viral infections in ME re lancet prof van-Kuppeveld & prof van der meer

Discussion in 'Fibromyalgia Main Forum' started by simpsons, Feb 5, 2012.

  1. simpsons

    simpsons Member

    the lancet feb 4th published comments to tony britton of me association uk on xmrv the sad end of xmrv story

    margaret williams has produced this very informative comment and it gives a history of viral infection in ME

    reposted with permission and permission to repost

    Questions for Professors Frank J M van Kuppeveld and Jos W M van der Meer

    Margaret Williams 4th February 2012

    Professors Frank J M van Kuppeveld and Jos W M van der Meer have recently
    stated in plain terms that “In the past, several infectious agents have
    been associated with CFS but none of these could be confirmed in subsequent
    studies….” (Lancet 4th February 2012: 379: 9814, e27 – e28

    Where is their evidence for the assertion that no infectious agent “could
    be confirmed in subsequent studies” in (ME)CFS patients?

    Is their assertion correct? Did The Lancet’s editorial team check the
    authenticity of that assertion before publishing it?

    Here is some evidence that Professors van Kuppeveld and van der Meer (and
    The Lancet’s editors) seem to have overlooked:


    “Virological studies revealed that 76% of the patients with suspected
    myalgic encephalomyelitis had elevated Coxsackie B neutralising titres (and
    symptoms included) malaise, exhaustion on physical or mental effort, chest
    pain, palpitations, tachycardia, polyarthralgia, muscle pains, back pain,
    true vertigo, dizziness, tinnitus, nausea, diarrhoea, abdominal cramps,
    epigastric pain, headaches, paraesthesiae, dysuria)….The group described
    here are patients who have had this miserable illness” (BD Keighley, EJ
    Bell. JRCP 1983:33:339-341).


    “Recently associations have been found between Coxsackie B infection and a
    more chronic multisystem illness….referred to as…myalgic
    encephalomyelitis…140 patients presenting with symptoms suggesting a
    postviral syndrome were entered into the study…Coxsackie B antibody levels
    were estimated in 100 control patients…All the Coxsackie B virus antibody
    tests were performed blind…Of the 140 ill patients, 46% were found to be
    Coxsackie B virus antibody positive…This study has confirmed our earlier
    finding that there is a group of symptoms with evidence of Coxsackie B
    infection. We have also shown that clinical improvement is slow and
    recovery does not correlate with a fall in Coxsackie B virus antibody
    titre” (BD Calder et al. JRCGP 1987:37:11-14).


    “These results show that chronic infection with enteroviruses occurs in
    many PVFS (post-viral fatigue syndrome, a classified synonym for ME/CFS)
    patients and that detection of enterovirus antigen in the serum is a
    sensitive and satisfactory method for investigating infection in these
    patients….Several studies have suggested that infection with enteroviruses
    is causally related to PVFS…The association of detectable IgM complexes and
    VP1 antigen in the serum of PVFS patients in our study was high…This
    suggests that enterovirus infection plays an important role in the
    aetiology of PVFS” (GE Yousef, EJ Bell, JF Mowbray et al. Lancet January
    23rd 1988:146-150).


    “The main features (of ME) are: prolonged fatigue following muscular
    exercise or mental strain, an extended relapsing course; an association
    with neurological, cardiac, and other characteristic enteroviral
    complications. Coxsackie B neutralisation tests show high titres in 41% of
    cases compared with 4% of normal adults…These (chronic enteroviral
    syndromes) affect a young, economically important age group and merit a
    major investment in research” (EG Dowsett. Journal of Hospital Infection


    “Skeletal samples were obtained by needle biopsy from patients diagnosed
    clinically as having CFS (and) most patients fulfilled the criteria of the
    Centres for Disease Control for the diagnosis of CFS (Holmes et al
    1988)…These data are the first demonstration of persistence of defective
    virus in clinical samples from patients with CFS…We are currently
    investigating the effects of persistence of enteroviral RNA on cellular
    gene expression leading to muscle dysfunction” (L Cunningham, RJM Lane, LC
    Archard et al. Journal of General Virology 1990:71:6:1399-1402).


