News Archive 2009
XMRV and ME/CFS - A Stunning Find
08/12/2009 Our latest newsletter gave the full report from MERUK (ME Research UK), the report from our local press, plus many links to useful articles.Also included was a link to the MEA's statement:
XMRV and ME/CFS: (VERSION 3) What do we know so far? And, what don't we know?
The MEA's 'XMRV and ME/CFS (Version 4) is now available
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.
BACKGROUND On Friday 9 October, the front page of the UK Independent newspaper carried a major news item under the heading 'Has science found the cause of ME?' This story referred to new research findings from America which indicate that a recently discovered retrovirus, known as XMRV (xenotropic murine leukaemia virus-related virus), could be playing an important role in causing or maintaining ME/CFS. The news item was accompanied by a very supportive editorial in the newspaper about the need for recognition and research into ME/CFS. These two items can be found in the MEA website (October news archive). The Independent story was soon followed up by the rest of the UK media, including the BBC. Most of the news reports gave a reasonably balanced and accurate account of the research. However, some reports incorrectly inferred that the cause of ME/CFS had now been discovered and that an effective antiviral treatment would soon be available. A selection of UK media reports can be found in the October news archive on the MEA website. The actual research paper was published in the online edition of Science, along with a perspective written by retroviral experts Dr John Coffin (Department of Molecular Microbiology, Tufts University, Boston, USA) and Dr Jonathan Stoye (National Institute for Medical Research, London).
References: Detection of an infectious retrovirus, XMRV, in blood cells of patients with chronic fatigue syndrome. Lombardi V et al. Science October 8 2009 Abstract
A new virus for old diseases? Coffin JM and Stoye JP. Science October 8 2009 326; p215 Abstract
These papers are also available on the WPI website. Additional online data from the study can be obtained if required.
Since then there has been a great deal of interest in this finding and researchers in a number of countries where ME/CFS is recognised are intending to see if the results can be replicated in other groups of patients. We know that some of this replication research is moving very quickly and could well result in early publication of results.
On Tuesday 10 November, around 70 scientists, including a UK representative, met at the Cleveland Clinic in America to discuss the findings. This was a closed meeting - so no summary of the discussions is currently available.
In the UK, the Medical Research Council's Expert Group Workshop on ME/CFS discussed the XMRV findings on 19-20 November. Present at this closed meeting were four researchers who are actively involved with XMRV research in the UK, including one who attended the meeting in America. Brief notes on this meeting can be found on the MEA website News section. Summaries and slides from this meeting are due to be placed on the ME/CFS section of the MRC website. The All Party Parliamentary Group (APPG) on ME will be discussing XMRV when they meet on Wednesday 2 December at the House of Commons. Minister of State for Health Services at the DoH, the Rt Hon Mike O'Brien MP will be there. This meeting is open to the public - details about times and venue (currently 3.15pm to 4.45pm in Committee Room 15) can be found on the MEA website news section at http://www.meassociation.org.uk . If you are coming to the House of Commons on Wednesday, please allow at least 30 minutes to get through security and find your way to the Committee Room.
XMRV AND PROSTATE CANCER XMRV has also been found in an American study in men who have an aggressive form of prostate cancer. This was partly why the ME/CFS study was carried out. However, the most recent study on XMRV in prostate cancer from Germany has queried any such a link and suggested that one possible reason could be a geographically restricted incidence of XMRV infection or that different strains of XMRV are present in different parts of the world. Additional explanations involve the differing methodology and the type of sensitive laboratory testing for XMRV used in the two studies. The precise role of XMRV in prostate cancer remains uncertain – as it does in ME/CFS.
Reference: Lack of evidence for xenotropic murine leukaemia virus-related virus (XMRV) in German prostate cancer patients. Retrovirology 2009, 6:92. Available on-line here.
MEA POSITION ON XMRV These are potentially very important research findings that could help with both the diagnosis and management of ME/CFS. We congratulate all those involved in deciding to do this research study.
However, a number of difficult questions have to be answered before anyone can conclude that XMRV plays a significant role in either the cause, transmission, clinical assessment or management of ME/CFS.
The research has demonstrated a correlation between ME/CFS and XMRV – not that it is the causative infection.
Much more epidemiology and laboratory work now needs to be done to answer the essential points set out below.Further and much larger studies must be carried out using people with well defined ME/CFS in different countries. This work should include people at different stages of the illness (to see if XMRV is present in the same percentages in both early and late cases) and in all degrees of severity. Research in different countries is vital in view of the conflicting geographical findings relating to XMRV in prostate cancer.
