Henipaviruses are implicated in severe and frequently fatal pneumonia and encephalitis in humans. There are no approved vaccines or treatments available for human use, and testing of candidates requires the use of well-characterized animal models that mimic human disease. We performed a comprehensive and statistically-powered evaluation of the African green monkey model to define parameters critical to disease progression and the extent to which they correlate with human disease. African green monkeys were inoculated by the intratracheal route with 2.5 × 10(4) plaque forming units of the Malaysia strain of Nipah virus. Physiological data captured using telemetry implants and assessed in conjunction with clinical pathology were consistent with shock, and histopathology confirmed widespread tissue involvement associated with systemic vasculitis in animals that succumbed to acute disease. In addition, relapse encephalitis was identified in 100% of animals that survived beyond the acute disease phase. Our data suggest that disease progression in the African green monkey is comparable to the variable outcome of Nipah virus infection in humans.
Emerging infectious diseases involving zoonosis have become important global health problems. The 1998 outbreak of severe febrile encephalitis among pig farmers in Malaysia caused by a newly emergent paramyxovirus, Nipah virus, is a good example. This disease has the potential to spread to other countries through infected animals and can cause considerable economic loss. The clinical presentation includes segmental myoclonus, areflexia, hypertension, and tachycardia, and histologic evidence includes endothelial damage and vasculitis of the brain and other major organs. Magnetic resonance imaging has demonstrated the presence of discrete high-signal-intensity lesions disseminated throughout the brain. Nipah virus causes syncytial formation in Vero cells and is antigenically related to Hendra virus. The Island flying fox (Pteropus hypomelanus; the fruit bat) is a likely reservoir of this virus. The outbreak in Malaysia was controlled through the culling of >1 million pigs.