Zoonotic spillover infections with Borna disease virus 1 leading to fatal human encephalitis, 1999-2019: an epidemiological investigation.
Abstract: 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. 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. 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. 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. German Federal Ministry of Education and Research.
Copyright © 2020 Elsevier Ltd. All rights reserved.
Publication Date: 2020-01-07 PubMed ID: 31924550DOI: 10.1016/S1473-3099(19)30546-8Google Scholar: Lookup
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Summary
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The study investigates an infectious virus known as Borna disease virus 1 (BoDV-1), which originated from animals and caused fatal brain inflammation (encephalitis) in humans in Germany between 1999 and 2019. The research provides critical analysis and information regarding the prevalence, clinical progression, and epidemiological patterns of the virus.
Study Methodology
- Researchers focused on 56 encephalitis subjects from Bavaria, Germany, believed to be of viral origin between 1999 and 2019. The subjects’ brain tissue samples were submitted for viral testing upon request from the attending physician and stored for a step-by-step diagnostic procedure.
- The researchers methodically screened the brain tissues for the presence of BoDV-1 RNA, a molecule that carries instructions from DNA to control protein synthesis which indicates the presence of the BoDV-1 virus.
- Two additional BoDV-1-positive cases were included in the investigation, provided by other diagnostic centers.
- Positive results for BoDV-1 were validated through deep sequencing, antigen detection, and determination of BoDV-1-reactive antibodies in blood serum and cerebrospinal fluid.
- Researchers collected and analyzed clinical and epidemiological data from the infected patients.
Study Findings
- The researchers found BoDV-1 RNA and bornavirus-reactive antibodies in eight of the newly analyzed encephalitis cases. The first human BoDV-1 isolate was obtained from a confirmed human BoDV-1 infection from an endemic area.
- Six out of the eight BoDV-1-positive patients were not recorded as immunocompromised prior to the onset of the disease. However, two patients had become immunocompromised after undergoing solid organ transplantation.
- Typically, initial symptoms of the BoDV-1 infection included headache, fever, and confusion, which evolved into various neurological signs, deep coma, and severe brainstem involvement.
- A significant seven out of nine patients with fatal encephalitis of uncertain cause tested positive for BoDV-1 within one diagnostic centre.
Epidemiological Analysis and Conclusions
- An analysis of the BoDV-1 sequence information and epidemiological data suggested independent spillover transmissions – instances where the virus jumped from animals to humans – likely originating from the local wild animal reservoir.
- BoDV-1 infection is concluded as a potentially lethal zoonosis (disease that can be transmitted from animals to humans) in endemic regions with reported spillover infections in horses and sheep.
- The researchers emphasized that BoDV-1 infection can result in fatal encephalitis both in immunocompromised patients and apparently healthy individuals.
- It was recommended that all severe encephalitis cases of unclear cause should be tested for bornaviruses, especially in regions where the virus is endemic. This study was funded by the German Federal Ministry of Education and Research.
Cite This Article
APA
Niller HH, Angstwurm K, Rubbenstroth D, Schlottau K, Ebinger A, Giese S, Wunderlich S, Banas B, Forth LF, Hoffmann D, Höper D, Schwemmle M, Tappe D, Schmidt-Chanasit J, Nobach D, Herden C, Brochhausen C, Velez-Char N, Mamilos A, Utpatel K, Evert M, Zoubaa S, Riemenschneider MJ, Ruf V, Herms J, Rieder G, Errath M, Matiasek K, Schlegel J, Liesche-Starnecker F, Neumann B, Fuchs K, Linker RA, Salzberger B, Freilinger T, Gartner L, Wenzel JJ, Reischl U, Jilg W, Gessner A, Jantsch J, Beer M, Schmidt B.
(2020).
Zoonotic spillover infections with Borna disease virus 1 leading to fatal human encephalitis, 1999-2019: an epidemiological investigation.
Lancet Infect Dis, 20(4), 467-477.
https://doi.org/10.1016/S1473-3099(19)30546-8 Publication
Researcher Affiliations
- Institute of Clinical Microbiology and Hygiene, Regensburg University Hospital, Regensburg, Germany.
- Department of Neurology, University of Regensburg, Regensburg, Germany.
- 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.
- Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Germany.
- 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.
- Department of Neurology, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany.
- Department of Nephrology, Regensburg University Hospital, Regensburg, Germany.
- Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Germany.
- Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Germany.
- 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.
- Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.
- Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany; Faculty of Mathematics, Informatics and Natural Sciences, University of Hamburg, Hamburg, Germany.
- Institute of Veterinary Pathology, Justus-Liebig-University Giessen, Giessen, Germany.
- Institute of Veterinary Pathology, Justus-Liebig-University Giessen, Giessen, Germany.
- Institute of Pathology, University of Regensburg, Regensburg, Germany.
- Institute of Pathology, University of Regensburg, Regensburg, Germany.
- Institute of Pathology, University of Regensburg, Regensburg, Germany.
- Institute of Pathology, University of Regensburg, Regensburg, Germany.
- Institute of Pathology, University of Regensburg, Regensburg, Germany.
- Department of Neuropathology, Regensburg University Hospital, Regensburg, Germany.
- Department of Neuropathology, Regensburg University Hospital, Regensburg, Germany.
- Center for Neuropathology and Prion Research, Ludwig-Maximilians-Universität München, Munich, Germany.
- Center for Neuropathology and Prion Research, Ludwig-Maximilians-Universität München, Munich, Germany.
- Department of Neurology, Klinikum Traunstein, Traunstein, Germany.
- Department of Neurology, Klinikum Traunstein, Traunstein, Germany.
- Section of Clinical & Comparative Neuropathology, Centre for Clinical Veterinary Medicine, Ludwig-Maximilians-Universität München, Munich, Germany.
- Department of Neuropathology, Technical University of Munich, Munich, Germany.
- Department of Neuropathology, Technical University of Munich, Munich, Germany.
- Department of Neurology, University of Regensburg, Regensburg, Germany.
- Department of Neurology, University of Regensburg, Regensburg, Germany.
- Department of Neurology, University of Regensburg, Regensburg, Germany.
- Infectious Diseases, Regensburg University Hospital, Regensburg, Germany.
- Department of Neurology, Klinikum Passau, Passau, Germany; Hertie-Institute for Clinical Brain Research, University Tuebingen, Tuebingen, Germany.
- Department of Neurology, Klinikum Passau, Passau, Germany.
- Institute of Clinical Microbiology and Hygiene, Regensburg University Hospital, Regensburg, Germany.
- Institute of Clinical Microbiology and Hygiene, Regensburg University Hospital, Regensburg, Germany.
- Institute of Clinical Microbiology and Hygiene, Regensburg University Hospital, Regensburg, Germany.
- Institute of Clinical Microbiology and Hygiene, Regensburg University Hospital, Regensburg, Germany.
- Institute of Clinical Microbiology and Hygiene, Regensburg University Hospital, Regensburg, Germany.
- Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Germany. Electronic address: martin.beer@fli.de.
- Institute of Clinical Microbiology and Hygiene, Regensburg University Hospital, Regensburg, Germany.
MeSH Terms
- Animals
- Antibodies, Viral / blood
- Borna Disease / complications
- Borna Disease / epidemiology
- Borna Disease / virology
- Borna disease virus / genetics
- Encephalitis / etiology
- Encephalitis / mortality
- Encephalitis / pathology
- Germany / epidemiology
- Horses / genetics
- Humans
- RNA, Viral / genetics
- Sheep / genetics
- Virus Replication
- Zoonoses
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