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Chronic Fatigue Syndrome: Searching for a Microbial Etiology

  • I. W. Fong
Chapter
Part of the Emerging Infectious Diseases of the 21st Century book series (EIDC, volume 1)

Abstract

Chronic fatigue syndrome [CFS] is a symptom complex of unknown cause which is commonly present in the population, and has been labeled as postinfectious neuromyasthenia for many decades. A microbial etiology has been considered for this disorder from the outset of its description as a distinct clinical entity. There is strong evidence that female sex and certain personality traits predispose to this condition. The link with infectious diseases is based on the acute onset of flu-like symptoms, subjective feelings of low grade fever, sore throat, myalgias, arthralgias, or generalized body pain. Various infectious synonyms have been applied to this disorder such as chronic brucellosis, chronic Epstein–Barr virus, and chronic Lyme disease syndromes, but no good evidence to support a causative role has been found. The current understanding of the pathogenesis is discussed and previous investigations to determine an infectious etiology, including studies on coxsackie virus and the murine retrovirus and others.

Keywords

Irritable Bowel Syndrome Chronic Fatigue Syndrome Multiple Chemical Sensitivity Functional Somatic Syndrome Sick Building Syndrome 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    Afari N, Buchwalk D. Chronic fatigue syndrome: a review. Am J Psychiatry. 2003;160:221–36.PubMedGoogle Scholar
  2. 2.
    Henderson DA, Shelokov A. Epidemic neuromyasthenia clinical syndrome. N Engl J Med. 1959;260:757–64, 814–8.PubMedGoogle Scholar
  3. 3.
    Levine PH. Reflections on epidemic neuromyasthenia (chronic fatigue syndrome). Clin Infect Dis. 1994;18 suppl 1:S7–8.Google Scholar
  4. 4.
    Henderson DA. Reflection on epidemic neuromyasthenia (chronic fatigue syndrome). Clin Infect Dis. 1994;18 suppl 1:S3–6.PubMedGoogle Scholar
  5. 5.
    Goldenberg DI, Simms RW, Geiger A, Komaroff AL. High frequency of fibromyalgia in patients with chronic fatigue seen in primary practice. Arthritis Rheum. 1990;33:3812–7.Google Scholar
  6. 6.
    Bell DS, Bell KM, Cheney PR. Primary juvenile fibromyalgia syndrome and chronic fatigue syndrome in adolescents. Clin Infect Dis. 1994;18 suppl 1:S21–3.PubMedGoogle Scholar
  7. 7.
    Holmes GP, Kaplan JE, Gantz NM, et al. Chronic fatigue syndrome: a working case definition. Ann Intern Med. 1998;108:387–9.Google Scholar
  8. 8.
    Fukuda K, Staus A, Hukie I, et al. International Chronic Fatigue Syndrome Study Group. The chronic fatigue syndrome: a comprehensive approach to its definition and study. Ann Intern Med. 1994;121:953–9.PubMedGoogle Scholar
  9. 9.
    Baker R, Shaw E. Diagnosis and management of chronic fatigue syndrome or myalgic encephalomyelitis (or encephalopathy): summary of NICE guidance. BMJ. 2007;335:446–8.PubMedPubMedCentralGoogle Scholar
  10. 10.
    Carruthers BM, van de Sande MI, DeMeirlier KI, et al. Myalgic encephalitis: international consensus criteria. J Intern Med. 2011;270:327–38.PubMedPubMedCentralGoogle Scholar
  11. 11.
    Cairns R, Hotopf M. A systematic review describing the prognosis of chronic fatigue syndrome. Occup Med. 2005;55:20–31.Google Scholar
  12. 12.
    Barsky AJ, Borus JF. Functional somatic syndromes. Ann Intern Med. 1999;130:910–21.PubMedGoogle Scholar
  13. 13.
    Wessley S, Childer T, Hirsch S, et al. Post-infectious fatigue: a prospective cohort study in primary care. Lancet. 1995;345:1333–8.Google Scholar
  14. 14.
