A new paper published online today concludes that no connection exists between chronic fatigue syndrome (CFS) and two viruses linked to the disease in a pair of earlier controversial studies—both of which have been debunked.

The paper, published in the open-access journal mBio, found no evidence of CFS infection from either xenotropic murine leukemia virus-related virus (XMRV) or polytropic murine leukemia virus (pMLV). The former was a finding published in a 2009 study in Science; the latter, a result published a year later in a study in Proceedings of the National Academy of Sciences.

“The bottom line is we found no evidence of infection with XMRV and pMLV. These results refute any correlation between these agents and disease,” W. Ian Lipkin, M.D., corresponding author on the latest study and John Snow Professor of Epidemiology at Columbia University’s Mailman School of Public Health, said in a statement by mBio’s publisher, the American Society for Microbiology.

While the earlier reports were trumpeted as landmark studies in combatting CFS—also called myalgic encephalomyelitis (ME)—later research failed to detect XMRV or pMLV in patients with the disease. None of the follow-up investigations examined a large-enough population of CFS patients to definitively challenge the validity of those findings.

Yet the investigations raised enough questions for Science to first partially, then fully retract its original 2009 study last year. The retractions came weeks after a formal Expression of Concern in May 2011, noting that at least 10 studies conducted by others up to then, plus another two published in the July 1 issue of Science, failed to replicate the original 2009 study.

Questions about that report and the PNAS study prompted NIH’s National Institute of Allergy and Infectious Diseases (NIAID) to commission its own study under the auspices of the Center for Infection and Immunity at Columbia University’s Mailman School of Public Health, together with CDC, FDA, and NIH’s National Cancer Institute and Warren G. Magnuson Clinical Center.

Several authors of the original papers participated in NIAID’s investigation, in which 293 patients—147 patients with CFS and 146 people without—were recruited from six U.S. clinical sites. All patients were tested for evidence of metabolic, endocrine, or infectious disease that might cause fatigue. Blood from both sets of patients was collected for blinded XMRV and/or pMLV analysis. However, no evidence of XMRV or pMLV was found in samples from either CFS or control patients.

[Read the full study from mBio here: http://mbio.asm.org/content/3/5/e00266-12.full]

“The consequences of the early reports linking these viruses to disease are that new resources and investigators have been recruited to address the challenge of the CFS/ME,” Dr. Lipkin said in a statement by Columbia.

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