More on Mycoplasmas

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International CFS Conference, Sydney, Australia, 1998

Mycoplasmal Infections in Blood from Patients with Chronic Fatigue Syndrome, Fibromyalgia Syndrome or Gulf War Illness

Marwan Nasralla, Ph.D., Joerg Haier, M.D., Ph.D. and Garth L. Nicolson, Ph.D.The Institute for Molecular Medicine, 15162 Triton Lane, Huntington Beach, CA 92649-1041 USA

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 Mycoplasma spp. 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. Specific primers for M. fermentans (SB1: forward probe, SB2: reverse probe, SB3: internal probe) were selected from the tuf gene sequence.

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 Mycoplasma spp. 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., Many well-known medical conditions are associated with chronic fatigue, 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 , They are characterized by their complex multi-organ chronic signs and symptoms, including muscle pain, chronic fatigue, 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 born after the Gulf War now have the signs and symptoms of GWI. 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 Mycoplasma fermentans infections. In addition, M. fermentans can cause renal and CNS complications in patients with AIDS. M. fermentans (incognitus strain) was shown in recent studies to be an unusually invasive mycoplasma found within respiratory epithelial cells. Other species of mycoplasmas are also associated with human illnesses, such as urogenital infections, arthritis, pneumonia and asthma.

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. fermentans and 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. 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., M. fermentans, M. hominis 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.

Mycoplasmal infections in CFS/FMS/GWI

In a majority of FMS, CFS and GWI patients examined we and others, principally Dr. Daryl See of the University of California College of Medicine, Irvine, are finding strong evidence for mycoplasmal blood infections that can explain much if not most of their chronic signs and symptoms. In our studies on GWI we have found mycoplasmal infections in about one-half of approximately 200 patients, and these patients were found to have principally one pathogenic species, M. fermentans. Moreover, in over one-half of the 200 civilians with CFS, FMS or arthritis that we have examined, we are finding a variety of pathogenic mycoplasma species in the leukocyte fraction of blood samples. The test that we use to identify mycoplasmal infections, polymerase chain reaction, is very sensitive and highly specific. This test is a dramatic improvement on the relatively insensitive serum antibody tests that are routinely used to assay for systemic mycoplasmal infections.,

Mycoplasma Criteria for Causing Disease

Before systemic mycoplasmal infections can be considered important in causing disease, certain criteria must be fulfilled: (1) The incidence rate among diseased patients must be higher than in those without disease. This has been found. Moreover, in asymptomatic adults mycoplasmal infections have been found in very low incidence. (2) More of the mycoplasma must be recoverable from diseased patients than from those without disease. This has been found. , (3) An antibody response must be found at higher frequency in diseased patients than in those without disease. This has been found with M. fermentans, but usually not until the disease has progressed. M. fermentans hides inside cells and does not elicits strong immune response until near death. , (4) A clinical response must be accompanied by elimination of the mycoplasma. Follow up studies on recovered patients indicate that they reverted to mycoplasma-negative phenotypes. , (5) Clinical response is differential depending on the type of antibiotics. Recovery is achieved only with antibiotics that are effective against the pathogenic mycoplasmas. , (6) The mycoplasma must cause a similar disease in animal models using monkeys. Injection of M. fermentans resulted in development of fulminant disease that leads to death. (7) The mycoplasma must cause a similar disease when administered to human subjects. The mycoplasmas were not administered to volunteers because of ethical considerations to investigate if they cause a similar disease. (8) A specific anti-mycoplasma antibody reagent or immunization protects against disease. To our knowledge this has not been done. Therefore, six out of eight of the above criteria have been fulfilled, at least for M. fermentans, strongly suggesting that certain mycoplasmas can cause human disease. Baseman and Tully have reviewed the literature on the role of mycoplasmal infections in human disease and have concluded that they are important factors or cofactors in a variety of chronic illnesses.

The identification of mycoplasmal infections in the leukocyte blood fractions of a rather large subset of GWI, CFS and FMS patients suggests that mycoplasmas, and possibly other chronic infections as well, may be important sources of morbidity in these patients. Our results show a high incidence of mycoplasmal infections in blood of patients diagnosed with CFS/FMS. Mycoplasmas are not easily detected but can be identified by Nucleoprotein Gene Tracking and forensic PCR. In previous studies using the Nucleoprotein Gene Tracking detection method, we found mycoplasmal infections in 50% of GWI patients.

New Treatments for FMS, CFS and GWI

If such infections are important in these disorders, then appropriate treatment with antibiotics should result in clinical improvement and even recovery. We have proposed treatment recommendations for mycoplasmal infections that are similar to those used to treat Lyme disease, caused by other slow-growing intracellular bacteria that are difficult to identify and treat. For mycoplasmal blood infections long-term antibiotic therapy, usually multiple 6-week cycles of doxycycline (200-300 mg/d), ciprofloxacin (1,500 mg/d), azithromycin (500 mg/d) and clarithromycin (800-1,000 mg/d), are required, possibly because of the intracellular location of mycoplasmas like M. fermentans and M. penetrans, and the slow-growing nature of these microorganisms. Nutritional support is also important, and vitamins (esp. B, C, E, CoQ10), minerals (Zinc, Selenium, Chromium), immunoenhancers, and replacement of gut flora (Lactobacillus acidophillus) are important as well as moderate exercise and dry saunas to remove contaminating chemicals.

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[Guest guest]

I was told that the French troups also took prophylactic doxycycline before

returning to France from the Gulf...I don't have any of my old information

when I was also diagnosed with mycoplasma fermentans back in 1996.

Donna