    White P, Thomas J, Kangro H, et al. Predictions and association of fatigue and mood disorders that occur after infectious mononucleosis. Lancet. 2001;358:1946–54.PubMedGoogle Scholar
  15. 15.
    Moss-Morris R, Spence M. To ‘lump’ or to ‘split’ the functional somatic syndromes: can infectious and emotional risk factors differentiate between the onset of chronic fatigue syndrome and irritable bowel syndrome? Psychosom Med. 2006;68:463–7.PubMedGoogle Scholar
  16. 16.
    Harvey S, Wadsworth M, Wessely S, et al. Etiology of chronic fatigue syndrome: testing popular hypothesis using a National Birth Cohort Study. Psychosom Med. 2008;70:488–95.PubMedGoogle Scholar
  17. 17.
    Moss-Morris R, Deary V, Castell B. Chronic fatigue syndrome. In: Barnes MP, Good DC, editors. Neurological rehabilitation, vol. 110 (3rd series). Edinburgh: Elsevier; 2013. p. 303–14.Google Scholar
  18. 18.
    Viner R, Hotpf M. Childhood predictors of self-reported chronic fatigue syndrome, myalgic encephalomyelitis in adults: national birth cohort study. BMJ. 2004;329:941–3.PubMedPubMedCentralGoogle Scholar
  19. 19.
    Kato K, Sullivan P, Evengard B, et al. Premorbid predicators of chronic fatigue syndrome. Arch Gen Psychiatry. 2006;63:1267–72.PubMedGoogle Scholar
  20. 20.
    Cho H, Skower A, Cleare A, et al. Chronic fatigue syndrome: an update focusing on phenomenology and pathophysiology. Curr Opin Psychiatry. 2006;19:67–73.PubMedGoogle Scholar
  21. 21.
    Klimas NG, Broderick G, Fletcher MA. Biomarkers for chronic fatigue syndrome. Brain Behav Immun. 2012;26:1202–10.PubMedGoogle Scholar
  22. 22.
    Harbve E, Tjensvoll AB, Vefring HK, Goransson LG, Kvaloy JT, Omdai R. Fatigue in primary Sjorgren’s syndrome—a link to sickness behavior in animals? Brain Behav Immun. 2009;23:1104–8.Google Scholar
  23. 23.
    Graff LA, Vincent N, Walker JR, et al. A population-based study of chronic fatigue syndrome and sleep difficulties in inflammatory bowel disease. Inflamm Bowel Dis. 2011;17:1882–9.PubMedGoogle Scholar
  24. 24.
    Stebbing S, Herbison P, Doyle TC, Treharne GJ, Highton J. A comparison of fatigue correlates in rheumatoid arthritis and osteoarthritis: disparity in association with disability, anxiety and sleep disturbance. Rheumatology (Oxford). 2010;49:361–7.Google Scholar
  25. 25.
    Raison CL, Lin JM, Reeves WC. Association of peripheral inflammatory markers with chronic fatigue in a population-based sample. Brain Behav Immun. 2009;23:327–37.PubMedGoogle Scholar
  26. 26.
    Allin AH, Norestgaard BG. Elevated C-reactive protein in the diagnosis, prognosis, and cause of cancer. Crit Rev Clin Lab Sci. 2011;48:155–70.PubMedGoogle Scholar
  27. 27.
    Broderick G, Fuite J, Kreitz A, Vernon SD, Klimas N, Flectcher MA. A formal analysis of cytokine networks in chronic fatigue syndrome. Brain Behav Immun. 2010;24:1209–174.PubMedPubMedCentralGoogle Scholar
  28. 28.
    Flecther MA, Zeng XR, Maher K, et al. Biomarkers in chronic fatigue syndrome: evaluation of natural killer cells function and dipeptide peptidase 1V/CD26. PLoS One. 2010;5:e10817.Google Scholar
  29. 29.
