Review

. 2021 Dec;21(12):e364-e374.

doi: 10.1016/S1473-3099(21)00191-2. Epub 2021 Aug 6.

Global guideline for the diagnosis and management of the endemic mycoses: an initiative of the European Confederation of Medical Mycology in cooperation with the International Society for Human and Animal Mycology

George R Thompson 3rd¹, Thuy Le², Ariya Chindamporn³, Carol A Kauffman⁴, Ana Alastruey-Izquierdo⁵, Neil M Ampel⁶, David R Andes⁷, Darius Armstrong-James⁸, Olusola Ayanlowo⁹, John W Baddley¹⁰, Bridget M Barker¹¹, Leila Lopes Bezerra¹², Maria J Buitrago⁵, Leili Chamani-Tabriz¹³, Jasper F W Chan¹⁴, Methee Chayakulkeeree¹⁵, Oliver A Cornely¹⁶, Cao Cunwei¹⁷, Jean-Pierre Gangneux¹⁸, Nelesh P Govender¹⁹, Ferry Hagen²⁰, Mohammad T Hedayati²¹, Tobias M Hohl²², Grégory Jouvion²³, Chris Kenyon²⁴, Christopher C Kibbler²⁵, Nikolai Klimko²⁶, David C M Kong²⁷, Robert Krause²⁸, Low Lee Lee²⁹, Graeme Meintjes³⁰, Marisa H Miceli³¹, Peter-Michael Rath³², Andrej Spec³³, Flavio Queiroz-Telles³⁴, Ebrahim Variava³⁵, Paul E Verweij³⁶, Ilan S Schwartz³⁷, Alessandro C Pasqualotto³⁸