    “Myalgic encephalomyelitis is a common disability but frequently
    misinterpreted…This illness is distinguished from a variety of other
    post-viral states by a unique clinical and epidemiological pattern
    characteristic of enteroviral infection…33% had titres indicative and 17%
    suggestive of recent CBV infection…Subsequently…31% had evidence of recent
    active enteroviral infection…There has been a failure to recognise the
    unique epidemiological pattern of ME…Coxsackie viruses are
    characteristically myotropic and enteroviral genomic sequences have been
    detected in muscle biopsies from patients with ME. Exercise related
    abnormalities of function have been demonstrated by nuclear magnetic
    resonance and single-fibre electromyography including a failure to
    coordinate oxidative metabolism with anaerobic glycolysis causing abnormal
    early intracellular acidosis, consistent with the early fatiguability and
    the slow recovery from exercise in ME. Coxsackie viruses can initiate
    non-cytolytic persistent infection in human cells. Animal models
    demonstrate similar enteroviral persistence in neurological disease… and
    the deleterious effect of forced exercise on persistently infected
    muscles. These studies elucidate the exercise-related morbidity and the
    chronic relapsing nature of ME” (EG Dowsett, AM Ramsay et al. Postgraduate
    Medical Journal 1990:66:526-530).


    “Persistent enteroviral infection of muscle may occur in some patients with
    postviral fatigue syndrome and may have an aetiological role….The features
    of this disorder suggest that the fatigue is caused by involvement of both
    muscle and the central nervous system…We used the polymerase chain reaction
    to search for the presence of enteroviral RNA sequences in a
    well-characterised group of patients with the postviral fatigue
    syndrome…53% were positive for enteroviral RNA sequences in
    muscle…Statistical analysis shows that these results are highly
    significant…On the basis of this study…there is persistent enteroviral
    infection in the muscle of some patients with the postviral fatigue
    syndrome and this interferes with cell metabolism and is causally related
    to the fatigue” (JW Gow et al. BMJ 1991:302:696-696).


    A major publication (Postviral Fatigue Syndrome. British Medical Bulletin
    1991:47:4: 793-907, published by Churchill Livingstone for The British
    Council) contains the following:

    “Molecular viral studies have recently proved to be extremely useful. They
    have confirmed the likely important role of enteroviral infections,
    particularly with Coxsackie B virus” (Postviral fatigue syndrome: Current
    neurobiological perspective. PGE Kennedy. BMB 1991:47:4:809-814)

    “We conclude that persistent enteroviral infection plays a role in the
    pathogenesis of PVFS…The strongest evidence implicates Coxsackie
    viruses…Patients with PVFS were 6.7 times more likely to have enteroviral
    persistence in their muscles” (JW Gow and WMH Behan. BMB 1991:47:4:872-885).


    “We will report at the First International Research Conference on Chronic
    Fatigue Syndrome to be held at Albany, New York, 2-4 October 1992, our new
    findings relating particularly to enteroviral infection…We have isolated
    RNA from patients and probed this with large enterovirus probes…detailed
    studies...showed that the material was true virus…Furthermore, this virus
    was shown to be replicating normally at the level of transcription.
    Sequence analysis of this isolated material showed that it had 80% homology
    with Coxsackie B viruses and 76% homology with poliomyelitis virus,
    demonstrating beyond any doubt that the material was enterovirus” (Press
    Release for the Albany Conference, Professor Peter O Behan, University of
    Glasgow, October 1992).


    “Samples from 25.9% of the PFS (postviral fatigue syndrome) were positive
    for the presence of enteroviral RNA, compared with only 1.3% of the
    controls…We propose that in PFS patients, a mutation affecting control of
    viral RNA synthesis occurs during the initial phase of active virus
    infection and allows persistence of replication defective virus which no
    longer attracts a cellular immune response” (NE Bowles, RJM Lane, L
    Cunningham and LC Archard. Journal of Medicine 1993:24:2&3:145-180).


