Hans Helmut Niller1, Klemens Angstwurm2, Dennis Rubbenstroth3, Kore Schlottau4, Arnt Ebinger4, Sebastian Giese5, Silke Wunderlich6, Bernhard Banas7, Leonie F Forth4, Donata Hoffmann4, Dirk Höper4, Martin Schwemmle5, Dennis Tappe8, Jonas Schmidt-Chanasit9, Daniel Nobach10, Christiane Herden10, Christoph Brochhausen11, Natalia Velez-Char11, Andreas Mamilos11, Kirsten Utpatel11, Matthias Evert11, Saida Zoubaa12, Markus J Riemenschneider12, Viktoria Ruf13, Jochen Herms13, Georg Rieder14, Mario Errath14, Kaspar Matiasek15, Jürgen Schlegel16, Friederike Liesche-Starnecker16, Bernhard Neumann2, Kornelius Fuchs2, Ralf A Linker2, Bernd Salzberger17, Tobias Freilinger18, Lisa Gartner19, Jürgen J Wenzel1, Udo Reischl1, Wolfgang Jilg1, André Gessner1, Jonathan Jantsch1, Martin Beer20, Barbara Schmidt1. 1. Institute of Clinical Microbiology and Hygiene, Regensburg University Hospital, Regensburg, Germany. 2. Department of Neurology, University of Regensburg, Regensburg, Germany. 3. Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Germany; Institute of Virology, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany. 4. Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Germany. 5. Institute of Virology, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany. 6. Department of Neurology, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany. 7. Department of Nephrology, Regensburg University Hospital, Regensburg, Germany. 8. Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany. 9. Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany; Faculty of Mathematics, Informatics and Natural Sciences, University of Hamburg, Hamburg, Germany. 10. Institute of Veterinary Pathology, Justus-Liebig-University Giessen, Giessen, Germany. 11. Institute of Pathology, University of Regensburg, Regensburg, Germany. 12. Department of Neuropathology, Regensburg University Hospital, Regensburg, Germany. 13. Center for Neuropathology and Prion Research, Ludwig-Maximilians-Universität München, Munich, Germany. 14. Department of Neurology, Klinikum Traunstein, Traunstein, Germany. 15. Section of Clinical & Comparative Neuropathology, Centre for Clinical Veterinary Medicine, Ludwig-Maximilians-Universität München, Munich, Germany. 16. Department of Neuropathology, Technical University of Munich, Munich, Germany. 17. Infectious Diseases, Regensburg University Hospital, Regensburg, Germany. 18. Department of Neurology, Klinikum Passau, Passau, Germany; Hertie-Institute for Clinical Brain Research, University Tuebingen, Tuebingen, Germany. 19. Department of Neurology, Klinikum Passau, Passau, Germany. 20. Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Germany. Electronic address: martin.beer@fli.de.
Abstract
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. FUNDING: German Federal Ministry of Education and Research.
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 humanpatients 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 infectedpatients were collected and analysed. FINDINGS:BoDV-1 RNA and bornavirus-reactive antibodies were detected in eight newly analysed encephalitis cases and the first humanBoDV-1 isolate was obtained from an unequivocally confirmed humanBoDV-1infection 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-1infection has to be considered as a potentially lethal zoonosis in endemic regions with reported spillover infections in horses and sheep. BoDV-1infection 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. FUNDING: German Federal Ministry of Education and Research.
Authors: Philip Eisermann; Dennis Rubbenstroth; Daniel Cadar; Corinna Thomé-Bolduan; Petra Eggert; Alexander Schlaphof; Frank Leypoldt; Martin Stangel; Thorsten Fortwängler; Florian Hoffmann; Andreas Osterman; Sabine Zange; Hans-Helmut Niller; Klemens Angstwurm; Kirsten Pörtner; Christina Frank; Hendrik Wilking; Martin Beer; Jonas Schmidt-Chanasit; Dennis Tappe Journal: Emerg Infect Dis Date: 2021-05 Impact factor: 6.883
Authors: Daniel Cadar; Valerie Allendorf; Vanessa Schulze; Rainer G Ulrich; Kore Schlottau; Arnt Ebinger; Bernd Hoffmann; Donata Hoffmann; Dennis Rubbenstroth; Gabriele Ismer; Chris Kibbey; Anna Marthaler; Jürgen Rissland; Frank Leypoldt; Martin Stangel; Jonas Schmidt-Chanasit; Franz J Conraths; Martin Beer; Timo Homeier-Bachmann; Dennis Tappe Journal: Emerg Microbes Infect Date: 2021-12 Impact factor: 7.163