|
For decades it has been known and shown that viruses play a role
in ME/CFS. Now there is evidence of a direct association with a
gamma retrovirus – XMRV -- that disables the immune system in
ME/CFS, thus allowing numerous latent viruses to re-activate,
which could result in the protean symptomatology.
As Professor Nancy Klimas said in her November 2009 lecture at
the University of Miami:
|
“We’ve
always thought something like that has to go on in (ME) CFS
because you all have some neuro-inflammation. Your brain has a
low grade level of inflammation. And you have some inflammation
in the tissues that make hormones, particularly in the
hypothalamic-pituitary-axis. And this is a virus that infects
that type of tissue…”
(see below). |
Latent viruses that have been particularly studied in relation
to ME/CFS include Coxsackie B virus (CBV), Epstein Barr virus
(EBV) and human herpes virus-6 (HHV-6), and illustrations are
provided below.
However, advised by psychiatrists of the Wessely School, in the
UK the NICE Guideline of 2007 recommends limited serology
testing for certain viruses only, which excludes testing for
Coxsackie B virus, for which there is the most evidence
(testing for Epstein Barr Virus, a particular interest of
Professor Peter White is, however, permitted).
Given that a classified synonym for ME/CFS is “post-viral
fatigue syndrome” (ICD-10 G93.3) and given that, like the MRC
PACE Trial, the NICE Guideline purports to apply to people with
“CFS/ME”, it is striking that the Guideline states on page 141:
|
“Serological testing should not be carried out unless the
history is indicative of an infection”. |
It is notable that the PACE Trial Investigators did not include
virological testing of participants in their trial that is based
on their theory that patients with “CFS/ME” are merely
deconditioned, so it needs to be ascertained what, exactly, do
the Wessely School psychiatrists understand the term
“post-viral” to mean if not a history indicative of an
infection?
The following are illustrations of viral involvement in ME/CFS:
1954
Describing an outbreak of infection of the central nervous
system complicated by intense myalgia in late summer 1952
affecting nurses at the Middlesex Hospital, London, the author
(ED Acheson, who later became UK Chief Medical Officer) reported
the clinical features to be severe muscular pain affecting the
back, limbs, abdomen and chest, with evidence of mild
involvement of the central nervous system, diarrhoea, vomiting,
respiratory distress, paresis and brain stem involvement that
included nystagmus, double vision and difficulty in swallowing;
additionally, bladder symptoms occurred in more than half the
patients. Acheson highlighted this small outbreak because of
the similarity to atypical poliomyelitis (ED Acheson. Lancet:
Nov 20th 1954:1044-1048). The label of “atypical
poliomyelitis” was originally given to ME (The Disease of a
Thousand Names. David S Bell. Pollard Publications, Lyndonville,
New York, 1991).
Many patients today
experience exactly the symptoms described by Acheson, but such
symptoms are dismissed by the Wessely School as somatisation and
as hypervigilance to normal bodily sensations.
1955
Acheson described and compared the outbreak at the Royal Free in
1955 with the outbreak at The Middlesex in 1952, noting the
relatively prolonged active course of the disease, marked
muscular pain and spasm, involvement of the lymph nodes, liver
and spleen, tenderness under the costal margins, and ulcers in
the mouth, all of which – if looked for and if not dismissed as
somatising -- are still to be found in “pure” ME today (ED
Acheson. Lancet: Aug 20th 1955:394-395).
1959
In his detailed review of numerous outbreaks of Benign Myalgic
Encephalomyelitis from 1934, Acheson described the common
characteristics of the disease and clinical picture, which
included agonising muscular pain, headache, nausea, sensory
disturbances, stiffness of the neck and back, dizziness,
muscular twitching, tremor and in-coordination, localised
muscular weakness, emotional lability, problems with memory and
concentration, hyperacusis, somnolence and insomnia, with
relapses being almost inevitable, together with variability of
symptoms. Signs included hepatic enlargement, lymphadenopathy
and evidence of CNS involvement, nystagmus being “almost
invariable” in some of the outbreaks. The question of
hysteria was addressed and discounted: “Final points against
mass hysteria as a major factor in the syndrome are the
consistency of the course of the illness and the similarities in
the symptoms…The disorder is not a manifestation of mass
hysteria” and Acheson specifically warned that the diagnosis
of ME should be reserved for those with (virally induced)
evidence of CNS damage:
|
“If not, the syndrome will become
a convenient dumping ground for non-specific illnesses
characterised by fluctuating aches and pains, fatigue and
depression”, exactly the situation that exists in
the UK 50 years after Acheson’s prophecy
(ED Acheson. American
Journal of Medicine, April 1959:569-595). |
1978
|
“The clinical picture was variable both in the time pattern of
its progression and the severity of the symptoms…It became clear
early on in the outbreak that there was organic involvement of
the central nervous system (and) there was objective evidence of
involvement of the central nervous system…The most
characteristic symptom was the prolonged painful muscle
spasms…Bladder dysfunction occurred in more than 25% of all the
patients…Case to case contact between patients and their
relatives also occurred…
McEvedy and Beard’s conclusions
(of mass hysteria) ignore the objective findings of the staff
of the hospital of fever, lymphadenopathy, cranial nerve palsies
and abnormal signs in the limbs…Objective evidence of brain stem
and spinal cord involvement was observed”
(Nigel D Compston.
