Prion diseases: Lessons from historical outbreaks and potential emerging ones.

Prion diseases (PrDs) are a unique and fatal class of neurodegenerative disorders caused by misfolded proteinaceous infectious particles, or prions. While the pathogenic form was first documented in humans nearly a century ago, the global monitoring of PrDs only gained momentum after the "Mad Cow" epizootic and its human counterpart of the 1980s and 1990s. Currently, 34 countries track human prion cases annually, with over 27,000 cases. However, true prevalence estimates suggest significantly higher numbers, millions, highlighting the urgency of addressing these enigmatic diseases. Prions are exceptionally resilient, resisting conventional sterilization methods and persisting in environmental reservoirs, such as soil and plants, raising concerns about environmental and cross-species transmission, particularly with the growing prevalence of chronic wasting disease (CWD) in cervids. This review explores the history, pathogenesis, presence, public health implications, and novel innovations in studying and treatment of PrDs. Future priorities should include the development of faster, cost-effective diagnostic tools and systemic therapies to neutralize prions in affected individuals and mitigate environmental risks. Understanding and addressing the challenges posed by prions is critical for global health security in the wake of CWD.