Affiliations

¹ Department of Internal Medicine, Division of Infectious Disease, UC Davis Medical Center, Sacramento, CA, USA; Department of Medical Microbiology and Immunology, University of California, Davis, CA, USA. Electronic address: grthompson@ucdavis.edu.
² Division of Infectious Diseases and International Health, Duke University School of Medicine, Durham, NC, USA; Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.
³ Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
⁴ VA Ann Arbor Healthcare System, Ann Arbor, MI, USA; Department of Internal Medicine, Division of Infectious Diseases, University of Michigan, Ann Arbor, MI, USA.
⁵ Mycology Reference Laboratory, National Centre for Microbiology, Instituto de Salud Carlos III, Madrid, Spain.
⁶ Division of Infectious Diseases, Mayo Clinic, Phoenix, AZ, USA; Department of Internal Medicine, Division of Infectious Diseases, University of Arizona College of Medicine, Tucson, AZ, USA.
⁷ Department of Internal Medicine, Division of Infectious Diseases, and Department of Medical Microbiology and Immunology, University of Wisconsin, Madison, WI, USA.
⁸ Department of Infectious Diseases, Imperial College London, London, UK.
⁹ Department of Medicine, Faculty of Clinical Sciences, University of Lagos, Lagos, Nigeria.
¹⁰ Department of Internal Medicine, Division of Infectious Disease, University of Maryland School of Medicine, Baltimore, MD, USA.
¹¹ Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ, USA.
¹² Cellular Mycology and Proteomics Laboratory, Rio de Janeiro State University, Rio de Janeiro, Brazil.
¹³ Infectious Diseases Unit, Department of Internal Medicine, Saudi German Hospital Dubai, Dubai, UAE.
¹⁴ State Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China; Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China.
¹⁵ Division of Infectious Diseases and Tropical Medicine, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
¹⁶ Department of Internal Medicine, Excellence Center for Medical Mycology, University Hospital of Cologne, Cologne, Germany; Department of Internal Medicine, Division of Infectious Diseases, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, Cologne, Germany.
¹⁷ Department of Dermatology and Venereology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
¹⁸ Department of Internal Medicine, Division of Infectious Diseases, Rennes University, CHU Rennes, Inserm, IRSET-UMR_S 1085, Rennes, France.
¹⁹ National Institute for Communicable Diseases, Division of the National Health Laboratory Service, Johannesburg, South Africa; Department of Internal Medicine, Division of Infectious Diseases, University of the Witwatersrand, Johannesburg, South Africa.
²⁰ Westerdijk Fungal Biodiversity Institute, Utrecht, Netherlands; Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, Netherlands; Laboratory of Medical Mycology, Jining No 1 People's Hospital, Jining, China.
²¹ Department of Medical Mycology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
²² Infectious Disease Service, Department of Medicine; Memorial Sloan Kettering Cancer Center, New York, NY, USA; Immunology Program, Sloan Kettering Institute, New York, NY, USA.
²³ Sorbonne Université, INSERM, Pathophysiology of Pediatric Genetic Diseases, Assistance Publique-Hôpitaux de Paris, Hôpital Armand-Trousseau, UF Génétique Moléculaire, Paris, France; Institut Pasteur, Experimental Neuropathology Unit, Paris, France.
²⁴ Institute of Tropical Medicine, Antwerp, Belgium.
²⁵ Centre for Medical Microbiology, University College London, London, UK.
²⁶ Department of Clinical Mycology, Allergy, and Immunology, I Mechnikov North-Western State Medical University, St Petersburg, Russia.
²⁷ Pharmacy Department, Ballarat Health Services, Ballarat, VIC, Australia; National Centre for Antimicrobial Stewardship, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.
²⁸ Section of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
²⁹ Department of Internal Medicine, Hospital Sultanah Bayiyah, Alor Setar, Kedah, Malaysia.
³⁰ Wellcome Centre for Infectious Diseases Research, University of Cape Town, Cape Town, South Africa; Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa; Department of Medicine, University of Cape Town, Cape Town, South Africa.
³¹ Department of Internal Medicine, Division of Infectious Diseases, University of Michigan, Ann Arbor, MI, USA.
³² Institute of Medical Microbiology, University Hospital Essen, Essen, Germany.
³³ Division of Infectious Disease, Washington University School of Medicine, St Louis, MO, USA.
³⁴ Department of Public Health, Hospital de Clínicas, Federal University of Paraná, Curitiba, Brazil.
³⁵ Department of Medicine, University of the Witwatersrand, Johannesburg, South Africa.
³⁶ Department of Medical Microbiology, Excellence Center for Medical Mycology, Radboudumc-CWZ Center of Expertise for Mycology, Radboud University Medical Center, Nijmegen, Netherlands.
³⁷ Division of Infectious Diseases, Department of Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada.
³⁸ Department of Clinical Medicine, Federal University of Health Sciences of Porto Alegre Porto Alegre, Brazil; Molecular Biology Laboratory, Santa Casa de Misericordia de Porto Alegre, Porto Alegre, Brazil.

PMID: 34364529
PMCID: PMC9450022
DOI: 10.1016/S1473-3099(21)00191-2

Review

Global guideline for the diagnosis and management of the endemic mycoses: an initiative of the European Confederation of Medical Mycology in cooperation with the International Society for Human and Animal Mycology

George R Thompson 3rd et al. Lancet Infect Dis. 2021 Dec.

. 2021 Dec;21(12):e364-e374.

doi: 10.1016/S1473-3099(21)00191-2. Epub 2021 Aug 6.

