The Emerging Global Fungal Crisis: Invasive Fungal Diseases, Antifungal Resistance, and One Health Responses

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.