Different international laboratories, with solid experience in dealing with retroviral research, need to test for evidence of XMRV. A battery of properly validated tests for XMRV, that can be consistently used in further research studies, need to be agreed by the scientific community.
Until these research findings have been properly replicated, and we have the answers to some of the above questions, there is no point in asking your doctor to be tested for XMRV. This is because the NHS does not currently have the facilities to do so and XMRV testing procedures are only being used in a research capacity at present. But if it does turn out that there is a consistent and strong association with ME/CFS then testing for XMRV would almost certainly have to be made available on the NHS.
We are not aware of any private pathology laboratories here in the UK that are able to test for XMRV, or intend to offer XMRV testing.
People need to carefully consider the value of spending several hundred pounds/dollars on individual testing for the presence of XMRV in the current situation. This because XMRV has not yet been established as either a diagnostic marker, disease causing virus, or something that needs treating with antiviral medication.
Dr Vincent Lombardi, primary investigator and lead author of the Science paper is Director of Operations for XMRV testing at Viral Immune Pathology Diagnostics (VIPDx) - a commercial laboratory in America. Website This company is offering XMRV tests but the testing facility is not available to people living outside the US. Contact details for anyone in Europe who does want to pursue XMRV testing, click here. 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.
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.
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.
WHAT CAN WE LEARN ABOUT THE ROLE OF INFECTION FROM OUTBREAKS OF ME/CFS? It should be noted that unlike the retroviral infection HIV, ME/CFS is an illness that occurs both sporadically and in highly localised acute geographical outbreaks, often involving closed communities such as schools and hospitals, where there is no obvious evidence of bodily fluid transmission. This fact would obviously question the role of XMRV as a precipitating infection in the onset of the illness.
In the pivotal Royal Free Hospital outbreak of ME back in 1955, far more than 4% of a previously healthy population of doctors and nurses contracted an unknown infection at roughly the same time (the hospital had to close due to lack of staff). This fact would question the role of XMRV as a key predisposing factor if it only occurs in 4% of the population.
TREATMENT OF XMRV: ANTIRETROVIRAL DRUGS AND VACCINE Until we know more about the possible role of XMRV in ME/CFS there is no point in asking your doctor about antiviral drug treatment. If it turns out that the virus does play a role in causing or maintaining ME/CFS then antiviral drug treatment will need to be investigated. But this will first involve clinical trials to test possible drug treatments for both safety and efficacy – a process that normally takes a considerable amount of time and money.
The 2007 NICE Guideline on ME/CFS specifically states that UK doctors should not use antiviral medication to treat ME/CFS. This dogmatic position is unlikely to change without clear evidence of benefit in good quality randomised clinical trials. The NICE guideline will be reviewed in late 2010.
Vaccination against XMRV has also been raised as a possibility.
ROLE OF THE MEA RAMSAY RESEARCH FUND The ME Association is keen to progress good-quality XMRV research here in the UK through any way we can help. We have already made contact with a number of virologists and retrovirologists who are involved with research into this virus here in the UK and are keen to pursue this work. Funding from the Ramsay Research Fund (RRF) could be made available very quickly if we receive a good quality research proposal – preferably UK-based. However, our contacts and discussions with UK researchers so far indicate that short-term funding is not an immediate problem and that initial plans can probably be covered from existing budgets.
More information on the work of the RRF can be found here
Since publication of these results it has become apparent that a number of international research groups outside the US and UK are also intending to try and confirm or refute the findings. The MEA has been contacted in relation to two such groups from overseas. This is obviously good news and should help to clear up some of the immediate uncertainties.
If we end up in a position where different research groups are obtaining conflicting findings on prevalence of the virus then it would be useful to swap samples between groups to see if different laboratories come up with the same results.
ROLE OF ME RESEARCH UK (MERUK) and IRISH ME TRUST MERUK and The Irish ME Trust have just announced that they are providing joint funding for a replication study that will be carried out in Sweden. This work will be carried out by Professor Blomberg, Head of the Research Group of Clinical Virology, University of Uppsala and Professor Gottfries, from the Sahgrenska University Hospital, Molndal. The researchers will retrospectively test previously stored samples from 3 groups of patients (20 Fukuda defined ME/CFS; 20 fibromyalgia; 20 irritable bowel) and 20 controls. In addition, they will prospectively test samples from 120 ME/CFS patients defined by Fukuda 1994 and Canadian 2003 clinical criteria. Results are expected in Spring/Summer 2010. More information on this study can be found on the MERUK website. VOLUNTEERING FOR XMRV RESEARCH If volunteers are required for any research taking place in the UK, we will place an announcement on the MEA website.
