Revised MEA statement on retrovirus XMRV and ME/CFS
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RETROVIRUS XMRV and ME/CFS: WHAT DO WE KNOW SO FAR? AND WHAT DON’T WE KNOW? (VERSION 2)
This is a considerably extended and updated version of our first summary on XMRV research. It includes additional information relating to questions that are coming to the MEA about the research findings, in particular questions concerning possible transmission and spread of XMRV, availability of private and NHS tests for the virus here in the UK, possible treatment of XMRV with antiviral drugs, and volunteering for UK research studies. We also report on a new research study from Germany that has queried the link between XMRV and prostate cancer.
This summary is intended to be a balanced account which not only raises questions but is also very cautious when it comes to drawing any firm conclusions about the role of XMRV at this very early stage in the research.
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 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 about the need for recognition and research into ME/CFS. These two items can be read here
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 conclusively discovered and that an 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 John Coffin (Department of Molecular Microbiology, Tufts University, Boston, USA) and Jonathan Stoye (National Institute for Medical Research, London).
Detection of an infectious retrovirus, XMRV, in blood cells of patients with chronic fatigue syndrome. Lombardi V et al. Science October 8 2009 Abstract: http://www.sciencemag.org/cgi/content/abstract/1179052
A new virus for old diseases? Coffin JM and Stoye JP. Science October 8 2009 326; p215 Abstract:
Additional online data from the study can be obtained if required.
XMRV has also been found in an American study in men who have 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 infections.
Lack of evidence for xenotropic murine leukaemia virus-related virus (XMRV) in German prostate cancer patients. Retrovirology 2009, 6:92. Available on-line: http://www.retrovirology.com/content/6/1/92
These are potentially 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 questions still have to be answered before anyone can conclude that this virus 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:
◦ Carrying out further and larger studies using different populations of people in different countries with ME/CFS. This work should include people at different stages of the illness (to see if the virus 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.
◦ Using different international laboratories to test for evidence of the virus.
◦ Assessing what, if any, correlation there is between the presence of this virus and (a) severity of symptoms, (b) a clear infectious onset with a known infection, (c) immune system abnormalities, CD4 abnormalities in particular, and (d) various other factors involved in sub-grouping of people under the ME/CFS umbrella.
◦ Assessing to what extent this particular retrovirus virus is also present in other chronic conditions, especially those such as multiple sclerosis and lymphoma where viral infections have been implicated as a causative factor.
◦ Assessing whether this virus is acting as a benign marker of disease or immune dysfunction, or is a ‘passenger virus’, or whether it has a role in the actual disease process and development of symptoms.
◦ Investigating whether the presence of the virus in healthy people acts as a predisposing factor in the development of ME/CFS (possibly when another infective trigger appears) and/or prostate cancer – rather than being involved in the actual disease process.
◦ Investigating what effect, if any, the virus has in healthy people who carry it over a period of time.
◦ Assessing whether people with evidence of the virus should be treated with antiretroviral medication, and if so developing a suitable antiviral drug or combination of antiviral drugs.
◦ Assessing whether animal model studies would help to increase our understanding of the way in which this virus may infects cells and possibly cause disease.
TESTING FOR XMRV
Until these research findings have been robustly 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 the 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.
We are not aware of any private pathology laboratories here in the UK that are able to test for XMRV, or are intending to start offering this test. Private testing is available in some countries outside the UK.
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. But these are complex decisions which can only be made in the light of further research studies.
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.
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 transission. 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, 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
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. This will involve clinical trials to test possible drug treatments for both safety and efficacy – a process that normally takes a comsiderable amount of time and money.
The 2007 NICE Guideline on ME/CFS specifically states that 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.
ROLE OF THE MEA RAMSAY RESEARCH FUND and VOLUNTEERING FOR RESEARCH
The ME Association is keen to progress this research here in the UK through any way we can help. We have already made contact with virologists who are interested in this virus here in the UK and funding from the Ramsay Research Fund (RRF) could be made available very quickly if we receive a good quality research proposal.
