Feeling tired all the time -- a complaint that many patients bring to their doctors and which has been popularly attributed to the Epstein-Barr virus -- probably is not caused by that virus, according to a study released today.
The report, in today's Journal of the American Medical Association, is one of the most sophisticated yet to search for a link between ordinary chronic fatigue and the Epstein-Barr virus, which also causes mononucleosis. Previous studies have found no correlation between the virus and chronic fatigue, but this is the first to use molecular biology techniques that can find viruses that hide from other methods of searching.
"It's another nail in the coffin of evidence that the Epstein-Barr virus is . . . a major factor in chronic fatigue," said Lawrence Corey, a professor of medicine at the University of Washington School of Medicine in Seattle and one of the report's authors.
Although no specific figures exist on how many Americans are chronically fatigued, the complaint is "one of the 10 most common reasons why people see a doctor," according to Anthony Komaroff, chief of general internal medicine at Boston's Brigham and Women's Hospital. Ordinary long-term fatigue, Komaroff said, should not be confused with a medical condition known as chronic fatigue syndrome. He estimates that only 5 percent of people who complain of being tired all the time have chronic fatigue syndrome, a type of malaise distinguished by its sudden onset. The syndrome has no known cause.
Chronic fatigue syndrome has also been called "yuppie flu," because of a popular misconception that the people diagnosed with it are frequently in their 30s. But Komaroff said the syndrome probably strikes people of other ages just as frequently and is not confined to any racial or economic group.
The study compared 26 patients who had long-term fatigue with 18 healthy people of similar background. Researchers looked for the virus in the blood and saliva of both groups. They isolated the virus from 13 percent of the patients and from 17 percent of the healthy people -- a difference they called insignificant.
The study also found that many of the chronically fatigued patients improved over time without treatment. Of the 21 patients who agreed to be followed by researchers, four recovered completely and eight improved within two years, without medication. Corey said he is not sure why.
"There's some good news in that about half of the patients got better over time without specific therapy," Corey said. "The less good news is, we didn't solve the problem of chronic fatigue."
The researchers also found that the chronic fatigue patients were more likely to be depressed than were the normal subjects. Of the fatigue patients, 11, or 42 percent, were depressed. None of the non-fatigued patients was depressed.
Corey said it is unclear whether the depression caused the fatigue or whether the patients were depressed because they were fatigued. "Here we have the classic cart-and-horse situation," he said. "Which came first?"
Researchers estimate that about 90 percent of American adults have been infected with the Epstein-Barr virus. One longstanding theory had been that the virus lies dormant in most people and, when reactivated, causes fatigue.
If so, researchers say, patients would have more of the virus in their blood and throat because the once-dormant virus would be reproducing. Since the fatigue patients didn't have a higher amount of virus, Epstein-Barr probably wasn't causing their symptoms.
This study is not the first to dismiss the dormant virus theory. A 1987 study found that many healthy people have levels of antibodies to the Epstein-Barr virus just as high as those of many chronic fatigue patients. Another study found that acyclovir, a drug that usually stops replication of Epstein-Barr virus, failed to relieve the fatigue.
But Corey said this study is unique because it is the first to use sophisticated viral detection techniques. The researchers used a technique called in situ hybridization, in which radioactive DNA is used to look for cells containing DNA from the virus. They also looked for isolated virus in throat washings and blood.