Dr Esther Crawley discusses XMRV and WPI, March 2010

Dr Esther Crawley discusses XMRV and Whittemore Peterson Institute (WPI), March 2010

Part transcript: Presentation to the Dorset CFS/ME Society Annual Medical Lecture: section on XMRV.

Shortlink: http://wp.me/p5foE-31g

XMRV: Whittemore Peterson Institute (WPI)  Opens on campus of University of Nevada (Parts 1 and 2)

Sam Shad for Nevada Newsmakers

Part 1

Part 2

 

Update: This transcript was revised on 20 August and supersedes previous versions.

May be reposted if posted in full, unedited and a link to source is given.

Dorset CFS/ME Society
Annual Medical Lecture

27th March 2010

The Future of Research in CFS/ME

Esther Crawley

Intro:

It’s a great pleasure to be here, everybody, and I’m really glad actually that my talk actually fits in very nicely with what William’s just said – Phew!

I’m going to be talking a lot about the collaborative research and the first half of my talk actually was given to the MRC Working Group at the end of last year. So you’ll actually see what we were talking about where the MRC gathered lots and lots of researchers together to discuss a way forward with chronic fatigue [sic] and I did the talk on Epidemiology.

[…]

[Slide]

I couldn’t resist talking about XMRV. I think we have to know about what’s actually happened and I will discuss that as well and what the implications are.

[…]

[Rest of intro and presentation skipped.]

Approx 27 mins in from start of presentation:

[Slide]

XMRV. OK, so in the next, last, remaining bit of the talk I want to summarise what’s happened about the XMRV story for you. I think it’s really important that we’re all informed about it.

Many of you will have woken up and read this story, in fact I knew about it 24 hours before it was about to break – “Has science found the cause of chronic fatigue syndrome?” – we’re all very excited and hopeful this might give us something we can treat. Great.

[Slide]

Don’t you think this is the most beautiful picture? That’s the XMRV virus. I don’t know how they get those colours on them – very beautiful.

Now this is the Centre that reported it. Do any of you notice anything about that picture? XXXX you’re not allowed to say.

Sorry?

Member of the audience: Sunshiny?

EC: Sunshiny, yeah. It’s in Reno, yeah, yeah. Anything else? It’s a bit far away.

Has anyone looked at the website? Isn’t that interesting? That doesn’t exist. That’s a fake picture – it’s what they would like to exist, when you donate money, when you go on the website. I thought everybody knew that! Yeah, sorry? This is Dorset.

OK. The Centre isn’t built. That’s their picture of what they would like to build and when you go on the website it has “Please donate.”

OK. What do the Lombardi group originally show?

[Slide]

OK. This is a complicated slide. I’m just going to take you through bit by bit because it’s really important when we look at all the research evidence.

OK. The gag sequences – the DNA that’s associated with these particular type of viruses – so they use PCR. PCR is basically when you get a tiny bit of DNA and you multiply and multiply and multiply and then you run it on a gel and see if it’s there. And what they found, and you’ll all remember these figures, I’m sure, is that they found it in 68 out of 100 [Ed: 101 on slide] chronic fatigue [sic] patients and 8 out of 218 controls.

They then looked in the cells and they found the protein in the cells and then they looked at whether it’s infectious. Now I have to say, this bit made me slightly worried – so they looked to see whether this virus could infect other cells within the lab and they showed that it’s infectious and they also looked at what happened if you put the virus with other cells in terms of did it develop an immune response?

[Slide]

And these are some of the pictures they showed. So when you multiply out the DNA, you then run it on a gel and you tag it with a thing that shines – I did my PhD doing this, I can tell you all sorts of awful stories of gels breaking and all sorts of other things going wrong. But these are the chronic fatigue [sic] patients – you see all these lines, here? That’s that gag sequence – here and here – that’s the end of the line and these are the controls.

Then they looked at the expression in cells and you could see it. And then they looked at the infection and this is the infection happening here.

Now this paper went out for review by virologists – not by clinicians and that’s a very important point and it was passed and it was published.

[Slide]

And this is what they said on their website and I think this is kind of interesting: “

“We have detected the retroviral infection XMRV is greater than 95%…”

Where did the 95% come from? Did anybody notice the 95%? Can anybody remember the percentage they found it in? Yeah, 66% [sic], slightly less.

OK. Says on the website “…95%…The current [working] hypothesis is that [XMRV]…” infects these cells…and I found this absolutely terrifying…viral chronic fatigue syndrome “causes the chronic inflammation and immune deficiency resulting in an inability to mount an effective immune response to opportunistic infections”.

OK. Have they shown any of that? Have they shown increased risk of opportunist infections? Have they shown a defect in the immune system that’s actually going to affect someone rather than just in a cell lab plate?

[Slide]

No. But that’s what’s on their website. That’s what they say they’ve found. So what happens? The research community runs to replicate the work.

[Slide]

OK. And you’ll all remember when this first paper came out “Failure to replicate…” – this is an English paper [Ed: the McClure PLoS ONE paper]. Well obviously this is wrong because they didn’t use the same techniques and it wasn’t the same patient group.

[Slide]

So in this particular experiment, they actually characterised the patients.

Now on the original paper, they say that the chronic fatigue [sic] patients were well-characterised but they do not describe them at all. We don’t know how many were girls – we don’t know how many…girls! – I’m such a paediatrician – we don’t know how many were female. We don’t know how long they had had the illness for. We don’t know who diagnosed them and we don’t know whether they had any blood tests to exclude other illnesses.

In this one, [Ed: the McClure paper], they actually had all the exclusion stuff excluded, they then used the DNA sequence. They had positive and negative controls. Why do you need positive and negative controls? Yes, so you’re worried that maybe when you do PCR it’ll pick up…you’ve all seen crime scenes, right? So PCR will pick up one bit of DNA, so if you’ve got a bit of DNA in your solution or something like that, you must have negative controls because you need to be certain that the DNA has come from the samples – not from your lab solutions.

Yes. OK. And you must have positive controls to make sure your experiments work.

They used a virus free laboratory. So they did it in a laboratory that had not had the virus in the past and they blinded the person doing the PCR. Does everyone know about “blinding”? So what they did, was that the person that was reading the gels didn’t know whether they were patients or not, because it’s really easy on those gels to over-interpret what you see.

OK and their results, you might all remember, they didn’t find any out of 186 patients – none of them had chronic fatigue [Ed: corrects herself] – XMRV.

[Slide]

And then a few days later, this one came out. This one had several people from England – Jonathan Kerr and so on. And they’re very open – they said, John Gow – these are all people that we’re collaborating with – they said we wanted to find chronic fatigue syndrome – we wanted to find the XMRV virus. We wanted to – we looked hard.

Now the criticism of the previous paper was that they hadn’t used the same techniques, so in this one they used the same techniques. They had 170 patients, 395 controls. You can already see the sample size is much bigger and they did both PCR and looked at the serology.

They found none in 299 samples of patients – had chronic fatigue [Ed: corrects herself] – had XMRV. And although they found what’s called “neutralising activity” they looked at this further and suggested that the immune response was actually related to other viruses and not to the XMRV.

[Slide]

And then this was published a couple of weeks later [Ed: BMJ paper] – from the Dutch group. Again, a very well described Dutch cohort – smaller, 76 patients 69 controls. And what they did, they actually went completely overboard with trying to find it. They used very, very sensitive techniques that should have detected – if any was there at all, they should have detected it – much more sensitive than the original paper and they looked at a variety of DNA and they tried several times to improve the sensitivity – all samples were negative for XMRV.

So what do you think’s going on?

Member of the audience: Publicity.

EC: Publicity…

….I have actually given a clue.

Member of the audience: Money?

EC: Sorry. Money…money…money…

Member of the audience: XXXX wants to tell us.

EC: OK, go on, XXXX…

EC’s young son (in front row): Did they all do it from one place?

[Slide]

EC: Ye…es! The first group – actually, the question is, was the first group chronic fatigue syndrome? And eventually, when they were asked, they told the research community that, this is in Lisbon, at the end of last year, that all the samples came from an outbreak of chronic fatigue syndrome in one village in Lake Tahoe.

And when you actually go and have a look at all the research data around that outbreak, everybody at that time thought it was a viral infection. And nobody could find the virus.

So most of us think that that was probably the issue – it was probably a viral outbreak that has certainly caused chronic fatigue syndrome but is not necessarily going to be relevant for us here in the UK.

[Slide]

It’s not clear about the PCR operator, the person that looks – it’s not clear from the paper, whether they were blinded. There might be issues about whether you work in a virus free lab, remember they showed that this was infectious.

And there’s a big question here [Ed: indicates on slide] – this XMRV virus was initially described with prostate cancer and the prostate research community has shown this in prostate cancer in two studies in the USA. These are different labs in different studies but no association in Europe.

So maybe this is a virus that’s important in America but not important in this country – it’s not clear.

And I think this is of interest. Within a week of their paper being published they produced a test for the XMRV virus at $650 a test. [Ed: Slide reads, at point 4: Conflict of interest?].

And if I was developing a test, I would declare that as a conflict of interest on the paper – “I’m developing a test for this.” Then people can make up their mind about whether it has affected the results. We don’t know, it wasn’t declared they’d produced a test.

[Slide]

Why are patients so upset?

OK, well I don’t know and you’ll probably be able to tell me more than I can tell. But I think when they first publicised this they went on everything, lots and lots of American television.

[Slide]

[Reads from slide]

“Vindication” they said, “This “[new] report has intrigued scientists, been seen as vindication by some parents [Ed: corrects herself] – patients and inspired hope for treatment.”

Well you know, the history of this condition is that patients have not been listened to, they’ve been dismissed, they’ve had a terrible time and if a virus comes along as a cause, that is going to be seen as a vindication – I can understand that.

And it’s very disappointing, isn’t it, the negative replications?

[Slide]

But I do think that there’s been other stuff that’s been going on that I have particular difficulties with. When I prepared this talk for an infectious diseases conference, I went through and I just got some quotes off the web from the research team.

[Slide]

Look at this:

[Reads from slide]

“Here you’ve got your immune system working well and the virus and the immune system are coexisting just fine and then some other bug, whether it be Lyme, a flu, anything gets you…and then you’ve just tipped the scale to where your immune system can’t handle [XMRV] or anything, and every day you’re seeing new infections.”

[Slide]

And then at one point, rumour has it (and I couldn’t find any evidence for this) that they started to suggest that patients with chronic fatigue syndrome should have anti-retrovirals, ie HIV drugs.

They’ve taken that back, and this is all I could find:

[Slide]

[Reads from slide quoting Dr Judy Mikovits; the “she says” refers to Dr Mikovits]:

“While it’s not advisable to take highly toxic anti-retrovirals [without tests confirming effectiveness], she says some available therapies may help, including: immune modulators; anti-inflammatories, because inflammation activates XMRV, things that improve natural killer cell function; medications that help [level progesterone levels, because progesterone up-regulates XMRV in lab tests]; avoiding stress.”

It appears – and this really upset me, OK. All of their studies are in adults. OK, all in adults. And then they say:

[Reads from slide]

“Early infection in children can lead to more severe disease later on.”

Early detection?

Oh, that’ll be that test that they produced for $605 [sic] a pop.

[Reads from slide]

“and intervention important to keep viral loads from getting high.”

I find that really frightening. If I had a child with chronic fatigue syndrome and I read that on the web, the first thing I’d do, I’d go and buy the test, and the second thing I’d be doing would be phoning an infectious disease doctor which is what’s happened and ask about anti-retrovirals for my child, having read that.

So I do feel as researchers, we do take some responsibility for saying “This is a first paper! Let’s wait and see what happens.”