Postgraduate Medical Journal 1978:54:722-724). |
1983
|
“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. Most have lost many weeks of employment or the
enjoyment of their family (and) marriages have been threatened…”
(BD
Keighley, EJ Bell. JRCP 1983:33:339-341). |
1985
|
“…from an immunological point of view, patients with
chronic active EBV infection appear ‘frozen’ in a
state typically found only briefly during
convalescence from acute EBV infection”
(G Tosato, S Straus et al. The Journal of Immunology
1985:134:5:3082-3088. Note that ”CFS” was then
thought to be caused by EBV). |
1985
|
“Epstein-Barr
virus infection may have induced or augmented an
immunoregulatory disorder that persisted in these patients”
(Stephen
E Straus et al. Ann Intern Med. 1985:102:7-16). |
1985
|
“The clinical, pathological, electrophysiological, immunological
and virological abnormalities in 50 patients with the postviral
fatigue syndrome are recorded. These findings confirm the
organic nature of the disease (and) suggest that it is
associated with disordered regulation of the immune system and
persistent viral infection”
(PO
Behan, WMH Behan, EJ Bell. Journal of Infection 1985:10:211-222. |
1987
|
“Ninety percent of the patients tested had antibodies to
Epstein-Barr virus and 45% tested had antibodies to
cytomegalovirus…if this fatigue syndrome is triggered by an
infectious agent, an abnormal immune response may be involved”
(TJ
Marrie et al. Clinical Ecology 1987:V:1:5-10). |
1987
|
“Recently associations have been found between
Coxsackie B infection and a more chronic multisystem
illness. A similar illness…has been 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). |
1987
|
“The illness has an acute onset after a variety of infections
and then enters a chronic phase characterised by fatigue and
numerous other symptoms….Other findings include a sleep
disorder, mild immunodeficiency, slightly low complement,
anti-DNA antibodies and elevated synthetase which is an
interferon-associated enzyme commonly increased in viral
infections”
(Irving
E Salit. Clinical Ecology 1987:V:3:103-107). |
1988
|
“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). |
1988
|
“Myalgic
encephalomyelitis was thought for some time to be produced by a
less virulent strain of poliovirus…chronic, persistent
viruses may often be reactivated during this illness…once
reactivated, do these viruses then go on to produce many of the
symptoms of the disease? And what reactivates these endogenous
viruses? Could it be environmental toxins? Could it be
infection with other, exogenous lymphotropic viruses?”
(Anthony
L Komaroff. Journal of Virological Methods. 1988:21:3-10). |
(In the light of the discovery in 2009 of the XMRV retrovirus –
see below -- this paper by Professor Komaroff 21 years in
advance of that discovery showed remarkable prescience).
1988
|
“Postviral
fatigue syndrome / myalgic encephalomyelitis… has attracted
increasing attention during the last five years…Its
distinguishing characteristic is severe muscle fatiguability
made worse by exercise…The chief organ affected is skeletal
muscle, and the severe fatiguability, with or without myalgia,
is the main symptom. The results of biochemical,
electrophysiological and pathological studies support the view
that muscle metabolism is disturbed, but there is no doubt that
other systems, such as nervous, cardiovascular and immune are
also affected…Recognition of the large number of patients
affected…indicates that a review of this intriguing disorder is
merited….The true syndrome is always associated with an
infection…Viral infections in muscle can indeed be
associated with a variety of enzyme
abnormalities…(Electrophysiological results) are important in
showing the organic nature of the illness and suggesting that
muscle abnormalities persist after the acute infection…there is
good evidence that Coxsackie B virus is present in the affected
muscle in some cases”
(PO Behan, WMH Behan. CRC Crit Rev
Neurobiol 1988:4:2:157-178). |
1988
|
“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 1988:11:103-115). |
1989
|
“Ten patients with post-viral fatigue syndrome and abnormal
serological, viral, immunological and histological studies were
examined by single fibre electromyographic technique….The
findings confirm the organic nature of the disease. A muscle
membrane disorder…is the likely mechanism for the fatigue and
the single-fibre EMG abnormalities. This muscle membrane defect
may be due to the effects of a persistent viral infection…There
seems to be evidence of a persistent viral infection and/or a
viral-induced disorder of the immune system…The infected cells
may not be killed but become unable to carry out differentiated
or specialised function”
(Goran A Jamal, Stig Hansen. Euro Neurol 1989:29:273-276). |
1990
|
“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). |
1990
|
“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). |
1991
A
paper reporting the discovery of a retrovirus associated with
(ME) CFS (Retroviral sequences related to human T-lymphotropic
virus type II in patients with chronic fatigue immune
dysfunction syndrome. Elaine DeFreitas, Paul R Cheney, David S
Bell et al. Proc Natl Acad Sci USA 1991:88:2922-2926) is
addressed in detail in the section “The role of Viruses in
ME/CFS”.
