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Paul H. Levine, MD; Steven Jacobson, PhD; Alan G. Pocinki, MD; Paul Cheney, MD; Daniel Peterson, MD; Roger R. Connelly, MSc; Roselyn Weil; Susan M. Robinson; Dharam V. Ablashi, DVM; S. Zaki Salahuddin, MSc; Gary R. Pearson, PhD; Robert Hoover, MD

Arch Intern Med. 1992;152(8):1611-1616.

Abstract
Background.—
The purpose of this study is to provide a case definition of chronic fatigue syndrome in an outbreak occurring in the Nevada-California region to evaluate candidate etiologic agents and observe the natural history of the illness.

Methods.—
Patients diagnosed as having chronic fatigue syndrome were studied by repeated interviews, questionnaires, and blood collection over a 3-year period. Serum samples were tested for antibodies to Epstein-Barr virus, human herpesvirus-6, and human T-Iymphotropic viruses I and II. Leukocytes from typical cases were also assayed for human T-Iymphotropic viruses I and II.

Results.—
Cases were defined as persons who had: (1) severe persistent fatigue following an acute illness appearing in an individual with no previous physical or psychological symptoms; (2) presenting signs and symptoms of an acute infection; (3) severe and persistent headache and/or mylagias; and (4) abrupt change in cognitive function or the appearance of a new mood disorder. After 3 years of followup, almost all study subjects were able to return to preillness activity. None of the viruses evaluated—human T-Iymphotropic viruses I and II, Epstein-Barr virus, or human herpesvirus-6—couldcould be etiologically linked to these outbreaks.

Conclusion.—
Clinical features of outbreaks of chronic fatigue syndrome differ sufficiently to suggest different etiologic agents. Giardiasis appears to have precipitated one of the four clusters in this study but the cause(s) of the other three outbreaks is as yet uncertain. The overall prognosis of chronic fatigue syndrome is usually favorable.

(Arch Intern Med. 1992;152:1611-1616)

Author Affiliations
From the National Institutes of Health, Bethesda, Md (Drs Levine, Jacobson, Pocinki, Ablashi, and Hoover, Messrs Salahuddin and Connelly, and Mss Weil and Robinson); the Cheney Clinic, Charlotte, NC (Dr Cheney); Dr Peterson is in private practice, Incline Village, Nev; and Georgetown University Medical Center, Washington, DC (Dr Pearson).

Footnotes
Accepted for publication February 21, 1992.

Reprint requests to the Environmental Epidemiology Branch, Division of Cancer Etiology, National Cancer Institute, National Institutes of Health, Executive Plaza North, Room 434, Bethesda, MD 20892 (Dr Levine).

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