Tuesday, March 27, 2018

ECDC: RRA On New Cluster Of Borna Disease Virus 1 - Germany


Readers with good memories will recall that just over three years ago, in ECDC: Rapid Risk Assessment On Novel Bornavirus Detected In EU, we looked at the apparent zoonotic transmission of a new bornavirus from variegated squirrels (Sciurus variegatoides) to three humans in the Saxony-Anhalt state of Germany.
All three cases died of acute fatal encephalitis, all raised imported (from South America) Variegated Squirrels, and all three tested positive for a previously unidentified bornavirus, which was also detected in at least one squirrel.
Three months later the ECDC announced that no additional cases had been detected (see RRA Update May 2015) where they wrote:
This cluster of acute fatal encephalitis in three breeders of variegated squirrels in the German state of Saxony-Anhalt is an unusual public health event with a potentially high impact on the small group of people who are exposed to this particular squirrel species.
Further investigations are ongoing to describe these cases. The role of a newly identified Borna disease virus isolate in the aetiology of these cases remains to be confirmed. Further work is required to identify natural hosts, reservoirs, vectors, transmission routes, and distribution.

Since then I've seen very little regarding bornavirus in Europe - at least until last October when Germany's FLI announced:
Research consortium aims at dangerous bornaviruses

10/13/2017 Press Releases

Greifswald - Insel Riems, 13 October 2017. Since its first description in 2015 four fatal cases of infections with the novel Variegated Squirrel Bornavirus VSBV-1 have been reported in Germany. This unexpected high incidence gives reason for serious concerns with regard to the transmissibility of VSBV-1 and related bornaviruses to humans and the pathogenic potential of these viruses. 

Therefore, the Research Consortium Zoonotic Bornavirus – abbreviated ZooBoCo – was launched on October 12 with a kick-off meeting. It is funded by the Federal Ministry of Education and Research (BMBF) in the frame of the “National Research Network Zoonotic Infectious Diseases”. Zoonoses are infectious diseases which can be transmitted between humans and animals.

So far, the exact number of squirrels or humans which are currently infected with or exposed to potentially dangerous bornaviruses is unknown. Investigations of approximately 800 squirrels from about 90 holdings revealed 28 positive results. Furthermore, it is unclear if only squirrels are able to transmit these viruses or if another host reservoir exists which remains to be identified. 

(Continue . . . )

While these squirrel related cases involved a new, never described before bornavirus - as the ECDC explains (below) - a number of other bornaviruses (and hosts) have been identified.
Taxonomy of Bornavirus
The genus Bornavirus includes eight species, according to the last International Committee on Taxonomy of Viruses (ICTV) accepted taxonomy, and 16 viruses. Five species include 12 avian bornaviruses (Passeriform 1 bornavirus, Passeriform 2 bornavirus,Psittaciform 1 bornavirus, Psittaciform 2 bornavirus and Waterbird 1 bornavirus), one species includes one reptile virus (Elapid 1 bornavirus), and two species include three mammalian viruses (Mammalian 1 bornavirus and Mammalian 2 bornavirus). In the Mammalian 1 bornavirus species, there are two viruses: Borna disease virus 1 and 2 (BoDV-1 and BoDV-2); in the Mammalian 2 bornavirus species there is one virus: the variegated squirrel bornavirus 1 (VSBV-1) [3].
Fast forward to the present day, and Germany has now reported 4 additional (three fatal) cases of Borna disease infection, three of which had recently received organ transplants from the same donor.
These latest cases involve BoDV-1 and not the VSBV-1 which produced the 2015 squirrel-related cluster.
The 4th (and possibly a 5th case) are described by the ECDC:
The additional case of encephalitis due to BoDV-1 was found during the investigation of this transmission cluster. No epidemiological link could be identified between this isolated case and the transplantation cluster.
Another patient with encephalitis is currently under investigation; this patient has not received any organ transplantation either.
First a new story from the ECDC and then the link to yesterday's Rapid Risk Assessment, after which I'll return with a postscript.
First cases of Borna disease virus 1 (BoDV-1) transmission through organ transplantation – ECDC risk assessment

26 Mar 2018

Germany reported four human cases of acute encephalitis or encephalopathy caused by infection with Borna disease virus 1 (BoDV-1). Three of the cases belong to a cluster of solid organ recipients. This is the first time that a possible BoDV-1 transmission through organ transplantation has been reported.

