XMRV and chronic fatigue syndrome: Netherlands, nope.

Posted by ERV on February 26, 2010
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Study from the Netherlands:

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

CFS/ME patients plus age/sex/neighborhood matched controls (patients brought in friends that lived in the same area– environment might play a role).
32 ME/CFS patients
43 controls
0 XMRV present in PBMC, using reagents verified in this paper (integrase) and this paper (gag- the same ones WPI used).

Cut/Paste summary:

A limitation of our study is that the numbers of patients and controls in our study were relatively small. Based on these low numbers, the upper limit of the 95% confidence interval is a prevalence of 9% for the patient group and 7% for the control group, as calculated according to Eypasch et al (by the formula p=3/n).18 Although we cannot formally rule out a role of XMRV, our data cast doubt on the claim that this virus is associated with chronic fatigue syndrome in the majority of patients…

… Technical aspects are unlikely to explain the difference in XMRV positivity rate between our data and their data…

… It is possible that the study of Lombardi et al has unravelled the viral cause of the chronic fatigue syndrome outbreak, but it seems unlikely that their study demonstrates a viral association for sporadic chronic fatigue syndrome cases, such as those we tested, or represents the majority of patients.

Now, this paper demonstrates the scientifically acceptable, normal way scientists bitch-slap one another (SPOILER: It doesnt involve calling other scientists frauds):

In conclusion, we found no evidence for a role of XMRV in the cause of chronic fatigue syndrome in Dutch patients. Over the past decades we have seen a series of papers prematurely claiming the discovery of the microbial cause of chronic fatigue syndrome. Regrettably, thus far none of these claims has been substantiated.

Still no XMRV in Europe.

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Comments

  1. #1 ragarth
    February 26, 2010

    What’s that I smell?

    I think it’s an empirical bitch-slap. Let’s see if it’s repeatable, and then measure its force.

  2. #2 Vene
    February 26, 2010

    This is simply beautiful.

  3. #3 Brian
    February 26, 2010

    I do appreciate a well-deserved scientific smacking-around.

  4. #4 Scott
    February 26, 2010

    What is the prevalence of XMRV in other parts of the world in comparison to the prevalence of CFS? Based on the data here, I could posit that XMRV causes CFS in over 50% of infectees.

  5. #5 pochoams
    February 26, 2010

    Just to let you know, I used to live in Holland, and the the CFS center of Holland was located in Nijmegen, I applied to go there at that time, and they only took patients from Nijmegen because they were overload, so I was from Amsterdam and could not apply.

    Besides the “treatments” they prescribed there were CBT (Cognitive Behavioural Therapy) and that was the only treatment supported by the government, as it is considered a psychological illness. So in my view this study is not very representative, first because of the sample, and secondly because of the psychological approach instead of biological.

    I think that in order to rule OUT XMRV as a strong association with CFS, further studies will need to REPLICATE the WPI study with exactly the SAME techniques and sample criteria, until that happens we can only speculate.

  6. #6 LM
    February 26, 2010

    They should have mentioned there use of the Oxford criteria (Which as Canadian psychiatrist Eleanor Stein says ‘fail to exclude patients with primary psychiatric diagnoses and are not often used by other researchers. And which could describe almost anyone) The Science study used the Fukuda & canadian. So different patients.

    The also seem to be under the impression that patients were from a ‘chronic fatigue syndrome outbreak’. The WPI said that the patients came from around the globe, i.e. UK, Australia, USA, etc.

    If technical aspects were not important, then why didn’t they do a replication study? Why use the same test for anything?

    On a separate issue, CBT and GET claims have never been substantiated, but biological abnormalities have been replicated. Making a statement does not make it fact. Therefore, not really a bitch slap, but a whimper, ‘Please stop looking into the biology, it troubles our beliefs.’

  7. #7 GK
    February 26, 2010

    “Still no XMRV in Europe”

    Erv, why don’t you read the literature before shooting your mouth off? Unless you don’t consider Germany to be in Europe. Ah, my mistake….

    J Clin Virol. 2008 Nov;43(3):277-83. Epub 2008 Sep 27.

    Prevalence of human gammaretrovirus XMRV in sporadic prostate cancer.
    Fischer N, Hellwinkel O, Schulz C, Chun FK, Huland H, Aepfelbacher M, Schlomm T.

