Articles15 February 1993
    Author, Article, and Disclosure Information
    Objective:

    To assess whether the human T-lymphotropic virus type 2 (HTLV-II) gag gene sequence, a purportedly new laboratory marker of the chronic fatigue syndrome (CFS), and other possible risk factors for CFS, particularly those associated with retroviral transmission, are associated with well-characterized CFS.

    Design:

    Two matched case–control studies.

    Setting:

    The metropolitan Atlanta area.

    Patients:

    Twenty-one patients with CFS who were identified by the Centers for Disease Control and Prevention CFS surveillance system; 21 CDC employee controls (laboratory study) and 42 neighborhood controls (risk-factor study) who were matched to patients by age, race, and gender.

    Measurements:

    Peripheral blood lymphocytes and leukocytes were assayed for the HTLV-II gag gene sequence by polymerase chain reaction and specific Southern blot hybridization. Questionnaires elicited demographic and clinical information and a history of exposures associated with retrovirus transmission (for example, blood transfusions, sexual practices, intravenous drug use).

    Results:

    All patients were white and 86% were female. The median age at illness onset was 34 years (range, 16 to 51 years). The HTLV-II gag gene sequence was not identified in the blood of any patient or control under conditions in which the appropriate assay controls were positive. No statistical differences were observed between patients and controls in frequency of blood transfusions (10% compared with 7%), median number of sex partners before illness (3 compared with 3), bisexual or homosexual behavior (14% compared with 7%), intravenous drug use (0% compared with 0%), and other factors associated with retroviral infection.

    Conclusions:

    The HTLV-II gag gene sequence was not a marker for CFS in this small study of well-defined patients, nor did other characteristics of the patients and controls support the hypothesis that a retrovirus, transmitted by usual modes, was a cause of CFS.

