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Original Article

Chronic Fatigue Syndrome (CFS): A Critical Evaluation of Testing for Active Human Herpesvirus-6 (HHV-6) Infection

Review of Data of 107 Cases

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Pages 3-16 | Published online: 04 Dec 2011
 

Abstract

Aim: To conduct a virologic study in patients with chronic fatigue syndrome (CFS, ICD-10: G 93.3) for identification of reactivated human herpesvirus-6 (HHV-6) infection. Patients and Method: One hundred seven patients (60 women, 47 men, f/m ratio: 1.27/1; age: between 7 and 76 years, medium 41.8 years) with clinical CFS were studied with follow-up periods from 10 months to 7.5 years. Patients were recruited for the study by answering a standard questionnaire and by matching the Holmes' criteria for CFS. This was followed by physical examination, conventional hematological and chemistry testing, lymphocyte phenotyping, and control of other immunologic parameters. Testing for HHV-6 infection included indirect immunofluorescence assays (IFA), antigen capture enzyme linked immunosorbent assay (antigen capture ELISA, ACE), nested polymerase chain reaction (nPCR) on peripheral blood cells, and virus isolation. Results: HHV-6 seroprevalence in CFS patients was 97%. Seventy-two percent of the CFS patients had elevated serum anti-HHV-6 IgG titers, but active HHV-6 infection was detected in only 38.6% of the cases as identified by ACE, nPCR, and virus isolation. In absence of anti-HHV-6-IgM, anti-HHV-6-IgG titers were less reliable for monitoring virus activity. Among other infections EBV was seen in 19.6% of the cases and, less frequently, HSV, Chlamydia, Campylobacter, coxsackie, CMV, Yersinia or Candida. In 46% of the patients there were evident signs of immune deficiency. In additional 20% evidence was less clear (e.g., decreased lymphocyte stimulation: PHA/ConA 46%; low NK cell levels: 35%; and low CD4/CD8 cell ratio: 21%). Conclusion: Active HHV-6 infection was prevalent in one third of our CFS patients, much less than expected. Additional testing besides routine IFA is necessary for confirminig virus activity.

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