    Brenu EW, van Driel ML, Staines DR, et al. Immunological abnormalities as potential biomarkers in chronic fatigue/myalgic encephalomyelitis. J Transl Med. 2011;28:8–90.Google Scholar
  30. 30.
    Whistler T, Fletcher MA, Lonergan W, et al. Impaired immune function in Gulf War Illness. BMC Med Genomics. 2009;2:12.PubMedPubMedCentralGoogle Scholar
  31. 31.
    Fletcher MA, Rosenthal M, Antoni M, et al. Plasma neuropeptide Y: a biomarker for symptom severity in chronic fatigue syndrome. Behav Brain Funct. 2010;6:76.PubMedPubMedCentralGoogle Scholar
  32. 32.
    Light AR, White AT, Hughes RW, Light KC. Moderate exercise increases expression for sensory adrenergic, and immune genes in chronic fatigue syndrome but not in normal subjects. J Pain. 2009;10:1099–112.PubMedPubMedCentralGoogle Scholar
  33. 33.
    Light AR, Bateman L, Jo D, Hughen RW, Vanhaitsma TA, White AT, Light KC. Gene expression alterations at baseline and following moderate exercise in patients with chronic fatigue syndrome and fibromyalgia syndrome. J Intern Med. 2012;271:64–81.PubMedPubMedCentralGoogle Scholar
  34. 34.
    Papadopoulas AS, Cleare AH. Hypothalamic-pituitary-adrenal axis dysfunction in chronic fatigue syndrome. Nat Rev Endocrinol. 2011;8:22–3.Google Scholar
  35. 35.
    Fernandez-de-Las-Penas C, Cantarero-Villanueva I, Fetrnandez-Lao C, et al. Influence of catechol-o-methyl transferase genotype (Val158Met) on endocrine, sympathetic nervous and mucosal immune systems in breast cancer survivors. Breast. 2012;21:199–203.PubMedGoogle Scholar
  36. 36.
    Lattie E, Antoni MH, Fletcher MA, et al. Stress management skills, neuroimmune process and fatigue levels in persons with chronic fatigue syndrome. Brain Behav Immun. 2012;26:849–58.PubMedPubMedCentralGoogle Scholar
  37. 37.
    Rajeevan MS, Smith AK, Dimulescu I, Unger ER, Vernon SD, Heim C, Reeves WC. Glucocorticoid receptor polymorphisms and haplotypes associated with chronic fatigue syndrome. Genes Brain Behav. 2007;6:67–76.Google Scholar
  38. 38.
    Schutzer SE, Angel TE, Liu T, et al. Distinct cerebrospinal fluid proteomes differentiate post-treatment Lyme disease from chronic fatigue syndrome. PLoS One. 2011;6(2):e17287.PubMedPubMedCentralGoogle Scholar
  39. 39.
    Baraniuk JB, Casadro B, Maibac H, Clauw DH, Pannell LK, Hess SA. A chronic fatigue syndrome—related proteome in human cerebrospinal fluid. BMC Neurol. 2005;5:22.PubMedPubMedCentralGoogle Scholar
  40. 40.
    Murrough JW, Mao X, Collins KA, et al. Increased ventricular lactate in chronic fatigue syndrome measured by IH MRS imaging at 3.0T. 11: comparison with major depressive disorder. NMR Biomed. 2010;23:643–50.PubMedGoogle Scholar
  41. 41.
    Mayhill S, Booth NE, McLaren-Howard J. Chronic fatigue syndrome and mitochondrial dysfunction. Int J Clin Exp Med. 2009;2:1–16.Google Scholar
  42. 42.
    Kerr JR, Pretty R, Burke B, et al. Gene expression subtypes in patients with chronic fatigue syndrome/myalgic encephalomyelitis. J Infect Dis. 2008;197:1171–84.PubMedGoogle Scholar
  43. 43.
