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Study Confirms Deadly New Cases of Human Borna Disease Virus 1 in Germany

JAN 10, 2020 | GRANT M. GALLAGHER
For decades, the potential zoonotic transmission of Borna disease virus 1 (BoDV-1), an infectious neurological syndrome mainly seen in horses and other animals, has been debated. Previous research has sought to link human infection to various psychiatric disorders such as bipolar disorder or schizophrenia, but results are contested.

On more stable footing are recent reports of human BoDV-1 infection leading to severe and fatal encephalitis in Germany. A new study in The Lancet Infectious Diseases provides detailed description of new cases, establishing BoDV-1 infection as a potentially lethal zoonosis which can impact immunocompromised and healthy individuals.

The investigators studied brain tissue from encephalitis and encephalopathy cases with possible viral cause that were sent to the diagnostic section of the Institute of Clinical Microbiology and Hygiene at Regensburg University Hospital, Germany, between January 1995, and August 2018.

A total of 56 patient samples were examined retrospectively for bornavirus infections through RNA testing. Of these patients, 28 (50%) had diagnosed causes of neurological disease. Of the 28, 15 had been diagnosed with malignant neoplasia, 10 with infectious diseases, 1 with an autoimmune disorder, 1 with an intracranial hemorrhage, and 1 with a cerebral infarction.

The remaining 28 patients did not have a diagnosed cause of neurological disease. Of these patients, 9 had died from encephalitis and 15 had survived the disease.

Brain tissue was tested for BoDV-1 in all 56 patients, using 2 independent quantitative reverse transcription polymerase chain reaction tests.

Of the 9 fatal cases of encephalitis, 7 tested positive for BoDV-1 RNA. None of the samples from the 28 patients with identifiable diagnosis and none of the samples from the 19 remaining undiagnosed cases tested positive for BoDV-1 RNA.

Study authors analyzed the 7 BoDV-1 positive cases, which included a previously published kidney transplant recipient, along with 2 additional fatal infections that had been diagnosed by other centers in Bavaria.

The 8 newly identified BoDV-1 infected patients died between 1999 and 2019. All were white European ethnicity between 17 and 65 years of age. The mean age of patients was 38.6 years (standard deviation (SD) 15). The patients included 2 men and 6 women.

Most patients (6) had no known record of immunosuppression before the onset of symptoms, but 2 had received immunosuppressive therapy after organ transplantation 3 or 16 months before hospitalization.

In 7 of 8 cases, disease onset was accompanied by headache and fever. In all cases, neurological symptoms arose, including unsteady gait, memory deficits, seizures, confusion, and gradual loss of consciousness. Patients entered comas after hospitalization and died within 16 to 57 days (mean 39.5 days [SD 14.2]).

All patients were given antibiotics, acyclovir, or ganciclovir. Steroids were given to 4 patients.

All human BoDV-1 sequences differed from each other and from widely used laboratory strains, making the possibility of cross-sample contamination more unlikely than in some past studies on BoDV-1’s potential relation to psychiatric disorder. Several sequences were found closely related to equine and sheep strains in Bavaria, lending support for independent zoonotic transmission from local sources as a means of infection.

Of 8 patients, 7 lived in rural or suburban areas where contact with bicolored white-toothed shrews (a suspected carrier animal) was possible.  

The cases described raise the number of confirmed and published human BoDV-1 infections in the endemic area of Germany to 14.

“Our data suggest that, although BoDV-1-associated encephalitis seems to be a relatively rare event in absolute numbers, it might constitute a high proportion of severe to fatal encephalitis cases of unknown cause within BoDV-1-endemic areas, in particular in immunosuppressed patients. Therefore, BoDV-1 has to be included in future differential diagnostic strategies for cases,” the study authors noted.

The investigators concluded by describing cases in which it would be especially important to screen for BoDV-1.

Clinicians should consider bornavirus infection in patients with febrile episodes featuring quickly evolving nervous system affections of unknown origin, with increased leucocyte, protein, and lactate concentrations in cerebrospinal fluid, diffuse slowing in electroencephalography during the early disease course, bilateral involvement of the frontal and temporal lobes, basal ganglia, brainstem, and insular cortex in MRI, living in rural or suburban areas with endemic BoDV-1, and potential contact with wild animals (including indirect contact, such as through a domestic cat bringing  small animals into the home).  
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