Press release in Germany: three deaths due to Borna disease virus

Sorry for the long post. Translation by Google and me. Mistakes and bold/italics by me.
http://www.zeit.de/news/2018-03/27/...er-menschen-doch-gefaehrlich-180327-99-652639


Berlin/Greifswald-Riems (dpa)

Three patients in Germany have died as a result of a viral disease previously only seen in animals.

Those affected had encephalitis, which was most likely triggered by the classic borna disease virus, said the head of the Institute for Viral Diagnostics at the Friedrich Loeffler Institute (FLI) in Greifswald, Martin Beer.

The Robert Koch Institute (RKI) in Berlin and the scientists assume that it is the first confirmed borna disease virus evidence in humans at all. The RKI recently reported the cases.

Two of the patients were infected with high probability via transplanted organs of the same donor. "We assume a very rare individual case in this event," Beer said.
The third death is not related to transplantation, but details were not disclosed.

Researchers from FLI, the federal research institute for animal health, were called in by the end of 2016 from the university clinics where the patients had been treated.
The cause of the brain inflammations was not to be found with the standard diagnostics.

The FLI was already involved in 2015 in the clarification of three unclear cases of brain inflammation:
In deceased breeders of variegated squirrels in Saxony-Anhalt, they found a new borna disease virus (variegated squirrel borna virus, VSBV-1).

This time, the researchers discovered, thanks to special analysis methods, the classic Borna disease virus (BoDV-1) known from horses and sheep.
"So far, brain inflammation has not been sought for this [virus] because there was no evidence that it could play a role," said Beer.

A consequence of the new findings for human medicine is that in unexplained cases of brain inflammation borna disease virus should be tested for- in addition to other possible pathogens.

The aim now is to develop new detection methods so that Bornavirus infections can be detected at an early or chronic stage, said Hartmut Hengel, President of the Society for Virology and virologist at the University of Freiburg.

Such an infection would have been present in the case of the organ donor, so that the person appeared healthy and organs could be transplanted. A third organ recipient of the same donor survived the infection.

However, Hengel currently does not think that further arrangements to safeguard organ donation are possible - nor is it necessary given the apparent rarity of the virus.
"We still do not have the tools to test organ donors," the professor said. It is also unclear whether pre-existing conditions play a role in the now documented cases.

In horses, bornavirus infections have been known for more than 100 years - with possible brain inflammation.
Diseased animals show movement disorders, behavioral problems and often die as a result.

How the animals are infected, is not finally clear. It is known, however, that in Germany the pathogen multiplies in bicolored shrew and can be excreted by them.

The pathway to infection in humans is unclear. Generally, according to RKI, the virus rarely occurs; in demarcated areas in eastern and southern Germany as well as parts of Austria, Liechtenstein and Switzerland. The virus is named after the city of Borna near Leipzig.

There has been a scientific controversy surrounding the virus and its dangers in the past. Scientists at the RKI had been researching possible human bornavirus infections since the early 1990s - but the work was discontinued in 2005.

Despite years of effort, they have found no reliable indication of a danger to humans, it was then. Suspected Bornavirus detection in human samples was later attributed to contamination in the laboratory.

Much attention was also given to the topic because some of the scientists described Bornavirus as a factor in the development of diseases such as depression and schizophrenia.
However, Martin Beer from the FLI emphasized: "One has to separate the current individual cases clearly from the discussions of the past 20 years and the investigations at that time.

„We now see a very clear symptom, we have deaths and in the samples of the deceased patients can be detected very large amounts of virus genome. "

In a federally funded consortium ("ZooBoCo"), researchers from several German institutions want to investigate the open questions about bornaviruses - such as infection routes and risk areas.

 

Borna disease virus (BDV), the bornavirus species which infects humans, has also been studied in the context of ME/CFS. Some studies found an association of BDV and ME/CFS: for example this Japanese study found BDV in 34% of ME/CFS patients.

But Ian Lipkin's study found no association between BDV and ME/CFS.

Some other Borna disease virus ME/CFS studies listed here.


Generally, the seroprevalence of BDV in healthy people is around 2%, but is around 13 to 14% in patients with chronic progressive diseases of the brain and the immune system, according to this study.

Though I have also seen claims that 30% of healthy adults have BDV.

