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Mycoplasma blood infection in chronic fatigue and fibromyalgia syndromes


Chronic fatigue syndrome (CFS) and fibromyalgia syndrome (FMS) are characterised by a lack of consistent laboratory and clinical abnormalities. Although they are distinguishable as separate syndromes based on established criteria, a great number of patients are diagnosed with both. In studies using polymerase chain reaction methods, mycoplasma blood infection has been detected in about 50% of patients with CFS and/or FMS, including patients with Gulf War illnesses and symptoms that overlap with one or both syndromes. Such infection is detected in only about 10% of healthy individuals, significantly less than in patients. Most patients with CFS/FMS who have mycoplasma infection appear to recover and reach their pre-illness state after long-term antibiotic therapy with doxycycline, and the infection can not be detected after recovery. By means of causation and therapy, mycoplasma blood infection may permit a further subclassification of CFS and FMS. It is not clear whether mycoplasmas are associated with CFS/FMS as causal agents, cofactors, or opportunistic infections in patients with immune disturbances. Whether mycoplasma infection can be detected in about 50% of all patient populations with CFS and/or FMS is yet to be determined.

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  1. 1.

    Aaron LA, Buchwald D (2001) A review of the evidence for overlap among unexplained clinical conditions. Ann Intern Med 134:868–881

    CAS  PubMed  Google Scholar 

  2. 2.

    White KP, Speechley M, Harth M, Østbye T (2000) Co-existence of chronic fatigue syndrome with fibromyalgia syndrome in the general population. Scand J Rheumatol 29:44–51

    Article  CAS  PubMed  Google Scholar 

  3. 3.

    Nicolson GL, Nicolson NL (1998) Gulf War illnesses: complex medical, scientific and political paradox. Med Confl Surviv 14:156–165

    CAS  PubMed  Google Scholar 

  4. 4.

    Escalante A, Fischbach M (1998) Musculoskeletal manifestations, pain, and quality of life in Persian Gulf War veterans referred for rheumatologic evaluation. J Rheumatol 25:2228–2235

    CAS  PubMed  Google Scholar 

  5. 5.

    Grady EP, Carpenter MT, Koenig CD, Older SA, Battafarano DF (1998) Rheumatic findings in Gulf War veterans. Arch Intern Med 158:367–371

    Article  CAS  PubMed  Google Scholar 

  6. 6.

    Bourdette DN, McCauley LA, Barkhuizen A, Johnston W, Wynn M, Joos SK, Storzbach D, Shuell T, Sticker D (2001) Symptom factor analysis, clinical findings, and functional status in a population-based case control study of Gulf War unexplained illness. J Occup Environ Med 43:1026–1040

    CAS  PubMed  Google Scholar 

  7. 7.

    Hotopf M, David A, Hull L, Ismail K, Unwin C, Wessely S (2000) Role of vaccinations as risk factors for ill health in veterans of the Gulf war: cross sectional study. BMJ 320:1363–1367

    CAS  PubMed  Google Scholar 

  8. 8.

    Baseman JB, Tully JG (1997) Mycoplasmas: sophisticated, reemerging, and burdened by their notoriety. Emerg Infect Dis 3:21–32

    CAS  PubMed  Google Scholar 

  9. 9.

    Razin S, Yogev D, Naot Y (1998) Molecular biology and pathogenicity of mycoplasmas. Microbiol Mol Biol Rev 62:1094–1156

    CAS  PubMed  Google Scholar 

  10. 10.

    Dallo SF, Baseman JB (2000) Intracellular DNA replication and long-term survival of pathogenic mycoplasmas. Microb Pathog 29:301–309

    Article  CAS  PubMed  Google Scholar 

  11. 11.

    Choppa PC, Vojdani A, Tagle C, Andrin R, Magtoto L (1998) Multiplex PCR for the detection of mycoplasma fermentans, m. hominis and m. penetrans in cell cultures and blood samples of patients with chronic fatigue syndrome. Mol Cell Probes 12:301–308

    Article  CAS  PubMed  Google Scholar 

  12. 12.