    Frampton D, Kerr J, Harrison TJ, Kellam P. Assessment of a 44 gene classifier for the evaluation of chronic fatigue syndrome from peripheral blood mononuclear cell gene expression. PLoS One. 2011;6:e16872.PubMedPubMedCentralGoogle Scholar
  44. 44.
    Brynes A, Jacks A, Dahlam-Wright K, Evengard B, Wright FA, Pedersen NL, Sullivan PF. Gene expression in peripheral blood leukocytes in monozygotic twins discordant for chronic fatigue syndrome; no evidence of a biomarker. PLoS One. 2009;4:e5805.Google Scholar
  45. 45.
    White AT, Light AR, Hugen RW, Vanhaitsma TA, Light KC. Difference in metabolite-detecting, adrenergic and immune gene expression after moderate exercise in patients with multiple sclerosis and healthy controls. Psychosom Med. 2012;74:46–54.PubMedPubMedCentralGoogle Scholar
  46. 46.
    Nijs J, Meeus M, Van Oosterwijck J, Ickmans K, Moorkens G, Hans G, De Clerck LS. In the mind or in the brain? Scientific evidence for central sensitization in chronic fatigue syndrome. Eur J Clin Invest. 2012;42:203–12.PubMedGoogle Scholar
  47. 47.
    Meeus M, Nijs J, Van de Wauwer N, Toeback L, Truijens S. Diffuse noxious inhibitory control is delayed in chronic fatigue syndrome: an experimental study. Pain. 2008;139:439–48.PubMedGoogle Scholar
  48. 48.
    Meeus M, Nijs J. Central sensitization: a biopsychosocial explanation for chronic widespread pain in patients with fibromyalgia and chronic fatigue syndrome. Clin Rheumatol. 2007;26:465–73.PubMedPubMedCentralGoogle Scholar
  49. 49.
    Seifert F, Maihofner C. Central mechanisms of experimental and chronic neuropathic pain: findings from functional imaging studies. Cell Mol Life Sci. 2009;66:375–90.PubMedGoogle Scholar
  50. 50.
    Nielsen LA, Henriksson KG. Pathophysiological mechanisms in chronic musculoskeletal pain (fibromyalgia): the role of central and peripheral sensitization pain disinhibition. Best Pract Res Clin Rheumatol. 2007;21:465–80.PubMedGoogle Scholar
  51. 51.
    Koltyin KF, Arbogast RW. Perception of pain after resistance exercise. Br J Sports Med. 1998;32:20–4.Google Scholar
  52. 52.
    Meeus M, Roussel N, Truijens S, Nijs J. Reduced pressure pain thresholds in response to exercise in chronic fatigue syndrome but not in chronic low back pain: an experimental study. J Rehabil Med. 2010;42:884–90.PubMedGoogle Scholar
  53. 53.
    Van Oosterwijck J, Nijs J, Meeus M, et al. Pain inhibition and post-exertional malaise in myalgic encephalomyelitis/chronic fatigue syndrome: an experimental study. J Intern Med. 2010;268:265–76.PubMedGoogle Scholar
  54. 54.
    Yamampto S, Ourchi Y, Onoe H, et al. Reduction of serontonin transporters of patients with chronic fatigue syndrome. Neuroreport. 2004;15:2571–4.Google Scholar
  55. 55.
    Evengard B, Nibson CG, Lindh G, et al. Chronic fatigue syndrome differs from fibromyalgia. No evidence for elevated substance P levels in cerebrospinal fluid of patients with chronic fatigue syndrome. Pain. 1998;78:153–5.PubMedGoogle Scholar
  56. 56.
    Jones JF, Ray CG, Minnich LL, Hicks MJ, Kibler R, Lucas DO. Evidence for active Epstein-Barr virus infection in patients with persistent, unexplained illness: elevated anti-early antigen antibodies. Ann Intern Med. 1985;102:1–7.PubMedGoogle Scholar
  57. 57.
