The Emerging Global Fungal Crisis: Invasive Fungal Diseases, Antifungal Resistance, and One Health Responses
-
Arash Ziaee
,
Alex Avakian
,
Sara Ebainejad
,
Samira Bahrami3
,
Amin Abdollahi
,
Pouya Pourkhaligh
,
Danial Hassan Nezhad
Abstract
Invasive fungal diseases are an escalating global health crisis, causing an estimated 6.5 million severe infections and up to 3.8 million deaths each year. Their disability burden likely reaches tens of millions of DALYs, yet remains underestimated because of sparse data and profound diagnostic gaps, especially in low- and middle-income countries. This narrative review synthesizes current evidence on three converging domains: the global burden and ecology of invasive fungal disease, the crisis of antifungal limitation and resistance, and emerging One Health responses. We summarize updated mortality, morbidity, and cost estimates and describe how demographic ageing, expanding immunosuppression, COVID-19, climate change, and agricultural azole fungicide use are enlarging the population at risk and selecting for resistant strains. Four WHO priority pathogen groups—Candida auris, azole-resistant Aspergillus fumigatus, Cryptococcus species, and Mucorales—are used to illustrate patterns of emergence, healthcare transmission, environmental selection, and multidrug resistance, linked to underlying molecular mechanisms such as ERG11 and cyp51A mutations, efflux pump upregulation, FKS-mediated echinocandin resistance, and biofilm-associated tolerance. We review strengths and gaps in diagnostics, including tiered essential diagnostic packages, resistance-aware molecular platforms, and early experience with GLASS Fungi and environmental surveillance. Finally, we discuss the constrained antifungal pipeline, novel agents and vaccines in development, and principles of antifungal stewardship aligned with improved access and agricultural regulation. We conclude with research and policy priorities to operationalize the WHO Fungal Priority Pathogens List and to embed fungal threats within broader antimicrobial resistance strategies, climate adaptation planning, and health system strengthening.
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[11] Toda M, Williams SR, Berkow EL, Farley MM, Harrison LH, Bonner L, et al. Population-based active surveillance for culture-confirmed candidemia-four sites, United States, 2012-2016. MMWR Surveill Summ. 2019;68(8):1-15. https://doi.org/10.15585/mmwr.ss6808a1
[12] Zubovskaia A. Azole-Resistant Aspergillus fumigatus: Epidemiology, Diagnosis, and Treatment Considerations. J Fungi (Basel). 2025;11(10):731. https://doi.org/10.3390/jof11100731
[13] Benedict K, Whitham HK, Jackson BR. Economic Burden of Fungal Diseases in the United States. Open Forum Infect Dis. 2022;9(4):ofac097. https://doi.org/10.1093/ofid/ofac097
[14] Tufa TB, Bongomin F, Fathallah A, Candido A, Hashad R, Abdallaoui MS, et al. Access to the World Health Organization-recommended essential diagnostics for invasive fungal infections in critical care and cancer patients in Africa: A diagnostic survey. J Infect Public Health. 2023;16(10):1666-74. https://doi.org/10.1016/j.jiph.2023.08.015
[15] Ortiz B, Varela D, Fontecha G, Torres K, Cornely OA, Salmanton-Garcia J. Strengthening Fungal Infection Diagnosis and Treatment: An In-depth Analysis of Capabilities in Honduras. Open Forum Infect Dis. 2024;11(10):ofae578. https://doi.org/10.1093/ofid/ofae578
[16] Rocatello G, El Faquir N, De Santis G, Iannaccone F, Bosmans J, De Backer O, et al. Patient-Specific Computer Simulation to Elucidate the Role of Contact Pressure in the Development of New Conduction Abnormalities After Catheter-Based Implantation of a Self-Expanding Aortic Valve. Circ Cardiovasc Interv. 2018;11(2):e005344. https://doi.org/10.1161/CIRCINTERVENTIONS.117.005344
[17] Temfack E, Lortholary O. Access to flucytosine for the treatment of HIV-associated cryptococcal meningitis in Africa. Lancet Infect Dis. 2022;22(9):1262-4. https://doi.org/10.1016/S1473-3099(22)00315-2
[18] Belanger CR, Locher K, Velapatino B, Dufresne PJ, Eckbo E, Charles M. Quick versus Quantitative: Evaluation of Two Commercial Real-Time PCR Assays for the Detection of Pneumocystis jirovecii from Bronchoalveolar Lavage Fluids. Microbiol Spectr. 2023;11(4):e0102123. https://doi.org/10.1128/spectrum.01021-23
[19] Roux A, Canet E, Valade S, Gangneux-Robert F, Hamane S, Lafabrie A, et al. Pneumocystis jirovecii pneumonia in patients with or without AIDS, France. Emerg Infect Dis. 2014;20(9):1490-7. https://doi.org/10.3201/eid2009.131668
[20] Garcia-Bustos V, Cabanero-Navalon MD, Ruiz-Gaitan A, Salavert M, Tormo-Mas MA, Peman J. Climate change, animals, and Candida auris: insights into the ecological niche of a new species from a One Health approach. Clin Microbiol Infect. 2023;29(7):858-62. https://doi.org/10.1016/j.cmi.2023.03.016
[21] Casadevall A, Kontoyiannis DP, Robert V. Environmental Candida auris and the Global Warming Emergence Hypothesis. mBio. 2021;12(2):e00360-21. https://doi.org/10.1128/mBio.00360-21
[22] Gorris ME, Treseder KK, Zender CS, Randerson JT. Expansion of Coccidioidomycosis Endemic Regions in the United States in Response to Climate Change. Geohealth. 2019;3(10):308-27. https://doi.org/10.1029/2019GH000209
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| Files | ||
| Issue | Vol 1 No 1 (2026) | |
| Section | Review Article(s) | |
| Keywords | ||
| Invasive Fungal Infections; Drug Resistance; One Health; Epidemiological Monitoring; Antifungal Agents; Candida Auris | ||
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How to Cite
1.
Ziaee A, Avakian A, Ebainejad S, Bahrami3S, Abdollahi A, Pourkhaligh P, Nezhad DH. The Emerging Global Fungal Crisis: Invasive Fungal Diseases, Antifungal Resistance, and One Health Responses. ipj. 2026;1(1):23-38.