You know, I think it’s really interesting, it look likes they did find something in a group of patients and we haven’t found it here. That’s really interesting and is deserving of more research. But let’s just say, it’s interesting at the moment, rather than all of this speculation, which I think can be very harmful for patients.

[Slide]

The future for infection

OK, I gather that this may well already have happened, not been published, the way forward in these things is to replicate the studies in both labs and try and look at why there are differences.

I think it may be important for a subtype of chronic fatigue syndrome.

I very much doubt it effects all of them, as they claim.

It doesn’t appear to be important in this country.

And there’s actually very beautiful research which we need to understand more, looking at the relationship between genetics, infection and other things like mood.

OK. After a whistle-stop tour of most research on chronic fatigue syndrome, this is now my summary slide – this is what I’ve talked about.

[Slide]

There are two arms for research in chronic fatigue syndrome and I don’t believe that one replaces the other. The funding for both arms is different in this country and they both need to be done together and both influence the other.

[Slide]

The first is important for providing services and treatment:

We need to know more about how common this is.

We need to understand who it affects.

And we need to know about the different types of chronic fatigue syndrome.

We need to understand how the different types influence treatment.

We need to know much, much more about the impact of this devastating condition on patients and carers.

The second one is that we need to know more about the aetiology, about the causes of this condition and in my view, the fastest way forward is to use the large, very large sample sizes that we have available in this country to conduct rigorous genome-wide association studies and I’m not so certain about the role of infection but I do think there is an interesting story with XMRV that we need to get to the bottom of.

And it just remains for me to thank my funders – I’m funded by the National Institute of Health Research and my Clinician Scientists Fellowship, the Linbury Trust, Action for M.E. and I’m the Medical Adviser for AYME.

[Slide]

And this is where I work.

Thank you very much.

——-

There was a Q and A session which included questions about the RNHRD NHS FT/University of Bristol Lightning Process pilot.

MRC CFS/ME Research Workshop: Note in text format

MRC CFS/ME Research Workshop: Note in text format

Shortlink: http://wp.me/p5foE-2T2

 MRC CFS/ME Research Workshop

19th and 20th November 2009

Heythrop Park Hotel, Oxfordshire

 _________________________________________________________________

1. Day 1 – Welcome & introduction

1.1 Professor Holgate welcomed the participants to the workshop and introduced the format for the two days.

1.2 An overview was provided of the MRC CFS/ME Expert Group and its Terms of Reference. The aims of the workshop were then detailed as follows:

• Identifying the underlying causes and mechanisms of CFS/ME:

o Clinical phenotypes

o Novel technologies and methodologies to help identify sub-phenotypes

o Molecular and cellular mechanisms of pathogenesis

• Consensus of priority areas.

• Encouraging new researchers into the field.

Areas proposed for consideration during the workshop included:

o capitalising on current issues and UK scientific strengths including national resources e.g. patient cohorts

o new technologies and technological platforms

o partnership models

o other issues

1.3 Professor Holgate referred to the recent interest in the publication of research linking the retrovirus XMRV to CFS/ME, before going on to summarise the key challenges in the field:

• A large clinical need without sufficient underpinning research.

• Low research capacity; need to encourage a multi-disciplinary approach.

• Grant applications that did not meet current competitive standards for funding.

• Absence of a clear pathogenetic mechanism(s) meant it was difficult to develop therapies “targeted” towards specific biological pathways. As a result current therapies tended to be directed towards symptom support rather than prevention or modifying/halting progress of the condition.

• The need to consider both physiological and psychological mechanisms in developing therapeutic approaches.

Page 2

• The difficulties inherent in defining phenotype and sub-phenotypes for a complex condition without good knowledge on underlying mechanisms.

• Knowing how best to incorporate new science and technological platforms.

1.4 Professor Holgate advocated a more collaborative approach to move the field forward.

A recent example of where such an approach had proved successful in increasing research capacity and impact was in respiratory research.

2. Presentations

(Full slide sets for each presentation are available at Annex 1)

2.1 Dr Esther Crawley provided an overview on the epidemiology of CFS/ME and the current research on phenotyping. The role of the British Association of CFS/ME (BACME) and the current specialist services available for patients were explained. The key points raised were as follows:

• Definitions of CFS/ME were important when investigating prevalence of the disease.

• In adults there were at least 3-6 different phenotypes identified to date and there were currently 3 paediatric phenotypes, suggesting the possibility of a stratified or targeted approach to treatment.

• CFS/ME was considered to be a heritable condition, and several latent factors and risk factors had been identified. Further gene/environment interaction studies were needed to understand the mechanisms at play in disease progression.

• BACME – in 2009 the 13 clinical service centres funded by Department of Health in 2004 were merged with the CFS/ME network. It was estimated that there would be 7,000-8,000 new patients/year assessed by the clinical teams.

• There were currently 30 teams contributing to the CFS/ME National Outcomes Database. Assessment data for more than 3,500 patients (adults and children) since summer 2009 had been collated. It was anticipated that this number would increase to 5,000 patients per year.

2.2 Professor Julia Newton presented an overview of the current research into the role of autonomic dysfunction in CFS/ME and briefly explained the research from her laboratory. She discussed the possible upstream and downstream mechanisms of autonomic dysfunction, such as those relating to control of blood pressure and heart rate, as well as treatment options. The key points raised were as follows:

• With regard to autonomic dysfunction in CFS/ME, there were currently problems regarding diagnosis of both CFS/ME itself as well as with the diagnosis of autonomic dysfunction. Further issues remained concerning the reproducibility, insensitivity of detection equipment and data interpretation.

• New assessment tools with increased sensitivity were progressively being made available.

Page 3

• Studies have shown that 50% of CFS/ME patients have neural-mediated hypotension.

• There were overlaps between hypotension in CFS/ME and other diseases e.g. cirrhosis and rheumatoid arthritis.

• A new treatment for patients with hypotension involving repeated daily tilt training was described. 2.3 Professor Jim Horne gave an overview of research into sleep disorders and the role of sleep dysfunction in CFS/ME. The key points raised were as follows:

• Some sleep disorders (eg apnoea/hypopnoea, restless leg syndrome, nocturnal myoclonus) can be manifested as CFS/ME, and it was important to screen for these.

• CFS/ME can produce sleep problems that can rebound back onto CFS/ME. For example, a disruption of the body clock (circadian rhythm), leading to sleeping excessively at the wrong time of day, to cause ‘post-sleep inertia’ (rather like ‘jet-lag’) with symptoms similar to/further aggravating CFS/ME.

• Stabilisation of the circadian rhythm can be helped by: 1) remaining under daylight/ fairly bright indoor light throughout daytime hours, and 2) using melatonin about 2h before bed-time (and avoiding bright light at night).

• Nevertheless, some patients with fairly normal circadian rhythms do take too many naps in the day, thus reducing sleep need at night and causing disrupted, unrefreshing night-time sleep. 2.4 Professor Maria Fitzgerald provided a comprehensive overview of the complex mechanisms and processes involved in pain. The role of pain in CFS/ME was also discussed. She highlighted the importance of pinpointing when pain became chronic. The key points raised were as follows:

• The purpose of pain was primarily defensive and a warning mechanism. However this mechanism could become maladaptive.

• Pain processing occurred at multiple sites. Furthermore, pain mechanisms were complex, combining sensory, motor, autonomic and affective components which could also lead to altered brain function resulting in, for example, anxiety and insomnia. These changes were dependent on individual differences, age, gender and culture.

• It was unclear whether pain in CFS/ME comprised either of peripheral components, altered central nervous system (CNS) processing and altered endogenous factors or a combination of these. In other conditions such as fibromyalgia, both altered CNS processing and altered endogenous factors were a feature of pain. There was also evidence of altered cortical pain processing in the brain.

• Potential causes of pain in CFS/ME may include an increased limbic system involvement, decreased endogenous descending control, enhanced temporal summation, nociceptor sensitisation, genetic determinants and early life experience.

Page 4

• Improved animal models of pain in CFS/ME were needed as a basis for research into underlying mechanisms, as were improved ways of defining and quantifying fatigue.

2.5 Professor Gijs Bleijenberg presented an overview of current research in clinical psychology in CFS/ME and outlined possible future directions in this area. The key points raised were as follows:

• The aetiology of CFS/ME could be divided into multi-factorial predisposing, precipitating and maintaining factors.

• Predisposing factors included neuroendocrine dysfunction; gender; psychiatric illness; high physical activity in adulthood; low physical activity in childhood.

• Precipitating factors included infectious triggers; fatigue; pain; physical inactivity.

• Less was known about perpetuating factors and the key question was how and when did certain factors become perpetuating.

• Current treatments were aimed at symptom management and included cognitive behavioural therapy and graded exercise therapy.

• Neurobiological changes were reported in CFS/ME e.g. changes in patterns of cerebral activity and decreased grey matter volume. However, it was not yet known whether these changes were as a result of the condition or whether they were central to the disease process.

• Possible future directions for research: o Large population based studies to increase insight in the development of CFS/ME.

o Smaller cohort studies of groups at high risk for developing CFS/ME with an emphasis on the development of the maintaining factors.

o Research and mediation analyses of treatment studies; experimental studies to discover mechanisms.

o Studies investigating neurobiological or physiological markers of CFS/ME in relation to treatment effect.

o Early detection of CFS/ME by physicians and promoting healthcare seeking by patients.

2.6 Professor Phil Cowen provided a summary of imaging techniques and studies in CFS/ME and other disorders. The key points raised were as follows:

• Technologies such as PET/SPECT, ligand PET, MRI, MR Spectroscopy and fMRI could be useful tools in helping to understand CFS/ME pathophysiology.

• In some respects, imaging studies of CFS/ME patients have shown similar findings to those using subjects with depression. For example:

o Structural morphometry studies have shown reduced grey matter volume.

Page 5

o Decreased binding of brain 5-HT1A receptors using PET. o Increased neural activation during tasks of working memory. Specifically in CFS/ME patients proton MRS detected an increase in ventricular lactate, which had been postulated as a potential biomarker for CFS/ME, perhaps representing evidence of mitochondrial dysfunction.

• Currently there was an overall lack of understanding of neural correlates of central fatigue in relation to functional brain imaging.

• The current evidence base in the field was unreliable due to the small patient numbers involved and the lack of consistency in experimental design. Increased sample sizes were needed coupled to more robust methodological approaches.

2.7 Professor Chris Ponting discussed new technologies in relation to genetic studies and their potential for use in CFS/ME research. The key points raised were as follows:

• Susceptibility: were viral or other environmental triggers impacting on a vulnerable host? Further study of gene/environmental interactions was needed.

• For successful genome wide association studies (GWAS) large sample numbers from well phenotyped patients were needed.

• It was possible to identify gene variants for low-moderate effects, which may be an issue for CFS/ME. For example a GWAS on height found that 40 genes account for only 5% of heritability.

• It was important to discover biological pathways implicated by genetic studies, as opposed to single abnormalities as these might prove to be more informative.

• Most complex disease associations appear in non-coding regions of the human genome whose mechanisms mostly remain enigmatic.

• There were currently limitations in analysis, storage and interpretation of the large data sets that will be generated in genomics and genetics in the next 5 years.

2.8 Professor Anthony Pinching gave an overview of the possible role of immunity and infection triggers in CFS/ME. The key points raised were as follows:

• Whilst chronic infection has been investigated for many years as a possible pathogenetic mechanism, the balance of evidence now tends to favour persistent immune activation or dysregulation, triggered by infection or other events that have similar impact.

• Patient histories indicate the common triggering role of a wide range of infections, and also provide clues to altered immune function in association with ongoing disease.

