Shahrekord University of Medical Sciences Epidemiology and Health System Journal 2980-7891 12 4 2025 12 30 H5N1 at the Pandemic Threshold: Military-Grade Preparedness for an Avian Influenza Crisis 243 247 10.34172/ehsj.26493 EN Gian Marco Ludovici https://orcid.org/0000-0002-0148-783X Paola Amelia Tassi https://orcid.org/0009-0006-8709-6165 Alba Iannotti https://orcid.org/0000-0001-5049-3614 Colomba Russo https://orcid.org/0000-0003-4298-4231 Riccardo Quaranta https://orcid.org/0000-0002-4065-3175 Andrea Malizia https://orcid.org/0000-0002-4123-1716 Journal Article 10.34172/ehsj.26493 2025 05 23 2025 12 13 Background and aims: The rapid evolution of highly pathogenic avian influenza H5N1, with recent spillover to mammals and sporadic human cases, may pose a serious pandemic risk. This study focused on examining how integrating CBRNe principles can address critical gaps in traditional preparedness frameworks. Methods: This narrative review comprehensively synthesized evidence from virological research (2003-2025), WHO outbreak reports, and military-civilian biosecurity collaborations. Results: H5N1’s pandemic potential is escalating through key mutations, such as HA-T160A and PB2-E627K, which enhance mammalian airway replication. Current surveillance systems remain inadequate, particularly at animal-human interfaces. Crucially, CBRNe adaptations demonstrated superior containment in simulations. NATO’s 2023 Global BioLock exercise achieved a 63% reduction in cross-border transmission through spectral biosensor checkpoints and coordinated alert protocols. Moreover, military-civilian partnerships proved effective in the rapid deployment of field hospitals, as observed in Spain’s establishment of a 72-hour biocontainment unit. Conclusion: In general, the convergence of H5N1’s virological risk factors and CBRNe’s operational capabilities suggests the necessity of a paradigm shift. Thus, it is proposed that an international task force be established to standardize CBRNe protocols for avian influenza, prioritizing environmental biosurveillance and dual-use training for health workers. This strategic integration offers a tangible solution to mitigate the most probable pandemic threat, as the WHO considers it to be.