    “These data support the view that while there may commonly be asymptomatic
    enterovirus infections of peripheral blood, it is the presence of
    persistent virus in muscle which is abnormal and this is associated with
    postviral fatigue syndrome…Evidence derived from epidemiological,
    serological, immunological, virological, molecular hybridisation and animal
    experiments suggests that persistent enteroviral infection may be involved
    in… PFS” (PO Behan et al. CFS: CIBA Foundation Symposium 173, 1993:146-159).


    “Individuals with CFS have characteristic clinical and laboratory findings
    including…evidence of viral reactivation…The object of this study was to
    evaluate the status of key parameters of the 2-5A synthetase/RNase L
    antiviral pathway in individuals with CFS who participated in a
    placebo-controlled, double-blind, multi-centre trial…The present work
    confirms the finding of elevated bioactive 2-5A and RNase L activity in
    CFS…RNase L, a 2-5A-dependent enzyme, is the terminal effector of an
    enzymatic pathway that is stimulated by either virus infection or exposure
    to exogenous lymphokines. Almost two-thirds of the subjects…displayed
    baseline RNase L activity that was elevated above the control mean”
    (Robert J Suhadolnik, Daniel L Peterson, Paul Cheney et al. In Vivo


    In his Summary of the Viral Studies of CFS, Dr Dharam V Ablashi concluded:
    “The presentations and discussions at this meeting strongly supported the
    hypothesis that CFS may be triggered by more than one viral agent…Komaroff
    suggests that, once reactivated, these viruses contribute directly to the
    morbidity of CFS by damaging certain tissues and indirectly by eliciting an
    on-going immune response” (Clin Inf Dis 1994:18 (Suppl 1):S130-133).


    “These results suggest there is persistence of enterovirus infection in
    some CFS patients and indicate the presence of distinct novel enterovirus
    sequences…Several studies have shown that a significant proportion of
    patients complaining of CFS have markers for enterovirus infection….It is
    worth noting that the enteroviral sequences obtained from patients without
    CFS were dissimilar to the sequences obtained from the CFS patients…This
    may provide corroborating evidence for the presence of a novel type of
    enterovirus associated with CFS” (DN Galbraith, C Nairn and GB Clements.
    Journal of General Virology 1995:76:1701-1707).


    “In the CFS study group, 42% of patients were positive for enteroviral
    sequences by PCR, compared to only 9% of the comparison group…Enteroviral
    PCR does, however, if positive, provide evidence for circulating viral
    sequences, and has been used to show that enteroviral specific sequences
    are present in a significantly greater proportion of CFS patients than
    other comparison groups” (C Nairn et al. Journal of Medical Virology


    “To prove formally that persistence rather than re-infection is occurring,
    it is necessary to identify a unique feature retained by serial viral
    isolates from one individual. We present here for the first time evidence
    for enteroviral persistence (in humans with CFS)…” (DN Galbraith et al.
    Journal of General Virology 1997:78:307-312).


    “Over the last decade a wide variety of infectious agents has been
    associated with CFS by researchers from all over the world. Many of these
    agents are neurotrophic and have been linked to other diseases involving
    the central nervous system (CNS)…Because patients with CFS manifest a wide
    range of symptoms involving the CNS as shown by abnormalities on brain
    MRIs, SPECT scans of the brain and results of tilt-table testing, we sought
    to determine the prevalence of HHV-6, HHV-8, EBV, CMV, Mycoplasma species,
    Chlamydia species and Coxsackie virus in the spinal fluid of a group of
    patients with CFS. Although we intended to search mainly for evidence of
    actively replicating HHV-6, a virus that has been associated by several
    researchers with this disorder, we found evidence of HHV-8, Chlamydia
    species, CMV and Coxsackie virus in (50% of patient) samples…It was also
    surprising to obtain such a relatively high yield of infectious agents on
    cell free specimens of spinal fluid that had not been centrifuged” (Susan
    Levine. JCFS 2002:9:1/2:41-51).