 

@Hip Thank you! Very interesting input.
As I understood the press release it was the first time at all that an infection with Bo-DV1 in humans could be proven. The older findings in psychological disorders were contested.

Well, this seems to be a german view only. The ECDC says 'Infection with Borna disease virus 1 (BoDV-1) is very rare in humans, however it can cause severe disease (acute encephalitis).' https://ecdc.europa.eu/en/news-even...-1-transmission-through-organ-transplantation
[bold mine]

'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.'
Maybe that is why it couldn't be detected in the Lipkin's study?
Maybe it could be found now because the endemic areas change due to climate change? As with Lyme borreliosis?

Since mice (bicolored shrew) are the natural reservoirs for this virus, I was reminded of another virus that was linked to CFS and later disputed as "laboratory contamination"... but that was a different cup of tea, I think...

 

I don't think the presence of BDV in humans is contested. Indeed, it was mentioned in the article that BDV was passed from transplanted organs coming from an infected donor.

What possibly is new is that these 3 people died from acute BDV infections. There is a difference between a virus lying mostly dormant (latent) in a person (where it may be linked to chronic disease), and an acute active infection (which may be fierce enough to kill).

 

I think it was the other way round: three organ recipients, who received their organs from the same donor, became ill with encephalitis. Two of them died. One survived. So they concluded that the donor must have been infected.

[blue added for clarity]

The "Deutsches Ärzteblatt" (an official source of information for german medical profession) says:
'Three patients who received organs from the same donor are the first people worldwide to have been proven to be infected with the classic bornavirus.'

'Borna disease has long been considered a pure animal disease that is not transmittable to humans'

[https://www.aerzteblatt.de/nachrich...aengern-sind-erste-Erkrankungen-beim-Menschen], 27.03.2017

I think they really dismissed Bo-DV as not infective to humans. Only in 2015, when the new Borna disease Virus was found (VSBV-1) the researchers came back on track...

[bold mine]

 

The 1997 Japanese study mentioned above for example found BDV in 12% of ME/CFS patients using PCR, so that is evidence that BDV can infect humans.

However, the article you translated above says:

I am not sure if the contamination applies just to the work at RKI, or to BDV studies everywhere including Japan.



Looks like the bornavirus involved, the variegated squirrel bornavirus 1, has been the subject of previous research (and previous human deaths in squirrel breeders).

 

It seems like the Robert Koch Institute had a research group (led by Dr. Liv Bode) on Bo-DV1 since the early 90's. Dr. Bode worked in cooperation with Prof Hanns Ludwig (Freie Universität Berlin). They found the virus in blood samples of blood donors and of psychiatry patients.
The Robert Koch Institute dismissed the results because the test method had not been validated. Also independently
conducted studies could not reproduce the results. Numerous other studies from Germany and abroad yielded inconsistent results.
In 2005 the Robert Koch Institute therefore stopped further research on this virus.
'Despite all the intensive and years of effort, there is no reliable evidence that the Borna virus is even a pathogen for humans.'

[https://www.rki.de/DE/Content/Forsc...geErreger/Einstellung_Projekt_Bornavirus.html]

I found a pdf from Prof Ludwig about Borna Virus disease in Humans, though (dating from 2010)
https://microbewiki.kenyon.edu/index.php/Borna_Disease_Virus_(Human)
[Link no 6 at the end of the page, 'References']

There, Prof Ludwig claims that 'at least 40%' of patients with CFS are associated with active Bornavirus infection... (criteria for diagnosis not apparent)
It seems to be treatable with a well known substance called amantadine sulfate, for about 3 months (dosages etc. in the pdf).


Sorry for my rambling on here, I find this really fascinating!

 

I am not quite sure whether amantadine (which is a drug ME/CFS patients sometimes use) will work for BDV, as several studies found that this drug does not have antiviral effects for BDV, although this study says that amantadine does work for human isolates of BDV in vitro, but not laboratory strains of BDV.

Funnily enough, when I was first infected with a mystery virus in 2003 that caused a lot of nasty neuropsychological symptoms (and later appeared to cause ME/CFS), one of the first viruses I started reading about was BDV. But many years later I realized the virus I caught was most likely coxsackievirus B4.

 

You might like a thread I started on BDV here: New Studies Show Borna Disease Virus Infection in Psychiatric Patients

 

Thank you, @Hip!