1991
|
“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). |
1991
|
“The findings described here provide the first evidence that
postviral fatigue syndrome may be due to a mitochondrial
disorder precipitated by a virus infection…Evidence of
mitochondrial abnormalities was present in 80% of the cases with
the commonest change (seen in 70%) being branching and fusion of
cristae, producing ‘compartmentalisation’. Mitochondrial
pleomorphism, size variation and occasional focal vacuolation
were detectable in 64%…Vacuolation of mitochondria was
frequent…In some cases there was swelling of the whole
mitochondrion with rupture of the outer membranes…prominent
secondary lysosomes were common in some of the worst affected
cases…The pleomorphism of the mitochondria in the patients’
muscle biopsies was in clear contrast to the findings in normal
control biopsies…Diffuse or focal atrophy of type II fibres has
been reported, and this does indicate muscle damage and not just
muscle disuse”
(WMH Behan et al. Acta Neuropathologica 1991:83:61-65). |
1991
Considerations in the Design of Studies of Chronic Fatigue
Syndrome. Reviews of Infectious Diseases. Volume 13,
Supplement 1: S1 – S140. University of Chicago Press.
Contributing authors included Anthony L Komaroff, David S Bell,
Daniel L Peterson, Sandra Daugherty and Sheila Bastien, whose
work has been referred to in other parts of this document.
1991
Postviral Fatigue Syndrome. British Medical Bulletin 1991:47:4:
793-907. Churchill Livingstone.
This major publication, published by Churchill
Livingstone for The British Council, includes papers by the
Wessely School considered by some to be misrepresentative of
ME/CFS (for example: “History of postviral fatigue syndrome” by
S Wessely; “Postviral fatigue syndrome and psychiatry” by AS
David -- in which David, a co-author of the Oxford criteria,
confirmed that
|
“British investigators have put forward an
alternative, less strict, operational definition which is
essentially chronic…fatigue in the absence of neurological
signs, (with) psychiatric symptoms…as common associated
features”
(AS David; BMB 1991:47:4:966-988) |
and “Psychiatric
management of PVFS” by M Sharpe) but also 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) |
|
“Our focus will be on the ability of certain viruses
to interfere subtly with the cell’s ability to
produce specific differentiated products as
hormones, neurotransmitters, cytokines and
immunoglobulins etc in the absence of their ability
to lyse the cell they infect. By this means
viruses can replicate in histologically normal
appearing cells and tissues…Viruses by this means
likely underlie a wide variety of clinical
illnesses, currently of unknown aetiology, that
affect the endocrine, immune, nervous and other
…systems”
(JC de la Torre, P Borrow, MBA Oldstone. BMB
1991:47:4:838-851). |
|
“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 peristence in their muscles”
(JW Gow and
WMH Behan. BMB 1991:47:4:872-885). |
|
“The
postviral fatigue syndrome (PVFS), with profound muscle fatigue
on exertion and slow recovery from exhaustion seems to be
related specifically to enteroviral infection. The form seen
with chronic reactivated EBV infection is superficially similar,
but without the profound muscle fatigue on exercise”
(JF Mowbray, GE Yousef. BMB 1991:47:4:886-894). |
1992
|
“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). |
1993
|
“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). |
1993
|
“These data support the view that while there may commonly be
asyptomatic 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). |
1994
|
“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
1994:8:599-604).
|
A
note on the significance of this paper
Viral infections of cells results in the production and
secretion of cytokines, including the interferons. Interferons
control the way that cells respond to a virus by means of a
group of inter-related enzymes that comprise an anti-viral
pathway. This pathway is known as the 2’,-5’-oligoadenylate
synthetase/RNase L pathway.
RNase L (ribonuclease latent) is the key enzyme in the
antiviral pathway and is designed to degrade viral RNA. It has
to be “turned on” by a small molecule, 2-5 A. Binding of 2-5A
to RNase L changes the enzyme from its latent (inactive) state
to its active state. When active, RNase L inhibits viral
protein synthesis and thereby prevents viral replication.
Several critical parts of the anti-viral pathway are not
functioning correctly in ME/CFS.