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 are intending to try and confirm or refute the findings. The MEA has been contacted in relation to four such groups already – two from overseas. This is obviously good news and should help to clear up some of the immediate uncertainties.
If volunteers are required for any research taking place in the UK we will place an annoucement on the MEA website.
KEY FACTS ABOUT THE XMRV RESEARCH
◦ An American group from the Whittemore Peterson Institute, in collaboration with the National Cancer Institute and the Cleveland Clinic, have reported finding evidence of a human retrovirus known as XMRV in blood samples taken from people with ME/CFS.
◦ Using peripheral blood mononuclear cells, DNA (viral genetic material) from the virus was found in 67% of patients (68/101) compared to 3.7% in healthy controls (8/218).
◦ The XMRV virus was shown to grow in cell culture in the laboratory.
◦ Further studies have found that 95% of people with ME/CFS have antibodies to the virus – indicating an immune response to a recent or past infection.
◦ Blood samples were collected from people with what is referred to in the paper as CFS who live in different parts of the United States, as well as from healthy controls.
◦ A more detailed, but easy to understand, summary of the XMRV research has been prepared by Dr Suzanne Vernon for the CFIDS Association of America. This can be read on their website: www.cfids.org/cfidslink/2009/110402.asp
◦ The paper in Science does not provide any detailed information about the patient group (ie age, gender, illness characteristics) or control group. However, a report on the research published in The Wall Street Journal states that 20/101 people in the CFS group also had a lymphoma, a type of cancer affecting the lymph nodes. Questions have therefore been raised about the inclusion of these patients in the CFS group, as well as the make up of the control group and how these patients were selected. See commentary from Professor Andrew Lloyd published on the website of the ME/CFS of NSW, Australia: www.me-cfs.org.au/node/448
KEY FACTS ABOUT RETROVIRUSES AND XMRV
◦ Retroviruses are a small group of human viruses that consist of HIV (causing AIDS) , HTLV-1 (causing T-cell leukaemias and lymphomas) and HTLV-2 (often asymptomatic not yet clearly linked to any specific disease).
◦ They were discovered in the 1980s when it became possible to culture T-cells in vitro.
◦ They infect CD4 bearing lymphocytes – a special type of immune system cell that is derived from the thymus gland.
◦ Endogenous retroviruses (ERVs) are also found in humans and usually cause no ill effects.
◦ XMRV is retrovirus that was first described about three years ago in some men who have prostate cancer.
◦ It may also be linked to other medical conditions, including fibromyalgia.
◦ XMRV is related to a group of viruses that can infect mice.
◦ This type of virus is thought to be transmitted through body fluids such as blood, semen and breast milk. It is not thought to be transmitted through the air – like a flu virus.
◦ Testing for evidence of the XMRV virus in blood is currently only available at a few specialised laboratories here in the UK.
◦ Demonstrating a link between a retrovirus and ME/CFS does not, by itself, resolve the physical vs psychological debate. Research studies have demonstrated links between retroviruses and diseases as diverse as autoimmune disorders (which could be relevant to ME/CFS), immunodeficiency diseases, multiple sclerosis, tumours, anaemias and schizophrenia.
The bottom line to this interesting research is that it currently raises more questions than answers.
◦ Does the presence of XMRV in healthy people make them more likely to develop ME/CFS when another infection appears?
◦ Does XMRV cause ME/CFS in some cases?
◦ Does XMRV become active as a result of having ME/CFS?
◦ Or is it simply an innocent bystander with no role in the illness?
◦ Should XMRV be treated?
When we have accurate answers to at least some of these questions we can move forward, if necessary, with testing and treatment.
We will update this summary as further information becomes available.
If you want to comment on it please do so via firstname.lastname@example.org
Dr Charles Shepherd
Hon Medical Adviser, ME Association
Summary 2 dated 22 October 2009