    References

    • 1. DuBois RE, Seeley JK, Brus I, Sakamoto K, Ballow M, Harada S, et al. Chronic mononucleosis syndrome. South Med J. 1984; 77:1376-82. Google Scholar
    • 2. Jones JF, Ray CG, Minnich LL, Hicks MJ, Kibler R, Lucas DO. Evidence for active Epstein-Barr virus infection in patients with persistent, unexplained illnesses: elevated anti-early antigen antibodies. Ann Intern Med. 1985; 102:1-7. Google Scholar
    • 3. Straus SE, Tosato G, Armstrong G, Lawley T, Preble OT, Henle W, et al. Persisting illness and fatigue in adults with evidence of Epstein-Barr virus infection. Ann Intern Med. 1985; 102:7-16. Google Scholar
    • 4. Holmes GP, Kaplan JE, Stewart JA, Hunt B, Pinsky PF, Schonberger LB. A cluster of patients with a chronic mononucleosis-like syndrome. Is Epstein-Barr virus the cause? JAMA. 1987; 257:2297-302. Google Scholar
    • 5. Yousef GE, Bell EJ, Mann GF, Murugesan V, Smith DG, McCartney RA, et al. Chronic enterovirus infection in patients with postviral fatigue syndrome. Lancet. 1988; 1:146-50. Google Scholar
    • 6. Gow JW, Behan WM, Clements GB, Woodall C, Riding M, Behan PO. Enteroviral RNA sequences detected by polymerase chain reaction in muscle of patients with postviral fatigue syndrome. BMJ. 1991; 302:692-6. Google Scholar
    • 7. Buchwald D, Freedman AS, Ablashi DV, Sullivan JL, Caligiuri M, Weinberg DS, et al. A chronic “postinfectious” fatigue syndrome associated with benign lymphoproliferation, B-cell proliferation, and active replication of human herpesvirus-6. J Clin Immunol. 1990; 10: 335-44. Google Scholar
    • 8. Gold D, Bowden R, Sixbey J, Riggs R, Katon WJ, Ashley R, et al. Chronic fatigue. A prospective clinical and virologic study. JAMA. 1990; 264:48-53. Google Scholar
    • 9. Crook WG. The Yeast Connection: A Medical Breakthrough. 3d ed. Jackson, Tennessee: Professional Books; 1983. Google Scholar
    • 10. DeFreitas E, Hilliard B, Cheney PR, Bell DS, Kiggundu E, Sankey D, et al. Retroviral sequences related to human T-lymphotropic virus type II in patients with chronic fatigue immune dysfunction syndrome. Proc Natl Acad Sci USA. 1991; 88:2922-6. Google Scholar
    • 11. Gunn WJ, Connell D, Randal B. Epidemiology of CFS: the Centers for Disease Control study. In: Bock G, Whelan J, eds. Chronic Fatigue Syndrome. CIBA Foundation Symposium 173. Chichester: Wiley; 1993. Google Scholar
    • 12. Holmes GP, Kaplan JE, Gantz NM, Komaroff AL, Schonberger LB, Straus SE, et al. Chronic fatigue syndrome: a working case definition. Ann Intern Med. 1988; 108:387-9. Google Scholar
    • 13. Lal RB, Heneine W, Rudolph DL, Present WB, Hofhienz D, Hartley TM, et al. Synthetic peptide-based immunoassays for distinguishing between human T-cell lymphotropic virus type I and type II infections in seropositive individuals. J Clin Microbiol. 1991; 29:2253-8. Google Scholar
    • 14. Buckner C, Roberts CR, Foung SK, Lipka J, Reyes GR, Hadlock K, et al. Immune responsiveness to the immunodominant envelope epitopes of HTLV-I and HTLV-II in diverse geographic populations. J Infect Dis. 1992; 166:1160-3. Google Scholar
    • 15. Ou CY, Kwok S, Mitchell SW, Mack DH, Sninsky JJ, Krebs JW, et al. DNA amplification for direct detection of HIV-1 in DNA of peripheral blood mononuclear cells. Science. 1988; 239:295-7. Google Scholar
    • 16. Maniatis T, Fritsch EF, Sambrook J. Molecular Cloning: A Laboratory Manual. Cold Spring Harbor, New York: Cold Spring Harbor Laboratory; 1982. Google Scholar
    • 17. Hashinaka K, Nishio C, Hur SJ, Sakiyama F, Tsunasawa S, Yamada M. Multiple species of myeloperoxidase messenger RNAs produced by alternative splicing and differential polyadenylation. Biochemistry. 1988; 27:5906-14. Google Scholar
    • 18. Kwok S, Higuchi R. Avoiding false positive with PCR. Nature. 1989; 339:237-8. Google Scholar
    • 19. Gart J. Point and interval estimation of the common odds ratio in combination of 2 × 2 tables with fixed marginals. Biometrika. 1970; 57:471-5. Google Scholar
    • 20. Cox DR. The Analysis of Binary Data. London: Metheun; 1970. Google Scholar
    • 21. Mehta CR, Patel NR, Gray R. On computing an exact confidence interval for the common odds ratio in several 2 × 2 contingency tables. Journal of the American Statistical Association. 1985; 80:969-73. Google Scholar
    • 22. Lehmann EL. Nonparametrics: Statistical Methods Based on Ranks. San Francisco: Holden-Day, Inc.; 1975. Google Scholar
    • 23. Bell KM, Cookfair D, Bell DS, Reese P, Cooper L. Risk factors associated with chronic fatigue syndrome in a cluster of pediatric cases. Rev Infect Dis. 1991; 13(Suppl 1):S32-8. Google Scholar
    • 24. Gow J, Simpson K, Rethwilm A, Behan WM, Morrison LJ, Cavanaugh H, et al. Search for retrovirus in the chronic fatigue syndrome. J Clin Pathol (In press). Google Scholar
    • 25. Folks TM, Heneine W, Khan AS, Chapman LE, Woods TC, Schonberger LB. Investigation of retroviral involvement in chronic fatigue syndrome. In: Whelan J, ed. Chronic Fatigue Syndrome. CIBA Foundation Symposium 173. Chichester: Wiley:160-75; 1993. Google Scholar
    • 26. Flugel RM, Mahnke C, Geiger A, Komaroff AL. Absence of antibody to human spumaretrovirus in patients with chronic fatigue syndrome. (Letter). Clin Infect Dis. 1992; 14:623-4. Google Scholar
    • 27. Kwok S, Ehrlich G, Poiesz B, Kalish R, Sninsky JJ. Enzymatic amplifications of HTLV-I viral sequences from peripheral blood mononuclear cells and infected tissues. Blood. 1988; 72:1117-23. Google Scholar
    • 28. Lane TJ, Manu P, Matthews D. Depression and somatization in the chronic fatigue syndrome. Am J Med. 1991; 91:335-44. Google Scholar