Natural History of Nipah Virus in Hamsters: Strain, Route, and Sex-Associated Variability Characterized Using Large Datasets to Inform Pre-Clinical Study Design

Nipah virus (NiV) comprises two strains, Malaysia and Bangladesh, associated with severe respiratory and/or neurological disease in humans. Experimentally infected Syrian hamsters demonstrate the full spectrum of clinical signs reported in humans, serving as valuable pre-clinical screening models for NiV disease. Medical countermeasure development relies on well-characterized disease models to understand disease progression, guiding pre-clinical and clinical trial design. Variability in NiV-disease presentation and outcome necessitates large group sizes in animal model natural history studies. To advance the use of hamsters in NiV pre-clinical studies, we analyzed in-house data from 19 independent studies comprising over 500 hamsters intranasally or intraperitoneally infected with NiV-Malaysia or NiV-Bangladesh. We demonstrate strain- and route-associated differences in clinical course, lethality, and viral loads, presenting cohort and individual data. These analyses provide key data to guide experimental design for pathogenesis, pathophysiology, and medical countermeasure studies.