Biennial Report of the Director

Research in Diseases, Disorders, and Health Conditions
Chronic Diseases and Organ Systems
Chronic Fatigue Syndrome

Chronic fatigue syndrome, sometimes referred to as myalgic encephalomyelitis, is a complex, multi-symptom condition characterized by overwhelming fatigue that is not improved by bed rest and that may be worsened by physical or mental activity. Chronic fatigue syndrome is diagnosed 2–6 times more often in women than men. Chronic fatigue syndrome is difficult to diagnose because of multiple diagnostic criteria used by various practitioners. Exacerbating the difficulty of diagnosis is a lengthy timeframe for occurrence and recurrence of the symptoms. For example, the definition used by the CDC Web site on chronic fatigue syndrome indicates that in order to be diagnosed with chronic fatigue syndrome, a patient’s symptoms must have persisted or recurred during six or more consecutive months of illness.

The etiology of chronic fatigue syndrome is unknown, and no specific diagnostic tests are available. Moreover, since many illnesses have incapacitating fatigue as a symptom, care must be taken to exclude other known and often treatable conditions before a diagnosis of chronic fatigue syndrome is made. Treatment programs are individualized and are based on a combination of therapies, such as traditional and alternative therapies, which address symptoms, activity management, and coping techniques.
NIAID is supporting a multi-site study designed to address whether a murine retrovirus (designated XMRV, xenotropic murine leukemia virus-related virus) is associated with chronic fatigue syndrome. Researchers at Columbia University are collaborating with geographically distributed clinicians to ensure enrollment of a definitive, representative sample of chronic fatigue syndrome patients across the U.S. Researchers are comparing blood and plasma samples from patients diagnosed with chronic fatigue syndrome to samples from healthy people who have not been diagnosed with chronic fatigue syndrome and who are matched to the affected patients by age, sex, and geography. Patient enrollment began in fall of 2011, and results are expected in 2012.

Several other ICs support research in this field. NCI supports both intramural and extramural research on viruses linked to both cancer and chronic fatigue syndrome, in addition to research on mechanisms underlying pain and fatigue in cancer, which may have applications to these symptoms in chronic fatigue syndrome. Chronic fatigue syndrome and cancer research primarily overlap in possible common etiological agents such as viruses and environmental toxins, common systemic changes such as immunologic profiles and cytokine levels, and common symptom clusters such as pain and fatigue. NHLBI has funded several investigator-initiated research projects predominately examining circulatory dysfunction, orthostatic intolerance, and autonomic nervous system in chronic fatigue. NINDS supports extramural chronic fatigue syndrome research directed at effects on the central nervous system, including the role of brain mast cells in central nervous system inflammation, cognitive behavioral stress management to improve symptoms of chronic fatigue syndrome, and categorization of affected patients based on cerebrospinal fluid assays for the purpose of developing personalized treatments.

NIH hosted a State of the Knowledge Workshop on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Research April 7–8, 2011, on the NIH campus in Bethesda. The conference was open to the public and was attended in person by over 100 people and viewed by over 900 virtual attendees. The workshop brought together 32 investigators from a wide variety of scientific disciplines to discuss chronic fatigue syndrome research. The workshop panelists identified gaps in knowledge and opportunities for new biomedical research on this disease. This workshop was sponsored by the ORWH in collaboration with the Trans-NIH ME/CFS Research Working Group.

The International Workshop on XMRV, co-sponsored by NIH, DHHS, and Abbott Diagnostics, was convened on September 7–8, 2011 on the NIH campus, Bethesda. Attracting an international audience of over 200 participants, the two-day event combined a series of plenary talks with updates on different aspects of XMRV research, addressing basic gammaretrovirus biology, host response, association of XMRV with chronic fatigue syndrome and prostate cancer, assay development, and epidemiology.

In May of 2011, NCI scientists, in collaboration with NCI-supported researchers from Tufts University, published a study in Science showing that XMRV was generated by recombination of two endogenous mouse viruses in a human tumor xenograft during passage in nude mice.252This study provided strong evidence that XMRV was a laboratory contaminant, not a virus that infects humans.
The NHLBI-led Blood XMRV Scientific Research Working Group published an article in Science in September 2011 stating that comprehensive independent investigation, with blinded samples tested across nine laboratories, failed to detect reproducibly the presence of Xenotropic Murine Leukemia Virus (MLV)-related Virus (XMRV) or MLVs in the blood of 15 subjects previously reported to be XMRV/MLV-positive (14 with chronic fatigue syndrome) and from 15 healthy donors previously determined to be negative for the viruses.253

A study from the CDC showed that commercial laboratory reagents and human DNAs were contaminated with mouse DNA, which could have contributed to false positive assays for XMRV.254These reports, and a number of other published reports that failed to find XMRV in samples from human patients, led to the retraction of the original study linking XMRV and chronic fatigue syndrome.255 A recent study from the NCI showed that at least three different types of contamination contributed to reports that there was XMRV in human patient samples: XMRV virus, XMRV DNA, and mouse DNA.256 Taken together, the available studies provide strong evidence that XMRV is not a virus that infects humans.

NIH will continue to encourage research on chronic fatigue syndrome through two funding opportunity announcements (Program Announcements): Chronic Fatigue Syndrome: Pathophysiology and Treatment257 and Chronic Fatigue Syndrome: Pathophysiology and Treatment.258

The Office of the Secretary of HHS has determined that an ad hoc HHS working group on chronic fatigue syndrome could be beneficial for developing a Department-wide strategy to address chronic fatigue syndrome. This working group will be responsible for outlining the breadth and depth of the Department’s activities on chronic fatigue syndrome and the identification of opportunities for interagency collaboration. Leadership and coordination for the development of the chronic fatigue syndrome strategy will be provided by the Deputy Assistant Secretary of Health – Women’s Health and Director of the Office on Women's Health, Office of the Assistant Secretary for Health. The HHS Chronic Fatigue Syndrome Advisory Committee will continue to provide advice and recommendations to the Secretary of HHS via the Assistant Secretary for Health of HHS on issues related to chronic fatigue syndrome.259

252 Paprotka T, et al. Science. 2011;333:97–101. PMID: 21628392.
253 Simmons G, et al. Science. 2011;334(6057):814–7. PMID: 21940862.
254 Zheng H, et al. PLoS One. 2011;6(12):e29050. PMID: 22205995.
255 Alberts B, Science. 2011;334(6063):1636. PMID: 22194552.
256 Kearney MF, et al. PLoS ONE. 2012;7(2):e30889. PMID: 22363509.
257 For more information, see https://grants.nih.gov/grants/guide/pa-files/PAR-12-032.html.
258 For more information, see https://grants.nih.gov/grants/guide/pa-files/PAR-12-033.html.
259 For more information, see https://www.hhs.gov/advcomcfs/.