The level of RNase L enzyme activity has been demonstrated to be
upregulated (i.e.. increased) by as much as 1,500 times above
normal levels, and researchers at Temple University School of
Medicine, Philadelphia, have shown that not only is the activity
of the RNase L enzyme significantly higher in patients with
(ME)CFS than in controls, but also that there is a significant
increase in the level of 2-5A (the molecule that converts RNase
L from its latent to its active state) and in the level
of 2-5A synthetase (the enzyme that synthesises the 2-5A
activator molecule).
The most striking finding in patients with (ME)CFS is, however,
that they have a unique form of the RNase L enzyme. The size of
the RNase L protein is normally 80 kDa (kiloDaltons), but in
many people with (ME)CFS, this 80 kDa enzyme is either scarce or
missing altogether. Instead, a unique low molecular weight
(LMW) form of RNase L is observed (30 kDa). Besides its smaller
size, the LMW RNase L seen in (ME)CFS patients has other
biochemical differences from the 80 kDa RNase L. The LMW RNase
L binds its activator more tightly and is more potent than the
80 kDa form of RNase L.
Studies have revealed several connections between the RNase L
pathway and the clinical status of (ME)CFS patients,
demonstrating that the increased activity of the RNase L pathway
is an indication of a lower state of health and that all three
measurements of the pathway are abnormal in (ME)CFS.
Studies carried out in various countries apart from the US
(including Australia, Belgium, France and Germany) have all
confirmed the presence of the LMW RNase L in (ME)CFS; moreover,
two different methods using different probes to detect RNase L
accurately identified (ME)CFS patients.
Importantly, the RNase L ratio also distinguished individuals
with (ME)CFS from those with fibromyalgia or depression.
In addition, studies have shown that the presence of LMW RNase L
is independent of the duration of (ME)CFS symptoms: the LMW
RNase L was detected in individuals who had (ME)CFS symptoms for
as long as 19 years.
The presence of the LMW RNase L identifies a group of people
with (ME)CFS who have an abnormally elevated anti-viral
response, and the anti-viral RNase L protein level and enzyme
activity are potentially powerful diagnostic tools for (ME)CFS
(with grateful acknowledgement to Nancy Reichenbach, associate
scientist in the Department of Biochemistry at Temple University
School of Medicine, and to the CFIDS Association of America:
http://www.cfids.org/archives/2000rr/2000-rr1-article01.asp
).
Although these important abnormalities were known about in 1994,
and despite the evidence of the reliability and reproducibility
of RNase L testing that was presented in 1999 at the Second
World Congress on (ME)CFS in Brussels, in the UK there has been
continued opposition to such testing, not only by the Wessely
School (who consistently advise that only limited investigations
should be carried out), but also by the ME Association.
For example, the Medical Director of the ME Association, Dr
Charles Shepherd, apparently intended to inform readers of the
ME Association’s Newsletter (Perspectives) that his view of the
international work on RNase L was that it
|
“may involve what I
and many of my colleagues regard as over-investigation for
highly speculative abnormalities in antiviral pathway activity”, |
which seemed to echo Professor Anthony Pinching’s view that
|
“over-investigation can (cause patients) to seek abnormal test
results to validate their illness”
(Prescribers’
Journal 2000: 40:2:99-106). |
The Spring 2001 Issue of the ME
Association’s Medical and Welfare Bulletin stated (on page 9)
about RNase L testing:
|
“Having
discussed the possible value of this type of blood test with
members of the MEA’s Scientific and Medical Advisory Panel,
there is general agreement that insufficient evidence exists to
recommend that this test should be carried out for either
diagnostic or management purposes”
(members of the SMAP included Professor Peter Behan, Professor
Leslie Findley, Dr John Gow, Professor Anthony Pinching and Dr
Shepherd himself). |
The ME Association did, however, co-fund with The Linbury Trust
studies examining RNase L activity: blood from patients
attending the Fatigue Service at St Bartholomew’s Hospital and
from Romford, Essex, was sent to Dr John Gow, who was working
with Professors Peter and Wilhelmina Behan and Dr Abhijit
Chaudhuri, all then at the University of Glasgow. Gow et al’s
work on a total of 22 patients with CFS was published in
Clinical Infectious Diseases (2001:33:12:2080-2081), the
conclusion being that
|
“patients with
CFS showed no significant activation”
of either part
of the RNase L pathway, and that
“assay of antiviral pathway activation is unlikely to form a
rational basis for a diagnostic test for CFS”. |
Professors Suhadolnik and De Meirleir robustly showed that Gow
et al’s study was fundamentally flawed. Pointing out that
|
“Over the years,
our teams have repeatedly observed an activation at the
enzymatic level of the antiviral pathway in subsets of CFS
patients”, |
they noted that
Gow et al had
(1) misunderstood the established knowledge of the IFN pathway,
(2) did not confirm their observations of genetic
expression at the transcriptional level (which would have
clarified their results),
(3) used the terms “genetic
expression” and “activity” interchangeably, when they are not
necessarily synonymous (particularly when the research involves
enzymes).
