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 |
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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). |
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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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