• Altered immune factors, e.g. decreased natural killer cell function, Th1-Th2 cell imbalance, elevation of both pro and anti-inflammatory cytokines have been associated in CFS/ME, and may be further elevated two days after exercise or activity.

Page 6

• The relationships between predisposing and perpetuating factors in these changes have yet to be established, but prior genetic and environmental factors are both likely to influence immune responses to infections.

• The recent XMRV retrovirus study had produced interesting results. However the involvement of XMRV remained unproven and the study would need to be replicated using fresh biological samples, different methodologies, other cohorts and disease controls. It would be premature to use tests for this agent in diagnosis, or to initiate treatment studies, until such replication had been achieved.

2.9 Professor Paul Moss discussed the possible role of virology in CFS/ME and presented a review of the current research in this area. The key points raised were as follows:

• Many studies have shown that infection is a strong candidate for triggering CFS/ME.

• Chronic infection was often linked to mood changes.

• CFS/ME had been associated with multiple viruses e.g. herpes viruses (CMV, EBV, HHV-6, HHV-7) as well as parvoviruses, enteroviruses and retroviruses such as XMRV.

• An imbalance between memory and naïve circulating and lymph node T cells has been shown in some studies.

• Small studies had been undertaken to investigate possible novel therapeutic interventions using antiviral approaches, e.g. acyclovir, monoclonal antibodies.

• A model was proposed by which a chronic response to infection might lead to fatigue and lack of exercise which could potentially escalate to a self-reinforcing cycle.

2.9 During the open session, the recent findings implicating a role for the XMRV retrovirus in CFS/ME were discussed. Attendees agreed that it would be important that the XMRV findings were replicated before treatment options could be considered, as well as extending the study to other CFS/ME patient groups in other countries. A consensus should be reached regarding the methodologies to be utilised between different research laboratories while research should be undertaken in well characterised cohorts. Studies in patients that have been recently diagnosed with CFS/ME should also be considered in order to minimise the number of patients with co-morbidities which could produce confounding results.

2.10 During the group discussion Sir Peter Spencer and Dr Charles Shepherd outlined a feasibility study for setting up CFS/ME post mortem and in vivo tissue banks which was being funded jointly by Action for ME and the ME Association. Sir Peter emphasised that the charities in this area were very small compared to other disease-related charities and therefore obtaining funding for large studies was challenging.

2.11 Attendees highlighted that there were potentially many opportunities that could open up research into CFS/ME. For example, little was known about fatigue mechanisms and investigating fatigue in healthy individuals could provide useful clues in understanding the aetiology of CFS/ME.

Page 7

Since anxiety and depression comprised a large part of the symptoms of CFS/ME alongside other symptoms such as pain, the interaction between biological and psychological mechanisms should be explored, particularly as there was scope to investigate anxiety from the perspective of autonomic nervous dysfunction. Another cross-cutting area that could prove fruitful to explore was that of mitochondrial function and energy metabolism.

2.12 In summing up the day’s discussions, Professor Holgate noted the many potential interesting avenues for research. Going forward, the right infrastructure needed to be in place, aided by the adoption of a collaborative approach.

3. Day 2 – Working group discussions

3.1 Participants were divided into three mixed groups for discussions at the beginning of the second day, before reporting back in a plenary session. Each group was asked to identify the research priorities and raise any other issues that they felt had not been addressed thus far during the workshop, as well as the following areas:

o group 1 – current UK strengths and resources

o group 2 – partnership models

o group 3 – new technologies and technological platforms

3.2 The reports from each group highlighted the following points:

Group 1 – Research priorities and UK strengths

UK Strengths

• Existing research cohorts of CFS/ME patients – there were several well characterised cohorts already established including trial cohorts such as PACE.

• Birth cohorts (e.g. “1958” and ALSPAC cohorts which had genetic information) for hypothesis generation. Whilst these were less well characterised it would still be possible to generate results in research studies.

• CFS/ME National Outcomes Database.

• Strong research teams particularly in epidemiology, imaging, gene sequencing, health psychology and non-pharmacological intervention. This was further enhanced by a general willingness to work in multi-disciplinary teams.

Research priorities

• To establish a large cohort with broad case definition identified early in primary care before CFS/ME became established e.g. first presentation following viral illness with fatigue and interference with normal activities. This could be followed up with more intensive phenotyping and obtaining biological samples (including samples for sequencing, metabonomics etc) to identify variables/predictors associated with developing confirmed CFS/ME.

Page 8

In addition to identifying priority groups for intervention studies this would also allow the exploration of the implications of different definitions/cut off points in defining established CFS/ME.

• To identify possible ‘early win’ interventions for phase 2 and early phase 3 clinical trials – e.g. targeted use of cytokines; melatonin for those with sleep problems.

 • To undertake genome-wide association studies (GWAS) to identify the genetic components of CFS/ME and possible new targets for intervention. This would be dependent on the availability of well characterised cohorts. • To develop more comprehensive outcome measures.

• To encourage work across the different existing cohorts (including trial cohorts), e.g. for assessing predictive markers of disease and confirming hypotheses generated in other data sets.

3.3 Group 2 – Research priorities and partnership models

Partnership models

• A co-ordinated, structured, strategic and collaborative research approach would be needed in moving the field forward.

• Exploring the use of other fatigue-related diseases (such as multiple sclerosis and cancer-related fatigue) as control models for CFS/ME, and utilising existing expertise from these areas in the CFS/ME field.

• Establishing a multi-disciplinary group involving not only scientists (e.g. immunologists, fatigue experts, neuroscientists, psychologists and psychiatrists, neurologists and geneticists) but also the clinical networks and health professionals.

• Pharmaceutical industry involvement would be beneficial, perhaps at a later stage. Research priorities

• Databases of patients with CFS/ME characterised according to agreed criteria. Phenotype identification could only progress if linked to good infrastructure with all groups using the same criteria. This could provide benefit not only in replication of studies but also of increasing ‘n’ numbers. It was also essential to collect biological samples from early-stage disease which would have no or minimal confounding factors which occurred with long-term disease. Good clinical diagnosis and standardised measurements and assessments were essential to enable comparisons across data sets. Therefore a collaborative approach with researchers working closely with clinicians and other health professionals would be important.

• Patient reported outcomes and quality of life measures.

• The establishment of tissue banks with samples from well characterised patients and controls.

• Improved definition of fatigue and improved understanding of fatigue mechanisms.

Page 9

• Virology and infection triggers – there was potential for virology to be studied in CFS/ME as part of the complex disease pathogenesis. In addition to continued research in this area it would be important for the XMRV study to be replicated before pursuing this avenue of investigation through to clinical trials.

3.4 Group 3 – Research priorities and new technologies and technological platforms.

New technologies/technological platforms

• Imaging technologies such as fMRI, EEG and MRS and pathological studies using tissue could be utilised for neuroanatomical studies and neurophysiological studies of fatigue.

• Better animal models were needed both of the whole disease and aspects of the disease physiology.

• Genetic studies (GWAS) – needed to be nationally and internationally standardised using well phenotyped samples.

• Improved data collection tools were needed. Research priorities

• Identification of phenotype and phenotypic subgroups. This would require access by researchers to raw data (not prior filtered) for replication studies and different measurable entities for different studies. It would also be important to extend the minimum clinical data currently collected.

• Psycho-physical studies – it was important to continue to undertake small and focussed pathophysiological studies investigating perception, behavioural and physiological response in patients.

• Establishment of longitudinal population-based studies including natural history cohorts which were well focussed and avoided selection bias. Data generated by these studies could be underpinned by co-ordinated tissue collections and repositories.

• Studies on neuro-immunological interactions.

3.5 During the plenary discussion the following points were highlighted:

• It was agreed to be important not to stigmatise the condition, both in terms of treating and caring for those with CFS/ME, and for attracting researchers to the field. CFS/ME was a complex disease that comprised the interaction of different biological, physical and psychological mechanisms. The interactions between these different mechanistic pathways were important and further mechanistic studies needed to be undertaken. Pathways may differ between individual patients and therefore the characterisation of phenotype(s) was paramount. Phenotype characterisation would facilitate the identification of biomarkers. However, given the complexity of the disease and the many current unknowns, this objective was likely to be achieved

Page 10

only in the longer term. The objective for the shorter term should be to increase the current knowledge base of the pathogenesis.

• Clarification of the definition of CFS/ME was important. Without this it would be difficult to encourage new researchers from other fields to undertake research in this area.

• Successful collaborative approaches required each stakeholder to take ownership of a particular area.

3.6 Professor Holgate briefly summarised the workshop outcomes which would be discussed by the CFS/ME Expert Group during the spring of 2010. The Group would prioritise the opportunities that were tractable for both the short and longer term and feed back the outcome to the community.

Professor Holgate thanked all the participants for their valuable contributions and closed the meeting.

For Presentation slides please refer to PDF

Open 3MB PDF on MRC website here Workshop Note and Presentation Slides 

or open here on ME agenda:

    Note of MRC CFS-ME Research Workshop 19-20 Nov 2009[1]

 

MRC Research workshop: Note and presentations published

MRC Research workshop: Note and presentations published

Shortlink: http://wp.me/p5foE-2SQ

I have been advised, today, by the MRC’s Corporate Information and Policy Officer, that the note and presentations relating to the November MRC CFS/ME Research workshop are now available on the MRC’s website.

The link for the web page is:

http://www.mrc.ac.uk/Ourresearch/ResearchInitiatives/CFSME/index.htm

The note can be found at:

http://www.mrc.ac.uk/Utilities/Documentrecord/index.htm?d=MRC006813

As previously agreed with the MRC, they will let me know once the note of the expert group meeting held on 1 March 2010 is also published on the MRC website.

Agenda:
http://www.mrc.ac.uk/Utilities/Documentrecord/index.htm?d=MRC006511

List of participants of the MRC CFS/ME Research Workshop
http://www.mrc.ac.uk/Utilities/Documentrecord/index.htm?d=MRC006510

Note of the MRC CFS/ME Research Workshop 19-20 November 2009
http://www.mrc.ac.uk/Utilities/Documentrecord/index.htm?d=MRC006813

(including copy of the presentations from the meeting at annex 1)

MRC CFS/ME Research Workshop
Issued: 14 May 2010

Primary audience: General public Document Summary

19 and 20 November 2009, Heythrop Park Hotel, Oxfordshire process and timetable.

Open 3MB PDF on MRC website here Workshop Note and Presentation Slides 

or open here on ME agenda:

    Note of MRC CFS-ME Research Workshop 19-20 Nov 2009[1]

Papers circulated prior to the meeting:

http://www.mrc.ac.uk/Utilities/Documentrecord/index.htm?d=MRC006509

CFS/ME Literature review Jan 2004 – June 2009
Detection of an infectious retrovirus, XMRV, in blood cells of patients with chronic fatigue syndrome: Lombardi VC et al. Science. 2009 326:585-9

ICD-10-CM codings raised at 10 May CFSAC meeting

ICD-10-CM raised at 10 May CFSAC meeting

Shortlink: http://wp.me/p5foE-2SF

A one day public meeting of the US Chronic Fatigue Syndrome Advisory Committee (CFSAC) was held on Monday, 10 May. Minutes of the previous two day meeting and a Videocast of the proceedings of both days (with subtitles) can be accessed here and here.

The Chronic Fatigue Syndrome Advisory Committee (CFSAC) provides advice and recommendations to the Secretary of Health and Human Services via the Assistant Secretary for Health of the U.S. Department of Health and Human Services on issues related to chronic fatigue syndrome (CFS). More information here [PDF].

Towards the end of the Spring meeting, Dr Leonard Jason, PhD, raised concerns in response to current proposals for the placement of CFS within the forthcoming US “Clinical Modification”, ICD-10-CM, due to be implemented in October 2013. (See foot of this Dx Revision Watch page for current ICD-10-CM proposals.)

