From spillover to preparedness: a One Health analysis of knowledge gaps in Nipah virus surveillance, prevention, and health system response.

Background: Nipah virus (NiV) is a highly pathogenic zoonotic henipavirus that continues to pose a significant threat to global health security because of its high case fatality rate, ability to cause human-to-human transmission, and absence of licensed vaccines or specific therapeutics. Although more than two decades of research have advanced the understanding of NiV ecology, epidemiology, and clinical disease, major uncertainties remain regarding spillover mechanisms, environmental drivers, surveillance integration, and outbreak preparedness. These persistent knowledge gaps limit the ability to predict, prevent, and respond effectively to future outbreaks. Objective: This review synthesises current evidence on Nipah virus across the human-animal-environment interface and identifies critical One Health knowledge gaps that hinder surveillance, risk forecasting, and health system preparedness. Methods: A structured narrative review was conducted using literature published between 1998 and 2025. Evidence was identified through systematic searches of major scientific databases and relevant outbreak reports and was synthesised according to three interconnected One Health domains: animal reservoirs and viral ecology, environmental and anthropogenic drivers of spillover, and human infection, transmission, and health system response. Additional emphasis was placed on diagnostics, surveillance, governance, and socio-behavioural determinants. Results: A total of 210 studies were included in the final synthesis. The evidence base was strongly concentrated in bat ecology and human clinical research, whereas environmental modelling, social science, governance, and implementation research remained comparatively limited. Key gaps included incomplete understanding of viral shedding dynamics in reservoir hosts, limited integration of climate and land-use data into spillover prediction models, insufficient evidence on asymptomatic infection and transmission patterns, restricted access to rapid diagnostics, fragmented surveillance systems, and weak cross-sectoral coordination. Significant deficiencies were also identified in governance frameworks, ethical preparedness, and evaluation of community-based prevention strategies. Conclusion: Current Nipah virus preparedness remains constrained by fragmented knowledge and limited operationalisation of the One Health approach. Strengthening integrated surveillance systems, ecological forecasting, decentralised diagnostics, implementation research, and cross-sector governance will be essential for improving outbreak prevention and response. Addressing these priorities can enhance resilience against Nipah virus and provide a framework for preparedness against future emerging zoonotic threats.