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Chronic fatigue syndrome (CFS), a debilitating chronic illness. The cause or causes of CFS are unknown. Patients with CFS have abnormal findings in the central nervous system (CNS) and autonomic nervous system, evidence of chronic activation of various parts of the immune system, and disordered energy metabolism.

For many, but not all, patients who meet criteria for CFS, the illness begins with an acute, infectious-like syndrome. Cases of CFS can follow well-documented infection with several infectious agents. A study of 259 patients with a “CFS-like” illness published shortly after HHV-6 was discovered used primary lymphocyte cultures to identify people with active replication of HHV-6. Such active replication was found in 70% of the patients vs. 20% of the control subjects (P< 10-8). The question raised but not answered by this study was whether the illness caused subtle immune deficiency that led to reactivation of HHV-6, or whether reactivation of HHV-6 led to the symptoms of the illness.

Subsequent studies employing only serological techniques that do not distinguish active from latent infection have produced mixed results: most, but not all, have found an association between CFS and HHV-6 infection.

Other studies have employed assays that can detect active infection: primary cell culture, PCR of serum or plasma or IgM early antigen antibodies. The majority of these studies have shown an association between CFS and active HHV-6 infection,    although a few have not.

In summary, active infection with HHV-6 is present in a substantial fraction of patients with CFS. Moreover, HHV-6 is known to infect cells of the nervous system and immune system, organ systems with demonstrable abnormalities in CFS. Despite this association, it remains unproven that reactivated HHV-6 infection is a cause of CFS.