Agenda for this Spring 2010 meeting here

CFSAC Agenda – May 10, 2010
Chronic Fatigue Syndrome Advisory Committee
US Department of Health and Human Services

Meeting was webcast live at http://videocast.nih.gov

Webcast of entire meeting with subtitles is now available to view here

Chronic Fatigue Syndrome Advisory Committee
Monday, May 10, 2010
HHS Office on Women’s Health (OWH)
Total Running Time: 05:47:57

More information here: http://videocast.nih.gov/Summary.asp?File=15884

Presentations, Public Testimonies and Written Testimonies here

Transcripts are being compiled on a dedicated Facebook site here

YouTubes videos here:

http://www.youtube.com/view_play_list?p=131A8EEA7ECD72CD&sort_field=original&page=1

http://www.youtube.com/view_play_list?p=131A8EEA7ECD72CD&sort_field=original&page=2

New Hillary Johnson blog post – “Sif-Sac, again.” here

Cort Johnson blog

A very different looking federal advisory committee on CFS (CFSAC) discussed its charter, its recommendations, XMRV and the blood supply, what the CDC program will look and more. Asst Secretary of Health Dr. Koh, Annette Whittemore and Kim McCleary spoke. Check out the goings on at the CFSAC meeting in

‘The CFSAC on Itself, XMRV, the CDC and More’ from the Bringing the Heat blog:

Phoenix Rising forum thread here

CFSAC Agenda – May 10, 2010

May 10, 2010

9:00 am
Call to Order
Opening Remarks

Roll Call, Housekeeping
Dr. Christopher Snell
Chair, CFSAC

Dr. Wanda Jones
Designated Federal Official

9:15 am
Welcome Statement from the Assistant Secretary for Health

New Members Statement on CFSAC Interests/Goals
Dr. Howard K. Koh

CFSAC New Members

10:00 am
Remarks from Dr. Elizabeth Unger
Dr. Elizabeth Unger

10:30 am
Blood Safety Update on XMRV
Dr. Jerry Holmberg

11:00 am
Review/Update of past CFSAC recommendations
Committee Members

12:30 pm
Subcommittee Lunch
Subcommittee Members

1:30 pm
Public Comment
(on CFSAC charter)
Public

2:00 pm
Review and Discussion of CFSAC Charter and ByLaws
Committee Members

4:00 pm
Adjourn

CFIDS Association of America submits response to DSM-5 draft proposals

CFIDS Association of America submits response to DSM-5 draft proposals

Shortlink Post: http://wp.me/p5foE-2Rp

Submissions

Patient organisations, professionals and advocates submitting comments in the DSM-5 draft proposal review process are invited to provide copies of their submissions for collation on this page: http://wp.me/PKrrB-AQ

The CFIDS Association of America

Working to make CFS widely understood, diagnosable, curable and preventable

The Diagnostic and Statistical Manual for Mental Disorders (DSM) is being revised by the American Psychiatric Association for release in 2013. Creation of a new category called “Complex Somatic Symptom Disorder” has generated concern and the CFIDS Association submitted its statement on April 1.

The APA will accept public comments until April 20 at http://www.dsm5.org/Pages/Default.aspx

Open PDF here on the CFIDS site:

or here on ME agenda: CFIDS DSM-5 Statement

The CFIDS Association of America

The CFIDS Association of America

April 1, 2010

DSM-5 Task Force

American Psychiatric Association
1000 Wilson Boulevard
Suite 1825
Arlington, VA 22209

Members of the DSM-5 Task Force,

In response to an open request for input on proposed changes to the fifth revision of the Diagnostic and Statistical Manual of Mental Disorders (DSM), the CFIDS Association of America submits the following statement and urgent recommendation.

The CFIDS Association strongly questions the utility of the proposed rubric of complex somatic symptom disorder (CSSD). According to the DSM-5 website

(http://www.dsm5.org/Documents/Somatic/APA%20Somatic%20Symptom%20Disorders%20description%20January29%202010.pdf, accessed March 28, 2010):

[Criteria superceded by third draft May 2012.]

The creation of CSSD appears to violate the charges to DSM-5 Work Groups to clarify boundaries between mental disorders, other disorders and normal psychological functioning

(http://www.dsm5.org/about/Pages/faq.aspx, accessed March 28, 2010). This is especially true with regard to patients coping with conditions characterized by unexplained medical symptoms, or individuals with medical conditions that presently lack a mature clinical testing regimen that provides the evidence required to substantiate the medical seriousness of their symptoms. For instance, all of the case definitions for CFS published since 1988 have required that in order to be classified/diagnosed as CFS, symptoms must produce substantial impact on the patient’s ability to engage in previous levels of occupational, educational, personal, social or leisure activity. Yet, all of the case definitions rely on patient report as evidence of the disabling nature of symptoms, rather than results of specific medical tests. So by definition, CFS patients will meet the CSSD criteria A and C for somatic symptoms and chronicity, and by virtue of the lack of widely available objective clinical tests sensitive and specific to its characteristic symptoms, CFS patients may also meet criterion B-4.

As drafted, the criteria for CSSD establish a “Catch-22” paradox in which six months or more of a single or multiple somatic symptoms – surely a distressing situation for a previously active individual – is classified as a mental disorder if the individual becomes “excessively” concerned about his or her health. Without establishing what “normal” behavior in response to the sustained loss of physical health and function would be and in the absence of an objective measure of what would constitute excessiveness, the creation of this category poses almost certain risk to patients without providing any offsetting improvement in diagnostic clarity or targeted treatment.

To provide another common example, back pain that is debilitating and severe, with negative MRIs, is still debilitating and severe back pain. A patient in this situation might be concerned about this back pain, might view it as detrimental to his quality of life and livelihood, and might direct time and resources to seeking care from multiple specialists (e.g., neurology, rheumatology, orthopedics, rehabilitation) to relieve it. Each of these specialists is likely to recommend slightly different therapies, compounding the patient’s focus on alternative explanations for and long-term impact of decreased function and diminished health. Such a patient could be diagnosed with CSSD, yet no empiric evidence has been provided by the Somatic Symptoms Disorders Work Group that applying the label of CSSD will facilitate communication with the patient, add clinical value to the patient’s experience, or improve the care any of these various specialists might provide.

The Somatic Symptoms Disorder Work Group states that patients fitting these criteria are generally encountered in general medical settings, rather than mental health settings

(http://www.dsm5.org/ProposedRevisions/Pages/proposedrevision.aspx?rid=368, accessed March 28, 2010), further limiting the usefulness of this classification in a manual written primarily for the benefit of mental health professionals.

The Somatic Symptoms Disorders Work Group conveys considerable uncertainty about the impact of this new label, in spite of the charge to all DSM-5 work groups to demonstrate the strength of research for the recommendations on as many evidence levels as possible. The Somatic Symptoms Disorders Work Group states:

“It is unclear how these changes would affect the base rate of disorders now recognized as somatoform disorders. One might conclude that the rate of diagnosis of CSSD would fall, particularly if some disorders previously diagnosed as somatoform were now diagnosed elsewhere (such as adjustment disorder). On the other hand, there are also considerable data to suggest that physicians actively avoid using the older diagnoses because they find them confusing or pejorative. So, with the CSSD classification, there may be an increase in diagnosis.”

(http://www.dsm5.org/ProposedRevisions/Pages/proposedrevision.aspx?rid=368, accessed March 28, 2010)

The proposed DSM-5 revision correctly does not identify chronic fatigue syndrome (CFS) as a condition within the domain of mental disorders and the DSM. However, past discussions of the Somatic Symptoms Disorder Work Group have included such physiological disorders as chronic fatigue syndrome, irritable bowel syndrome and fibromyalgia

(http://www.dsm5.org/Research/Pages/SomaticPresentationsofMentalDisorders%28September6-8,2006%29.aspx)

as “somatic presentations of mental disorders.” None of the research and/or clinical criteria for chronic fatigue syndrome published since 1988 have established CFS as a mental disorder and a continuously growing body of literature demonstrates CFS to be a physiological disorder marked by abnormalities in the central and autonomic nervous systems, the immune system and the endocrine system. The role of infectious agents in the onset and/or persistence of CFS has received renewed attention since the DSM-5 revision process began in 1999. Most recently, the October 2009 report of evidence of a human retrovirus, xenotropic murine leukemia-related retrovirus (XMRV), in CFS patients in Science (Lombardi, 2009) has generated new investigations into this and other infectious agents in CFS.

The conceptual framework for CFS detailed in the “Clinical Working Case Definition, Diagnostic and Treatment Protocols” (Carruthers, 2003) serves as a useful tool for professionals to establish a diagnosis of CFS, address comorbidities that may complicate the clinical presentation and distinguish CFS from conditions with overlapping symptomotology. Research on CFS continues to explore and document important biomarkers. Lack of known causation does not make CFS – or the CFS patient’s illness experience – psychopathological any more than multiple sclerosis, diabetes, or other chronic illnesses with objective diagnostic measures, would be so considered.

For the reasons stated above and the general failure of the proposed creation of the CSSD to satisfy the stated objectives of the DSM-5 without risking increased harm to patients through confusion with other conditions or attaching further stigma, the CFIDS Association strongly urges the DSM-5 Task Force to abandon the proposed creation of CSSD.

Sincerely,

K. Kimberly McCleary

President & CEO

The CFIDS Association of America

US Federal Chronic Fatigue Syndrome Advisory Committee: Minutes of October meeting

The Minutes of the October 2009 meeting of the US Federal Chronic Fatigue Syndrome Advisory Committee (CFSAC) are now available

Shortlink: http://wp.me/p5foE-2QP

CHRONIC FATIGUE SYNDROME ADVISORY COMMITTEE (CFSAC)

http://www.hhs.gov/advcomcfs/

Meeting

Thursday, October 29, 2009
9:00 a.m. to 5:00 p.m.

Friday, October 30, 2009
9:00 a.m. to 4:00 p.m.

Room 800, Hubert H. Humphrey Building
200 Independence Avenue, SW
Washington, DC 20201

The document minutes the proceedings of the Chronic Fatigue Syndrome Advisory Committee (CFSAC) Meeting held on October 29-30, 2009.

Download PDF version: http://tinyurl.com/yjarxlf or open here on ME agenda: CFSAC meeting 29.10.09

HTML version: http://www.hhs.gov/advcomcfs/meetings/minutes/cfsac102909min.html

 

Access a podcast video of entire meeting proceedings for Day One and Day Two at:

Day One: http://videocast.nih.gov/Summary.asp?File=15408

Day Two: http://videocast.nih.gov/Summary.asp?File=15409

[Video transmission has Auto Subtitles. RealPlayer required]

Invest in ME: Letter to UK Secretary of State for Health (Blood donation)

Invest in ME: Letter to UK Secretary of State for Health (Blood donation)

Shortlink: http://wp.me/p5foE-2QL

Update @ 19 March 2010

House of Commons Written Answers: 16 March 2010

Hansard transcript

Chronic Fatigue Syndrome: Research

Mr. Drew: To ask the Secretary of State for Health whether his Department has (a) commissioned and (b) evaluated any research on a relationship between myalgic encephalomyelitis and blood-related disorders. [322011]

Gillian Merron: The Department has, to date, not commissioned or evaluated any research. However, others, such as the Medical Research Council, the Health Protection Agency and the UK Blood Services, are currently considering these issues. I refer the hon. Member to the written answer I gave him on 27 January 2010, Official Report, column 942W.