    “Differences in bacterial and/or viral infections in (ME)CFS patients
    compared to controls were significant…The results indicate that a large
    subset of (ME)CFS patients show evidence of bacterial and/or viral
    infection(s), and these infections may contribute to the severity of signs
    and symptoms found in these patients” (Nicolson GL et al. APMIS


    Seeking to detect and characterise enterovirus RNA in skeletal muscle from
    patients with (ME)CFS and to compare efficiency of muscle metabolism in
    enterovirus positive and negative (ME)CFS patients, Lane et al obtained
    quadriceps biopsy samples from 48 patients with (ME)CFS. Muscle biopsy
    samples from 20.8% of patients were positive, while 100% of the controls
    were negative for enterovirus sequences. Lane et al concluded: “There is
    an association between abnormal lactate response to exercise, reflecting
    impaired muscle energy metabolism, and the presence of enterovirus
    sequences in muscle in a proportion of (ME)CFS patients” (RJM Lane, LC
    Archard et al. JNNP 2003:74:1382-1386).


    In a review of the role of enteroviruses in (ME)CFS, Chia noted that
    initial reports of chronic enteroviral infections causing debilitating
    symptoms in (ME)CFS patients were met with scepticism and largely
    forgotten, but observations from in vitro experiments and from animal
    models clearly established a state of chronic persistence through the
    formation of double stranded RNA, similar to findings reported in muscle
    biopsies of patients with (ME)CFS. Recent evidence not only confirmed the
    earlier studies, but also clarified the pathogenic role of viral RNA (JKS
    Chia. Journal of Clinical Pathology 2005:58:1126-1132).


    “Early beliefs that (ME)CFS may be triggered or caused by a single virus
    have been shown to be unsubstantiated (and) it is likely that different
    viruses affect different individuals differently, dependent upon the
    …immune competence of the individual…Infections are known to trigger and
    perpetuate the disease in many cases. Therefore, one valuable approach
    that has not been widely adopted in the management of (ME)CFS patients is
    to exhaustively investigate such patients in the hope of identifying
    evidence for a specific persistent infection (but in the UK, NICE
    specifically does not permit such investigations)….Enteroviruses have been
    reported to trigger approximately 20% of cases of (ME)CFS…Antibodies to
    Coxsackie B virus are frequently detected in (ME)CFS patients, and
    enterovirus protein and RNA occur in the muscle and blood of (ME)CFS
    patients and their presence has been associated with altered metabolism in
    the muscle upon exercise in the context of (ME)CFS” (LD Devanur, JR Kerr.
    Journal of Clinical Virology 2006: 37(3):139-150).


    “(ME)CFS is associated with objective underlying biological abnormalities,
    particularly involving the nervous and immune system. Most studies have
    found that active infection with HHV-6 – a neurotropic, gliotropic and
    immunotropic virus – is present more often in patients with (ME)CFS than in
    healthy control subjects…Moreover, HHV-6 has been associated with many of
    the neurological and immunological findings in patients with (ME)CFS”
    Anthony L Komaroff. Journal of Clinical Virology 2006:37:S1:S39-S46.


    “Research studies have identified various features relevant to the
    pathogenesis of CFS/ME such as viral infection, immune abnormalities and
    immune activation, exposure to toxins, chemicals and pesticides, stress,
    hypotension…and neuroendocrine dysfunction….Various viruses have been shown
    to play a triggering or perpetuating role, or both, in this complex
    disease….The role of enterovirus infection as a trigger and perpetuating
    factor in CFS/ME has been recognised for decades” (Jonathan R Kerr.
    Editorial. J Clin Pathol 14th September 2007. Epub ahead of print).


    “Since most (ME)CFS patients have persistent or intermittent
    gastrointestinal (GI) symptoms, the presence of viral capsid protein 1
    (VP1), enterovirus RNA and culturable virus in the stomach biopsy specimens
    of patients with (ME)CFS was evaluated…Our recent analysis of 200 patients
    suggests that… enteroviruses may be the causative agents in more than half
    of the patients…At the time of oesophagogastroduodenoscopy, the majority of
    patients had mild, focal inflammation in the antrum…95% of biopsy specimens
    had microscopic evidence of mild chronic inflammation…82% of biopsy
    specimens stained positive for VP1 within parietal cells, whereas 20% of
    the controls stained positive…An estimated 80-90% of our 1,400 (ME)CFS
    patients have recurring gastrointestinal symptoms of varying severity, and
    epigastric and/or lower quadrant tenderness by examination…Finding
    enterovirus protein in 82% of stomach biopsy samples seems to correlate
    with the high percentage of (ME)CFS patients with GI
    complaints…Interestingly, the intensity of VP1 staining of the stomach
    biopsy correlated inversely with functional capacity…A significant subset
    of (ME)CFS patients may have a chronic, disseminated, non-cytolytic form of
    enteroviral infection which can lead to diffuse symptomatology without true
    organ damage” (Chia JK, Chia AY. J Clin Pathol 13th September 2007 Epub
    ahead of print).


