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Research Project: Viral Ecology of Henipaviruses in Endemic Settings and Intervention Strategies to Prevent their Spread to Domestic Animals

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Title: Natural history of nipah virus in hamsters: Strain, route, and sex-associated variability characterized using large datasets to inform pre-clinical study design

Author
item DAVIES, KATHERINE - Oak Ridge Institute For Science And Education (ORISE)
item WELCH, STEPHEN - Centers For Disease Control And Prevention (CDC) - United States
item COLEMAN-MCCRAY, JOANN - Centers For Disease Control And Prevention (CDC) - United States
item SORVILLO, TERESA - Centers For Disease Control And Prevention (CDC) - United States
item AIDA-FICKEN, VIRGINIA - Centers For Disease Control And Prevention (CDC) - United States
item SPIROPOULOU, CHRISTINA - Centers For Disease Control And Prevention (CDC) - United States
item SPENGLER, JESSICA - Centers For Disease Control And Prevention (CDC) - United States

Submitted to: Journal of Infectious Diseases
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/29/2025
Publication Date: 11/17/2025
Citation: Davies, K.A., Welch, S.R., Coleman-Mccray, J.D., Sorvillo, T.E., Aida-Ficken, V., Spiropoulou, C.F., Spengler, J.R. 2025. Natural history of nipah virus in hamsters: Strain, route, and sex-associated variability characterized using large datasets to inform pre-clinical study design. Journal of Infectious Diseases. Article jiaf549. https://doi.org/10.1093/infdis/jiaf549.
DOI: https://doi.org/10.1093/infdis/jiaf549

Interpretive Summary: Henipaviruses, including the Nipah and Hendra viruses, are highly lethal pathogens causing severe respiratory and neurological disease in humans. Mortality rates range from 30% to 80%, and no approved treatments are currently available. These viruses pose a serious global health threat, particularly in regions where outbreaks occur frequently. Here, we analyzed in-house data from 19 independent historic studies, comprising over 500 hamsters infected with Nipah virus to demonstrate strain-, route- and dose- associated variability in clinical presentation, outcome and viral loads. This data can be used to guide experimental design for pre-clinical evaluation of therapeutics and pathogenesis studies.

Technical Abstract: 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.