On 7 March 2018, Germany reported four human cases of acute encephalitis or encephalopathy caused by infection with Borna disease virus 1 (BoDV-1). Three of the cases belong to a cluster of solid organ recipients from a single donor from southern Germany, two of them died. One additional case of encephalitis due to BoDV-1, who also died, was also found in southern Germany.

This is the first time that a possible BoDV-1 transmission through organ transplantation has been reported. Infection with Borna disease virus 1 (BoDV-1) is very rare in humans, however it can cause severe disease (acute encephalitis).

Transplantation professionals and clinicians should be aware of possible BoDV-1 related encephalitis and the possibility of transmission through donated organs especially in areas where Borna disease is endemic, states today’s ECDC risk assessment.

Endemic areas so far have been identified in central Europe including eastern and southern Germany, the eastern part of Switzerland, Liechtenstein, the most western federal state of Austria and more recently in Upper Austria.

The bicoloured white-toothed shrew has been proposed as the animal reservoir of BoDV-1. The routes of transmission of BoDV-1 to humans from the animal reservoir, remain unknown and the zoonotic transmission pathways should be further investigated, says the risk assessment.

Viral encephalitis is literally inflammation of the brain, and can be caused by a wide variety of infections, including bacterial, fungal, and parasitic - but is most often caused by viral infection.

As the 2017 review below illustrates, despite advances in laboratory testing, the cause of more than half of all viral encephalitis infections remain unknown.

Viral Encephalitis of Unknown Cause: Current Perspective and Recent Advances

Peter G. E. Kennedy,1,* Phenix-Lan Quan,2 and W. Ian Lipkin2
Stacey Schultz-Cherry, Academic Editor


Viral encephalitis causes acute inflammation of the brain parenchyma and is a significant cause of human morbidity and mortality. Although Herpes Simplex encephalitis is the most frequent known cause of fatal sporadic encephalitis in humans, an increasingly wide range of viruses and other microbial pathogens are implicated.
Up to 60% of cases of presumed viral encephalitis remain unexplained due to the failure of conventional laboratory techniques to detect an infectious agent. High-throughput DNA sequencing technologies have the potential to detect any microbial nucleic acid present in a biological specimen without any prior knowledge of the target sequence. While there remain challenges intrinsic to these technologies, they have great promise in virus discovery in unexplained encephalitis.
        (Continue . . . .)

Scientists – with better tools available today – are identifying `new’ viruses all of the time. A few recently `discovered' viruses include:
  • The human metapneumovirus (HMPV) was identified in Dutch children with bronchiolitis about a 17 years ago.  Since then, it has been found to be ubiquitous around the world, and responsible for a significant percentage of childhood respiratory infections . . . yet until 2001, no one knew it existed.
  • Human Bocavirus-infection (HBoV) wasn’t identified until 2005, when it was detected in 48 (9.1%) of 527 children with gastroenteritis in Spain (cite).  It has since been found around the globe using PCR testing.
  • In 2014 a new tick borne virus was discovered in Missouri (see  CDC & EID Journal On The Recently Discovered Bourbon Virus)
  • While before that, in 2012, another tick borne virus - similar to SFTS in Asia - was also identified (see MMWR: Heartland Virus Disease — United States, 2012–2013).
It is likely that rare, sporadic BoDV-1 infections have been flying under the radar in Europe for years - producing only mild illness or clumped within that 60% unidentified category - and it is only now, with better testing, we are finally recognizing them.
But it is also possible this is an emerging virus, and that the number of cases are actually increasing.
With better testing, heightened awareness, and a newly formed research consortium, we should get better answers in the next couple of years.

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