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

Abstract

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.

Human Borna disease virus 1 (BoDV-1) encephalitis cases in the north and east of Germany

“…The viral sequence of the case described herein is marked with an arrow, clustering with various animal sequences (cluster 4). Colour code of the clusters according to [ 6 , 7 , 11 ]. The scale bar indicates nucleotide substitutions per site.…”

“…Prior to 2021, a prospective screening study from 2018 to 2020 for bornavirus infections in acute encephalitis cases of unknown etiology had detected three acute BoDV-1 encephalitis cases, all from the southern federal state of Bavaria [ 7 ]. All other previously published cases were also from Bavaria or with exposure linked to that specific federal state, except for one recently diagnosed case from a pathology archive in the federal state of Brandenburg in the north of Germany [ 11 ]. The now known four cases outside Bavaria are broadly distributed in the northern half of Germany’s established area endemic for animal BD.…”

“…In a recent study with 19 BoDV-1 encephalitis patients from Bavaria, 53% showed MRI changes at a mean of 11 ± 10 days after symptom onset [ 10 ]. Thus, depending on the time the MRI is performed, typical changes may not be visible as exemplified by the case from Brandenburg [ 11 ].…”

“…Controversy exists on its applicability [ 27 ]. We here show that the BoDV-1 sequence of case 2 from Thuringia belongs to cluster 4, a cluster encompassing BoDV-1 sequences from infected shrews and domestic animals in the neighbouring federal states of Saxony-Anhalt and Lower Saxony, as well as from humans and domestic mammals from adjacent Bavaria and domestic mammals from Brandenburg [ 11 ]. In some federal states, different clusters are present.…”

“…All these cases were fatal, and, prior to the cases described here, all but one patient lived in BD endemic areas in the southern German state of Bavaria. North of Bavaria, previously only one confirmed BoDV-1 encephalitis case living in the state of Brandenburg had been retrospectively diagnosed in 2020 from archived autopsy material [ 11 ]. BoDV-1 is believed to have a high case-fatality rate and the virus may be responsible for a considerable proportion of fatal encephalitis cases of previously unknown origin [ 6 , 7 ].…”