    Straus SE, Tosato G, Armstrong G, et al. Persisting illness and fatigue in adults with evidence of Epstein-Barr virus infection. Ann Intern Med. 1985;102:7–16.PubMedGoogle Scholar
  58. 58.
    Horwitz CA, Henle W, Henle G, Rudnick H, Latts E. Long-term serological follow-up of patients for Epstein-Barr virus after recovery from infectious mononucleosis. J Infect Dis. 1985;151:1150–3.PubMedGoogle Scholar
  59. 59.
    Straus SE. The chronic mononucleosis syndrome. J Infect Dis. 1988;157:405–12.PubMedGoogle Scholar
  60. 60.
    Schooley RT, Carey RW, Miller G, et al. Chronic Epstein-Barr virus infection associated with fever and interstitial pneumonitits. Clinical and serological features and response to antiviral chemotherapy. Ann Intern Med. 1986;104:636–43.PubMedGoogle Scholar
  61. 61.
    Gotoch K, Ito Y, Shibata-Wanatabe Y, et al. Clinical and virological characteristics of 15 patients with chronic active Epstein-Barr virus infection treated with hematopoiectic stem cell transplantation. Clin Infect Dis. 2008;46:1525–34.Google Scholar
  62. 62.
    Moss-Morris R, Spence MJ, Hou R. The pathway from glandular fever to chronic fatigue syndrome; can the cognitive behavioral model provide a map? Psychol Med. 2011;41:1099–107.PubMedGoogle Scholar
  63. 63.
    Huang Y, Katz BZ, Mears C, Kielhofner GW, Taylor R. Post-infectious fatigue in adolescents and physical activity. Arch Pediatr Adolesc Med. 2010;164:803–9.PubMedPubMedCentralGoogle Scholar
  64. 64.
    Katz BZ, Shireishi Y, Mers CJ, Binns J, Taylor R. Chronic fatigue syndrome after infectious mononucleosis in adolescents. Pediatrics. 2009;124:189–93.PubMedPubMedCentralGoogle Scholar
  65. 65.
    Hickie I, Davenport T, Wakefield D, et al. Post-infective and chronic fatigue syndrome precipitated by viral and non-viral pathogens: prospective cohort study. BMJ. 2006;333:575.PubMedPubMedCentralGoogle Scholar
  66. 66.
    Naess H, Sundal E, Myhr KM, Nyland HI. Post-infectious and chronic fatigue syndromes: clinical experience from a tertiary referral center in Norway. In Vivo. 2010;24:185–8.PubMedGoogle Scholar
  67. 67.
    Boshwald D, Ashley RL, Peralman T, Kith P, Komaroff AL. Viral serologies in patients with chronic fatigue and chronic fatigue syndrome. J Med Virol. 1994;50:25–30.Google Scholar
  68. 68.
    Galbraith DN, Nairn C, Clements GB. Evidence for enteroviral persistence in humans. J Gen Virol. 1997;78:307–12.PubMedGoogle Scholar
  69. 69.
    Yousef GE, Mann GF, Smith DF, et al. Chronic enterovirus infection in patients with post-viral fatigue syndrome. Lancet. 1998;1:146–7.Google Scholar
  70. 70.
    Landay AL, Jessop C, Lennette ET, et al. Chronic fatigue syndrome: clinical condition associated with immune activation. Lancet. 1991;338:707–12.PubMedGoogle Scholar
  71. 71.
    Miller NA, Carmichael HA, Calder BD, et al. Antibody to coxsackie B virus in diagnosing post viral syndrome. BMJ. 1991;302:140–3.PubMedPubMedCentralGoogle Scholar
  72. 72.
    Gow JW, Behm WMH, Clements GB, et al. Enteroviral RNA sequences detected by polymerase chain reaction in muscle of patients with post-viral fatigue syndrome. BMJ. 1991;302:692–6.PubMedPubMedCentralGoogle Scholar
  73. 73.