    Vojdani A, Choppa PC, Tagle C, Andrin R, Samimi B, Lapp CW (1998) Detection of mycoplasma genus and mycoplasma fermentans by PCR in patients with chronic fatigue syndrome. FEMS Immunol Med Microbiol 22:355–365

    Article  CAS  PubMed  Google Scholar 

  13. 13.

    Vojdani A, Franco AR (1999) Multiplex PCR for the detection of mycoplasma fermentans, m. hominis, and m. penetrans in patients with chronic fatigue syndrome, fibromyalgia, rheumatoid arthritis, and Gulf War syndrome. J Chronic Fatigue Syndr vol T (no 3/4):187–197

  14. 14.

    Nicolson GL, Nicolson NL (1996) Diagnosis and treatment of mycoplasmal infections in Persian Gulf War illness-CFIDS patients. Int J Occup Med Immunol Tox 5:69–78

    Google Scholar 

  15. 15.

    Nicolson GL, Nicolson NL, Nasralla M (1998) Mycoplasmal infections and fibromyalgia/chronic fatigue illness (Gulf War illness) associated with deployment to Operation Desert Storm. Int J Med 1:80–92

    Google Scholar 

  16. 16.

    Nicolson GL, Nasralla M, Haier J, Nicolson NL (1998) Diagnosis and treatment of chronic mycoplasmal infections in fibromyalgia and chronic fatigue syndromes: relationship to Gulf War illness. Biomed Therapy 16:266–271

    Google Scholar 

  17. 17.

    Nasralla M, Haier J, Nicolson GL (1999) Multiple mycoplasmal infections detected in blood of patients with chronic fatigue syndrome and/or fibromyalgia syndrome. Eur J Clin Microbiol Infect Dis 18:859–865

    Article  CAS  PubMed  Google Scholar 

  18. 18.

    Nasralla MY, Haier J, Nicolson NL, Nicolson GL (2000) Examination of mycoplasmas in blood of 565 chronic illness patients by polymerase chain reaction. Int J Med Biol Environ 28:15–23

    Google Scholar 

  19. 19.

    Nijs J, Nicolson GL, De Becker P, Coomans D, De Meirleir K (2002) High prevalence of mycoplasma infections among European chronic fatigue syndrome patients: examination of four mycoplasma species in blood of chronic fatigue syndrome patients. FEMS Immunol Med Microbiol 34:209–214

    Article  CAS  PubMed  Google Scholar 

  20. 20.

    Gray GC, Kaiser KS, Hawksworth AW, Watson HL (1999) No serologic evidence of an association found between Gulf War service and mycoplasma fermentans infection. Am J Trop Med Hyg 60:752–757

    CAS  PubMed  Google Scholar 

  21. 21.

    Lo SC, Levin L, Ribas J, Chung R, Wang RY, Wear D, Shih JW (2000) Lack of serological evidence for mycoplasma fermentans infection in army Gulf War veterans: a large scale case-control study. Epidemiol Infect 125:609–616

    Article  CAS  PubMed  Google Scholar 

  22. 22.

    Blanchard A, Montagnier L (1994) AIDS-associated mycoplasmas. Annu Rev Microbiol 48:687–712

    Article  CAS  PubMed  Google Scholar 

  23. 23.

    Grau O, Slizewicz B, Tuppin P, Launay V, Bourgeois E, Sagot N, Moynier M, Lafeuillade A, Bachelez H, Clauvel JP (1995) Association of mycoplasma penetrans with human immunodeficiency virus infection. J Infect Dis 172:672–681

    CAS  PubMed  Google Scholar 

  24. 24.

    Patarca R, Mark T, Fletcher MA, Klimas N (2000) Review: immunology of chronic fatigue syndrome. J Chronic Fatigue Syndr 6:69–107

    Google Scholar 

  25. 25.

    Patarca R (2001) Cytokines and chronic fatigue syndrome. Ann N Y Acad Sci 933:185–200

    CAS  PubMed  Google Scholar 

  26. 26.

