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Chronic Fatigue Link to Virus Gains Support

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A growing body of evidence suggests that a virus or some other physiological agent—and not psychiatric troubles—is a cause of the mysterious ailment known as chronic fatigue syndrome.

Researchers who met recently in Atlanta said one of at least four different viruses could be a cause of the syndrome. None has yet emerged as a leading prospect and there is no assurance that any of them will be shown to cause the illness. But the number of candidates itself is viewed as bolstering the case that some identifiable agent underlies the illness.

“Research shows that chronic fatigue sufferers have abnormal immune systems that may fail to clear the body of invading viruses. ”

Meanwhile, a study published Saturday in Lancet, a British medical journal, found that many chronic fatigue patients, particularly those with severe symptoms, suffer from immune system irregularities that could provoke many characteristics of the illness. And an official at the U.S. Centers for Disease Control in Atlanta said data collected in the agency’s study of chronic fatigue are consistent with a physical cause for the ailment.

The syndrome is marked by severe fatigue, muscle and joint pain, and often by cognitive and neurological impairments such as loss of balance and trouble adding and subtracting. Such symptoms resemble those of many other illnesses and they vary widely from patient to patient, making diagnosis difficult. Some scientists and physicians believe an infectious agent such as a virus causes the illness, but many others think psychological or other yet-to-be identified problems cause the symptoms.

Finding a physical cause would be a major breakthrough for efforts to improve diagnosis, develop treatments and determine whether the syndrome is contagious and how it might spread. It would also give both patients and researchers more credibility in the medical community, where chronic fatigue continues to face high levels of skepticism. “One of the major problems with this disease is having it believed,” says Jay A. Levy, a researcher at University of California at San Francisco and principal investigator for the research just published in Lancet.

But the recent developments also underscore the enormous complexity that surrounds chronic fatigue and the hurdles ahead for people who have it and for researchers. “All of us would like this to be a simpler story than it’s going to turn out to be,” says Anthony Komaroff, chief of general medicine at Brigham and Women’s Hospital, Boston, and chairman of the National Chronic Fatigue Syndrome Advisory Council. That panel met Saturday at the CDC to discuss research on the ailment.

Leading investigators and the viruses they are focusing on include: Elaine DeFreitas of the Wistar Institute in Philadelphia, who is looking at an unidentified retrovirus similar to one known as HTLV-2; John Martin of the University of Southern California, Los Angeles, who is focusing on a spumavirus, a retrovirus known as human foamy virus; Peter Behan of the University of Glasgow, Scotland, who is studying enteroviruses that include the polio virus; and Dr. Komaroff at Harvard University, who thinks the human herpes virus might be responsible.

“Finding a physical cause would be a major breakthrough for efforts to improve diagnosis…and develop treatments.”

Such viruses already reside in most people but are held at bay by the immune system. But research by Drs. Levy and Nancy Klimas, an immunologist at the University of Miami School of Medicine, shows that chronic fatigue sufferers have abnormal immune systems that may fail to clear the body of invading viruses or to prevent reactivation of latent ones. That raises the question of whether they are a cause or effect of chronic fatigue, Dr. Klimas said.

In the Lancet article, Dr. Levy and his colleagues reported that patients with severe chronic fatigue symptoms have abnormalities in a group of infection-fighting cells known as CD8 cells. The patients had increased numbers of CD8 cells that launch an attack on an invader, but lower than normal amounts of CD8 suppressor cells that damp the immune system after the system’s job is done. The result is a hyperactive immune system that pours uncontrolled amounts of agents called cytokines into the body, apparently provoking fatigue, muscle pain and other symptoms. The research compared 147 people with chronic fatigue and 145 without.

In blood tests, Dr. Levy found no correlation between any of several viruses and chronic fatigue. One question Dr. Levy is investigating is whether an unidentified virus is involved in killing the suppressor cells that would moderate the action of the immune system.

Meanwhile, Waiter Gunn, principal investigator for the CDC’s chronic fatigue research, says about 42% of 525 people with symptoms referred to his agency by U.S. physicians approximated CDC criteria for the illness. Among them, 30% had evidence of depression near the onset of symptoms; half had no history of depression. “These data don’t compel one to think this is a psychiatric illness,” he says.

His agency is trying to replicate findings of Dr. DeFreitas at Wistar and others in a study of Georgia patients with chronic fatigue in an effort to find a physical marker that in a blood or other test would clearly identify those with the illness, thus aiding diagnosis.

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