Virus link to CFS 'in doubt'

Behind the Headlines

Wednesday January 6 2010

CFS is a complex disease, and its causes are not well understood.

“Serious doubt has been cast on the theory that... chronic fatigue syndrome is caused by a new retrovirus,” The Guardian reported. The newspaper said researchers from London have failed to replicate findings from the US that suggested a possible role for a virus called XMRV in causing CFS, also known as ME (myalgic encephalomyelitis).

In the new study none of the 186 UK CFS patients tested carried the XMRV virus, in contrast to the US study in 2009, which found that about two-thirds of 101 CFS patients tested had the virus. Why the two studies have different findings is not clear, but the results of the UK study do not support an association between XMRV infection and CFS in UK patients. This highlights the importance of different research groups repeating experiments in different populations.

CFS is a complex disease, and its causes are not well understood. Although an association with XMRV has not been established, this does not rule out the possibility that viral infection is involved. More research will be needed in this area.


Where did the story come from?

The research was carried out by Dr Otto Erlwein and colleagues from Imperial College London and King’s College London. The researchers were funded by the South London and Maudsley NHS Foundation Trust, the Institute of Psychiatry and the National Institute for Health Research Biomedical Research Centre. The study was published in the peer-reviewed open access journal PLoS ONE.

The Guardian, Daily Mail and The Independent reported the story. In general, the coverage is balanced and accurate. The headline of the Daily Mail story that “British experts say ME virus is a myth” might be taken to mean that this research excludes any role for viral infection in CFS/ME, but this research only looked at one virus (XMRV).

 

What kind of research was this?

This cross-sectional study investigated whether people in the UK with chronic fatigue syndrome (CFS) were infected with the xenotropic murine leukaemia virus-related virus (XMRV). In 2009, a case-control study from the US found that more people with CFS carried the virus than people without the condition. The researchers in this study wanted to see if XMRV was similarly common in people from the UK with CFS.

A cross-sectional study design is appropriate for determining how common a particular trait is among a certain group of people. However, neither this study, nor the original case-control study could prove whether XMRV potentially caused CFS, as neither would be able to establish whether people with XMRV had been infected before they developed CFS or after. The current study would also not have been able to say whether the XMRV virus was more or less common in people with CFS than in those without it, as it did not include a control group of people without the disease.

 


What did the research involve?

The researchers enrolled 186 people with CFS who were living in the UK. These people had been medically examined and diagnosed with CFS according to standard criteria, and other potential causes of their symptoms had been ruled out. Blood samples were taken and tested for the presence of DNA from XMRV or a related virus called murine leukaemia virus (MLV). A number of control tests was also carried out to show that the DNA in these samples was intact, that any positive findings were not a result of contamination of their experiment and that their test would identify XMRV if it was present. The inclusion of these controls is important for ensuring that the experiments were working well and were reliable. The researcher who carried out the DNA tests did not know which of the samples came from people with CFS.

The participants, all of whom had been referred to a CFS clinic, were mainly female (62%) with an average age of 39.6 years. They had been unwell for an average (median) of four years (range one to 28 years), and had high levels of fatigue. Few participants were working and about a fifth (19%) belonged to CFS/ME support groups. Just under half of the participants (45%) said that their CFS definitely related to a viral infection and 45% said that it might relate to a viral infection. The researchers suggested that the characteristics of their sample were typical of those seen in CFS patients attending specialist clinical services in the UK.



What were the basic results?

The researchers did not identify XMRV or MLV in the blood from any of the 186 CFS patients tested. Their control tests showed that the DNA being tested was intact, that there was no contamination in their experiments and that when XMRV was present (in a positive control sample containing XMRV DNA) their test detected it.

 


How did the researchers interpret the results?

The researchers concluded that they “found no evidence that XMRV is associated with CFS in the UK”. They suggested that the reason for the differences between their findings and those from the US might be due to differences in how common XMRV infection is in the different countries.

 

Conclusion

This study suggests that the XMRV infection is not common in CFS patients in the UK. A previous case-control study from the US found that about two-thirds of the 101 CFS patients tested carried XMRV, compared to about 4% of 218 healthy controls. This led the researchers from the US study to suggest that XMRV might be the cause of CFS in these patients. The reason for the differences between the US and UK studies is not clear, but the authors of the UK study suggest that it could be due to XMRV infection being more common in the US than in Europe.

The findings of this current study highlight the importance of different research groups repeating experiments in different populations. The study does have some limitations in that it was relatively small and all participants came from one CFS centre in London. Further studies in more participants from different centres in the UK would be useful in determining whether these findings are typical of the UK as a whole.

Even if this study had found significant levels of XMRV in CFS patients, it would not have been able to prove the virus actually caused the condition. This is because, like the original US case-control study, it could not establish whether people with XMRV had been infected before they developed CFS or after.

The current study would also not have been able to say whether the XMRV virus was more or less common in people with CFS than those without, as it did not include a control group of people without the disease.

The results of this UK study do not support an association between the XMRV virus and CFS in UK patients. The researchers do not rule out a role for all viruses in CFS, and say that “prospective epidemiological studies have confirmed that certain infective agents, for example Epstein Barr virus, are unequivocally associated with subsequent CFS, even if the mechanisms are unclear and almost certainly multi-factorial”. CFS is a complex disease, and its causes are not well understood. Much more research will be needed in this area.