House of Commons Written Answers: 27 January 2010

Hansard transcript

Chronic Fatigue Syndrome

Mr. Drew: To ask the Secretary of State for Health what recent representations he has received on making myalgic encephalomyelitis a notifiable illness for the purposes of blood donation. [313595]

27 Jan 2010 : Column 942W

Ann Keen: The Department has received 31 representations on making myalgic encephalomyelitis a notifiable illness in the last six months. There have also been a number of representations on this subject received by the Chief Medical Officer.

Mr. Drew: To ask the Secretary of State for Health whether his Department plans to (a) commission and (b) evaluate research on the possible health effects of receiving blood donated by a person with myalgic encephalomyelitis. [313596]

Ann Keen: The Department has no current plans to directly commission research on this issue. However, the Medical research Council has designated myalgic encephalomyelitis/chronic fatigue syndrome a priority research area, and will fund proposals of sufficient quality. The UK Blood Services together with the Health Protection Agency are undertaking a study of the prevalence of a rodent virus recently linked to myalgic encephomyelitis, which will be used to inform a risk assessment.

Mr. Drew: To ask the Secretary of State for Health whether his Department plans to test patients for xenotropic murine leukaemia virus-related illnesses. [313607]

Ann Keen: There are currently no plans to test patients for xenotropic murine leukaemia virus-related virus.

House of Commons Written Answers: 10 March 2010

Hansard transcript

10 Mar 2010 : Column 350W

Chronic Fatigue Syndrome: Blood

Mr. Drew: To ask the Secretary of State for Health for what reasons people with myalgic encephalomyelitis may not donate blood. [321320]

Ann Keen: People with myalgic encephalomyelitis (ME), also known as chronic fatigue syndrome (CFS), are not able to donate blood until they have fully recovered. The reasons for this are: first, blood donors need to be in good health, and people with ME/CFS often experience a range of symptoms which could be made worse by donating blood; and second, as the causes of ME/CFS are not currently fully understood, people with the condition are deferred from donating blood as a precautionary measure to protect the safety of the blood supply for patients.

In response , Invest in ME has written to Rt Hon Andy Burnham MP, Secretary of State for Health:

Invest in ME

Letter to UK Secretary of State for Health

Recently Mrs Ann Keen, Under-Secretary of State for Health, commented that people with Myalgic Encephalomyelitis were not able to donate blood. Invest in ME have written the following letter to the Secretary of State for Health, Mr Andy Burnham.

Myalgic Encephalomyelitis and Blood Donations

Rt Hon Andy Burnham MP

Secretary of State for Health

Department of Health

Richmond House

79 Whitehall

London SW1A 2NS

cc: Mrs Ann Keen MP

14th March 2010

Dear Mr. Burnham,

Recently Mrs Ann Keen (in her capacity as Under-Secretary of State for Health) made the following comments in relation to Myalgic Encephalomyelitis and blood donations –

“People with myalgic encephalomyelitis (ME), also known as chronic fatigue syndrome (CFS), are not able to donate blood until they have fully recovered.

The reasons for this are: first, blood donors need to be in good health, and people with ME/CFS often experience a range of symptoms which could be made worse by donating blood; and second, as the causes of ME/CFS are not currently fully understood, people with the condition are deferred from donating blood as a precautionary measure to protect the safety of the blood supply for patients.”

Mrs Keen’s comments are, we assume, representative of the government and your department.

Firstly it is good that your government recognises that people with ME are in poor health. This implies that all people with ME are therefore in need of proper healthcare provision which treats the disease properly.

Secondly it is good that you and your government recognise, by the implication from your statement, that blood supplies may be compromised by accepting people with ME as donors due to the organic nature of this disease.

Thirdly it follows that an embargo on people with ME donating blood would mean that there is an infectious agent at work which could be passed on via blood.

There follows several questions which lead on from this.

It seems to be crucial to use the most stringent diagnostic criteria available for diagnosing ME (which even NICE acknowledge as being the Canadian Consensus Criteria). Yet your department, NICE and the MRC do not standardise on this internationally accepted standard for diagnosis of ME.

When you state that people with ME are not able to donate blood are you employing the NICE guidelines for defining patients as having ME? If so then why does NICE proscribe serological testing unless there is an indicative history of infection? If no initial indication of infection is present then no further blood tests are performed and a patient may receive a diagnosis of ME based on ongoing fatigue and one other symptom such as sleep disturbance. Why then would those patients be excluded from donating blood?

As your government officially accepts ME as a neurological illness, as described by the World Health Organisation ICD-10 G93.3 code, and as the issue of blood contamination from an infectious agent demands the utmost care and attention, is it not of absolute necessity for your government to demand that a consistent set of up-to-date diagnostic criteria are used as standard by all organisations?

Your department often states that the Medical Research Council is an independent body. Yet as it is apparent that the MRC only funds psychiatric studies which presume that ME is a behavioural illness why does your department refuse to comment on the MRC’s usage of the Oxford criteria for research into ME which expressly excludes people with a neurological illness?

Why does your department not criticise the MRC for funding purely psychiatric research into ME if you fully recognise that ME is a disease of organic and infectious nature? Since when did a psychiatric illness prevent blood donations? Does this not clearly show the MRC policy of research into ME for the last generation to be completely flawed and a waste of precious funding and patients’ lives?

When you state that people with ME are not able to donate until fully recovered please can you define what “fully recovered” means?

Could you also provide a description of how a person with ME is defined as no longer having ME?

What biomedical tests are available to determine that a person with ME is “fully recovered”?

Could you inform of how and when clinicians perform such tests in order to ensure that a person is “fully recovered” from ME?

Bearing in mind the seriousness of a possible contamination of blood supplies from people with ME please could you indicate what measures are in place to ensure that doctors do enforce testing to ensure that people with ME are “fully recovered” and will not therefore donate blood?

If such a test exists then presumably people with ME who are not recovered are entitled to appropriate benefits due to incapacity and/or disability?

As relapses are common with people with ME please could you explain if there is any minimum period which a person with ME needs to be “recovered” to be able to donate blood?

Could you also provide information which your government has on the number of people with ME in this country, the proportion of patients who have had ME for longer than five years and how many people with ME have “fully recovered”?

With regard to your statement that “the causes of ME/CFS are not currently fully understood” is it not inherent on the Chief Medical officer of the UK to attend the 5th Invest in ME International ME/CFS Conference 2010 on 24th May in Westminster, as guest of Invest in ME?

As the foremost experts on ME in the world are presenting at the conference, along with the Whittemore-Peterson Institute – who have recently been involved in the discovery of the XMRV retro-virus which has possibly huge considerations for the blood supply of this country – would it not be sensible for anyone who is involved in healthcare and particularly in the treatment of people with ME to attend this event?

Should not the government of this country also be sending a representative to the conference given that contamination of the blood supply by people with ME may be occurring and that education about the disease needs to be a pre-requisite for anyone involved in healthcare provision for people with ME?

We would request that you provide a full and complete answer to every single one of the questions which we have asked in this letter and we look forward to your reply,

Yours Sincerely,

The Chairman and Trustees of Invest in ME

Invest in ME

Registered UK Charity Nr. 1114035

PO BOX 561, Eastleigh SO50 0GQ

Support ME Awareness – Invest in ME

Related material:

Donations and transfusions: Safety of the UK blood supply  13 February 2010

FOI responses: XMRV testing by Molecular Diagnostics Unit, Imperial College, London

FOI responses: XMRV testing by Molecular Diagnostics Unit, Imperial College, London

Shortlink: http://wp.me/p5foE-2Pr

Update @ 11 March

In response to my querying the discrepancy between responses given under FOIA , ICL has responded:

“There is a slight distinction between the questions being asked and though it is the case that the test has been made available for researchers to test for any disease or condition, the patients for which the test is intended are those with prostate cancer, since it is the association of XMRV with this disease that the scientists are particularly interested in.”

———————

This mailing may be reposted provided it is published in full, unedited and https://meagenda.wordpress.com is credited as the source.

08 March 2010

In order to obtain clarification in relation to the advertising of XMRV testing by the Molecular Diagnostics Unit, Imperial College, London, three advocates submitted requests for information under the Freedom of Information Act (FOIA), in February.

Responses were fulfilled for all three on 08 March and are reproduced with kind consent of the recipients.

A copy of the complete text of the Molecular Diagnostics Unit, Imperial College, London XMRV Detection Testing web pages, which were taken offline on Monday, 8 February, has been archived on ME agenda site at this posting

Note my red highlighting of the inconsistancy between the response received by Suzy Chapman and the response received by Kim LeMoon in response to: “For what diseases/conditions/study domains is the XMRV test being made available to researchers?” and “If the XMVR Diagnostic Test was not being offered for people who are concerned that they might have CFS, or who have been diagnosed with CFS, what patient population was the test intended for?” and this is going to need further clarification.

R = Response by Imperial College, London Freedom of Information Office foi@imperial.ac.uk

[1] Request for information under FOIA by Suzy Chapman, UK:

To: Imperial College London, Freedom of Information Office
Date: 21 February 2010
Subject: XMRV testing available via ICL Molecular Diagnostics Unit (MDU)

A revised notice on the website for the MDU states:

“The MDU offers XMRV testing for research purposes only. If you are a researcher who is interested in XMRV testing, please contact the unit with an outline of your requirements.

“There has been some confusion around the availability of the XMRV test, for which we apologise. We would like to clarify that it is only available as part of an ethically approved research project. We emphasise that our laboratory does not deal directly with patients and we are not advising people who are concerned that they might have CFS, or who have been diagnosed with CFS, to request this test.”

On 6 February, The ME Association had published a notice on its website stating that it had been informed that an earlier announcement about XMRV testing on the MDU website:

“did not apply to people with ME/CFS, or suspected ME/CFS”

and that the test related only to:

“the availability of the Imperial College XMRV test to referring doctors who are dealing with cases of prostate cancer. A full clarification will appear on the Imperial College website on Monday.”

Although it has since been clarified by ICL that the XMRV testing being made available through the MDU is for researchers only, confusion persists over which diseases/conditions this test is being offered for.

I request the following information under the FOI Act:

1] For what diseases/conditions/study domains is the XMRV test being made available to researchers?

R: Further to your request for information regarding the diseases/conditions/study domains for which the XMRV test was made available to researchers (below) which was received by us on 22 February 2010, any physician or laboratory scientist can request the test for any disease or condition as part of an ethically approved research study. Our group at Imperial College London is currently focused on neoplasms of the genital tract but the clinical implications of XMRV infection are not yet fully understood. Our group is no longer studying CFS.

[2] Request for information under FOIA by Kim LeMoon, USA:

From: foi@imperial.ac.uk
Date: 08 March 2010
Subject: RE: Request for Information – XMRV Research

R: Further to your request for information received by us on 8 February 2010, please find below the College’s response to your questions.

Request for information under FOIA in respect of all ongoing research projects or scheduled research projects relating to XMRV (Xenotropic murine leukemia virus-related virus) detection via blood  samples, tissue samples or any other methods of detection

I should be pleased if receipt of this request for information could be acknowledged, together with the date by which a response will be provided.

Project Supervisors:

R: Professor Myra O McClure, Dr Steve Kaye, Professor Jonathan Weber

Project title:

R: XMRV and its association with Prostate cancer

Laboratory supervisor:

R: Dr Steve Kaye

Clinical supervisor:

R: Dr Anup Patel

1] Any Identification or Reference code assigned to Project:

R: n/a

2] Project’s Public Title; Project’s Scientific Title:

R: XMRV and its association with Prostate cancer

3] Study hypothesis/rationale (where applicable):

R: n/a

4] Ethics approval and any reference numbers attached to this approval:

R: Tissue bank ethics number 98CC141. A study to collect blood & urine specimens, prostate tissue &/bone marrow specimens to help establish methods for diagnosing and treating prostatic cancer.

