Active Case Finding of Current Bornavirus Infections in Human Encephalitis Cases of Unknown Etiology, Germany, 2018–2020

Eisermann, Philip; Rubbenstroth, Dennis; Cadar, Dániel; Thomé-Bolduan, Corinna; Eggert, Petra; Schlaphof, Alexander; Leypoldt, Frank; Stangel, Martin; Fortwängler, Thorsten; Hoffmann, Florian; Osterman, Andreas; Zange, Sabine; Niller, Hans-Helmut; Angstwurm, Klemens; Pörtner, Kirsten; Frank, Christina; Wilking, Hendrik; Beer, Martin; Schmidt‐Chanasit, Jonas; Tappe, Dennis

doi:10.3201/eid2705.204490

Cited by 47 publications

(147 citation statements)

References 23 publications

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“…However, a recent retrospective study in a diagnostic center within the endemic are in the German federal state of Bavaria has demonstrated that BoDV-1 may be responsible for a considerable proportion of fatal encephalitis cases of previously unknown origin [ 2 ]. The same may apply to endemic regions in other parts of Germany as well as in Austria, Liechtenstein and Switzerland [ 7 , 17 ].…”

Section: Discussionmentioning

confidence: 99%

“…Cluster designations, host and geographic origin are indicated according to previously published work [ 1 – 3 , 7 , 9 – 13 ]. B The human case reported in this study is presented together with previously published BoDV-1 infections of alpacas and horses in Brandenburg and sequence-confirmed BoDV-1 infections of shrews (triangles), domestic mammals (circles) and humans (squares) with available geographic localization in known endemic regions [ 1 – 3 , 7 , 9 – 13 ]. Colors represent regional BoDV-1 sequence clusters (see Figure 1A).…”

Section: Case Presentationmentioning

confidence: 99%

“…The patient’s partner and her son had occasionally helped on the farm but never lived permanently on the premises. Bornavirus serology based on an indirect fluorescence antibody test and line blot with recombinant antigens [ 7 , 14 ] of the patient’s partner and her son yielded negative results in February 2020.…”

Section: Case Presentationmentioning

confidence: 99%

“…The virus has long been known for causing animal Borna disease (BD), a non-purulent meningomyelo-encephalitis of mainly horses and sheep in endemic regions of Germany, Liechtenstein, Switzerland and Austria [ 1 ]. Since 2018, the zoonotic potential of BoDV-1 has been demonstrated by at least 17 naturally acquired sporadic or transplant-related human encephalitis cases with 16 fatalities [ 2 – 7 ]. All sporadic human BoDV-1 cases occurred in the federal state of Bavaria in Southern Germany.…”

Section: Introductionmentioning

confidence: 99%

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Investigation of fatal human Borna disease virus 1 encephalitis outside the previously known area for human cases, Brandenburg, Germany – a case report

et al. 2021

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Background The true burden and geographical distribution of human Borna disease virus 1 (BoDV-1) encephalitis is unknown. All detected cases so far have been recorded in Bavaria, southern Germany. Case presentation A retrospective laboratory and epidemiological investigation of a 2017 case of fatal encephalitis in a farmer in Brandenburg, northeast Germany, demonstrated BoDV-1 as causative agent by polymerase chain reaction, immunohistochemistry and in situ hybridization. Next-generation sequencing showed that the virus belonged to a cluster not known to be endemic in Brandenburg. The investigation was triggered by a recent outbreak of animal Borna disease in the region. Multiple possible exposures were identified. The next-of-kin were seronegative. Conclusions The investigation highlights clinical awareness for human BoDV-1 encephalitis which should be extended to all areas endemic for animal Borna disease. All previously diagnosed human cases had occurred > 350 km further south. Further testing of shrews and livestock with Borna disease may show whether this BoDV-1 cluster is additionally endemic in the northwest of Brandenburg.

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Section: Discussionmentioning

confidence: 99%

Section: Case Presentationmentioning

confidence: 99%

Section: Case Presentationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Investigation of fatal human Borna disease virus 1 encephalitis outside the previously known area for human cases, Brandenburg, Germany – a case report

et al. 2021

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“…The variegated squirrel bornavirus 1 (VSBV-1; family Bornaviridae, species Mammalian 2 orthobornavirus) is an emerging zoonotic pathogen discovered in 2015 as the causative agent of fatal encephalitis of three men breeding exotic variegated squirrels in eastern Germany [1]. In 2018 and 2020, the virus was retrospectively shown to be responsible for two deadly encephalitis cases of animal caretakers in 2013 and 2007, respectively, in northern Germany [2,3]. The animal caretakers had occupational contact with exotic Prevost's squirrels in the same zoological garden.…”

Section: Introductionmentioning

confidence: 99%

Genomic and Micro-Evolutionary Features of Mammalian 2 orthobornavirus (Variegated Squirrel Bornavirus 1, VSBV-1)

2021

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Mammalian 2 orthobornavirus (VSBV-1) is an emerging zoonotic pathogen discovered in several exotic squirrel species and associated with fatal human encephalitis. The dynamics of VSBV-1 spread and evolution in its presumed natural hosts are unknown. Here, we present the phylogeny, micro-evolution, cross-species transmission and spread of VSBV-1 at a temporal and spatial resolution within the limits of animal husbandry. The results showed that VSBV-1 can be classified into six distinct groups and that the most recent common ancestor of the known German strains emerged at least 20 years ago. We here demonstrate that the genetic diversity of the VSBV-1 groups is shaped primarily by in situ evolution and most of the amino acid changes are deleterious polymorphisms removed by purifying selection. Evidence of adaptive evolution has been found in the G and L genes which might have an influence on transmission fitness. Furthermore, there was also evidence for some form of adaptive changes in the glycoprotein which suggests that many sites might be subjected to positive pressure evolving under episodic directional selection, indicating past occurrence of positive selection. Host switching events were detected as dominant evolutionary mechanisms driving the virus-host associations. Virus spread by animal trade followed by subsequent local micro-evolution in zoos and holdings is responsible for diversifying strains. Time-resolved phylogeny indicated that Prevost’s squirrels might be the original squirrel species carrying and seeding the virus in Germany. This study provides the first insight into the ecology and micro-evolutionary dynamics of this novel viral pathogen in the captive exotic squirrel population under artificial ecological conditions (zoos and animal husbandry) and co-housing of different squirrel species.

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Borna Disease (Borna Disease Virus-1, BoDV-1)

Böhmer¹,

Bauswein²

2023

Zoonoses: Infections Affecting Humans and Animals

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Active Case Finding of Current Bornavirus Infections in Human Encephalitis Cases of Unknown Etiology, Germany, 2018–2020

Cited by 47 publications

References 23 publications

Investigation of fatal human Borna disease virus 1 encephalitis outside the previously known area for human cases, Brandenburg, Germany – a case report

Investigation of fatal human Borna disease virus 1 encephalitis outside the previously known area for human cases, Brandenburg, Germany – a case report

Genomic and Micro-Evolutionary Features of Mammalian 2 orthobornavirus (Variegated Squirrel Bornavirus 1, VSBV-1)

Borna Disease (Borna Disease Virus-1, BoDV-1)

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