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      The importance of antimicrobial resistance in medical mycology

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          Abstract

          Prior to the SARS-CoV-2 pandemic, antibiotic resistance was listed as the major global health care priority. Some analyses, including the O’Neill report, have predicted that deaths due to drug-resistant bacterial infections may eclipse the total number of cancer deaths by 2050. Although fungal infections remain in the shadow of public awareness, total attributable annual deaths are similar to, or exceeds, global mortalities due to malaria, tuberculosis or HIV. The impact of fungal infections has been exacerbated by the steady rise of antifungal drug resistant strains and species which reflects the widespread use of antifungals for prophylaxis and therapy, and in the case of azole resistance in Aspergillus, has been linked to the widespread agricultural use of antifungals. This review, based on a workshop hosted by the Medical Research Council and the University of Exeter, illuminates the problem of antifungal resistance and suggests how this growing threat might be mitigated.

          Abstract

          The impact of fungal infections on human health has been exacerbated by the rise of antifungal drug resistance. In this Review, the authors outline the problem of antifungal resistance and suggest how this growing threat might be mitigated.

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          Hidden killers: human fungal infections.

          Although fungal infections contribute substantially to human morbidity and mortality, the impact of these diseases on human health is not widely appreciated. Moreover, despite the urgent need for efficient diagnostic tests and safe and effective new drugs and vaccines, research into the pathophysiology of human fungal infections lags behind that of diseases caused by other pathogens. In this Review, we highlight the importance of fungi as human pathogens and discuss the challenges we face in combating the devastating invasive infections caused by these microorganisms, in particular in immunocompromised individuals.
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            Global and Multi-National Prevalence of Fungal Diseases—Estimate Precision

            Fungal diseases kill more than 1.5 million and affect over a billion people. However, they are still a neglected topic by public health authorities even though most deaths from fungal diseases are avoidable. Serious fungal infections occur as a consequence of other health problems including asthma, AIDS, cancer, organ transplantation and corticosteroid therapies. Early accurate diagnosis allows prompt antifungal therapy; however this is often delayed or unavailable leading to death, serious chronic illness or blindness. Recent global estimates have found 3,000,000 cases of chronic pulmonary aspergillosis, ~223,100 cases of cryptococcal meningitis complicating HIV/AIDS, ~700,000 cases of invasive candidiasis, ~500,000 cases of Pneumocystis jirovecii pneumonia, ~250,000 cases of invasive aspergillosis, ~100,000 cases of disseminated histoplasmosis, over 10,000,000 cases of fungal asthma and ~1,000,000 cases of fungal keratitis occur annually. Since 2013, the Leading International Fungal Education (LIFE) portal has facilitated the estimation of the burden of serious fungal infections country by country for over 5.7 billion people (>80% of the world’s population). These studies have shown differences in the global burden between countries, within regions of the same country and between at risk populations. Here we interrogate the accuracy of these fungal infection burden estimates in the 43 published papers within the LIFE initiative.
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              Global burden of disease of HIV-associated cryptococcal meningitis: an updated analysis.

              Cryptococcus is the most common cause of meningitis in adults living with HIV in sub-Saharan Africa. Global burden estimates are crucial to guide prevention strategies and to determine treatment needs, and we aimed to provide an updated estimate of global incidence of HIV-associated cryptococcal disease.
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                Author and article information

