Disease Service, Department of Medicine; and Immunology Program, Sloan 60 Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 61 24 Sorbonne Université, INSERM, Pathophysiology of pediatric genetic diseases, Assistance 62 Publique-Hôpitaux de Paris, Hôpital Armand-Trousseau, UF Génétique moléculaire, Paris, 63 France, and Institut Pasteur, Experimental neuropathology unit, Paris, France 64 25 Institute of Tropical Medicine, Antwerp, Belgium 65 26 Centre for Medical Microbiology, University College London, UK. 66 27 Department of Clinical Mycology, Allergy and Immunology, I. Mechnikov North Western 67 State Medical University, St. Petersburg, Russian Federation 68 28 Pharmacy Department, Ballarat Health Services, Victoria, Australia. 69 National Centre for Antimicrobial Stewardship, Peter Doherty Institute, Victoria, Australia 70 29 Section of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, 71 Medical University of Graz, Austria 72 30 Department of Internal Medicine, Hospital Sultanah Bayiyah, Alor Setar, Kedah, Malaysia 2 73 31 Wellcome Centre for Infectious Diseases Research in Africa, University of Cape Town, 74 Cape Town, South Africa; Institute of Infectious Disease and Molecular Medicine, Univer- 75 sity of Cape Town, Cape Town, South Africa; Department of Medicine, University of Cape 76 Town, Cape Town, South Africa 77 32 University of Michigan, Ann Arbor, Michigan 78 33 Institute for Medical Microbiology University Hospital Essen, Germany 79 34 Division of Infectious Disease, Washington University in St. Louis School of Medicine, St. 80 Louis Missouri 81 35 Department of Public Health, Hospital de Clínicas, Federal University of Paraná, Curitiba, 82 Brazil 83 36 Department of Medicine, University of the Witwatersrand, Johannesburg, Gauteng, South 84 Africa 85 37 Department of Medical Microbiology, Excellence Center for Medical Mycology (ECMM), 86 Center of Expertise in Mycology Radboudumc/CWZ, Radboud University Medical Center, 87 Nijmegen, The Netherlands. 88 38 Federal University of Health Sciences of Porto Alegre (UFCSPA); and Molecular Biology 89 Laboratory at Santa Casa de Misericordia de Porto Alegre, Porto Alegre, Brazil 90 3 91 INTRODUCTION 92 The endemic mycoses are caused by a diverse group of fungi that share several charac- 93 teristics: they each occupy a specific ecologic niche in the environment, are located within 94 specific geographic regions, and exhibit temperature dimorphism – existing as yeast-like fungi 95 in the human host and moulds in the environment.1 There are numerous species of dimorphic 96 fungi, however Blastomyces, Coccidioides, Histoplasma, Paracoccidioides, and Sporothrix 97 spp., and Talaromyces marneffei (formerly Penicillium marneffei) represent the most com- 98 monly encountered causes of infections in clinical care. Biosafety is an important considera- 99 tion when handling these organisms, and laboratories should incorporate national guidance and 100 regulations into their processes and practices to ensure the safety of laboratory staff. There are 101 substantial differences in the geographical distribution, clinical presentation, radiographic 102 manifestations, diagnostic approach, and therapeutic interventions between these mycoses. 103 Management requires recognition of risk factors (e.g. environmental exposure in an endemic 104 region) and appropriate use of diagnostic and therapeutic interventions. Readily available guid- 105 ance is important to ensure efficient diagnosis and treatment and to optimize patient outcomes. 106 We issue this comprehensive guidance document to facilitate clinical decision-making 107 and to provide an overview of the areas of uncertainty in the field. We aim to address limita- 108 tions of previous recommendations, by engaging physicians and scientists involved in various 109 aspects of the endemic mycoses, representing the fields of dermatology, haematology, infec- 110 tious diseases, intensive care, microbiology, paediatrics, pathology, pharmacology, radiology 111 and surgery. In addition, the guideline group updates current knowledge in the field, and com- 112 prises experts from all parts of the world. 113 Each of the recommendations tabulated can easily be traced back to the source refer- 114 ences for maximum transparency. Any new relevant information, published after this docu- 115 ment, can be placed in context, and this approach facilitates the writing of future updates. For 4 116 consistency, a strict methodology was used, consistent with previous guideline documents.2 117 As with any other guidance document, this guideline intends to assist in management decisions. 118 Whether specific recommendations are appropriate when managing individual patients needs 119 to be carefully assessed by treating clinicians. Recommendations aim to assist, not to replace, 120 clinical judgment, and management of a patient with an endemic mycosis will always need to 121 be individualized. Moreover, recommendations do not guarantee the availability of specific 122 diagnostics or treatments, or reimbursement by healthcare systems. However, recommenda- 123 tions do reflect the current best available diagnostic and therapeutic management for each of 124 the endemic mycoses. 125 Guideline development 126 The general