5] Study design:

R: Molecular and serological methods

6] Countries of recruitment:

R: UK.

Centres of recruitment:

R: Imperial College Healthcare Trust.

Other methods of Recruitment:

R: n/a

* Through what means will prospective participants be recruited?

R: Signed consent to use biopsy tissue for retroviral analysis. Not yet underway.

7] For what diseases/conditions/study domains are patient samples to be collected?

R: Prostate cancer

* Through what means will control samples be assembled?

R: Not being assembled currently

8] Participants – inclusion criteria:

R: Participants will be restricted to those patients who are having a prostate biopsy for diagnostic purposes and have given consent for a small (10 micron) slice of their biopsy tissue to be used for research purposes.

9] Participants – exclusion criteria:

R: n/a

10] Target number of participants:

R: Open

11] Patient information material: please provide copies of any patient information material:

R: n/a

12] Anticipated start date:

R: January 2010

13] Anticipated project completion date:

R: December 2010

14] Sources of funding:

R: BRC [Ed: ICL has since clarified that “BRC” stands for Biomedical Research Centre ]

15] Sponsor details:

R: None

——————

[3] Addendum to Request for information under FOIA by Kim LeMoon, USA:

R: Further to the addendum to your request for information which was received by us on 8 February 2010, please find below the College’s response to your questions.

In addition to the earlier request that was made today, I request the following information under the Act

1] Principal Investigator(s):

R: Dr Otto Erlwein, Dr Steve Kaye, Professor Myra O McClure, Professor Jonathan Weber.

2] Names of Project Collaborator(s):

R: Dr Anup Patel

3] Names of Collaborating Institution(s):

R: Imperial College Healthcare Trust

From 27 Jan 2010 until 8 Feb 2010, XMRV Detection Testing was offered for £200 by the Molecular Diagnostic Unit via the Imperial College London website. On 8 Feb 2010, the information was removed from the website and replaced with this notification:

“We wish to apologise for any confusion concerning the availability of this test and would like to clarify that it is only available as part of an ethically approved research project. We emphasis that our laboratory does not deal directly with patients and we are not advising people who are concerned that they might have CFS, or who have been diagnosed with CFS, to request this test.”

Please provide answers to the following questions:

4] Why was the Molecular Diagnostic Unit charging £200 if the XMRV Diagnostic Testing is to be carried out as part of an ethically approved research study?

R: There are costs associated with providing this test. Therefore, if we are contacted by individuals from organisations outside Imperial requesting this test for a research study, we will charge them to test their samples.

5] Why was the XMRV Diagnostic Test being advertised to referring medical practitioners (GPs or hospital doctors) if the testing is being carried out as part of an ethically approved research study?

R: Medical practitioners such as GPs and hospital doctors are involved in research studies and we would expect any referring medical practitioner to be requesting samples as part of an ethically approved research study. We do not deal directly with patients.

6] If the XMVR Diagnostic Test was not being offered for people who are concerned that they might have CFS, or who have been diagnosed with CFS, what patient population was the test intended for?

R: Clinicians and clinical research scientists who are interested in the association of XMRV with prostate cancer.

[4] Request for information under FOIA by Julius, Canada

To: Imperial College London, Freedom of Information Office
Date: 09 February 2010
Subject: Request for information under FOIA in respect of Molecular Diagnostic Unit XMRV Test

Please acknowledge receipt of this request along with a Reference Number, and the date by which a response will be provided.

From 27 Jan 2010 until 8 Feb 2010, XMRV Detection Testing was offered for £200 by the Molecular Diagnostic Unit via the Imperial College London website.

Please provide information regarding the exact testing methods employed in the test offered including, but not limited to the following:

1) blood sample volumes and processing

2) does the test use a molecular plasmid control in water or a positive blood sample

3) primer sequences and amplification protocol used

R: Further to your request for information dated 9 February 2010 regarding the exact testing methods employed in XMRV testing carried out at the College (below) technical details associated with testing CFS tissue for the presence of XMRV are published in PLoS 1 January 6th 2010. Modifications of the assay for prostate cancer are not yet published and are not available to the public. The College hopes to publish this information before the end of the year.

FOIs and questions to Imperial College, London re XMRV testing

FOIs and questions to Imperial College, London re XMRV testing

Shortlink: http://wp.me/p5foE-2NL

Update @ 21 February

The following request for information has also been submitted:

To: Imperial College London, Freedom of Information Office

Re: XMRV testing available via ICL Molecular Diagnostics Unit (MDU)

21 February 2010

I would appreciate acknowledgement of this request for information.

A revised notice on the website for the MDU states:

“The MDU offers XMRV testing for research purposes only. If you are a researcher who is interested in XMRV testing, please contact the unit with an outline of your requirements.

“There has been some confusion around the availability of the XMRV test, for which we apologise. We would like to clarify that it is only available as part of an ethically approved research project. We emphasise that our laboratory does not deal directly with patients and we are not advising people who are concerned that they might have CFS, or who have been diagnosed with CFS, to request this test.”

On 6 February, The ME Association had published a notice on its website stating that it had been informed that an earlier announcement about XMRV testing on the MDU website:

“did not apply to people with ME/CFS, or suspected ME/CFS”

and that the test related only to:

“the availability of the Imperial College XMRV test to referring doctors who are dealing with cases of prostate cancer. A full clarification will appear on the Imperial College website on Monday.”

Although it has since been clarified by ICL that the XMRV testing being made available through the MDU is for researchers only, confusion persists over which diseases/conditions this test is being offered for.

I request the following information under the FOI Act:

1] For what diseases/conditions/study domains is the XMRV test being made available to researchers?

Sincerely,

etc.

 

The following requests for information under the Freedom of Information Act have been submitted to Imperial College, London and are published with permission. Information has also been requested direct from the Molecular Diagnostic Unit, Imperial College London. This issue will be updated when requests have been fulfilled.

Submitted by: Kim LeMoon
Date: 08 February 2010
Receipted: 09 February 2010

To: Imperial College London Freedom of Information Officer

Re: Request for information under FOIA in respect of all ongoing research projects or scheduled research projects relating to XMRV (Xenotropic murine leukemia virus-related virus) detection via blood samples, tissue samples or any other methods of detection

I should be pleased if receipt of this request for information could be acknowledged, together with the date by which a response will be provided.

I request the following information under the Act:

Project Supervisors:

Project title:

Laboratory supervisor:

Clinical supervisor:

1] Any Identification or Reference code assigned to Project

2] Project’s Public Title; Project’s Scientific Title

3] Study hypothesis/rationale (where applicable)

4] Ethics approval and any reference numbers attached to this approval

5] Study design

6] Countries of recruitment; Centres of recruitment; Other methods of recruitment

* Through what means will prospective participants be recruited?

7] For what diseases/conditions/study domains are patient samples to be collected?

* Through what means will control samples be assembled?

8] Participants – inclusion criteria

9] Participants – exclusion criteria

10] Target number of participants

11] Patient information material: please provide copies of any patient information material

12] Anticipated start date

13] Anticipated project completion date

14] Sources of funding

15] Sponsor details

Re: Addendum To Previous Request for information under FOIA in respect of all ongoing research projects or scheduled research projects relating to XMRV (Xenotropic murine leukemia virus-related virus) detection via blood samples, tissue samples or any other methods of detection

I should be pleased if this addendum is processed together with my first request that was sent earlier today 8 Feb 2010.

Please acknowledge receipt of both requests along with a Reference Number, and the date by which a response will be provided.

In addition to the earlier request that was made today, I request the following information under the Act:

1] Principal Investigator(s):

2] Names of Project Collaborator(s):

3] Names of Collaborating Institution(s):

From 27 Jan 2010 until 8 Feb 2010, XMRV Detection Testing was offered for £200 by the Molecular Diagnostic Unit via the Imperial College London website. On 8 Feb 2010, the information was removed from the website and replaced with this notification:

We wish to apologise for any confusion concerning the availability of this test and would like to clarify that it is only available as part of an ethically approved research project. We emphasis that our laboratory does not deal directly with patients and we are not advising people who are concerned that they might have CFS, or who have been diagnosed with CFS, to request this test.

Please provide answers to the following questions:

4] Why was the Molecular Diagnostic Unit charging £200 if the XMRV Diagnostic Testing is to be carried out as part of an ethically approved research study?

5] Why was the XMRV Diagnosic Test being advertised to referring medical practitioners (GPs or hospital doctors) if the testing is being carried out as part of an ethically approved research study?

6] If the XMVR Diagnostic Test was not being offered for people who are concerned that they might have CFS, or who have been diagnosed with CFS, what patient population was the test intended for?

Submitted by: Richard Dagg
Date: 09 February 2010
Receipted: 10 February 2010

To: Imperial College London
Freedom of Information Officer

Re: Request for information under FOIA in respect of Molecular Diagnostic Unit XMRV Test

Please acknowledge receipt of this request along with a Reference Number, and the date by which a response will be provided.

From 27 Jan 2010 until 8 Feb 2010, XMRV Detection Testing was offered for £200 by the Molecular Diagnostic Unit via the Imperial College London website.

Please provide information regarding the exact testing methods employed in the test offered including, but not limited to the following:

1) blood sample volumes and processing
2) does the test use a molecular plasmid control in water or a positive blood sample
3) primer sequences and amplification protocol used

From Stephen Ralph via Co-Cure

09 February 10

[CO-CURE] ACT: Questions for Dr Steve Kaye and Professor Simon Wessely at Imperial College

It was recently announced that the test offered on the Imperial College website for XMRV in relation to CFS/ME and prostate cancer was now being withdrawn with immediate effect.

Imperial’s excuse for withdrawing the XMRV test from their website for “CFS/ME” and prostate cancer was because it wasn’t meant for patients and that it was only meant for “an ethically approved research project.”

Well, if this was the case then where does that leave all the other tests it offers on its website?

http://tinyurl.com/ylpmnq3

STI’s for £40 (each),

HCV genotyping for £100,

HBV for Genotypic Drug Resistance costing £100,

HTLV (costs covered by the NHS) and

HIV-1 (costs covered by the NHS)

Question 1 – Was this test that Imperial was offering (on the same basis as all the other test above) the same test used for the recent Imperial/PLoS One study?

Question 2 – Was the test different and if so – how was it different?

Question 3 – As all the other tests (shown above) are still available under the same framework then regardless of whether or not such tests are only available via requests from GP’s or Specialists – opposed to being offered direct to patients; why was the XMRV test removed?

Question 4 – If the answer to Question 2 was “No” and it wasn’t different then where does this leave the credibility of the PLoS One/Imperial study?

Question 5 – Was the Imperial test removed from the website because it was inherently unreliable? (Go back to Question 4)

Readers wanting answers to these question need to contact Dr Steve Kaye who was cited on the Imperial website as being the contact for the XMRV test (now withdrawn)..

http://wwwfom.sk.med.ic.ac.uk/resources/543939B5-003D-4709-B6EC-238FC0D5502F

Email: steve.kaye@imperial.ac.uk
Tel: 020 759 43917 (direct)

FAO Dr Steve Kaye
Molecular Diagnostic Unit,
Imperial College London
4th Floor, Medical School Building
St. Mary’s Hospital
Norfolk Place
London W2 1PG

I have asked Dr Kaye these questions and so far I have not received a reply.