    Cunnigham L, Bowles NE, Lane RJM, et al. Persistence of enteroviral RNA in chronic fatigue syndrome is associated with abnormal production of equal amounts of positive and negative strand of enteroviral RNA. J Gen Virol. 1990;71:1399–402.Google Scholar
  74. 74.
    Lane RJ, Soteriou BA, Zhang H, et al. Enterovirus related metabolic myopathy: a postviral fatigue syndrome. J Neurol Neurosurg Psychiatry. 2003;74:1382–6.PubMedPubMedCentralGoogle Scholar
  75. 75.
    Gow JW, Behas WMH, Simpson K, et al. Studies on enterovirus in patients with chronic fatigue syndrome. Clin Infect Dis. 1994;18(suppl):S126–9.PubMedGoogle Scholar
  76. 76.
    Yousef GE, Isenberg DA, Mowbray JF. Detection of enteroviral-specific RNA sequence in muscle biopsy specimens from patients with adult-onset myositis. Ann Rheum Dis. 1990;49:492–6.Google Scholar
  77. 77.
    Douche-Aourik F, Berlier W, Feusson L, et al. Detection of enteroviruse in human skeletal muscle from patients from inflammatory disease, fibromyalgia, and healthy subjects. J Med Virol. 1995;76:170–7.Google Scholar
  78. 78.
    Galbraith DN, Nairn C, Clements GB. Phylogenetic analysis of short enteroviral sequences from patients with chronic fatigue syndrome. J Gen Virol. 1995;76:1701–7.PubMedGoogle Scholar
  79. 79.
    Mc Ardle A, Mc Ardle F, Jackson MJ, et al. Investigations by polymerase chain reaction of enterviral infection in patients with chronic fatigue syndrome. Clin Sci. 1996;90:295–300.Google Scholar
  80. 80.
    Lindh G, Samuelson A, Hedlund KO, et al. No finding of enteroviruses in Swedish patients chronic fatigue syndrome. Scand J Infect Dis. 1996;28:305–7.PubMedGoogle Scholar
  81. 81.
    Chin JKS. The role of enterovirus in chronic fatigue syndrome. J Clin Pathol. 2005;58:1126–32.Google Scholar
  82. 82.
    Chin J, Chia A. Ribavirin and interferon–α for the treatment of patients with chronic fatigue syndrome associated with coxsackievirus B infection: a preliminary observation. J Appl Res. 2004;4:286–92.Google Scholar
  83. 83.
    Kerr JR, Gough J, Selwyn C, et al. Antibody to parvovirus B19 nonstructural protein is associated with chronic fatigue syndrome/myalgic encephalomyelitis. J Gen Virol. 2000;91:893–7.Google Scholar
  84. 84.
    Seishema M, Mizutami Y, Shibuya Y, Arakawa C. Chronic fatigue syndrome after human parvovirus B 19 infection without persistent viremia. Dermatology. 2008;216:341–6.Google Scholar
  85. 85.
    Lerner AM, Beqaj SH, Deeter RGT. IgM serum antibodies to human cytomegalovirus non-structural gene product p52 and CM2 (UL44 and UL57) are uniquely present in a subset of patients with chronic fatigue syndrome. In Vivo. 2002;16:153–9.PubMedGoogle Scholar
  86. 86.
    Beqal SH, Lerner AM, Fitzgeral JT. Immunoassay with cytomegalovirus early antigens from gene products p52 and CM2 (UL44 and UL55) detects active infection in patients with chronic fatigue syndrome. J Clin Pathol. 2008;61:623–6.Google Scholar
  87. 87.
    Krug LT, Teo CG, Tanaka Taya K, Inoue N. Newly identified human herpesviruses: HHv-6, HHV-7, and HHV-8. In: Fong IW, Albek K, editors. New and evolving infections of the 21st century. New York: Springer; 2007. p. 195–276.Google Scholar
  88. 88.
