Hendra and Nipah viruses: Biosafety evidence for risk-based containment, inactivation practices, and one health preparedness.

Hendra virus (HeV) and Nipah virus (NiV) are highly pathogenic zoonotic henipaviruses that pose persistent risks at the human-animal-environment interface. Implementation of the WHO Laboratory Biosafety Manual fourth edition (LBM4) requires evidence-based risk assessments tailored to specific pathogens, activities, and operational settings; however, the adequacy of biosafety evidence supporting risk-based containment decisions for henipaviruses remains unclear. Spillover from bat reservoirs, amplification in domestic animals, and subsequent human infection have resulted in recurrent outbreaks with high case fatality rates and significant occupational exposure risks for veterinarians, healthcare workers, and laboratory personnel. Effective management of these hazards requires coordinated biosafety approaches across human, animal, and laboratory systems within a One Health framework. We conducted a structured narrative review of evidence relevant to biosafety risk assessment for HeV and NiV, focusing on laboratory diagnostics, occupational exposure, and validated inactivation and decontamination practices. Evidence from experimental studies, outbreak investigations, occupational exposure reports, regulatory guidance, and biosafety literature was critically synthesised across human, veterinary, and laboratory domains using the LBM4 risk-based framework as an organising structure. Substantial gaps were identified in the biosafety evidence base. Human infectious dose thresholds remain undefined, transmission pathways, particularly for NiV, are incompletely characterised, and many recommended inactivation and decontamination procedures lack formal validation across relevant matrices and operational contexts. Key risk factors underpinning spillover and occupational exposure are poorly quantified, and for HeV, the causes of pronounced spatial and temporal clustering of cases remain unresolved. These limitations complicate risk-based decision-making, particularly for diagnostic, field, and laboratory activities conducted outside maximum containment facilities. Addressing these evidence gaps will strengthen implementation of the WHO LBM4 risk-based framework, improve protection of laboratory and field personnel, and enhance One Health preparedness for future spillover events.