Authors

Affiliations

¹ Department of Internal Medicine, Division of Infectious Disease, UC Davis Medical Center, Sacramento, CA, USA; Department of Medical Microbiology and Immunology, University of California, Davis, CA, USA. Electronic address: grthompson@ucdavis.edu.
² Division of Infectious Diseases and International Health, Duke University School of Medicine, Durham, NC, USA; Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.
³ Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
⁴ VA Ann Arbor Healthcare System, Ann Arbor, MI, USA; Department of Internal Medicine, Division of Infectious Diseases, University of Michigan, Ann Arbor, MI, USA.
⁵ Mycology Reference Laboratory, National Centre for Microbiology, Instituto de Salud Carlos III, Madrid, Spain.
⁶ Division of Infectious Diseases, Mayo Clinic, Phoenix, AZ, USA; Department of Internal Medicine, Division of Infectious Diseases, University of Arizona College of Medicine, Tucson, AZ, USA.
⁷ Department of Internal Medicine, Division of Infectious Diseases, and Department of Medical Microbiology and Immunology, University of Wisconsin, Madison, WI, USA.
⁸ Department of Infectious Diseases, Imperial College London, London, UK.
⁹ Department of Medicine, Faculty of Clinical Sciences, University of Lagos, Lagos, Nigeria.
¹⁰ Department of Internal Medicine, Division of Infectious Disease, University of Maryland School of Medicine, Baltimore, MD, USA.
¹¹ Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ, USA.
¹² Cellular Mycology and Proteomics Laboratory, Rio de Janeiro State University, Rio de Janeiro, Brazil.
¹³ Infectious Diseases Unit, Department of Internal Medicine, Saudi German Hospital Dubai, Dubai, UAE.
¹⁴ State Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China; Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China.
¹⁵ Division of Infectious Diseases and Tropical Medicine, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
¹⁶ Department of Internal Medicine, Excellence Center for Medical Mycology, University Hospital of Cologne, Cologne, Germany; Department of Internal Medicine, Division of Infectious Diseases, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, Cologne, Germany.
¹⁷ Department of Dermatology and Venereology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
¹⁸ Department of Internal Medicine, Division of Infectious Diseases, Rennes University, CHU Rennes, Inserm, IRSET-UMR_S 1085, Rennes, France.
¹⁹ National Institute for Communicable Diseases, Division of the National Health Laboratory Service, Johannesburg, South Africa; Department of Internal Medicine, Division of Infectious Diseases, University of the Witwatersrand, Johannesburg, South Africa.
²⁰ Westerdijk Fungal Biodiversity Institute, Utrecht, Netherlands; Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, Netherlands; Laboratory of Medical Mycology, Jining No 1 People's Hospital, Jining, China.
²¹ Department of Medical Mycology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
²² Infectious Disease Service, Department of Medicine; Memorial Sloan Kettering Cancer Center, New York, NY, USA; Immunology Program, Sloan Kettering Institute, New York, NY, USA.
²³ Sorbonne Université, INSERM, Pathophysiology of Pediatric Genetic Diseases, Assistance Publique-Hôpitaux de Paris, Hôpital Armand-Trousseau, UF Génétique Moléculaire, Paris, France; Institut Pasteur, Experimental Neuropathology Unit, Paris, France.
²⁴ Institute of Tropical Medicine, Antwerp, Belgium.
²⁵ Centre for Medical Microbiology, University College London, London, UK.
²⁶ Department of Clinical Mycology, Allergy, and Immunology, I Mechnikov North-Western State Medical University, St Petersburg, Russia.
²⁷ Pharmacy Department, Ballarat Health Services, Ballarat, VIC, Australia; National Centre for Antimicrobial Stewardship, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.
²⁸ Section of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
²⁹ Department of Internal Medicine, Hospital Sultanah Bayiyah, Alor Setar, Kedah, Malaysia.
³⁰ Wellcome Centre for Infectious Diseases Research, University of Cape Town, Cape Town, South Africa; Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa; Department of Medicine, University of Cape Town, Cape Town, South Africa.
³¹ Department of Internal Medicine, Division of Infectious Diseases, University of Michigan, Ann Arbor, MI, USA.
³² Institute of Medical Microbiology, University Hospital Essen, Essen, Germany.
³³ Division of Infectious Disease, Washington University School of Medicine, St Louis, MO, USA.
³⁴ Department of Public Health, Hospital de Clínicas, Federal University of Paraná, Curitiba, Brazil.
³⁵ Department of Medicine, University of the Witwatersrand, Johannesburg, South Africa.
³⁶ Department of Medical Microbiology, Excellence Center for Medical Mycology, Radboudumc-CWZ Center of Expertise for Mycology, Radboud University Medical Center, Nijmegen, Netherlands.
³⁷ Division of Infectious Diseases, Department of Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada.
³⁸ Department of Clinical Medicine, Federal University of Health Sciences of Porto Alegre Porto Alegre, Brazil; Molecular Biology Laboratory, Santa Casa de Misericordia de Porto Alegre, Porto Alegre, Brazil.