They also noted that confusion in the mind of Gow et
al about these issues led them to misquote their articles:
|
“On
the basis of their limited observations, Gow et al challenge our
observations and further deny any rational basis to our proposal
regarding the use of 37-kDa RNase L detection as a biological
marker for CFS. In our study, which they clearly misquoted, we
did not measure the enzymatic activity of the fragment and,
hence, the 2-5A pathway activation as Gow and colleagues
claimed. Instead, we limited our study to the quantitative
detection of the 37-kDa truncated enzyme…We observed a
significant increase in the 37-kDa RNase L level in patients
with CFS compared with that observed in healthy control
subjects, patients with fibromyalgia, and patients with
depression….
Consequently, this does not support the claim that
the presence of the 37-kDa RNase L in CFS could only be imparted
to non-specific increases in the antiviral pathway
activation…Our data demonstrate that there is a more
comprehensive downstream cellular role for the signal
transduction by IFN than what Gow and colleagues pretend to
present to the readers of Clinical Infectious Diseases”
(Clin Inf Dis 2002:34:1420-1421).
|
The ME Association and its medical advisors, however, remained
convinced that Gow et al were correct:
|
“A
very important conclusion from this study is that costly
investigations such as the RNase L test, which assess the amount
of antiviral activity in ME/CFS, are unlikely to provide the
basis for a diagnostic test. Such tests are therefore of very
questionable value in the assessment of people with ME/CFS”
(MEA Medical and Welfare Bulletin, Spring 2002, Issue No 6,
page 10). |
At the AACFS International Research Conference in 2003 held in
Washington, Wilhelmina Behan, as co-author of the Gow et al
study, was publicly challenged by Professor Suhadolnik to defend
it, but was unable to do so.
Notwithstanding, on the basis of the Gow / Behan results, the ME
Association’s Medical Advisor remains of the view that
|
“the presence of
…abnormalities in antiviral pathways has been assessed in
research studies funded by the ME Association”
and that the results of these tests are not
“of proven
value”
(ME/CFS/PVFS: An exploration of the key clinical issues. Dr
Charles Shepherd and Dr Abhijit Chaudhuri, for The ME
Association, 2007). |
In contrast to such UK views about the significance of RNase L,
in 2000 Professor Anthony Komaroff from Harvard had written
about Professor De Meirleir’s work on RNase L in an Editorial in
the American Journal of Medicine:
|
“What is this
research telling us? It is another piece of evidence that the
immune system is affected in chronic fatigue syndrome and it
reproduces and extends the work of another investigator
(Professor Suhadolnik from the US), lending credibility to the
result”
(Am J Med 2000:108:169-171). |
It is worth noting that elevated levels of RNase L are
associated with reduced maximal oxygen consumption (VO2
max) and exercise duration in ME/CFS patients; Snell et al found
that both abnormal RNase L activity and low oxygen consumption
were observed in most (ME)CFS patients, findings that
demonstrate that patients’ extremely low tolerance for physical
activity is likely to be linked to abnormal oxidative
metabolism, perhaps resulting from defective interferon
responses (Comparison of maximal oxygen consumption and RNase L
enzyme in patients with CFS. C Snell et al. AACFS Fifth
International Research and Clinical Conference, Seattle, January
2001; #026).
It is also worth noting that the 37 kDa LMW RNase L fragment
found in ME/CFS patients is produced by cleavage of calpain (an
apoptotic enzyme), and the whole process affects the calcium and
potassium ion channels, a channelopathy that will lead to low
body potassium (a known finding in ME-CFS patients --Burnett et
al found that total body potassium (TBK) was lower in patients
with (ME)CFS and suggest that abnormal potassium handling by
muscle in the context of low overall body potassium may
contribute to fatigue in (ME)CFS (Medical Journal of Australia,
1996:164:6:384).
It is also important to note that patients who express the low
molecular weight RNase L may have problems with enzymatic
detoxification pathways, particularly in the liver. This is
significant because of the resultant adverse effect on thyroid
function.
It has long been noted by practitioners that ME/CFS patients are
often clinically hypothyroid even though biochemically
euthyroid. Evidence suggests that such patients may not really
be euthyroid, especially at the tissue level. (Chopra IJ. J Clin
Endocrinol Metab 1997:82(2):329-334), so particular attention
needs to be paid to investigating the bioavailablity of T3
because in ME/CFS, T3 levels are often low (or at the low end of
the normal range). Consequently, selenium levels need to be
investigated in patients with ME/CFS who have reduced T3
levels: this is because selenium (as selenocysteine) is an
integral component of two important enzymes, glutathione
peroxidase and iodothryonine deiodinase; it is expressed in the
liver and it regulates the conversion of thyroxine (T4) to the
active and more potent T3. Individuals who have a deficiency of
5’ deiodinase cannot produce T3 from T4, thus it is necessary to
establish baseline levels of selenium in ME/CFS patients whose
T3 levels are low.
