“Serious doubt has been cast on the theory that...chronic fatigue syndrome is caused by a new retrovirus,” The Guardian reported. The newspaper said researchers from London have failed to replicate findings from the US that suggested a possible role for a virus called XMRV in causing CFS, also known as ME (myalgic encephalomyelitis).
In the new study none of the 186 UK CFS patients tested carried the XMRV virus, in contrast to the US study in 2009, which found that about two-thirds of 101 CFS patients tested had the virus. Why the two studies have different findings is not clear, but the results of the UK study do not support an association between XMRV infection and CFS in UK patients. This highlights the importance of different research groups repeating experiments in different populations.
CFS is a complex disease, and its causes are not well understood. Although an association with XMRV has not been established, this does not rule out the possibility that viral infection is involved. Much more research will be needed in this area.
Where did the story come from?
The research was carried out by Dr Otto Erlwein and colleagues from Imperial College London and King’s College London. The researchers were funded by the South London and Maudsley NHS Foundation Trust, the Institute of Psychiatry and the National Institute for Health Research Biomedical Research Centre. The study was published in the peer-reviewed open access journal PLoS ONE.
The Guardian, Daily Mail and The Independent reported the story. In general, the coverage is balanced and accurate. The headline of the Daily Mail story that “British experts say ME virus is a myth” might be taken to mean that this research excludes any role for viral infection in CFS/ME, but this research only looked at one virus (XMRV).
What kind of research was this?
This cross-sectional study investigated whether people in the UK with chronic fatigue syndrome (CFS) were infected with the xenotropic murine leukaemia virus-related virus (XMRV). In 2009, a case control study from the US found that more people with CFS carried the virus than people without the condition. The researchers in this study wanted to see if XMRV was similarly common in people from the UK with CFS.
A cross-sectional study design is appropriate for determining how common a particular trait is among a certain group of people. However, neither this study, not the original case-control study could prove whether XMRV potentially caused CFS, as neither would be able to establish whether people with XMRV had been infected before they developed CFS or after. The current study would also not have been able to say whether the XMRV virus was more or less common in people with CFS than in those without it, as it did not include a control group of people without the disease.
What did the research involve?
The researchers enrolled 186 people with CFS who were living in the UK. These people had been medically examined and diagnosed with CFS according to standard criteria, and other potential causes of their symptoms had been ruled out. Blood samples were taken and tested for the presence of DNA from XMRV or a related virus called murine leukaemia virus (MLV). A number of control tests were also carried out to show that the DNA in these samples was intact, that any positive findings were not a result of contamination of their experiment and that their test would identify XMRV if it was present. The inclusion of these controls is important for ensuring that the experiments were working well and were reliable. The researcher who carried out the DNA tests did not know which of the samples came from people with CFS.
The participants, all of whom had been referred to a CFS clinic, were mainly female (62%) with an average age of 39.6 years. They had been unwell for an average (median) of four years (range one to 28 years), and had high levels of fatigue. Few participants were working and about a fifth (19%) belonged to CFS/ME support groups. Just under half of the participants (45%) said that their CFS definitely related to a viral infection and 45% said that it might relate to a viral infection. The researchers suggested that the characteristics of their sample were typical of those seen in CFS patients attending specialist clinical services in the UK.
What were the basic results?
The researchers did not identify XMRV or MLV in the blood from any of the 186 CFS patients tested. Their control tests showed that the DNA being tested was intact, that there was no contamination in their experiments and that when XMRV was present (in a positive control sample containing XMRV DNA) their test detected it.
How did the researchers interpret the results?
The researchers concluded that they “found no evidence that XMRV is associated with CFS in the UK”. They suggested that the reason for the differences between their findings and those from the US might be due to differences in how common XMRV infection is in the different countries.
This study suggests that the XMRV infection is not common in CFS patients in the UK. A previous case-control study from the US found that about two-thirds of the 101 CFS patients tested carried XMRV, compared to about 4% of 218 healthy controls. This led the researchers from the US study to suggest that XMRV might be the cause of CFS in these patients. The reason for the differences between the US and UK studies is not clear, but the authors of the UK study suggest that it could be due to XMRV infection being more common in the US than in Europe.
The findings of this current study highlight the importance of different research groups repeating experiments in different populations. The study does have some limitations in that it was relatively small and all participants came from one CFS centre in London. Further studies in more participants from different centres in the UK would be useful in determining whether these findings are typical of the UK as a whole.
Even if this study had found significant levels of XMRV in CFS patients, it would not have been able to prove the virus actually caused the condition. This is because, like the original US case-control study, it could not establish whether people with XMRV had been infected before they developed CFS or after.
The current study would also not have been able to say whether the XMRV virus was more or less common in people with CFS than those without, as it did not include a control group of people without the disease.
The results of this UK study do not support an association between the XMRV virus and CFS in UK patients. The researchers do not rule out a role for all viruses in CFS, and say that “prospective epidemiological studies have confirmed that certain infective agents, for example Epstein Barr virus, are unequivocally associated with subsequent CFS, even if the mechanisms are unclear and almost certainly multi factorial”. CFS is a complex disease, and its causes are not well understood. Much more research will be needed in this area.