    Institute for Medical Microbiology and Virology, University Medical Center Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany. nfischer@uke.de

    BACKGROUND: We previously identified a novel exogenous gammaretrovirus (xenotropic murine leukemia virus-related gammaretrovirus (XMRV)) using a pan-viral microarray. XMRV is the first MLV-related virus found in human infection. Forty percent (8/20) of familial prostate cancer patients homozygous for a mutation in RNase L (R462Q) were positive for XMRV, while the virus was rarely (1/66) detected in familial prostate cancer patients heterozygous for R462Q or carrying the wild type allele. OBJECTIVES: To determine the presence of XMRV in non-familial prostate cancer samples. STUDY DESIGN: RNA from prostate tissue was analyzed for XMRV using nested RT-PCR. In all samples, RNase L (R462Q) genotyping was performed using an allele-specific PCR. RESULTS: XMRV-specific sequences were detected in one of 105 tissue samples from non-familial prostate cancer patients and from one of 70 tissue samples from men without prostate cancer. The two XMRV-positive patients were wild type or heterozygous for the R462Q mutation and thus carried at least one fully functional RNase L allele. CONCLUSIONS: XMRV was rarely detected in non-familial prostate cancer samples from Northern European patients. The homozygous mutation R462Q (QQ) was significantly underrepresented (<6%) in this cohort when compared to other studies (11-17%).

  8. #8 MS
    February 27, 2010

    GK:
    “There’s very little XMRV, and it’s not asscociated with CFS” isn’t as catchy, or as relevant to the topic (XMRV and CFS) at hand.

    pochoams:
    I don’t see any reference to psychological selection in the paper, and unless there was some sort of screening to remove the “biological” patients, a significant number should still have XMRV (according to the numbers from the WPI paper anyway).

    LM:
    Who exactly IS Elanor Stein? She doesn’t appear on Web of Knowledge, or Pubmed and google tells me she is a psychiatrist who sees CFS patients as part of her practice, and then tells people that CFS isn’t a psych illness. Colour me skeptical and confused. Mostly skeptical.

  9. #9 LM
    February 27, 2010

    MS

    Yes, I guess the difference between psychiatrists who treats some patients who get depression because of a disease, and those that say all disease are perpetuated by a psychosocial mode, could be difficult to understand. However there are two groups, the first being the largest, the second, tending to work for insurance companies. There are many more ME/CFS experts who say the same thing about the Oxford criteria.

    These psychosocial psychiatrists rely on your confusion by the way.

    It is early days in the XMRV ME/CFS/PVFS debate, so no one can say either way, so don’t pretend your words are fact.

    The Oxford criteria includes psychological patient selection, i.e. those who only have fatigue (as in Fatigue syndrome, WHO F48) It may interest you to know that in Scotland they recognise the difference. They use the Canadian criteria for ME/CFS, and the NICE guidelines for Chronic fatigue. They are not the same disease. On is a mental health disorder, the other is neurological.

    Oxford criteria 1990 is:
    Fatigue, 6 months or more, there more than 50% of the time, excluding established medical conditions (i.e. ME, since 1969 WHO)

    It’s very simple.

  10. #10 LM
    February 27, 2010

    I should add, that the 36 patients would not necessarily include those who meet Fukuda and Canadian.

    Oxford = 2.6% prevalence
    Fukuda = 0.24% to 0.42% prevalence
    Bill Reeves attempted to operationalise the Fukuda, prevalence jumped from 0.4% to 2.5%. He no longer heads the CFS CDC program. Makes a big difference doesn’t it.

    Add to this the patients that will refuse to subscribe to the treatment dolled out by psychosocial lovers.

  11. #11 LM
    February 27, 2010

    Theoretical models that cannot be empirically tested do not have explanatory power, because any theoretical model that claim to provide explanations of empirical phenomena must be testable. (1996 Scheper and Scheper)

  12. #12 windy
    February 27, 2010

    Therefore, not really a bitch slap, but a whimper, ‘Please stop looking into the biology, it troubles our beliefs.’

    Why would a group mostly composed of medical microbiologists, virologists and internal medicine experts be ideologically opposed to the possibility of a viral illness? *scratches head* I doubt that the lone psychologist was pulling all the strings… maybe it’s the urologist?