    Ablashi DV, Eastran HB, Owen CB, et al. Frequent HHV-6 reactivation in multiple sclerosis (MS) and chronic fatigue syndrome (CFS) patients. J Clin Virol. 2000;16:179–91.PubMedGoogle Scholar
  89. 89.
    Buchwald D, Cheney PR, Peterson DL, et al. A chronic illness characterized by fatigue, neurologic and immunologic disorders, and active herpesvirus type-6 infections. Ann Intern Med. 1992;116:103–13.PubMedGoogle Scholar
  90. 90.
    Zorzenon M, Rukh G, Botta GA, Colle R, Barsanti LA, Ceccherini-Nelli L. Active HHV-6 infection in chronic fatigue syndrome from Italy: new data. J Chronic Fatigue Syndrome. 1996;2:3–12.Google Scholar
  91. 91.
    Komaroff AL. Is human herpesvirus-6 trigger for chronic fatigue syndrome? J Clin Virol. 2006;37 suppl 1:S39–46.PubMedGoogle Scholar
  92. 92.
    Ablashi DV, Berneman ZN, Williams M, et al. Ampligen inhibits human herpesvirus-6 in vitro. In Vivo. 1994;8:587–92.PubMedGoogle Scholar
  93. 93.
    Strayer DR, Cater WA, Brodsky I, et al. A controlled clinical trial with a specifically confined RNA drug, poly (I) poly (C12U), in patients with chronic fatigue syndrome. Clin Infect Dis. 1994;18 suppl 1:S88–95.PubMedGoogle Scholar
  94. 94.
    Kogelnik AM, Loomis K, Hoegh-Petersen M, Rosso F, Hischier C, Montoya JG. Use of valganciclovir in patients with elevated antibody titers against human herpesvirus (HHV-6) and Epstein-Barr virus (EBV) who were experiencing central nervous system dysfunction including long-standing fatigue. J Clin Virol. 2006;37 suppl 1:S33–8.PubMedGoogle Scholar
  95. 95.
    Bansal AS, Bradley AS, Bishop KN, Kiani-Alickhan S, Ford B. Chronic fatigue syndrome, the immune system and viral infection. Brain Behav Immun. 2012;26:24–31.PubMedGoogle Scholar
  96. 96.
    Learner AM, Beqaj S, Fitzgerald JT, Gill K, Gill C, Edington J. Subset directed antiviral treatment of 142 herpes virus patients with chronic fatigue syndrome. Virus Adapt Treat. 2010;2:47–57.Google Scholar
  97. 97.
    Lombardi VC, Ruscetti FW, Das Gupta J et al. Detection of an infectious retrovirus, XMRV in blood cells of patients with chronic fatigue syndrome. Sci. 2009;326:585–9.Google Scholar
  98. 98.
    Knox K, Carrigan D, Simmons G et al. No evidence of murine-like gamma retroviruses in CFS patients previously identified as XMRV-infected. Sci. 2011;333:94–7.Google Scholar
  99. 99.
    Galbraith S, Cameron B, Li H, Lau D, Vollmer-Conna U, Lloyd AR. Peripheral blood gene expression post infection fatigue syndrome following three different triggering infections. J Infect Dis. 2011;63:1632–40.Google Scholar
  100. 100.
    Zhang L, Gough J, Christmas D, et al. Microbial infections in eight genomic subtypes of chronic fatigue syndrome/myalgic encephalomyelitis. J Clin Pathol. 2010;63:156–64.PubMedPubMedCentralGoogle Scholar
  101. 101.
    Maes M. An intriguing and hitherto unexplained co-occurrence: depression and chronic fatigue syndrome are manifestations of shared inflammatory, oxidative and nitrosative (10 & NS) pathways. Progress neuro-physchopharm. Biol Psychiatry. 2011;35:784–94.Google Scholar
  102. 102.
