INTERNATIONAL CFS   CONFERENCE, SYDNEY, AUSTRALIA, 1998
MYCOPLASMAL INFECTIONS IN BLOOD FROM   PATIENTS WITH CHRONIC FATIGUE SYNDROME, FIBROMYALGIA SYNDROME OR GULF WAR   ILLNESS
MarwanNasralla,   Ph.D., JoergHaier, M.D.,   Ph.D. and Garth L. Nicolson, Ph.D.
The   Institute for Molecular Medicine, 15162 Triton Lane, Huntington Beach, CA92649-1041USA
ABSTRACT
Background:Mycoplasmal   infections are associated with several acute and chronic illnesses. Since we   previously found that about one-half of Gulf War Illness (GWI   )patients had mycoplasmal infections, such   as M. fermentans, patients with Chronic   Fatigue Syndrome (CFS) and/or Fibromyalgia Syndrome   (FMS) were examined for system-wide mycoplasmal   infections by examining their blood leukocytes.

Methods:
Patients: Blood samples from 203 patients (148 female,   55 male) diagnosed with CFS or FMS were investigated for Mycoplasmaspp. and M. fermentans   infections using forensic Polymerase Chain Reaction. Clinical characteristics   of CFS/FMS patients and GWI patients were similar. In particular, major signs   and symptoms, such as chronic fatigue, joint/muscle pain, depression, paraesthesia, cognitive, gastrointestinal, skin and   vision problems, were found in all of these diagnoses. PCR Amplification: Genus-specific   primers for mycoplasma were selected from 16S mRNA   sequences. The universal probes GPO 1 and MGSO were used for the detection of   all mycoplasmas and the UNI- probe was used as an   internal probe for confirmation with hybridization. (i)   Specific primers for M. fermentans(SB1:   forward probe, SB2: reverse probe, SB3: internal probe) were selected from   the tuf gene sequence.(ii)

Results:
Using the genus-specific primers positive PCR results were   obtained if the PCR product was 717 base pair in size (or 850 bp for M. fermentans-specific   primers). The results were confirmed by hybridization with the specific   internal 32P-labeled probe. (see Figure 1) In the healthy control group   (n=32) no PCR product was obtained, and hybridization signals were not   observed. The Mycoplasmaspp. sequence was amplified from the peripheral blood   of 144 patients (71.4 %). No specific PCR product could be detected in the 57   negative patients (28.6 %) and a significant difference (p<0.001) was   found between patients and healthy controls. Moreover, the incidence rate was   similar in female and male patients. The incidence (41.5%) of M. fermentans infection was significantly higher in   patients than in healthy controls (p<0.001).
Conclusion: Systemic mycoplasmal infections   can be considered important in causing morbidity in CFS/FMS patients. These   infections can be treated with multiple cycles of antibiotics (doxycycline, ciprofloxacin, azithromycin   or clarithromycin) along with vitamins, minerals   and nutritional supplements that enhance immune responses.
Chronic fatigue is reported by 20% of all   patients seeking medical care.(iii,iv)   Many well-known medical conditions are associated with chronic fatigue(v),   and it is often an important secondary condition. Although chronic fatigue is   associated with many illnesses, CFS and FMS are distinguishable as separate   syndromes based on established clinical criteria (vi, vii). They are   characterized by their complex multi-organ chronic signs and symptoms,   including muscle pain, chronic fitigue, headaches,   memory loss, nausea, gastrointestinal problems, joint pain, vision and breathing problems, among others. Although the   signs and symptoms of CFS and FMS overlap, the distinguishing feature of FMS   is the presence of chronic widespread pain and tenderness. Often included in   this complex clinical picture are increased sensitivities to various   environmental agents and enhanced allergic responses.

CHRONIC INFECTIONS

Many patients with FMS/CFS or Gulf War Illness (GWI) have cognitive,   psychiatric and neurological problems. Since other physical and laboratory   results are not available to find pathogenic agents or other causes, these   conditions are often considered as somatoforensic   disorders. Of course, psychological problems, such as stress can exacerbate   chronic illnesses, but most patients doubt that stress is the cause of their   illness. In addition, in many cases family members of these patients suffer   from similar signs and symptoms. For example, according to one governmental   study, 77% of spouses and a majority of children bom   after the Gulf War now have the signs and symptoms of GWI.(viii)   These facts strongly support the hypothesis of a transmittable disease in at   least some chronic illness patients who may suffer from system-wide or   systemic chronic infections that can penetrate various tissues and organs,   including the central and peripheral nervous systems. When such illnesses   progress, autoimmune-like signs and symptoms can be present, such as MS-,   ALS- or Lupus-like illnesses.

   Recent studies have shown that certain species of mycoplasmas   are associated with human disease, including acute fatal illness seen with
Mycoplasmafermentans   infections.( ix) In addition, M fermentanscan   cause renal and CNS complications in patients with AIDS.(x) M. fermentans(incognitus   strain) was shown in recent studies to be an unusually invasive mycoplasma found within respiratory epithelial cells.(xi)   Other species of mycot)lasmas   are also associated with human illnesses, such as urogenital   infections, arthritis, pneumonia and asthma.(xii)

   Although mycoplasmas can exist in the oral cavity   and gut as normal flora, when they penetrate into the blood and organs they   can cause acute and chronic illnesses. Some species, such as
M. penetrans, M. fermentansand   M. pirum, can enter tissues and cells   resulting in complex systemic signs and symptoms. Mycoplasmas   have also been shown to share a complex relationship with the immune system.   They can have specific or nonspecific stimulatory or suppressive effects on   lymphocytes, as measured by B- and T-cell activation, and they can induce   cytokine secretion.(xiii) Mycoplasmas   are very effective at evading the immune system, and synergism with other   infectious agents has been seen. Recently a possible role for mycoplasmas in the pathogenesis of rheumatoid arthritis   and other chronic arthritides has been   investigated. (xiv, xv) M. fermentans, M. bominis and M. salivarum   have been found in synovial fluids of these   patients, suggesting the possible role of mycoplasmas   in triggering and/or maintenance of inflammatory rheumatic diseases.
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