The Silent Spillover Threat: Nipah Virus Epidemiology, Pathogenesis, Clinical Manifestations, and Advances in Therapeutics and Vaccine Development.

Nipah virus (NiV) is an animal-borne RNA virus of the genus Henipavirus that poses a significant global health threat. This threat is driven by the virus's high mortality rate, its capacity to cause epidemics, and the lack of licensed therapeutic interventions or vaccines. Since its initial identification during the 1998-1999 outbreak in Malaysia and Singapore, recurrent episodes have occurred primarily in Bangladesh and India, with mortality rates frequently exceeding 70%. Fruit bats of the genus Pteropus serve as the biological host for the virus. Transmission to humans occurs via contact with infected wildlife, consumption of contaminated products, such as freshly harvested date palm sap, or direct person-to-person exposure. Other modes of transmission, such as transplacentally or via breast milk, are still under investigation. The clinical presentation of NiV infection varies widely, from mild flu-like symptoms to life-threatening respiratory disease and acute encephalitis. It frequently attacks the nervous system, which can lead to coma, permanent neurological damage, or relapsing encephalitis. The virus enters host cells via ephrin-B2/B3 receptors, enabling systemic dissemination and infiltration of the central nervous system. Diagnosis relies primarily on RT-PCR and serological assays, and virus isolation requires high-containment laboratories. Management remains largely supportive, as no approved antiviral therapy exists. Experimental agents, such as remdesivir, favipiravir, and monoclonal antibodies such as m102.4, have shown promise in preclinical studies. Multiple vaccine platforms-including subunit, viral vector, mRNA, and nanoparticle-based approaches-are under development, though none is yet licensed for human use. Strengthened surveillance, infection control measures, and continued research are essential to mitigate the threat posed by this emerging pathogen. This review summarizes current knowledge on NiV, including its virology, epidemiology, pathogenesis, transmission, and recent progress in therapeutic and vaccine development.