Link between chronic fatigue and virus not proven

04/06/2010 - Articles

Link between chronic fatigue and virus not proven

By: Susan Aldridge, medical journalist, PhD


Chronic fatigue affects millions of people worldwide. It is associated with disabling fatigue, pain, and other symptoms. The causes of chronic fatigue remain unclear – various physical and psychological factors have been investigated, however. Nor is there any effective cure for chronic fatigue. If the cause could be established, then effective therapies for chronic fatigue are more likely to be developed. A recent study from the United States suggested a link between a human retrovirus known as xenotropic murine leukaemia virus-related virus (XMRV) and chronic fatigue. In this study, XMRV was found in two thirds of a group of patients with chronic fatigue. Then, in January 2010, there was a study from the UK which did not support these findings – no evidence of XMRV was detected in a group of 186 patients. A third study also failed to find XMRV in chronic fatigue patients. So, is there a link between XMRV and chronic fatigue – or not?

Researchers from The Netherlands now report a more advanced study. They used a very sensitive DNA test to check for XMRV in a group of 32 Dutch patients with chronic fatigue and a group of healthy controls. No evidence of XMRV was found in either group. It may be that the patients in the American study had a form of chronic fatigue that is linked to – maybe even caused by – XMRV. But the virus does not play a role in other cases of chronic fatigue. In other words, chronic fatigue may not be a single illness. There are more studies going on with XMRV and chronic fatigue which may help clarify the role the virus plays in this, and maybe in other human diseases.



Kuppeveld F et al Prevalence of xenotropic murine leukaemia virus-related virus in patients with chronic fatigue syndrome in the Netherlands: retrospective analysis of samples from an established cohort 25th February 2010 (BMJ 2010;340:c1018)


Created on: 04/06/2010
Reviewed on: 04/06/2010

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Anonymous wrote 18 weeks 1 day ago

Dear anonymous,

Thanks for your very concise summary. I've responded to few of these types of blog posts But your summary is the best.

The wheel will turn. But will those who played games peoples lives be called to account? I wish that there was someone collating evidence that could be used in future legal cases.

Peter / Melbourne Australia

Anonymous wrote 18 weeks 1 day ago

Consider the failed XMRV/CFS studies. An analysis of the British Medical Journal’s (Van Kuppeveld et al's) science on XMRV, presented as the "trump card" in negative XMRV/CFS research, reveals that their 20 year old blood samples were not from Chronic Fatigue Syndrome (ME/CFS) patients, and not remotely comparable to the Science CFS cohort. The BMJ (Nijmegen team) represented their cohort as CFS, when in fact they were studying the blood of tired, depressed patients. Here's the evidence:

Some shocking quotes from the study where the BMJ and Nijmegen’s 20 year old blood came from:
• “Information on physical abnormalities and treatment relied on self-report”.
• “Using a score of 16 or more, 36% of patients could be considered as having a clinical depression.”
• “To test generalizability, the present study sample was compared with a recently tested group of 68 patients with Unexplained Fatigue” (not CFS).
• And the clincher: the source of the blood came from a study where they, “Minimalized the risk of including patients with delayed convalescence of a viral infection”.

For a detailed analysis of the BMJ article's flaws, complete with meticulous references, see: the 5-part article Scandal in BMJ’s XMRV/CFS Research, posts #1,2,4,6,7. The BMJ stated their XMRV research was on a “well-defined cohort” of CFS patients, when it was on a group of depressed patients with Unexplained Fatigue – which had been explicitly screened to remove patients with “delayed convalescence of a viral infection”. Not much chance of finding XMRV in that cohort. How strong are the BMJ’s conclusions that XMRV isn’t in the UK – and that it isn’t associated with CFS! GSK has clearly distanced themselves from these failed studies.

In contrast, consider the latest research happening at ARUP, with the involvement of world-renowned Dr Ila Singh, one of the pioneers in XMRV/prostate cancer research. Cutting edge patient cohort selection. Cutting edge blood draws and analysis. And involvement by a world-renowned prostate cancer researcher Dr Singh in XMRV - who is clearly putting her reputation behind further XMRV/CFS research. After all, many patients in prostate and CFS cohorts have the RNase-L antiviral deficiency that she studied. Thank you to Dr Singh and her team for forging full-speed ahead in XMRV research on prostate cancer and Chronic Fatigue Syndrome (ME/CFS). She has wasted no time, testing 45 compounds and 28 drugs on XMRV - and being reported widely in media such as USA Today and Scientific American. Dr Singh clearly "gets" the plausability of the potential link with ME/CFS. As her team commented in their source article:

"... the notion that a retrovirus might be involved in both cancer and a neuroimmune illness in humans is not without precedence. Human T-cell lymphotrophic virus, type 1 (HTLV-1), another retrovirus, causes both T-cell lymphoma/leukemia as well as tropical spastic paraparesis, a myelopathy due to immune defects
resulting from the viral infection."

Psychiatrists studying this viral neuro-immune disease have been stating for years that the most rigorous Canadian Criteria are just too difficult to apply in research. It’s a little like saying one should abandon speed limits because no one likes to follow them. Or lumping together appendicitis patients with diffuse stomach ache patients to "simplify" research. Like appendicitis, which has right-sided flank pain as a cardinal sign, ME/CFS's hallmark is post-exertional malaise - something the BMJ and other failed studies have conveniently dismissed. Pharma Giant GSK, it appears, does not agree with this cavalier treatment of ME/CFS, and thankfully will be dotting their i's and crossing their t's in their XMRV/CFS research.

Pharma giant Glaxo Smith Kline just announced their own study into XMRV and ME/CFS using none other than the rigorous Canadian AND Fukuda-Criteria patients (as per the Science study); and positive XMRV samples from patients studied by the Science researchers (See: ). In other words, GSK “gets” the difference between research on cohorts of depressed, tired patients; versus patients with rigorously defined Canadian/Fukuda criteria ME/CFS, reproducible immune abnormalities, and severe, disabling fatigue. Further, by using positive samples from actual CFS patients with XMRV in the Science study, GSK is in effect saying:
1) We believe that XMRV exists; and
2) We believe that you found XMRV in CFS patients.
3) Further, we believe that it is necessary to look for XMRV in rigorously defined cohorts of ME/CFS patients, particularly those with a viral onset - rather than 20-year old samples of tired, depressed patients. Now, can we please use your samples as a positive control?

Pharma company Abbott Laboratories are among the players stating that XMRV is not easy to find. Now consider, whether 20 years ago, the BMJ Nijmegen blood samples received this kind of attention to preserving retroviral samples. And consider the other names who have drawn their lines in the sand. The renowned Cleveland Clinic has very publicly announced the linkage between XMRV, prostate cancer, CFS, and RNase-L (See 2-minute video @ the Cleveland Clinic's YouTube site: ). The discoverers of this linkage: Drs Silverman and Klein are being compared to the likes of Dr Sones, who pioneered the use of injectable dye imaging in cardiac surgery.

These are fascinating times, as retrovirologists and politically-motivated psychiatrists jockey for position. After all, psychiatrists have built an entire industry of exercise and "positive attitude" clinics for patients who may have a cancer-causing retrovirus. Whose science are you going to trust? It is nothing short of earth-shaking that the BMJ's XMRV research team will need to step aside for the "big boys" in immunology, molecular biology, retrovirology and oncology to take over the exploration of what may indeed be the next AIDS.



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