Viral studies to continue in chronic fatigue syndrome; two viruses ruled out

The association of two viruses with Myalgic Encephalomyelitis, also known as Chronic Fatigue Syndrome, has been definitively ruled out. No association was found with either Xenotropic Murine Leukemia Virus-Related Virus (XMRV) or Polytropic Murine Leukemia Virus (pMLV) in an NIH funded study published Tuesday.

The latest study in the hunt for the cause of ME/CFS comes nearly three years after XMRV was first studied as a possible etiological pathogen in ME/CFS and two years after a similar virus, pMLV, was associated with ME/CFS.

In the intervening years multiple groups of scientists searched for XMRV or pMLV in not only ME/CFS patients, but prostate patients and other diseases as well.
Questions lingered however as many of the subsequent ME/CFS studies used substantially different case definitions for ME/CFS or geographical locations other than the original studies and some were insufficiently powered. However, many scientists concluded that the retroviruses which originated in mice were contaminants.

An estimated 42 out of every 10,000 people in the United States have ME/CFS, with annual direct medical costs of $7 billion and an estimated annual total value of lost productivity in the United States at $9.1 billion.  ME/CFS is characterized by post-exertional fatigue unrelieved by rest accompanied by memory and concentration difficulties, headache, sore throat, and muscle or joint pain.

In the study published online in mBio, several of the key researchers from the previous two positive studies joined other ME/CFS experts and virologists. Like the original 2009 study positively associating ME/CFS with XMRV, ME/CFS patients in this study cohort were defined using the Centers for Disease Control’s 1994 Fukuda research criteria and the 2003 Canadian consensus criteria.

Like the first study, patients were selected from a variety of geographical locations in the United States and had an infectious onset. Patients and controls with infections from HIV and hepatitis, as well as those with medical or psychiatric illness that might be associated with fatigue were excluded.

Blood samples from 147 patients and 146 healthy matched volunteers were tested in three labs including two original labs and then sent to the Columbia University Center for Infection and Immunity where molecular epidemiologist Dr. Ian Lipkin presides for cutting edge analysis.
According to Dr. Lipkin, the cost of the over $2 million dollars invested in the study was primarily in the selection of patients and obtaining samples. Sufficient samples remain for numerous studies.

Although 10-12 viruses have been associated over the years with ME/CFS, many of the studies were too small or used different case definitions among other variables and results have been inconsistent. A 2006 CDC study looking at several viruses found that severity of the infection was the key rather than the specific virus or psychological factors.

Dr. Lipkin emphasizes that this study is the end of one chapter, but the beginning of additional research opportunities.

He states that there are currently two additional efforts under way in which he is involved. The Hutchins Family Foundation is providing funding to pursue pathogen discovery and biomarker discovery in patients with ME/CFS. Dr. Lipkin states many of the researchers who have previously found an association with various viruses in ME/CFS have been contacted and a Mass Tag system constructed allowing rapid evaluation of leading candidates. Additionally researchers will be pursuing high-throughput sequencing on the Illumina platform as well as RNA sequencing as well as a large proteomic project.

“I am heavily invested, professionally, in that search,” said Dr. Lipkin.

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