Sincerely,

Stephen.

http://www.meactionuk.org.uk

Donations and transfusions: Safety of the UK blood supply

Donations and transfusions: Safety of the UK blood supply

Shortlink: http://wp.me/p5foE-2ML

Update:  Additional information from US organisation AABB (formerly known as the American Association of Blood Banks)

http://www.aabb.org/Content/About_Blood/Emerging_Infectious_Disease_Agents

Emerging Infectious Disease Agents and their Potential Threat to Transfusion Safety

Xenotropic Murine Leukemia Virus-related Virus (XMRV) January 2010 (PDF)

http://www.aabb.org/documents/About_Blood/EID/XMRV_factsheet_fromWB_010510.pdf

See also Media Statement: Issued 17 February 2010

http://www.aabb.org/Content/News_and_Media/Statements/statement021710.htm

 

1] Advisory Committee on the Virological Safety of Blood

Minutes Meeting 25 February 1991

CHRONIC FATIGUE SYNDROME (ME) AND BLOOD TRANSFUSION (ACVSB 9/10) (Minute 31, 32)

Source: Website ScotBlood: http://www.scotblood.co.uk/subfreedom.asp?scatid=7

Specific document URL: http://www.scotblood.co.uk/site/pubdocs/19910225_acvsb_9th_meeting_7.pdf

Note: the copy of the Minutes currently uploaded to the Freedom of Information documents webpage of ScotBlood website is incomplete. When originally placed on line, historically, following an FOI request for a number of documents, the document had been scanned to PDF odd numbered pages only. A recent request has been made to ScotBlood for a copy of the complete document and this has now been fulfilled. There are a number of additional documents on the ScotBlood site associated with this meeting – appendices and other material, but not the meeting Agenda.

Senior Public Affairs Officer, Scottish National Blood Transfusion Service confirmed on 5 March 2010 that copies of the ACVSB minutes held by SNBTS were released in response to a Freedom Of Information request in March 2006; that they would have been placed on the SNBTS website shortly after the FOI response was issued.

The full document, which is not yet available on the ScotBlood website, can be opened here in PDF:

25.02.91 ACVSB 9th Meeting Minutes (Full doc)

PDF of Page 10 only: Minutes Meeting 25 February 1991: ME_Chronic_Fatigue_Syndrome_ACVSB_Vol_9

The PDF of Page 10, only, kindly provided by Tainted Blood Committee: http://www.taintedblood.info/index.php

Word document: Transcript, Page 10, Minute 31 and 32: Transcript Page 10 Minutes 9th Meeting ACVSB 25.02.91

Transcript Page 10, Minutes: Meeting of the ACVSB 25 February 1991

CHRONIC FATIGUE SYNDROME (ME) AND BLOOD TRANSFUSION (ACVSB 9/10)

31 Dr Pickles said that it had been suggested that the Department should introduce routine testing of blood donations for ME to prevent transmission of the infection(s) responsible for this disorder. It was feasible that infection may be transmitted to transfusion recipients, a small proportion of whom might develop chronic symptoms, themselves.

32 It was agreed that the evidence available did not support the introduction of a test. The Committee, however, would continue to watch any developments with interest.

ANY OTHER BUSINESS

[…]

2] Letter to Secretary of State for Health from Mr Mark XXXXXXX, Tainted Blood Committee, 6 January 2010

[A PDF of the original letter of request for information is held on file]

Open Word document: Mr Burnham 06.01.10

[Sender address redacted]

6th January 2010

Secretary of State for Health
Department of Health
Richmond House
79 Whitehall
London
SW1A 2NS

Dear Mr Burnham.

My name is XXXXXXXXXX, one of the now 300 surviving haemophiliacs from the contaminated blood disaster of the late 70’s, 80’s and 90’s. I was infected with HIV, Hepatitis B and C, CMV, Bovine TB and await the validation of the current vCJD test used by the Nation Blood transfusion service. This will reveal whether the factor 8 treatment taken from someone who later went of to die from vCJD I received, has infected me with yet another deadly contaminant. As you will understand I live a life of fear, pain, exclusion and most of all a sense of complete failure by those who are meant to help. Even now after of the many years of campaigning your department continues to add to the suffering caused by the NHS treatments and products I have received. I therefore ask for your assistance in getting this scandal rectified once and for all and the safety of the blood supply in this country secured.

I recently spoke to an infected haemophiliac friend of mine, who asked if I had any information regarding Retro-viruses and Hepatitis G. It appears he was told both, Retro-viruses and HGV or the Delta virus as it otherwise known is easily transmitted via blood or blood products and haemophiliacs are at high risk from this. He went on to tell me that because I am infected with HIV and HCV, Hepatitis G is commonly found and this accelerates the rate of progression of the other viruses and I should therefore speak to my doctor regarding my infection status.

After, speaking to the Haemophilia Society, who could offer very little advice on this subject? I wrote to my haemophilia centre director, asking him for any information he could give me. In his reply he told me, “We do not have current plans to test for the viruses I mentioned”. I have also written to Dr N Connor at the HPA, on the 16th of November 2009 but have still not received a reply.

Could you possibly give me your understanding or any information on what the Department of Health know and what they are doing about these retro-viruses and Hepatitis G here in Britain? Although, the internet is a very useful tool, the huge amount of data I have found so far, shows that haemophiliacs with HGV have been studied for many years across the globe. On the Caribbean island of Martinique, routine blood samples are taken to monitor their viral infections, with a cohort study that has been ongoing since 1992. Also in Japan numerous papers have been released to the medical profession on this subject.

It has also been bought to my attention that sufferers of the disorder ME or “Yuppy flu” have been lobbying MP’s for some considerable time, along with talks at the APPG, Chaired by Dr Des Turner MP, to try and protect the blood supply have failed.

The medical data proving the retro virus XMRV found in those suffering from ME can be easily transfused into others through blood and blood products, has once again been ignored and they are still permitted to donate blood. If this is true, then something that speeds up my past viral infections along with further pathogens still allowed to be pumped into innocent victims, surely is something health officials here in Britain are fully aware of. The procedure for being tested for this and other retro viruses is also widely published via the internet.

I look forward to your reply and your comments.

Best wishes

XXXXXXXXXX

Open Word document: Response Department of Health 26.01.10

[A PDF of the original response is held on file]

3] Response from Customer Service Centre, Department of Health, 26 January 2010

Our ref: TO00000471780

Department of Health

Richmond House
79 Whitehall
London
SW1A 2NS

Tel: 020 7210 4850

26 January 2010

[Recipient address redacted]

Dear XXXXXXXXXX

Thank you for your letter of 6 January to Andy Burnham about contaminated blood. I have been asked to reply on his behalf.

The Government is deeply sorry that patients were infected through treatment with contaminated blood products. I can assure you that, since the mid-80s, with the development of new testing and processing technologies, the measures now in place to assure the safety and quality of human blood and blood components, and blood products manufactured from them, have developed significantly.

I note your concerns about the possible presence of retroviruses, including the Hepatitis G virus (HGV). There is no evidence of any disease associated with this virus, which is now usually referred to as the GB Virus C (GBV-C), and which appears not to cause any hepatitis at all.

However, with reference to Factor VIII treatment, coagulation products are all subject to heat treatment, which has been demonstrated to be effective against viruses such as HBV, HCV and HIV. There is every reason to believe that other retroviruses, and other hepatitis viruses, will be similarly inactivated.

Retroviruses, of which HIV is the most talked about for human infection, and GBV-C, are enveloped viruses. The viral removal/destruction processes used by international fractionators are validated to remove enveloped viruses during the manufacture of plasma-derived products.

Any new findings about emerging viruses, such as the xenotropic murine leukemia virus-related virus (XMRV), which may have implications for the safety of the UK’s blood supply, are assessed through the Standing Advisory Committee on Transfusion Transmitted Infections (SACTTI) and then consideration is given by the Joint United Kingdom Blood Transfusion Services and National Institute of Biological Standards and Control Professional Advisory Committee (JPAC) and the Advisory Committee on the Safety of Blood, Tissues and Organs (SaBTO).

It is worth noting that the recent paper Failure to Detect the Novel Retrovirus XMRV in Chromic Fatigue Syndrome, published on 6 January 2010, in the online journal PLoS ONE, stated that there was no evidence of infection in ME sufferers. This article can be accessed on the website http://www.plosone.org by clicking on the link ‘Browse all recently published articles’ then clicking on the link ‘Jan 06’ [sic] and scrolling down. The UK group reported the findings of a study in which DNA from the blood of 186 patients with chronic fatigue syndrome (CFS) was tested for XMRV. All blood sample were negative. Based on the molecular data they received, the authors conclude that they: do not share the conviction that XMRV may be a contributory factor in the pathogenesis of CFS, at least in the UK.

I hope this reply reassures you about the safety of the UK’s blood supplies.

Yours sincerely,

Mary Heaton [Signed]
Customer Service Centre

4] Written questions

Source: UK House of Commons
Date: 27 January 2010
URL:
http://www.publications.parliament.uk/pa/cm200910/cmhansrd/cm100127/text/100127w0022.htm
Ref: http://www.me-net.combidom.com/meweb/web1.4.htm#westminster

[Written Questions]

Chronic Fatigue Syndrome

Mr. Drew

To ask the Secretary of State for Health what recent representations he has received on making myalgic encephalomyelitis a notifiable illness for the purposes of blood donation. [313595]

Ann Keen

The Department has received 31 representations on making myalgic encephalomyelitis a notifiable illness in the last six months. There have also been a number of representations on this subject received by the Chief Medical Officer.

Mr. Drew

To ask the Secretary of State for Health whether his Department plans to (a) commission and (b) evaluate research on the possible health effects of receiving blood donated by a person with myalgic encephalomyelitis. [313596]

Ann Keen

The Department has no current plans to directly commission research on this issue. However, the Medical research Council has designated myalgic encephalomyelitis/chronic fatigue syndrome a priority research area, and will fund  proposals of sufficient quality. The UK Blood Services together with the Health Protection Agency are undertaking a study of the prevalence of a rodent virus recently linked to myalgic encephomyelitis, which will be used to inform a risk assessment.

Mr. Drew

To ask the Secretary of State for Health whether his Department plans to test patients for xenotropic murine leukaemia virus-related illnesses. [313607]

Ann Keen

There are currently no plans to test patients for xenotropic murine leukaemia virus-related virus.

(c) 2010 Parliamentary copyright

 

Additional material:

5] BBC News: 3 February 2010  Video report http://news.bbc.co.uk/1/hi/england/8496533.stm

Haemophiliacs lobby for support  Haemophiliacs who contracted HIV and Hepatitis C after being given contaminated blood lobby MPs to back a Bill to give them financial support. The Bill has its second reading on Friday. 

READ MORE: Protest anger at blood ‘scandal’  
READ MORE: Contaminated blood inquiry opens

 

6] Third Reading

Contaminated Blood (Support for Infected and Bereaved Persons) Bill [HL]
House of Lords debates, 21 January 2010, 4:43 pm
Clause 2 : Blood donations  http://www.theyworkforyou.com/lords/?id=2010-01-21a.1180.2

Amendment 1

Moved by Baroness Masham of Ilton

1: Clause 2, page 2, line 22, at end insert “the blood supply is made safe through the implementation of prion filtration and that”…

 

7] Lord Archer Report [Word doc] 

Independent Public Inquiry Report On NHS Supplied Contaminated Blood and Blood Products

Published: 23 February 2009  www.archercbbp.com

“To investigate the circumstances surrounding the supply to patients of contaminated NHS blood and blood products; its consequences for the haemophilia community and others afflicted; and suggest further steps to address both their problems and needs and those of bereaved families”.