    Dr John Chia, an infectious diseases specialist from Torrance, California,
    who specialises in ME/CFS, is on record: “I believe that the main reason
    (ME)CFS patients are symptomatic is due to continuing inflammatory response
    toward viruses living within the cells, enteroviruses in most of the cases
    I see. We have clearly documented certain enterovirus infections
    triggering autoimmune responses in some patients” (

    These few illustrations from the many available serve to illustrate that
    Professors van Kuppeveld and van der Meer’s assertion that: “In the past,
    several infectious agents have been associated with CFS but none of these
    could be confirmed in subsequent studies….” is demonstrably incorrect.

    The ignoring of the evidence-base of infection in ME/CFS is all the more
    disturbing given that Frank van Kuppeveld is Associate Professor (Infection
    and Inflammation) in the Department of Medical Microbiology, Radboud
    University Nijmegen Medical Centre and his research focuses on
    enteroviruses, and Jos van der Meer is Professor of Internal Medicine and
    Chairman of the Division of General Internal Medicine at Radboud University
    Nijmegen Medical Centre who also works in the Nijmegen Institute for
    Infection, Inflammation and Immunity.

    Do Professors van Kuppeveld and van der Meer have no concern for accuracy?

    Another article in which Professor van der Meer was a co-author appeared to
    show a similar lack of attention to the existing biomedical evidence-base:
    (A controversial consensus – comment on article by Broderick et al”:
    Professor van der Meer accuses the International Consensus Panel of bias
    towards the biomedical construct: “the authors seek to discard the findings
    in published studies that have applied the existing international criteria,
    if the result do not fit with their notions of causation….In a 21st century
    consensus document, accounting in a balanced fashion for the strength of
    the evidence is an essential element”, yet he does exactly the same by
    ignoring the biomedical evidence in his own articles.

    From his two latest articles, one must question whether Professor van der
    Meer contributes to scientific progress in what everyone agrees is a
    controversial condition.

    Equally, do editors of medical journals no longer see the need to adhere to
    elementary rules of procedure by assuring themselves that what they publish
    represents a potentially useful and original development of knowledge, and
    that any contribution is squarely built on the foundations of existing

    By publishing items that disregard the pre-existing body of knowledge,
    authors and editors fail in their duty to provide readers with information
    that can be relied upon and which can serve as a dependable basis for
    future work.

    Investigators are not free to declare established knowledge disproven
    simply by ignoring the data on which that knowledge is predicated.

    Merely ignoring and/or denying the existing knowledge-base, as Professors
    van Kuppeveld and van der Meer appear to have done, serves no scientific
    purpose but may actively delay the advancement of science and thus prolong
    the incalculable suffering of people with ME/CFS.

  2. Mikie

    Mikie Moderator

    For citing your source and stmt of permission to reproduce. We appreciate it.

    Love, Mikie
  3. simpsons

    simpsons Member

    you are welcome mikie i know it makes your life easier to know. i always have permission to repost margaret williams and hooper articles.

    it is a very interesting post and i thought it good for people to know the history of viral infections in ME

    knowledge is power as they say

    love simps
  4. Mikie

    Mikie Moderator

    I believe we are human Petri dishes of more than just one chronic infection. In GWI, it's mycoplasma infections which are the common denominator. The symptoms of GWI are identical to CFIDS and ME. I think we are genetically predisposed to these illnesses and all it takes is a heavy-duty infection to trigger them full blown. The question is a chicken-'n-egg one: Which came first? The genetic predisposition or an infection which caused changes to DNA, leaving the descendents predisposed to our illnesses?

    This article is very comprehensive and I thank you for posting it.

    Love, Mikie

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