Zoonotic spill-over infections with Borna disease virus 1 leading to fatal human encephalitis in 1999 to 2019. Zoonotic spill-over infections with Borna disease virus 1 leading to fatal human encephalitis in 1999 to 2019

Borna disease virus 1 (BoDV-1), the causative agent of Borna disease in horses, sheep, and other domestic mammals, was recently identified in five patients with severe to fatal encephalitis in Germany. However, information on case frequencies, clinical courses, and detailed epidemiological analyses is still lacking.Brain tissue from more than 50 encephalitis cases of putative viral origin were screened for BoDV-1 RNA. Positive results were confirmed by deep sequencing, antigen detection and determination of BoDV-1-reactive antibodies in serum and cerebrospinal fluid. Clinical and epidemiological data from infected patients were collected and analysed.BoDV-1 RNA and bornavirus-reactive antibodies were detected in eight newly analyzed encephalitis cases and the first human BoDV-1 isolate was obtained from one of the patients. Six of the eight BoDV-1-positive patients were apparently healthy until onset of fatal disease, whereas two were immunocompromised after solid organ transplantation. Typical initial symptoms were headache, fever, and confusion, followed by various neurologic signs, deep coma and severe brain stem involvement. Strikingly, BoDV-1-positive cases made up for 78% (7/9) of tested fatal encephalitic cases of unclear aetiology in one diagnostic centre. BoDV-1 sequence information and epidemiological analyses indicated independent spill-over transmissions most likely from the local wild animal reservoir.BoDV-1 infection has to be considered as a potentially lethal zoonosis in endemic regions with reported spill-over infections in horses and sheep. BoDV-1 infection can result in fatal encephalitis in immunocompromised and apparently healthy persons. Consequently, all severe encephalitis cases of unclear causality should be tested for bornaviruses especially in endemic regions.