In the UK, the NICE Guideline does not recommend such testing.
In relation to RNase L, a recent literature review of the
immunological similarities between cancer and (ME)CFS pointed
out:
|
“Cancer and CFS are both characterised by fatigue and severe
disability (and) certain aspects of immune dysfunctions appear
to be present in both illnesses…A literature review of
overlapping immune dysfunctions in CFS and cancer is provided.
Abnormalities in ribonuclease (RNase L) and
hyperactivation of nuclear factor kappa-beta (NF-kappab)
are present in CFS and in prostate cancer. Malfunctioning of
natural killer (NK) cells has long been recognised as an
important factor in the development and recurrence of cancer,
and has been documented repeatedly in CFS patients. The
dysregulation of the RNase L pathway, hyperactive NF-kappab
leading to disturbed apoptotic mechanisms and oxidative stress
or excessive nitric oxide, and low NK activity may play a role
in the two diseases (and)… are present in both diseases. These
anomalies may be part of the physiopathology of some of the
common complaints, such as fatigue”
(Meeus M et al. Anticancer Res 2009:29(11):4717-4726).
|
It seems that, even if not a specific biomarker for ME/CFS, the
significance of the abnormal RNase L anti-viral pathway in
ME/CFS patients cannot be sufficiently emphasised, but through
the undoubted influence of the Wessely School, ME/CFS sufferers
in the UK are not permitted to have their anti-viral pathway
status investigated.
1994
Chronic Fatigue Syndrome: Current Concepts.
Clinical Infectious Diseases 1994: Volume 18: Supplement 1: S1 –
S167. Ed. Paul H Levine. University of Chicago Press.
Contributing authors include: Paul H Levine, Alexis Shelokov,
Anthony L Komaroff, David S Bell, Paul R Cheney, Leonard H
Calabrese, Leonard A Jason, Seymour Grufferman, Hirohiko
Kuratsune, Charles Bombadier, Nancy G Klimas, Mary Ann Fletcher,
Roberto Patarca-Montero, Benjamin H Natelson, Robert J
Suhadolnik, Daniel L Peterson, Dharam V Ablashi, Fred Friedberg,
Jay A Levy, Peter O Behan, Wilhelmina MH Behan and Mark O
Loveless.
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). It is recommended that the
entire 167-page Journal be read to show how ill-founded is the
Wessely School’s “CBT model” of ME/CFS. |
In their Closing Remarks, Professors Komaroff and Klimas said:
|
“Few
studies by psychiatrists are presented in this supplement. Many
investigators who have argued that CFS is primarily a
psychiatric disorder chose not to present their work”
(Clin Inf Dis 1994:18:(Suppl 1):S166-167).
|
1995
|
“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….From the data
presented here…the CFS sequences may indicate the presence of
novel enteroviruses…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). |
1995
|
“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 1995:46:310-313). |
1997
|
“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). |
1998
|
“Recent developments in molecular biology…have revealed a
hitherto unrecognised association between enteroviruses and some
of the most disabling, chronic and disheartening neurological,
cardiac and endocrine diseases…Persistent infection (by
enteroviruses) is associated with ME/CFS…The difficulty of
making a differential diagnosis between ME/CFS and post-polio
sequelae cannot be over-emphasised…
(EG
Dowsett. Commissioned for the BASEM meeting at the RCGP, 26th
April 1998:1-10). |
2000
An important paper by Ablashi and Peterson et al suggested that
in both multiple sclerosis (MS) and (ME)CFS, HHV-6 reactivation
plays a role in the pathogenesis.
|
“Two
disorders of significant importance, MS and CFS, appear to be
associated with HHV-6 infection…the data presented here show
that both MS and CFS patients tend to carry a higher rate of
HHV-6 infection or reactivation compared to normal controls.
This immunological and virological data supports a role of HHV-6
in the symptomatology of these diseases…Based on
biological, immunological and molecular analysis, the data show
that HHV-6 isolates from 70% of CFS patients were Variant
A…Interestingly, the majority of HHV-6 isolates from MS patients
were Variant B…These data demonstrate that the CFS patients
exhibited HHV-6 specific immune responses…Seventy percent of
the HHV-6 isolates from CFS patients were Variant A, similar to
those reported in AIDS…It has already been shown that active
HHV-6 infection in HIV-infected patients enhanced the AIDS
disease process. We suspect that the same scenario is occurring
in the pathogenesis of MS and CFS…The immunological data
presented here clearly shows a significantly high frequency of
HHV-6 reactivation in CFS and MS patients. We postulate that
active HHV-6 infection is a major contributory factor in the
aetiologies of MS and CFS”
(DV Ablashi, DL Peterson et al.