SELECTING PEOPLE FOR FURTHER RESEARCH STUDIES There is clearly an immediate need for international agreement and co-operation on the research criteria being used to select well-characterised ME/CFS patients for further research into XMRV. Otherwise, we could end up in spring/summer 2010 with a collection of conflicting results on prevalence because different international research groups have been using different patient selection criteria.
In the present situation, many research groups are reluctant or unwilling to use Canadian criteria. This is because these are essentially clinical criteria and in the eyes of many researchers they have not been validated for use in research studies as stand alone criteria. There is also the problem in that most research groups do not having ready access to stored blood samples from ME/CFS patients that meet Canadian criteria.
So the best way forward may be for everyone to agree to use either Fukuda-defined CFS - which would obviously help to define which sub-groups of patients are XMRV positive under this CFS umbrella - or, if possible, to use patients that meet both Fukuda CFS and Canadian clinical criteria. It is worth noting that a significant proportion of people with Ramsay-described ME will not meet Fukuda criteria for CFS - so they are likely to be excluded from research currently taking place.
We do not believe that it is sensible to extend the entry criteria into research studies by using the 2005 'empirical' definition of CFS for patient selection purposes as this will bring in an even more diverse group of patients who have chronic fatigue. This point has also been made by Dr Nancy Klimas when she addressed the CFSAC meeting in Washington in October.
Provided there is careful selection of ME/CFS patients, healthy controls and disease controls, we may then be able to draw some meaningful conclusions about which people who come under the wide clinical spectrum of CFS clinical presentation have XMRV and which do not.
Besides using stored blood samples, research needs to involve fresh clinical cases, as well as other disease groups (particularly inflammatory conditions with immune activation) and properly matched healthy controls.
KEY FACTS ABOUT THE XMRV RESEARCH
The bottom line to this interesting research is that it currently raises more questions than answers.
We will update this summary as further information becomes available.
Dr Charles Shepherd
Hon Medical Adviser, ME Association 08/12/09
All Party Parliamentary Group INQUIRY INTO NHS SERVICES FOR PEOPLE WITH M.E. / CFS - closed for submissions
Ian Logan, our Chairman, urges everyone to respond to the APPG Inquiry on NHS Service provision. The Worcestershire ME Support Group has posted questionnaires to all members, plus people who have contacted the group during the last five years (you will see this includes a covering letter to Dr Turner, Chair of the APPG Inquiry). The Terms of Reference, our Group’s forthcoming events, and a group leaflet were enclosed updating everyone. 2009.06
All Party Parliamentary Group (APPG) on ME
The All-Party Parliamentary Group (APPG) on Myalgic Encephalomyelitis (ME) was set up in 1999 to raise awareness of ME.
The Group campaigns within Westminster to support the improvement of health, social care, education and employment opportunities for people affected by ME. The Group also aims/campaigns to obtain wider recognition of the need for biomedical research into the underlying cause of ME and effective forms of treatment.
This website gives a link to the "APPG Inquiry on NHS service provision for people with ME". 2009.06
All Party Parliamentary Group Inquiry into NHS service provision for people with M.E.
Peter Luff MP for Mid-Worcestershire, and the Countess of Mar join this inquiriy's committee.
Announcing the terms of reference, Dr Des Turner MP , chairman of the All Party Parliamentary Group on ME, said:
“The committee will consider written evidence from patients and professionals before inviting individuals and organisations to make oral presentations. “Written evidence will include the findings of questionnaires, for patients and NHS service providers, which are currently being drawn up. “People with M.E., carers and professionals are invited to submit suggestions for specific questions which should be asked in these surveys. Our deadline for receiving people’s ideas is 5 May 2009. “The cut-off point for the submission of written evidence will be 30 June 2009. Oral hearings are likely to take place in the middle of July.”
Further details on the M.E Association website or via this attached document 2009.04
Lost Voices from a hidden illness
Congratulations to Invest in ME for the publication of this book.
And, very many thanks to all the sufferers of severe ME - 31 lost
voices - and their families/carers, for their involvement.
"Lost Voices" is available from the Invest in ME website. 2009.02.01
BBC Radio 4 Saturday Live:
M. E. and my Shadow poem