 

8] http://www.slowlyslowlycatchymonkey.com/4.html

The Shredding Fiasco (1989-1992)
“Papers were not adequately archived and were unfortunately destroyed in error.”
           Caroline Flint, 23 May, 2006

 

9] Hansard 7 June 2007

http://www.parliament.the-stationery-office.co.uk/pa/cm200607/cmhansrd/cm070607/text/70607w0004.htm

Health
Blood: Contamination

Jenny Willott: To ask the Secretary of State for Health (1) if her Department will release the audit certificates for files containing documents mistakenly destroyed by the Department in the 1990s and which were the subject of an Internal Audit Report in April 2000 before the end of the inquiry chaired by Lord Archer into contaminated blood and blood products; and if she will make a statement; [141006]

7 Jun 2007 : Column 647W

(2) what records her Department holds on the work of the Advisory Committee on the Virological Safety of Blood relating to the years 1989 to 1993; and if she will make a statement. [141032]

Caroline Flint: The Department holds seven files on the work of the Advisory Committee on the Virological Safety of Blood for the period 1989-93.

I regret that some volumes were destroyed in the 1990s, and this was the subject of an internal review and report in 2000 which is now in the public domain. The internal audit report clearly sets out the sequence of events which led to the destruction of files.

Jenny Willott: To ask the Secretary of State for Health if she will release the documents returned to the Department by solicitors in a previous litigation against the Department as referred to in the Review of Documentation relating to the Safety of Blood Products 1970 to 1985 to the independent public inquiry chaired by Lord Archer into contaminated blood and blood products; and if she will make a statement. [141029]

Caroline Flint: The papers returned to the Department by solicitors have already been released in line with the Freedom of Information Act, and are in the public domain.

The Department has given an undertaking to release all the papers held on the issue of blood safety between 1970-85. The papers returned from solicitors and the references to the report “Self Sufficiency in Blood Products in England and Wales” will consequently be sent to the independent inquiry.

Jenny Willott: To ask the Secretary of State for Health (1) what plans her Department has to submit (a) written evidence and (b) oral evidence from (i) Ministers, (ii) civil servants and (iii) NHS staff to the independent public inquiry chaired by Lord Archer into contaminated blood and blood products; and if she will make a statement; [141030]

(2) whether her Department has been asked to provide (a) Ministers, (b) civil servants and (c) NHS staff as witnesses for oral evidence in the independent public inquiry chaired by Lord Archer into contaminated blood and blood products; and if she will make a statement. [141031]

7 Jun 2007 : Column 648W

Caroline Flint: Lord Archer of Sandwell wrote to the Secretary of State for Health in February to invite the Department to give evidence at the independent inquiry.

Officials met with members of the inquiry team on 25 April 2007 to discuss what information the Department may be able to provide to the inquiry. We have made available a recently completed document on the “Review of Documentation Relating to the Safety of Blood Products 1970-1985 (Non A Non B Hepatitis)”, and the supporting references. Copies of the document are available in the Library.

Officials continue to liaise with the secretary to the inquiry team.

 

10] ME Association  28 November 2009

November 27 update on XMRV and ME/CFS XMRV and ME/CFS? What do we know so far? And what don’t we know? (version 4)

Version 4 of the MEA position statement on XMRV clarifies some of the points and queries raised in the previous three summaries. Version 4 also updates the situation on XMRV research in the UK, testing for XMRV, and refers to our correspondence with the Chief Medical Officer regarding blood supplies and blood donation.

This summary is intended to be a balanced account of the current situation. It therefore not only raises questions but is also very cautious when it comes to drawing any firm conclusions about the role of XMRV in ME/CFS as either a diagnostic marker, causative agent, or abnormality that requires active treatment with antiviral medication.

[…]

VIRAL TRANSMISSION

We know that some people with ME/CFS are now very concerned about the possibility of transmission of XMRV through what are termed body fluids (ie blood, saliva, semen). However, until we know more about what this virus does in the body it would be premature to start arriving at firm conclusions and recommending all kinds of restrictions to normal daily living.

Remember: we still do not know for certain whether this is a disease-causing virus in humans and whether it plays a role in causing or maintaining ME/CFS.

And if this virus was behaving as an ‘ME virus’ in the way that HIV, another retrovirus, causes and transmits HIV infection, often leading to AIDS, there would be a significant number of sexual partners of people with ME/CFS developing ME/CFS. But this is clearly not the case.

One simple way of obtaining some early clues about viral transmission of XMRV would be to test for the presence of the virus in healthy partners and offspring of people who have the infection and comparing the findings to a control group of people that have no such link.

PRESENCE OF XMRV IN THE HEALTHY POPULATION

If this virus is also present in up to 4% of the normal healthy population here in the UK (ie around 2.4 million, or ten times the number of people who have ME/CFS), as appears to be the case in America, and it does play a significant role in diseases such as ME/CFS and prostate cancer, there will be widespread and very serious implications for public health, blood donation etc. This could also include vaccination against the virus and treating people who are XMRV positive.

These are complex decisions which can only be made in the light of further research studies. And this will take time.

BLOOD DONATION AND XMRV

In relation to blood donation in the UK, current advice is that people with ME/CFS who have symptoms, or are receiving treatment, should not donate blood. It would seem sensible in the short term, until we know more about transmission and pathogenicity of XMRV, to consider extending this restriction to people who have recovered from ME/CFS. It seems strange that many overseas countries have not followed the UK lead on blood donation and ME/CFS.

The MEA has written to Sir Liam Donaldson, Chief Medical Officer at the Department of Health, regarding the possibility of XMRV being transmitted via human blood products and the implications that this has for blood donation. A copy of this letter can be read here. (Ed: copy at [11])

The reply from the CMO, which outlines the various expert bodies to whom attention has been drawn and advice is being sought, can be found here. (Ed: copy at [12])

The CFIDS Association of America has been issued with guidance from the National Cancer Institute regarding blood donation in the US. The guidance can be read on the CFIDS website here (Ed: copy at [13])

[…]

 

11] ME Association 

Archived news XMRV and ME/CFS: The MEA writes to the Chief Medical Officer

Dear Sir Liam

Implications of research findings concerning XMRV and ME/CFS

I assume you are aware of the new research findings from America, published in Scienceon 8 October 2009,which relate to the retrovirus known as XMRV (xenotropic murine leukaemia virus) and ME/CFS.

The ME Association has produced some information which summarises the research findings and the practical implications they may have in relation to disease management. Our position statement acknowledges that many uncertainties remain and that further research studies are needed before anyone can conclude that this virus plays a significant role in either the cause, assessment or management of ME/CFS. We are in contact with several research groups (UK and overseas) who have experience in retroviral research and it is encouraging to note that there is a strong desire in the research community to take this forward as a matter of urgency. I can supply further information if necessary. The ME Association summary, which also contains a link to the XMRV research paper, can be found on our website.

I would also like to draw your attention to two statements that have been issued by the National Cancer Institute in America in relation to XMRV. The first statement, which refers to the research findings, can be found here. The second statement, which refers to transmission and blood donation, can be found here. The NCI interim guidelines relating to blood donation in the second statement (>> point 2) are very similar to those contained in the MEA summary, and the issue of XMRV transmission is something that obviously needs to be brought to the attention of the National Blood Service and Health Protection Agency if not already done so. A clear statement from the National Blood Service in relation to blood donation from people with ME/CFS would obviously be very helpful to people at this time.

If the Department of Health, or the National Blood Service, would like to add anything to the MEA information, which is being updated at regular intervals, we would be happy to include it.

Yours sincerely

Dr Charles Shepherd
Honorary Medical Adviser, The ME Association
7 Apollo Office Court
Radclive Road
Gawcott
Bucks MK18 4DF

Formerly a member of the CMO Working Group on ME/CFS

Copies:
Dr Des Turner MP – Chair of the All Party Parliamentary Group on ME
Countess of Mar – Chair of Forward ME Group
Dr Jonathan Stoye – National Institute for Medical Research
Professor Stephen Holgate – Chair of MRC Expert Group on ME/CFS Research
Professor Tony Pinching – Peninsular Medical School

 

12] ME Association  13 November 2009

XMRV – comments from the Chief Medical Officer on blood donation and blood transfusion services

The ME Association wrote to Sir Liam Donaldson, Chief Medical Officer at the Department of Health, in October in relation to XMRV research – in particular the situation regarding blood donation and blood transfusion services here in the UK.

Click here to read a copy of this letter.

We have now received a reply from the CMO, with the following key points:

• The Standing Advisory Committee on Transfusion Transmitted Infections (SACTTI), part of UK Blood Services, will be producing a risk assessment for this virus.

• The current advice from UK Blood Services in relation to ME/CFS has been further clarified: Individuals suffering from ME/CFS are deferred from blood donation until their condition has resolved and they are feeling completely well.

• The research has also been drawn to the attention of the secretariats for the Advisory Committee on the Safety of Blood, Tissues and Organs (SaBTO) and the National Expert Panel on New and Emerging Infections (NEPNEI), who will continue to monitor developments in conjunction with UK Blood Services and the Health Protection Agency.

• A copy of the MEA letter and information on XMRV has also been passed to the Professional Director of the UK Blood Services Joint Professional Advisory Committee, along with all the UK virology and retrovirology experts who were copied into our original correspondence.

The MEA would like to thank everyone who has been in contact with information regarding blood donation by people with ME/CFS in other countries. We are keen to continue building up this database and any further help here would be much appreciated. It appears that there are very few countries who currently take the same position, or a similar position on blood donation, to that in the UK.

XMRV research will obviously feature during discussions that will be taking place at the Medical Research Council’s Expert Group Workshop on ME/CFS next week in Oxfordshire.

Dr Charles Shepherd
Hon Medical Adviser, ME Association
Member of the MRC Expert Group

 

13] CFIDS Association of America  23 October 2009

Interim XMRV Guidelines from National Cancer Institute

John E. Niederhuber, M.D., Director, National Cancer Institute
23 October, 2009

Interim XMRV Guidelines from National Cancer Institute

(Following the Oct. 8 publication by Lombardi et al in Science linking CFS and xenotropic murine-related retrovirus (XMRV), the CFIDS Association of America requested guidance from the National Cancer Institute about XMRV for persons diagnosed with CFS, their loved ones and the general public. The following are interim guidelines excerpted from a letter received from NCI director Dr. John E. Niederhuber.)

Interim XMRV Guidelines from National Cancer Institute

We at the National Cancer Institute (NCI) have great interest in these initial research findings. At present, we agree that a critical issue to be addressed is whether the exciting recent results obtained using samples from the Nevada cohort can be reproduced in additional cohorts of CFS-afflicted individuals. The NCI is striving to develop tools so that the general prevalence of XMRV in the population can be ascertained, and the association of XMRV with disease can be examined.

In the meantime, it is very important to reiterate what we do not know at this point, specifically:

1  We do not know whether XMRV is a causative agent for CFS, prostate cancer, or any other disease. Even if a causal association can be established, it may be only one of many causes, and there may be other factors, genetic or environmental, that determine the outcome of infection. At the moment, there is no evidence of CFS transmission between family members, even though XMRV appears to be an infectious agent. Thus, it is unclear whether XMRV alone underlies CFS.

2  We do not know how XMRV is transmitted from individual to individual. Recent suggestions of sexual or salivary transmission are not based on direct evidence, and conclusions regarding transmission are not credible at this point. Given the frequent isolation of virus from white blood cells, blood-borne transmission is a real possibility, and, while we are not in a position to establish firm guidelines, prudence would dictate that potentially infected individuals refrain from blood donation at this time.

3  We do not know how many apparently healthy individuals are infected, and what the distribution of infection is within the U.S. and in the worldwide population. The National Cancer Institute is involved in coordinating a global effort to study these issues.

It is very important to keep in mind that there is no evidence for a new increasing or spreading XMRV infection. Further, no credible evidence exists for direct transmission of either CFS or prostate cancer.

John E. Niederhuber, M.D.
Director, National Cancer Institute
U.S. National Institutes of Health
Department of Health and Human Services
October 23, 2009