Journal of Clinical Virology 2000:16:179-191). |
(HHV-6 is one of eight known members of the human herpes virus
family. It has two variants [A and B]; the A strain is much more
pathogenic and infects the immune and central nervous systems.
Reactivation in adults has been associated with glandular fever,
autoimmune disorders and diseases of the nervous system. Active
HHV-6 infections are not found in healthy people without disease
associations and reactivation can result in suppression of bone
marrow function and inflammation, and can cause damage in
tissues such as brain, liver or lungs. HHV-6 has been
specifically linked to MS, AIDS and (ME)CFS [Co-Cure MED: 2nd
March 2002]. HHV-6 used to be called human B-lymphotropic virus
(HBLV); it was discovered in 1986 from the blood of patients
with AIDS. HHV-6 also correlates with 37kDa – the low molecular
weight form of RNase L that is known to exist as part of a
dysregulated antiviral pathway in ME/CFS patients).
2001
|
“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). |
(HHV-8 is associated with Kaposi’s sarcoma which is found in HIV
AIDS and with some B-cell lymphomas).
2003
Nicolson et al showed that multiple co-infections (Mycoplasma,
Chlamydia, HHV-6) in blood of chronic fatigue syndrome patients
are associated with signs and symptoms:
|
“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 2003:111(5):557-566).
|
2003
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).
|
2005
In their presentation to the US Assembly Committee, Drs Dharam
Ablashi and Kristin Loomis said:
|
“Reasons
to suspect viruses as a cause of CFS and MS:
In CFS,
symptoms wax and wane; antiviral pathways are activated;
symptoms are similar to many viral conditions; geographic
outbreaks have been reported; gene expression profiling found
genetic variants that reduce antiviral defences. In MS,
antiviral pathways are activated; geographic outbreaks have been
reported; all demyelinating disorders with known aetiology have
been caused by viruses; symptoms wax and wane and worsen with
viral infections.
“Evidence of central nervous system abnormalities in (ME)CFS are
similar to those in MS: reduced grey matter volume in bilateral
prefrontal cortex; abnormal uptake of acetyl-L carnitine in the
prefrontal cortex; enlarged ventricle volumes; increased small
punctate lesions on MRI in MS and in a subset of (ME)CFS;
fatigue is present in more than 85% of people with MS and in
100% of people with (ME)CFS; reduced information processing
speed; memory and cognitive problems”. |
Ablashi and Loomis pointed out that an analysis of studies of
HHV-6 in (ME)CFS differentiated between active and latent virus,
with 83% being positive (Assessment and Implications of
Viruses in Debilitating Fatigue in CFS and MS Patients. Dharam V
Ablashi et al. HHV-6 Foundation, Santa Barbara, USA.
Submission to Assembly Committee/Ways & Means, Exhibit B1-20,
submitted by Annette Whittemore 1st June 2005).
2005
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).
2006
|
“We
now recognise that the immune system plays a crucial role in the
pathogenesis of (ME)CFS…A disruption of the HPA axis has been
implicated in the pathogenesis of (ME)CFS…A link between the
immune system and the HPA axis has long been established…it is
likely that HPA axis dysfunction is not the cause of (ME)CFS,
but that it is secondary to the primary pathogenesis. However,
once invoked, HPA axis dysfunction may contribute towards the
perpetuation of the illness…Stress is known to have a
significant modulating effect on the pathogenesis of viral
infection (and) the principal means by which this influence
occurs is likely to be via the HPA axis…
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 if
(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”. |
Kerr et al then go on to provide evidence of other triggers of
(ME)CFS which include Parvovirus; C. pneumoniae; C.
burnetti; toxin exposure and vaccination including MMR,
pneumovax, influenza, hepatitis B, tetanus, typhoid and
poliovirus (LD Devanur, JR Kerr. Journal of Clinical Virology
2006: 37(3):139-150).