    Natelson BH, Haghighi MH, Ponzio NM (2002) Evidence for the presence of immune dysfunction in chronic fatigue syndrome. Clin Diag Lab Immunol 9:747–752

    Article  CAS  Google Scholar 

  27. 27.

    Kaufmann A, Muhlradt PF, Gemsa D, Sprenger H (1999) Induction of cytokines and chemokines in human monocytes by mycoplasma fermentans-derived lipoprotein MALP-2. Infect Immun 67:6303–6308

    CAS  PubMed  Google Scholar 

  28. 28.

    Kikkawa S, Matsumoto M, Sasaki T, Nishiguchi M, Tanaka K, Toyoshima K, Seya T (2000) Complement activation in mycoplasma fermentans-induced mycoplasma clearance from infected cells: probing of the organism with monoclonal antibodies against M161Ag. Infect Immun 68:1672–1680

    Article  CAS  PubMed  Google Scholar 

  29. 29.

    Seya T, Matsumoto M (2002) A lipoprotein family from mycoplasma fermentans confers host immune activation through toll-like receptor 2. Int J Biochem Cell Biol 34:901–906

    Article  CAS  PubMed  Google Scholar 

  30. 30.

    Into T, Nodasaka Y, Hasebe A, Okuzawa T, Nakamura J, Ohata N, Shibata K (2002) Mycoplasmal lipoproteins induce toll-like receptor 2- and caspases-mediated cell death in lymphocytes and monocytes. Microbiol Immunol 46:265–276

    CAS  PubMed  Google Scholar 

  31. 31.

    Brightbill HD, Libraty DH, Krutzik SR, Yang RB, Belisle JT, Bleharski JR, Maitland M, Norgard MV, Plevy SE, Smale ST, Brennan PJ, Bloom BR, Godowski PJ, Modlin RL (1999) Host defense mechanisms triggered by microbial lipoproteins through toll-like receptors. Science 285:732–736

    Article  CAS  PubMed  Google Scholar 

  32. 32.

    Bernet C, Garret M, Barbeyrac BD, Bebear C, Bonnet J (1989) Detection of mycoplasma pneumoniae by using the polymerase chain reaction. J Clin Microbiol 27:2492–2496

    CAS  PubMed  Google Scholar 

  33. 33.

    Taylor-Robinson D, Bebear C (1997) Antibiotic susceptibilities of mycoplasmas and treatment of mycoplasmal infections. J Antimicrob Chemother 40:622–630

    Article  CAS  PubMed  Google Scholar 

  34. 34.

    Collins JF, Donta ST, Engel CC, Baseman JB, Dever LL, Taylor T, Boardman KD, Martin SE, Wiseman AL, Feussner JR (2002) The antibiotic treatment trial of Gulf War veterans' illnesses: issues, design, screening, and baseline characteristics. Control Clin Trials 23:333–353

    Article  CAS  PubMed  Google Scholar 

  35. 35.

    Buskila D, Shnaider A, Neumann L, Zilberman D, Hilzenrat N, Sikuler E (1997) Fibromyalgia in hepatitis C virus infection: another infectious disease relationship. Arch Intern Med 157:2497–2500

    CAS  PubMed  Google Scholar 

  36. 36.

    White PD, Thomas JM, Amess J, Crawford DH, Grover SA, Kangro HO, Clare AW (1998) Incidence, risk and prognosis of acute and chronic fatigue syndromes and psychiatric disorders after glandular fever. Br J Psychiatry 173:475–481

    CAS  PubMed  Google Scholar 

  37. 37.

    Rea T, Russo J, Katon W, Ashley RL, Buchwald D (1999) A prospective study of tender points and fibromyalgia during and after an acute viral infection. Arch Intern Med 159:865–870

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Gerhard K. M. Endresen.

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Endresen, G.K.M. Mycoplasma blood infection in chronic fatigue and fibromyalgia syndromes. Rheumatol Int 23, 211–215 (2003).

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  • Chronic fatigue syndrome
  • Fibromyalgia
  • Mycoplasma infection
  • Persian Gulf syndrome
  • Polymerase chain reaction