Links to the headlines

Research casts doubt over US chronic fatigue virus claim. The Guardian, January 6 2010



British experts dash ME breakthrough hopes following American promise of new treatment. Daily Mail, January 6 2010



Scientists' claim to have found the cause of ME is 'premature'. The Independent, January 6 2010

Links to the science

 

Erlwein O, Kaye S, McClure MO, et al. Failure to Detect the Novel Retrovirus XMRV in Chronic Fatigue Syndrome. PLoS ONE, 2010; 5/

 

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Comments

The 7 comments posted are personal views. Any information they give has not been checked and may not be accurate.

ontheup said on 11 February 2010

this article masquerades as objective and balanced but from the headline and the patronising picture to the conclusion it pushes the 'party line'.
The comments and links above highlight what has been omitted from this piece.
CFS is a serious disease and deserves better than sloppy journalism.

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JustinReilly said on 21 January 2010

Wessley Study Does Not Cast Much Doubt on WPI Findings.

The Wessley study was not a replication as erroneously stated in this piece. It was a very limited study and the statements by the authors to the media were unsupported by fact.

By contrast, WPI's study was extremely rigorous and included three top labs with some of the world's top retrovirologists (not psychiatrists). Published in Science, the ne plus ultra of journals, after six months of rigorous review. Wessley study was published in an on-line journal three days after submission. The Wessley groups' prior publications which do not acknowledge medical literature on ME/CFIDS and explicitly state that ME is not a physical illness, but merely an imagined illness, creates serious questions in the mind of the objective reviewer as to the validity of this study.

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Pete59 said on 17 January 2010

The title of this article is misleading. It is the link between a virus (XMRV) and CFS that was not observed in this study.

Given there seems to be links between CFS and other viruses (eg Epstein Barr), the idea that the viral infection is the primary instigator of CFS has not been weakened. These viruses have a number of active and latent states and it is probably the interaction between virus and the immune system that produces the symptoms.

I have had Epstein Barr virus induced CFS. I can guarantee that it is not 'all in the mind', it could be of course that the immune system is damaging the brain in a similar way to MS. Oddly, another disease associated with Epstein Barr and a genetic predisposition.

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wingfingers said on 17 January 2010

"The newspaper said researchers from London have failed to replicate findings from the US that suggested a possible role for a virus called XMRV in causing CFS, also known as ME (myalgic encephalomyelitis)."
This was in no way a replication study. They did not follow any of the protocols in the original paper.
M.E. (used to be called CFS in America for political reasons) just has to have a single cause. As a vet, I know that all basic diseases are caused by a single organism. How about anthrax? rabies? Chicken pox? even Swine Flu? Secondary infections can play a part, and diseases like Border disease in sheep involve lots of bugs but the Pasteurella causing the basic pneumonia is the main one. The symptomatology may be "complex" but the disease isn't - if you assume that a single agent, possibly XMRV retrovirus, causes it, all the physical signs fit like pieces of a jigsaw. The virus invades the mitochondria of your cells and makes you feel very weak as you have no energy. Now this XMRV is a difficult beggar to find - you need exactly the right techniques - this is probably why even the WPI didn't find it in some cases of obvious M.E. And of course the Imperial study used all the wrong techniques so didn't find it at all - surprise surprise. They didn't want to find it, it would remove their raison d'etre, their income. To me as a sufferer of M.E. for 15 years but gradually recovering, I welcome the news. I fully expect that in a matter of months, the arguments will be over bar the shouting, and we can get down to some serious study of antiviral therapy, having learned the hard way from the AIDS/HIV history.

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KALUS said on 07 January 2010

Excellent article as are the very pertinent comments above.

There are many organic diseases such as MS, Parkinson's Disease, Diabetes, Alzheimer's Disease and CFS , as well as all psychiatric disorders, for which there is no cut and dried causative explanation.

However, that does not mean that scientists do not know quite a bit about the organic abnormalities for example. Nor does it automatically make a disease a psychosomatic disorder because psychiatrists disagree with the explanation.

CFS, along with ME and Post Viral Fatigue Syndrome are listed by the WHO ICD-10 under G93.3 which specifically excludes them from an F48 listing.

Viral involvement in CFS makes sense because many of the more common symptoms of CFS are most often found in an infectious process. Retroviral involvement, in at least a subset, would also explain the many reactivated latent viruses found in CFS patients.

It is curious that three psychiatrists are listed as authors in such a hasty virological study. Perhaps it is best to use Dr. Wessely's own words to explain his take on viral involvement:

"...indeed, the search for infective causes and triggers for psychiatric disorders has never ceased..."
"...it is clear that the drive to find a somatic biomarker for chronic fatigue syndrome is driven not so much by a dispassionate thirst for knowledge but more by an overwhelming desire to get rid of the psychiatrists."

It is rather curious that a psychiatrist who holds the above views would be a part of viral study looking into a somatic explanation for CFS.

Wessely S (2009). Surgery for the treatment of mental illness: the need to test untested theories. James Lind Library (http://www.jameslindlibrary.org).

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conkerama said on 07 January 2010

The Institute of Psychiatry have a deep interest in disproving any viral link as currently in the UK CFS/ME is treated using psychiatric methods. This results in a lot of public funding being steered into the psychiatric field.

Simon Wessely and his colleagues fought long and hard for their methods of treating CFS/ME to be rolled out nationally. I would urge people reporting on this study to look a little more closely at its reason, sources and methods before assuming that it definitively proves or disproves anything.

The simple fact that the Institute of Psychiatry is studying a viral link rings many alarm bells for me.

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Whittemore Peterson Institute said on 06 January 2010

Official Statement from the Whittemore Peterson Institute Regarding UK Study

please visit www.wpinstitute.org/news/news_current.html

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Analysis by Bazian

Edited by NHS Choices