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Chronic Fatigue Syndrome Not Linked to Suspected Viruses, Study Shows

Some clinicians mistakenly prescribe off-label antiretroviral drugs (Sept. 18)

The causes of chronic fatigue syndrome (CFS) have long eluded scientists. In 2009, a paper in the journal Science linked the syndrome — sometimes called myalgic encephalomyelitis (ME) — to infection with xenotropic murine leukemia virus (MLV)-related virus (XMRV), a mouse retrovirus. Given that affected patients often have symptoms consistent with a chronic infection, this viral connection seemed plausible, and the findings were celebrated as a major achievement for a complex disease that affects nearly 1 million people in the U.S.

Another study in early 2010, published in the Proceedings of the National Academy of Sciences, detected murine retrovirus-like sequences (designated pMLV:polytropic MLV) in CFS/ME patients, which provided further support for a viral theory.

Follow-up investigations by several laboratories were unable to detect XMRV or pMLV in CFS patients. However, none of them examined a sufficiently large population of well-characterized CFS/ME patients to rigorously test the validity of those findings. In the absence of a definitive study, the general public may have continued to believe that XMRV and pMLV are responsible for the disease, and some clinicians continue to prescribe off-label antiretroviral drugs.

To definitively resolve this issue, the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health (NIH), commissioned a study under the auspices of the Center for Infection and Immunity at Columbia University’s Mailman School of Public Health. Results of the research were announced by Columbia University on September 18 and were published in mBio.

A total of 293 subjects — 147 with CFS/ME and 146 matched controls — were recruited at six sites in the U.S. None of the laboratories found evidence of XMRV or pMLV in samples from either the CFS/ME or control subjects.

Nine control and nine CFS/ME blood samples were positive for XMRV/pMLV-reactive antibodies. The accuracy of this assay cannot be determined because there are no positive controls in the general population with XMRV serology. Nonetheless, there was no correlation of antibody reactivity in blood from CFS/ME and controls.

“Although the once promising XMRV and pMLV hypotheses have been excluded, 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 CFS/ME,” said W. Ian Lipkin, MD, director of the study.

For more information, visit the Columbia University Web site.