By Heidi Ledford

A key study on chronic fatigue syndrome was delayed from publication after officials from the Centers for Disease Control and Prevention (CDC) in Atlanta, Ga., learned of a conflicting report published by other government agencies.

The paper, which was published online July 2 by the journal Retrovirology, finds no evidence of a controversial link between the xenotropic murine leukaemia virus (XMRV) and chronic fatigue syndrome. Retrovirologist William Switzer and his colleagues at the CDC conducted a blinded study of 51 people with chronic fatigue syndrome and 56 healthy controls. The team used two different methods to assay for the virus but found no signs of infection.

On July 1, reports surfaced that publication of the paper had been held back because the results conflicted with a manuscript prepared by another team of government researchers at the National Institutes of Health (NIH) and the Food and Drug Administration (FDA) and submitted to the journal Proceedings of the National Academy of Sciences.

Chronic fatigue syndrome is a mysterious condition that afflicts roughly one million people in the United States. The condition causes debilitating fatigue and often also joint pain and headaches. The cause of the syndrome is unknown, and some have charged that it may be psychosomatic, much to the chagrin of patients and their advocates.

The possible association between XMRV and chronic fatigue syndrome first surfaced last year, when scientists lead by Judy Mikovits at the Whittemore Peterson Institute in Reno, Nev., reported that the virus was present in 68 of 101 patients with chronic fatigue syndrome, but in only 8 of 218 healthy controls2. Since then, however, other groups have reported that they could find no such link.

The paper published July 2 in Retrovirology adds another negative finding to the pile. Switzer says his study improves upon previous work because it was blinded--meaning that researchers did not know which samples were from people with chronic fatigue syndrome and which were from healthy controls until after the tests were completed. Also, the tests came from patients in the United States, countering critics who said that geographical variability may explain why groups in the United Kingdom and Europe had been unable to reproduce the XMRV link, which was discovered in U.S. patients.

Switzer's paper was delayed to give the CDC a chance to review his paper and methods in more detail, and to give Switzer's team a chance to perform more tests, says Stephen Monroe, director of the CDC's Division of High-Consequence Pathogens and Pathology. The delay lasted three weeks, and resulted in no changes to the manuscript, Switzer says.

Strong association

Monroe called the delay a "strategic pause," initiated after CDC officials learned of a contradictory study by the NIH and FDA team, reported at a meeting by NIH researcher Harvey Alter. Although a PNAS spokeswoman reportedly told The Wall Street Journal that the study had been accepted for publication, press officers at PNAS refused to comment on the matter July 2. One scientist familiar with the issue said that the journal's editor-in-chief, cell biologist Randy Schekman of the University of California, Berkeley, sent the paper out for further review after government agencies requested the publication delay. That review came back with requests for additional studies, the scientist says.

Schekman declined to comment, noting that it is the journal's policy not to discuss papers in progress.

Alter could not be reached for comment, but the Dutch medical magazine ORTHO issued a press release last week after learning of a presentation Alter gave at a meeting in Zagreb last May. According to the press release, Alter said that researchers at the FDA and NIH had independently confirmed Mikovits's findings, saying, "The association with CFS is very strong."

If the PNAS paper is published, it will be the first published study to back up the work reported last year by Mikovits.

This would be welcome news to patient advocates who are concerned about how patients were classified in Switzer's study. Fred Friedberg, president of the International Association for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME), says the CDC used an assessment that could lump together those with chronic fatigue syndrome and those with other conditions, such as major depression. And Kim McCleary, president of the Chronic Fatigue and Immune Dysfunction Syndrome Association of America, notes that the study included only three patients with "acute onset" chronic fatigue syndrome; the rest had gradual onset of the condition. "That is a very low number," says McCleary. "If you're looking for a virus, it seems like you would have wanted to screen [people with] the acute cases."