PMID: 34364529
PMCID: PMC9450022
DOI: 10.1016/S1473-3099(21)00191-2

Erratum in

Correction to Lancet Infect Dis 2020; published online Aug 5. https://doi.org/10.1016/S1473-3099(21)00191-2.
[No authors listed] [No authors listed] Lancet Infect Dis. 2021 Nov;21(11):e341. doi: 10.1016/S1473-3099(21)00588-0. Epub 2021 Sep 6. Lancet Infect Dis. 2021. PMID: 34499864 No abstract available.

Abstract

The global burden of the endemic mycoses (blastomycosis, coccidioidomycosis, emergomycosis, histoplasmosis, paracoccidioidomycosis, sporotrichosis, and talaromycosis) continues to rise yearly and these infectious diseases remain a leading cause of patient morbidity and mortality worldwide. Management of the associated pathogens requires a thorough understanding of the epidemiology, risk factors, diagnostic methods and performance characteristics in different patient populations, and treatment options unique to each infection. Guidance on the management of these infections has the potential to improve prognosis. The recommendations outlined in this Review are part of the "One World, One Guideline" initiative of the European Confederation of Medical Mycology. Experts from 23 countries contributed to the development of these guidelines. The aim of this Review is to provide an up-to-date consensus and practical guidance in clinical decision making, by engaging physicians and scientists involved in various aspects of clinical management.

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Conflict of interest statement

Declaration of Interests GRT received research funding from Amplyx Pharmaceuticals, Astellas, Basilea Pharmaceutica, Cidara Therapeutics, F2G, IMMY, Mayne Pharma, and Scynexis, and served as a consultant for Amplyx Pharmaceuticals, Astellas, Basilea Pharmaceutica, Cidara Therapeutics, F2G, IMMY, Mayne Pharma, Scynexis, and Pfizer. MJB is a founding partner and holds shares of Micología Molecular SL, she has received grant support from the Instituto de Salud Carlos III and has been paid for talks on behalf of United Medical LTDA. AA-I has received research grants to their institution from F2G and honoraria as a speaker from Gilead Sciences and Pfizer. DA-J holds share options in Pulmocide and has received grant support from Pulmocide, Astellas Pharma, Pfizer, and Gilead Sciences. He has received lecture honoraria from Astellas Pharma, Pfizer, Gilead Sciences, and AstraZeneca. JWB has served as a consultant for Pfizer. JFWC has received travel grants from Pfizer Corporation Hong Kong and Astellas Pharma Hong Kong, and was an invited speaker for Gilead Sciences Hong Kong and Luminex Corporation. OAC is funded by the German Federal Ministry of Education and Research, is funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany's Excellence Strategy (CECAD, EXC 2030—390661388), and has received research grants from Actelion, Amplyx Pharmaceuticals, Astellas Pharma, Basilea Pharmaceutica, Cidara Therapeutics, Da Volterra, F2G, Gilead Sciences, Janssen Pharmaceuticals, Medicines Company, MedPace, Melinta Therapeutics, Merck/MSD, Pfizer, and, Scynexis. OAC is also a consultant to Actelion, Allecra Therapeutics, Amplyx Pharmaceuticals, Astellas, Basilea Pharmaceutica, Biosys UK, Cidara Therapeutics, Da Volterra, Entasis, F2G, Gilead Sciences, Matinas BioPharma, MedPace, Menarini Ricerche, Roche Diagnostics, Merck/MSD, Nabriva Therapeutics, Octapharma, Paratek Pharmaceuticals, Pfizer, PSI, Rempex, Scynexis, Seres Therapeutics, Tetraphase, and Vical, and received lecture honoraria from Astellas, Basilea Pharmaceutica, Gilead Sciences, Grupo Biotoscana, Merck/MSD, and Pfizer. NK received honoraria from Astellas, Gilead Sciences, Merck/MSD, and Pfizer, and received grants from Merck/MSD and Pfizer. NK was a speaker for Astellas, Gilead Sciences, Merck/MSD, and Pfizer and an adviser for Gilead Sciences, Merck/MSD, and Pfizer. DCMK has sat on advisory boards for Becton Dickinson and Merck/MSD, and received financial and travel support unrelated to the current work from Merck/MSD. MHM has received research support and served as a consultant for Astellas and Scynexis. ISS has served as an adviser to Avir Pharma. AS has received grant funding from Astellas and has consulted for Scynexis, Minnetronix Medical, Mayne Pharma, and Viamet Pharmaceuticals. J-PG has received research grant support from Pfizer. FQ-T has received research grants from Astellas, Merck/MSD, and Pfizer, and also received payments for presentations and continued medical education from Merck/MSD, Pfizer, United Medical, and Teva Brazil. PEV reported grants from Gilead Sciences, Merck/MSD, Pfizer, F2G, and Thermo Fisher Scientific, and travel support from OLM Systems and IMMY, outside of the submitted work. ACP has received research grant support on behalf of Pfizer, Gilead Sciences, Merck/MSD, and IMMY. He has also given paid talks for Pfizer, United Medical, Gilead Sciences, Merck/MSD, Astellas, and IMMY, and participated on the medical board of Pfizer, United Medical, Gilead Sciences, and Merck/MSD. All other authors declare no competing interests.

