When the journal Science published an attention-grabbing study last fall linking chronic fatigue syndrome to a recently discovered retrovirus, many experts remained skeptical — especially after four other studies found no such association.
Now a second research team has reported a link between the fatigue syndrome and the same class of virus, a category known as MLV-related viruses. In a paper published Monday by The Proceedings of the National Academy of Sciences, scientists found gene sequences from several MLV-related viruses in blood cells from 32 out of 37 chronic-fatigue patients but only 3 of 44 healthy ones.
Scientists found evidence of murine leukaemia virus – known to cause cancer in mice – in 86 per cent of chronic fatigue patients.
However, traces from this family of bugs were only found in seven per cent of samples from healthy blood donors.
It adds to the growing body of evidence that an infection could play a role in the complicated illness.
ME – also known as chronic fatigue syndrome – affects around 250,000 Britons. It usually develops in people in their early 20s to mid-40s.
Chronic fatigue syndrome
Symptoms include extreme exhaustion, sleep disturbances, memory and concentration difficulties, a sore throat, headaches and pain in the muscles and joints. At present, there is no test or cure for the condition.
In its most extreme form, it can leave sufferers – who include Dame Kelly Holmes and Emily Wilcox, the daughter of television presenter Esther Rantzen – bedridden and can even be fatal.
The researchers did not find XMRV, the specific retrovirus identified in patients last fall. But by confirming the presence of a cluster of genetically similar viruses, the new study represents a significant advance, experts and advocates say.
“I think it settles the issue of whether the initial report was real or not,” said K. Kimberly McCleary, president of the CFIDS Association of America, the leading organization for people with chronic fatigue syndrome.
?hronic fatigue syndrome (CFS) is the most common name given to a variably debilitating disorder or disorders generally defined by persistent fatigue unrelated to exertion, not substantially relieved by rest and accompanied by the presence of other specific symptoms for a minimum of six months.The disorder may also be referred to as post-viral fatigue syndrome (PVFS, when the condition arises following a flu-like illness), myalgic encephalomyelitis (ME), or several other terms. The disease process in CFS displays a range of neurological, immunological, and endocrine system abnormalities. Although classified by the World Health Organization under Diseases of the nervous system, the etiology (cause or origin) of CFS is currently unknown and there is no diagnostic laboratory test or biomarker.
Fatigue is a common symptom in many illnesses, but CFS is a multi-systemic disease and is relatively rare by comparison. Symptoms of CFS include widespread muscle and joint pain; cognitive difficulties; chronic, often severe, mental and physical exhaustion; and other characteristic symptoms in a previously healthy and active person. CFS patients may report additional symptoms including muscle weakness, hypersensitivity, orthostatic intolerance, digestive disturbances, depression, poor immune response, and cardiac and respiratory problems. It is unclear if these symptoms represent co-morbid conditions or are produced by an underlying etiology of CFS. All diagnostic criteria require that the symptoms must not be caused by other medical conditions.
Studies have reported numbers on the prevalence of CFS that vary widely, from 7 to 3,000 cases of CFS for every 100,000 adults, but national health organizations have estimated more than 1 million Americans and approximately a quarter of a million people in the UK have CFS. For unknown reasons CFS occurs most often in people in their 40s and 50s, more often in women than men, and is less prevalent among children and adolescents. The quality of life is “particularly and uniquely disrupted” in CFS. A prognosis study review calculated a median untreated patient full recovery rate of 5%, and the median improvement rate at approximately 40% compared to pre morbid status.
Whereas there is agreement on the genuine threat to health, happiness and productivity posed by CFS, various physicians’ groups, researchers and patient advocates promote different nomenclature, diagnostic criteria, etiologic hypotheses and treatments, resulting in controversy about many aspects of the disorder. The name CFS itself is controversial as many patients and advocacy groups, as well as some experts, want the name changed as they believe that it stigmatizes by not conveying the seriousness of the illness.
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Scientists who first linked chronic fatigue syndrome, also known as ME, to a virus have withdrawn some of their findings.
They have said some of their findings were based on “contaminated data”.
Meanwhile, a study in Science claimed the virus could not be reliably detected in ME patients, even in the labs which originally made the link.
Understanding of chronic fatigue syndrome is poor. It may be many diseases and the causes are uncertain.
There was a sense of hope for many patients when a study published in Science in 2009 showed that DNA from a mouse virus, XMRV, was present in 67% of patients with the illness, but only 4% of the general population.
Yet other scientists around the world could not find evidence of the virus. Many researchers began to argue that the most likely explanation was contamination of the laboratory samples.
It led to Science asking the authors to withdraw their findings and it published an editorial “expression of concern” saying that the validity of the study was “seriously in question”.
The authors have now issued a partial retraction after some of the scientists involved reported contamination, but this only calls into question the information in one table and two diagrams, not the rest of the paper and not the final conclusion.
One of the labs involved, the Whittemore Peterson Institute in Nevada, is standing by the conclusion. One of its lead researchers, Dr Vincent Lombardi, said it was “participating” in the retraction but: “We want to make it very clear that we are continuing the important work of studying retroviruses in association with ME/CFS and other similarly complex illnesses.
“WPI’s more recent retroviral work, although still in the early stages of discovery, continues to warrant additional investigations.”
Dr Jonathan Stoye, virologist at the Medical Research Council National Institute of Medical Research in the UK, said: “I don’t think this partial retraction has any meaning, it would have been nice to have a complete rather than a partial retraction.
“They’re saying the rest of the paper still stands, but that is becoming increasingly difficult for them to maintain.”
A fresh study on XMRV published in Science, which the researchers behind the original study participated in, again questioned the link.
Samples of blood were collected from 15 patients who had previously tested positive for XMRV, 14 of whom also had chronic fatigue syndrome, and from 15 patients without XMRV.
These samples were sent to nine laboratories, including two which had found the link previously. No lab knew which samples were from which patients.
Only two laboratories, the two which initially proposed the link, detected any cases of XMRV. However, the virus was detected at “similar rates” in both groups of patients, the study said.
The results from the two laboratories were also “inconsistent” even when testing blood from the same patient.
Dr Charles Shepherd, medical adviser to the ME Association said: “These are very emphatic negative or inconsistent findings from the Blood Working Group study, along with the retraction of some of the original supporting data that was published in Science.
“So it is now looking extremely unlikely that XMRV is either linked to ME/CFS or that it has a disease-causing role.
“Having had their hopes raised that a treatable component to ME/CFS had been identified, it’s not surprising that people are becoming increasingly disappointed at the way things are turning out.
But it’s too early to send out the scientific jury to make a final definitive decision on XMRV and ME/CFS – we still need the results from the other major multi-centre study on XMRV and ME/CFS being carried out in America by Prof Ian Lipkin.”