  13. #13 LM
    February 27, 2010

    Windy, the bitch slap was not referring to the psychologicalisation of CFS, but the study of XMRV and CFS. An area that is still under plenty of investigation. Therefore how is it a bitch slap? That implies that they have concluded the search for XMRV in CFS.

    My comments on the psychologicalisation of CFS, refer to the use to the use of the Oxford criteria to identify patients, as being ideologically opposed to the possibility of a viral illness. The microbiologists, virologists, and internal medicine experts, are unlikely to be aware of these issues, as they wont be treating CFS patients, particularly in a country that embraces the theory of the CBT model. The Oxford criteria has been largely condemn by ME/CFS/PVFS experts, and quiet clearly combines disease that are separated by the WHO.

    On 23rd January 2004, Andre l’Hours from the WHO headquarters provided the following clarification (in writing):

    “This is to confirm that according to the taxonomic principles governing the Tenth Revision of the World Health Organization’s International Statistical Classification of Diseases and Related Health Problems (ICD-10), it is not permitted for the same condition to be classified to more than one rubric as this would mean that the individual categories and subcategories were no longer mutually exclusive”.

    Andre l’Hours also stated that if a country accepts the WHO Regulations concerning nomenclature (which the UK does), then that country is obliged to accept the ICD classification. For the avoidance of doubt, the UK has registered no reservations about the ICD-10 and therefore formally accepts it.

    I was attempting to point out how these psychiatrists are trying to wipe out the existence of a legitimate disease, ME. Hope this helps. If it doesn’t I am positive I can explain further.

  14. #14 LM
    February 28, 2010

    This is the extract from the Cheif Medical Officers report into ME.

    Oxford criteria’[10] are used. These are even more broadly inclusive of a heterogeneous population than the definition of CFS by the US Centers for Disease Control and Prevention previously referred to.[11] Indeed, one of the co-authors of the ‘Oxford’ criteria has described them as follows:

    “British investigators have put forward an alternative, less strict, operational definition which is essentially chronic fatigue in the absence of neurological signs [but] with psychiatric symptoms as common associated features.”

    note the absence of neurological signs and common psychiatric symptoms. No patients with ME

  15. #15 LM
    February 28, 2010

    This is what Dr Goff said at the 17th Conference on Retroviral Infections and Opportunistic Infections

    The most recent exciting work of course is the discovery in Chronic Fatigue Syndrome and that too is very controversial. Some people are finding it, some not. I think that will have to be worked out in the coming months and years.

    So no bitch slap.

  16. #16 windy
    February 28, 2010

    the bitch slap was not referring to the psychologicalisation of CFS, but the study of XMRV and CFS.

    Then why did you imply that the authors’ beliefs were threatened somehow?

    “bitch slap” means that they used appropriate language for scientists to diss one another, not that this study settles the question once and for all. Note that they refer to people “prematurely” claiming a connection.

  17. #17 GK
    February 28, 2010

    “Still no XMRV in Europe”

    What’s up, erv ? Are you not part of the school of scientists who own up when they’ve got it just plain wrong ? Here’s a link to the paper so you might actually bother to read it before ranting about XMRV again….

    http://dx.doi.org/10.1016/j.jcv.2008.04.016

    J Clin Virol. 2008 Nov;43(3):277-83. Epub 2008 Sep 27.

    Prevalence of human gammaretrovirus XMRV in sporadic prostate cancer.
    Fischer N, Hellwinkel O, Schulz C, Chun FK, Huland H, Aepfelbacher M, Schlomm T.

    Institute for Medical Microbiology and Virology, University Medical Center Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany. nfischer@uke.de