Figures

**Figure 1:. Geographical regions of the endemic mycoses (A–G)**

**Figure 2:. Microscopic findings of endemic mycoses**
(A) Grocott methenamine silver staining of *Blastomyces* spp yeast from a tissue sample with broad-based budding apparent in centre (400× magnification; courtesy of Dr Carol Kauffman). (B) Hematoxylin and eosin staining of *Coccidioides* spp spherule containing numerous endospores (40× magnification; courtesy of Dr Bridget Barker). (C) Silver staining shows yeast forms of *Histoplasma* spp (40× magnification; courtesy of Dr John Baddley). (D) Lactophenol cotton blue staining of a smear paracoccidioidomycosis (400× magnification; courtesy of Dr Flavio Telles). (E) Lactophenol cotton blue stain shows rosette-like clusters at the tips of the conidiophores, which are characteristic of *Sporothrix* spp (40× magnification; courtesy of Dr Flavio Telles). (F) Giemsa stain shows transverse septum (arrow) in a dividing yeast cell, which is characteristic of *Talaromyces marneffei* (60× magnification; courtesy of Dr Thuy Le).

See this image and copyright information in PMC

Comment in

Endemic mycoses: geographical distribution is still a work in progress - Authors' reply.
Le T, Pasqualotto AC, Thompson GR 3rd. Le T, et al. Lancet Infect Dis. 2022 Apr;22(4):451-452. doi: 10.1016/S1473-3099(22)00121-9. Lancet Infect Dis. 2022. PMID: 35338870 Free PMC article. No abstract available.
Endemic mycoses: geographical distribution is still a work in progress.
Antinori S, Ridolfo AL, Casalini G, Giacomelli A. Antinori S, et al. Lancet Infect Dis. 2022 Apr;22(4):451. doi: 10.1016/S1473-3099(22)00131-1. Lancet Infect Dis. 2022. PMID: 35338871 No abstract available.

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1. McTaggart LR, Brown EM, Richardson SE. Phylogeographic analysis of Blastomyces dermatitidis and Blastomyces gilchristii reveals an association with North American freshwater drainage basins. PLoS One 2016; 11: e0159396. - PMC - PubMed
1. Schwartz IS, Wiederhold NP, Hanson KE, Patterson TF, Sigler L. Blastomyces helicus, a new dimorphic fungus causing fatal pulmonary and systemic disease in humans and animals in western Canada and the United States. Clin Infect Dis 2019; 68: 188–95. - PMC - PubMed
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1. Bariola JR, Hage CA, Durkin M, et al. Detection of Blastomyces dermatitidis antigen in patients with newly diagnosed blastomycosis. Diagn Microbiol Infect Dis 2011; 69: 187–91. - PubMed

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Global guideline for the diagnosis and management of the endemic mycoses: an initiative of the European Confederation of Medical Mycology in cooperation with the International Society for Human and Animal Mycology

Affiliations

Global guideline for the diagnosis and management of the endemic mycoses: an initiative of the European Confederation of Medical Mycology in cooperation with the International Society for Human and Animal Mycology

Authors

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Erratum in

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Conflict of interest statement

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Comment in

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