    Cameron B, Flammand L, Juwanna H, et al. Serological and virological investigation of the role of the herpesviruses EBV, CMV and HHV-6 in post infective fatigue syndrome. J Med Virol. 2010;82:1644–8.Google Scholar
  103. 103.
    Morch K, Hanevik K, Rivenes AC, et al. Chronic fatigue syndrome 5 years after giardiasis: differential diagnosis, characteristics and natural course. BMC Gastroenterol. 2013;13:28.PubMedPubMedCentralGoogle Scholar
  104. 104.
    Hooper PL, Hightower LE, Hooper P. Loss of stress response as a consequence of viral infection: implications for disease and therapy. Cell Stress Chaperones. 2012;17:647–53.PubMedPubMedCentralGoogle Scholar
  105. 105.
    Arnett SV, Alleva LM, Korossy-Horwood R, Clark IA. Chronic fatigue syndrome a neuoimmunological model. Med Hypotheses. 2011;77:77–83.PubMedGoogle Scholar
  106. 106.
    Chen R, Moriya J, Yamakawa J, et al. Brain atrophy in a murine model of chronic fatigue syndrome and beneficial effect of Hochu-ekki-to (TJ-41). Neurochem Res. 2008;33:1754–67.Google Scholar
  107. 107.
    Moriya J, Chen R, Yamakawa J, Sasaki K, Ishigalli Y, Takahashi T. Resveratrol improves hippocampal atrophy in chronic fatigue mice by enhancing neurogenesis and inhibit apoptosis of granular cells. Biol Pharm Bull. 2011;34:354–9.PubMedGoogle Scholar
  108. 108.
    Yoshiuchi K, Farrkas J, Natelson BH. Patients with chronic fatigue syndrome have reduced absolute cortical blood flow. Clin Physiol Funct Imaging. 2006;26:83–6.PubMedGoogle Scholar
  109. 109.
    de Lange FP, Kalkman JS, Bleijenberg G, et al. Gray matter volume reduction in the chronic fatigue syndrome. Neuroimage. 2005;26:777–81.PubMedGoogle Scholar
  110. 110.
    Okada T, Tanaka M, Kurtasume H, et al. Mechanisms underlying fatigue: a voxel based morphometric study of chronic fatigue syndrome. BMC Neurol. 2004;4:14.Google Scholar
  111. 111.
    Cook DB, O’Connor PJ, Lange G. Functional neuroimaging correlates of mental fatigue induced cognition among chronic fatigue syndrome patients and controls. Neuroimage. 2007;36:108–22.Google Scholar
  112. 112.
    Singh PK, Chopra K, Kuhad A, Kaur IP. Role of Lactobacillus acidophilus loaded floating beads in chronic fatigue syndrome: behavioral and biochemical evidences. Neurogastroenterol Motil. 2012;24:366-e170.PubMedGoogle Scholar
  113. 113.
    Sheedy RJ, Wettenhall REH, Scanlon D, et al. Increased d-lactic acid intestinal bacteria in patients with chronic fatigue syndrome. Vivo. 2009;23:621–8.Google Scholar
  114. 114.
    Hamilton WT, Gallagher AM, Thomas JM, White PD. Risk markers for both chronic fatigue syndrome and irritable bowel syndrome: a prospective case-controls study in primary care. Psychological Med. 2009;39:1913–21.Google Scholar
  115. 115.
    Jason LA, Benton MC, Valentine C, Johnson A, Torreo-Harding S. The economic impact of ME/CFS: individual and societal costs. Dyn Med. 2008;7:6.PubMedPubMedCentralGoogle Scholar
  116. 116.
    Castell B, Kazantzis N, Moss-Morris R. Cognitive behavior therapy and graded exercise for chronic fatigue syndrome: a meta-analysis. Clin Psychol Sci Pract. 2011;18:311–24.Google Scholar

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© Springer Science+Business Media New York 2014

Authors and Affiliations

  • I. W. Fong
    • 1
  1. 1.University of TorontoTorontoCanada

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