Zoonotic spillover infections with Borna disease virus 1 leading to fatal human encephalitis, 1999–2019: an epidemiological investigation
Creators: name: Niller, Hans Helmut
name: Angstwurm, Klemens
name: Rubbenstroth, Dennis
name: Schlottau, Kore
name: Ebinger, Arnt
name: Giese, Sebastian
name: Wunderlich, Silke
name: Banas, Bernhard
name: Forth, Leonie F.
name: Hoffmann, Donata
name: Höper, Dirk
name: Schwemmle, Martin
name: Tappe, Dennis
name: Schmidt-Chanasit, Jonas
name: Nobach, Daniel
name: Herden, Christiane
name: Brochhausen, Christoph
name: Velez-Char, Natalia
name: Mamilos, Andreas
name: Utpatel, Kirsten
name: Evert, Matthias
name: Zoubaa, Saida
name: Riemenschneider, Markus J.
name: Ruf, Viktoria
name: Herms, Jochen
name: Rieder, Georg
name: Errath, Mario
name: Matiasek, Kaspar
name: Schlegel, Jürgen
name: Liesche-Starnecker, Friederike
name: Neumann, Bernhard
name: Fuchs, Kornelius
name: Linker, Ralf A.
name: Salzberger, Bernd
name: Freilinger, Tobias
name: Gartner, Lisa
name: Wenzel, Jürgen J.
name: Reischl, Udo
name: Jilg, Wolfgang
name: Gessner, André
name: Jantsch, Jonathan
name: Beer, Martin
name: Schmidt, Barbara
Publisher: name: Universität Regensburg
Year: 2020
Subjects: subject: 610 Medizin

description: BACKGROUND: In 2018-19, Borna disease virus 1 (BoDV-1), the causative agent of Borna disease in horses, sheep, and other domestic mammals, was reported in five human patients with severe to fatal encephalitis in Germany. However, information on case frequencies, clinical courses, and detailed epidemiological analyses are still lacking. We report the occurrence of BoDV-1-associated encephalitis in cases submitted to the Institute of Clinical Microbiology and Hygiene, Regensburg University Hospital, Regensburg, Germany, and provide a detailed description of newly identified cases of BoDV-1-induced encephalitis. METHODS: All brain tissues from 56 encephalitis cases from Bavaria, Germany, of putative viral origin (1999-2019), which had been submitted for virological testing upon request of the attending clinician and stored for stepwise diagnostic procedure, were systematically screened for BoDV-1 RNA. Two additional BoDV-1-positive cases were contributed by other diagnostic centres. 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. FINDINGS: BoDV-1 RNA and bornavirus-reactive antibodies were detected in eight newly analysed encephalitis cases and the first human BoDV-1 isolate was obtained from an unequivocally confirmed human BoDV-1 infection from the endemic area. Six of the eight BoDV-1-positive patients had no record of immunosuppression before the onset of fatal disease, whereas two were immunocompromised after solid organ transplantation. Typical initial symptoms were headache, fever, and confusion, followed by various neurological signs, deep coma, and severe brainstem involvement. Seven of nine patients with fatal encephalitis of unclear cause were BoDV-1 positive within one diagnostic centre. BoDV-1 sequence information and epidemiological analyses indicated independent spillover transmissions most likely from the local wild animal reservoir. INTERPRETATION: BoDV-1 infection has to be considered as a potentially lethal zoonosis in endemic regions with reported spillover infections in horses and sheep. BoDV-1 infection can result in fatal encephalitis in immunocompromised and apparently healthy people. Consequently, all severe encephalitis cases of unclear cause should be tested for bornaviruses especially in endemic regions.