    BACKGROUND: We previously identified a novel exogenous gammaretrovirus (xenotropic murine leukemia virus-related gammaretrovirus (XMRV)) using a pan-viral microarray. XMRV is the first MLV-related virus found in human infection. Forty percent (8/20) of familial prostate cancer patients homozygous for a mutation in RNase L (R462Q) were positive for XMRV, while the virus was rarely (1/66) detected in familial prostate cancer patients heterozygous for R462Q or carrying the wild type allele. OBJECTIVES: To determine the presence of XMRV in non-familial prostate cancer samples. STUDY DESIGN: RNA from prostate tissue was analyzed for XMRV using nested RT-PCR. In all samples, RNase L (R462Q) genotyping was performed using an allele-specific PCR. RESULTS: XMRV-specific sequences were detected in one of 105 tissue samples from non-familial prostate cancer patients and from one of 70 tissue samples from men without prostate cancer. The two XMRV-positive patients were wild type or heterozygous for the R462Q mutation and thus carried at least one fully functional RNase L allele. CONCLUSIONS: XMRV was rarely detected in non-familial prostate cancer samples from Northern European patients. The homozygous mutation R462Q (QQ) was significantly underrepresented (<6%) in this cohort when compared to other studies (11-17%).

  18. #18 LM
    February 28, 2010

    I was referring to Gijs Bleijenberg and Jos W M van der Meer (I should have said) They are both ideologically opposed to the possibility of a viral illness. A 2007 study of there’s states.

    http://www.cfids-cab.org/rc/Knoop-2.pdf
    “CFS is neither the result of an organic disease or ongoing exertion nor alleviated by rest.”

    Hence the use of the Oxford criteria. Also, it is not a research definition and differs substantially from Fukuda/ Canadian.

    Bitch slap in this context implied, if you are going to do it, do it this way.

    The McClure/ Wessely study said, they only wanted to get the truth out. one study and they know the truth?

    The van Kuppeveld study said, Over the past decades we have seen a series of papers prematurely claiming the discovery of the microbial cause of chronic fatigue syndrome. Regrettably, thus far none of these claims has been substantiated. Why mention this. To imply that it is pointless looking, as it is psychosocial disorder, which has never proven. They drop in the word regrettable to seem reasonable, but they are anything but. See above.

    Unfortunately, you do need to have read much of the papers on this subject, to grasp how devious this bunch they are. They say one thing in public, and quiet the opposite behind closed doors. A lot of this information has been obtained under the Freedom of Information Act, and through other means.

    Have a look at this complaint document, by Professor Hooper, to the MRC regarding the PACE trial. http://www.meactionuk.org.uk/magical-medicine.htm

    It’s all smoke are mirrors with them. They say things like, it a heterogeneous disorder, so one retrovirus wont be the cause. (This was days after the Science publication.) Yet, when using their theory, they claim it’s no longer a heterogeneous disorder, its the same mental health disorder as IBS, Fibromyalgia, somatoform disorders.

    The WPI were not bitch slapping, they were fighting back against those who would shut down all biomedical research into the disease tomorrow. In the UK they have effectively done this, the MRC has never funded any biomedical research, and the NICE guidelines tell GP’s to do nothing more than basic testing, and so ME/CFS/PVFS gets mixed in with Fatigue syndrome, and any other disease that has fatigue, which wont show up on basic testing.

    Finally, the WPI/ NCI/ Cleveland clinic only said it was ‘significant’, this was approved by ‘Science’. They said they don’t know if it is the cause or whether it can cause disease, but that the finding was ‘significant’.

  19. #19 KAL
    February 28, 2010

    “…Over the past decades we have seen a series of papers prematurely claiming the discovery of the microbial cause of chronic fatigue syndrome. Regrettably, thus far none of these claims has been substantiated…”

    According to whom? It could just as easily be said that there are very few studies contraindicating viruses in CFS. Point being – research is always preliminary.

    Koch’s Postulates are so 19th Century. Surely the Dutch virologists are aware that many viruses can cause one disease just as one virus can cause many different diseases. Or it could be a synergistic combination.

    More research needed.

  20. #20 gf1
    March 5, 2010

    re patient selection: The Oxford criteria is so weak it could have dramatically skewed results, and is a surprising choice for an XMRV study. In that sense, this seems to be the weakest of the CFS/XMRV studies, but as it comes after two other negatives, it still adds weight to them.

  21. #21 gf1
    March 22, 2010

    I’ve just read about the cohort in more detail, and it really does sound quite unusual, even compared to other Oxford criteria patients, nevermind the more stringent criteria the WPI used. They seem to have quite different symptoms to those typically found in CFS patients. You’d still expect some over-lap between the two groups of patients, and to have found some XMRV were the WPI’s figures to hold up… but possibly not. A really strange choice of patients for this one.