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Classical Borna Disease virus causes fatal encephalitis

Short Messages

Study results published in New England Journal of Medicine

For a long time Classical Borna Disease virus (BoDV-1) was considered to be the causative agent of often fatal encephalitis in horses, sheep and other domestic mammals. The risk potential for humans, however, was discussed most controversially, until in March the Robert-Koch Institute first reported clearly confirmed cases. Backgrounds and scientific details have now been published in the renowned scientific journal „New England Journal of Medicine“ (NEJM).

In 2016, three cases of severe encephalitis occurred in Germany in organ recipients from a single donor. Two of the patients died about six months after transplantation, the third one developed severe disease but survived the infection. A consortium of different medical and scientific institutions under the direction of the Friedrich-Loeffler-Institut succeeded in identifying transmission of BoDV-1 by the transplanted organs as cause of the disease. The pathogen could be detected with different methods, and genome sequence analysis revealed a close relationship with strains from horses and shrews in the home region of the donor in Bavaria. Similar results were obtained for another independent case of infection from Bavaria, also published in NEJM. The latter case, however, where the patient also died from encephalitis, is not associated with organ transplantation.

Thus, according to the latest knowledge BoDV-1 infection is a zoonosis. „The known reservoir of the virus is the bicolored white-toothed shrew, which however does not develop disease itself. Clinical disease, often severe, occurs after transmission to other species, including humans“, says Martin Beer, corresponding author of the study. Distribution of the virus in bicolored white-toothed shrew populations seems to be limited to certain regions of Germany, Austria, Switzerland, and Liechtenstein. So far, the transmission route to humans is unknown. This and other questions with regard to the significance of zoonotic bornavirus infections are the subject of current research projects of the „Zoonotic Bornavirus Consortium“ (ZooboCo) funded by the Federal Ministry of Education and Research. 

After the now published cases had been reported, further cases of fatal BoDV-1 infections in humans were detected. All patients originated from the known area of distribution of the virus, and the analyzed gene sequences indicate independent regional sources of infection. In none of these cases, an association of the infection with organ transplantation could be found. 

In contrast to earlier and meanwhile disproved hypotheses, the disease is a rare zoonotic infection. Human-to-human transmission by organ transplantation seems to be an isolated event and is not to be considered as a new specific risk associated with organ transplantation. 

New England Journal of Medicine:
Fatal Encephalitic Borna Disease Virus 1 in Solid-Organ Transplant Recipients
DOI: 10.1056/NEJMc1803115

Contacts
Corresponding author:
Prof. Dr. Martin Beer (Chamber recognized specialist in virology)
Friedrich-Loeffler-Institut (FLI), Institute of Diagnostic Virology
martin.beerflide
+49 38 3517 1200

Questions on transplantation medicine:
Dr. med. Axel Rahmel
German Organ Transplantation Foundation
axel.rahmeldsode
+49 (69) 677 328 - 9000      

Univ.-Prof. Dr. med. Bernhard Banas, MBA
Department of Nephrology
Regensburg University Hospital
bernhard.banasklinik.uni-regensburgde 
+49-941-944-7301

Foto: Probenuntersuchung im FLI (© FLI)

© FLI

Links

Fatal Encephalitic Borna Disease Virus 1 in Solid-Organ Transplant Recipients. N Engl J Med 2018; 379:1377-1379
DOI: 10.1056/NEJMc1803115

Homepage of the projekt ZooBoCo