2006
Having carried out a prospective cohort study of post-infective
and chronic fatigue syndromes precipitated by viral and
non-viral pathogens, the authors concluded:
|
“The syndrome
was predicted largely by the severity of the acute illness
rather than by demographic, psychological or microbiological
factors…Importantly, premorbid and intercurrent
psychiatric disorder did not show predictive power for
post-infective fatigue at any time point…We propose that
…neurobiological mechanisms triggered during the severe, acute
illness…underpin the persistent symptoms domains of
post-infective fatigue syndrome”
(Ian Hickie et al. BMJ
2006: 333:575). |
2006
|
“CFS is a poorly-defined medical condition…which, besides severe
chronic fatigue as the hallmark symptom, involves inflammatory
and immune activation…
The type I interferon antiviral pathway
has been repeatedly shown to be activated in peripheral blood
mononuclear cells of the most severely afflicted
patients…
Recently, the levels of this abnormal protein have been
significantly correlated to the extent of inflammatory symptoms
displayed by (ME)CFS patients. We report here that active
double-stranded RNA-dependent kinase (PKR) is expressed and
activated in parallel to the presence of the 37 kDa RNase L and
to an increase in nitric oxide production by immune cells…
These
results suggest that chronic inflammation due to excess nitric
oxide production plays a role in (ME)CFS and that the normal
resolution of the inflammatory process by NFK-b
activation and apoptotic induction is impaired”
(Marc
Fremont, Kenny De Meirleir et al. JCFS 2006:13:4:17-28). |
2006
|
“(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. |
2007
|
“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…
The
importance of gastrointestinal symptoms in CFS/ME and the known
ability of enteroviruses to cause gastrointestinal infections
led John and Andrew Chia to study the role of enterovirus
infection in the stomach of CFS/ME patients…They describe a
systematic study of enterovirus infection in the stomach of 165
CFS/ME patients, demonstrating a detection rate of enterovirus
VP1 protein in 82% of patients…the possibility of an EV
outbreak…seems unlikely, as these patients developed their
diseases at different times over a 20 year period”
(Jonathan R Kerr. Editorial. J Clin Pathol 14th
September 2007. Epub ahead of print) |
2007
|
“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). |
2009
As mentioned elsewhere, researchers from the Enterovirus
Research Laboratory, Department of Pathology and Microbiology,
University of Nebraska Medical Centre wrote a
specially-commissioned explanatory article for the UK charity
Invest in ME, in which they stated that human enteroviruses were
not generally thought to persist in the host after an acute
infection, but they had discovered that Coxsackie B viruses can
naturally delete sequence from the 5’ end of the RNA genome, and
that this results in long-term viral persistence, and that
In her lecture in November 2009 at the University of Miami,
Professor Nancy Klimas said about viruses and ME/CFS that much
of the research at Miami and internationally found that the
viruses studied all have several things in common: they infect
cells of the immune system and the neurological system; they are
capable of causing latent infections and they can reactivate
under certain conditions.
She also said that their early work at Miami in the late 1980s
(published in the Journal of Clinical Microbiology in 1989)
showed that ME/CFS patients had immune activation and poor
anti-viral cell function. She then went on to discuss the
importance of the findings of the retrovirus XMRV (evidence of
which was published in Science on 8th October 2009),
saying that it was “very impressive work”. She
continued:
“This Science paper was amazing for a number of
reasons. First, this team had put together such strong science
that they could go for a Science paper.
Science is like the
Mecca of publication.
If you get your stuff in Science, that’s
the best place you could possibly (get it published).
And they
don’t take just anything and they sure, sure, sure don’t take
anything unless it’s extremely well done, validated and tested
out.
So they took this paper – they not only took it, they put
it in Science Express. They thought it was so important, they
published on a very fast track…
The way (the researchers at the
Whittemore Peterson Institute) looked is very sophisticated…
They
then tried to find (the virus) in all these other ways…they
looked from a whole different angle. Still found it.
Backed up
and looked from another angle. Still found it…
they had five
different kinds of ways they looked for this virus. And they
were able to find the virus.
That’s why Science was so
impressed…
It is a virus that can infect tissues that aren’t
white blood cells…
We’ve always thought something like that
has to go on in (ME)CFS because you all have some
neuro-inflammation. Your brain has a low grade level of
inflammation. And you have some inflammation in the tissues
that make hormones, particularly in the
hypothalamic-pituitary-axis. And this is a virus that infects
that type of tissue…
t’s pretty impressive that out of 101 (ME)CFS
cases defined by clinical case definition or a research case
definition that they found 99 with the virus…
And, oh, by the
way, we have a biomarker. Not a small deal.
A biomarker – the
virus itself.
No better biomarker than something that’s
clearly, tightly associated with an illness…
So the conclusion,
it really is a big thing. It’s a big thing…
That work we were
already doing plays right into this. All the genomics work and
all the immunology work. This is all critical to the better
understanding of this illness and how this virus plays into it”
(with grateful acknowledgement to PANDORA and
http://aboutmecfs.org/Rsrch/XMRVKlimas.aspx and
http://aboutmecfs.org/Rsrch/XMRVKlimasII.aspx). |
The Whittemore-Peterson Institute’s study that found the new
human retrovirus XMRV was listed as one of the top 100
scientific discoveries in 2009 in Discovery magazine’s January
2010 issue (Co-Cure NOT: 30th December 2009).
There can be no dismissing the evidence of viral involvement in ME/CFS,
much of which pre-dated the PACE Trial.
The Trial Investigators, the MRC Data Monitoring and Ethics Committee,
the Trial Steering Committee and the Trial Management Group
surely have a duty to provide a convincing explanation for their
decision not to inform Trial participants of this fundamental
evidence as, without it, participants may not have been in a
position to provide fully informed consent before agreeing to
enter the Trial.
|