                Contributors
                N.Gow@exeter.ac.uk
                Carolyn.Johnson@mrc.ukri.org
                Journal
                Nat Commun
                Nat Commun
                Nature Communications
                Nature Publishing Group UK (London )
                2041-1723
                12 September 2022
                12 September 2022
                2022
                : 13
                : 5352
                Affiliations
                [1 ]GRID grid.8391.3, ISNI 0000 0004 1936 8024, MRC Centre for Medical Mycology, School of Biosciences, , University of Exeter, Geoffrey Pope Building, ; Exeter, EX4 4QD UK
                [2 ]GRID grid.14105.31, ISNI 0000000122478951, Medical Research Council, Polaris House, ; Swindon, SN2 1FL UK
                [3 ]GRID grid.12136.37, ISNI 0000 0004 1937 0546, Shmunis School of Biomedical and Cancer Research, George S. Wise Faculty of Life Sciences, , Tel Aviv University, ; 418 Britannia Building, Ramat Aviv, 69978 Israel
                [4 ]GRID grid.8515.9, ISNI 0000 0001 0423 4662, Microbiology Institute, , University Hospital Lausanne, ; rue du Bugnon 48, 1011 Lausanne, Switzerland
                [5 ]GRID grid.66859.34, ISNI 0000 0004 0546 1623, (CAC) Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, ; Cambridge, MA 02142 USA
                [6 ]GRID grid.429392.7, ISNI 0000 0004 6010 5947, Center for Discovery and Innovation, , Hackensack Meridian health, ; Nutley, NJ 07110 USA
                [7 ]GRID grid.264200.2, ISNI 0000 0000 8546 682X, Institute of Infection and Immunity, , St George’s University of London, ; London, SW17 0RE UK
                [8 ]GRID grid.451349.e, Clinical Academic Group in Infection, , St George’s University Hospitals NHS Foundation Trust, ; London, SW17 0QT UK
                [9 ]GRID grid.267309.9, ISNI 0000 0001 0629 5880, Department of Pathology and Laboratory Medicine, , University of Texas Health Science Center at San Antonio, ; San Antonio, TX 78229 USA
                [10 ]GRID grid.5379.8, ISNI 0000000121662407, Manchester Fungal Infection Group, Division of Evolution, Infection, and Genomics, Faculty of Biology, Medicine and Health, , University of Manchester, CTF Building, ; 46 Grafton Street, Manchester, M13 9NT UK
                [11 ]GRID grid.416738.f, ISNI 0000 0001 2163 0069, Center for Disease Control and Prevention Mycotic Disease Branch 1600 Clifton Rd, MSC-09, ; Atlanta, 30333 GA USA
                Author information
                http://orcid.org/0000-0002-2776-5850
                http://orcid.org/0000-0002-0494-8136
                http://orcid.org/0000-0001-9481-9778
                http://orcid.org/0000-0002-5778-960X
                http://orcid.org/0000-0002-1268-5524
                http://orcid.org/0000-0002-2676-838X
                http://orcid.org/0000-0002-2225-5122
                http://orcid.org/0000-0002-7611-0201
                Article
                32249
                10.1038/s41467-022-32249-5
                9466305
                36097014
                f8f553ee-b4a8-449b-88d4-55c4056a2b7d
                © The Author(s) 2022

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 31 March 2022
                : 22 July 2022
                Funding
                Funded by: FundRef https://doi.org/10.13039/501100000265, RCUK | Medical Research Council (MRC);
                Award ID: MR/N006364/2
                Award Recipient :
                Funded by: FundRef https://doi.org/10.13039/100004440, Wellcome Trust (Wellcome);
                Award ID: 101873/Z/13/Z
                Award ID: 200208/A/15/Z
                Award ID: 215599/Z/19/Z
                Award ID: 219551/Z/19/Z
                Award ID: 219551/Z/19/Z, 208396/Z/17/Z
                Award Recipient :
                Funded by: FundRef https://doi.org/10.13039/100010663, EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council);
                Award ID: 951475, ERC SYN FungalTolerance
                Award Recipient :
                Funded by: FundRef https://doi.org/10.13039/100000093, U.S. Department of Health & Human Services | NIH | Center for Information Technology (Center for Information Technology, National Institutes of Health);
                Award ID: AI10902
                Award Recipient :
                Funded by: FundRef https://doi.org/10.13039/100000009, Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.);
                Award ID: AI109025
                Award Recipient :
                Funded by: FundRef https://doi.org/10.13039/501100009187, RCUK | MRC | Medical Research Foundation;
                Award ID: MRF-160-0009-ELP-BICA-C0802
                Award Recipient :
                Funded by: FundRef https://doi.org/10.13039/100006492, Division of Intramural Research, National Institute of Allergy and Infectious Diseases (Division of Intramural Research of the NIAID);
                Categories
                Review Article
                Custom metadata
                © The Author(s) 2022

                Uncategorized
                antifungal agents,antimicrobial resistance,clinical microbiology,fungi
                Uncategorized
                antifungal agents, antimicrobial resistance, clinical microbiology, fungi

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