Nipah virus (NiV), a highly pathogenic zoonotic henipavirus with case fatality rates ranging from 40 to 75%, remains a recurrent public health threat in Kerala, India. Despite rapid containment of previous outbreaks, repeated spillover events underscore persistent ecological and systemic vulnerabilities.

We conducted a narrative policy and systems analysis integrating outbreak investigations, national laboratory guidelines, ecological evidence, and recent global research priorities (2020–2026)n the objectives being to identify structural preparedness gaps and to propose operationally feasible enhancements.

Five strategic domains were identified: (1) optimization of diagnostic systems through a tiered hybrid laboratory model; (2) expansion of integrated One Health surveillance beyond bat reservoirs to livestock and ecological interfaces; (3) uniform health system preparedness across all tiers of care; (4) targeted digital outbreak intelligence systems adapted to localized transmission dynamics; and (5) spillover prevention strategies addressing human–animal interfaces. For each axis, resource implications, feasibility constraints, and implementation barriers are discussed.

Sustainable NiV preparedness in Kerala requires calibrated investment in diagnostic decentralization, cross-sectoral surveillance integration, workforce strengthening, and targeted digital augmentation. System-level interventions may serve as a template for other NiV-endemic regions facing recurrent zoonotic spillover.

Sustaining Nipah Virus Preparedness in Kerala: A Feasible, Integrated Operational Framework.

This graphical abstract illustrates a five-axis operational strategy to strengthen long-term preparedness against recurrent Nipah virus (NiV) outbreaks in Kerala, India. Building on documented outbreak containment successes, the framework shifts from reactive response to sustainable system reinforcement. The proposed model includes: (1) a tiered hybrid diagnostic system combining regional BSL-3 hubs with rapid specimen transport and district-level stabilization capacity; (2) integrated One Health surveillance linking public health, veterinary, and ecological sectors; (3) standardized healthcare preparedness across all tiers through simulation-based training, triage protocols, and PPE management; (4) targeted digital outbreak intelligence tools designed for localized clusters with privacy safeguards; and (5) proactive spillover prevention strategies addressing the human–animal interface through community engagement and farm biosecurity.

The framework balances feasibility, cost-awareness, and cross-sectoral coordination, offering a scalable model for regions facing recurrent zoonotic spillover threats.