mycoplasma and fibromyalgia / CFS


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Nasralla M, Haier J, Nicolson GL.
Multiple mycoplasmal infections detected in blood of patients with chronic fatigue syndrome and/or fibromyalgia syndrome.
Eur J Clin Microbiol Infect Dis 1999 Dec;18(12):859-65
"The aim of this study was to investigate the presence of different mycoplasmal species in blood samples from patients with chronic fatigue syndrome and/or fibromyalgia syndrome. Previously, more than 60% of patients with chronic fatigue syndrome/fibromyalgia syndrome were found to have mycoplasmal blood infections, such as Mycoplasma fermentans infection. In this study, patients with chronic fatigue syndrome/fibromyalgia syndrome were examined for multiple mycoplasmal infections in their blood. A total of 91 patients diagnosed with chronic fatigue syndrome/fibromyalgia syndrome and with a positive test for any mycoplasmal infection were investigated for the presence of Mycoplasma fermentans, Mycoplasma pneumoniae, Mycoplasma hominis and Mycoplasma penetrans in blood using forensic polymerase chain reaction. Among these mycoplasma-positive patients, infections were detected with Mycoplasma pneumoniae (54/91), Mycoplasma fermentans (44/91), Mycoplasma hominis (28/91) and Mycoplasma penetrans (18/91). Multiple mycoplasmal infections were found in 48 of 91 patients, with double infections being detected in 30.8% and triple infections in 22%, but only when one of the species was Mycoplasma pneumoniae or Mycoplasma fermentans. Patients infected with more than one mycoplasmal species generally had a longer history of illness, suggesting that they may have contracted additional mycoplasmal infections with time." [Abstract]

Nicolson GL, Gan R, Haier J.
Multiple co-infections (Mycoplasma, Chlamydia, human herpes virus-6) in blood of chronic fatigue syndrome patients: association with signs and symptoms.
APMIS. 2003 May; 111(5): 557-66.
"Previously we and others found that a majority of chronic fatigue syndrome (CFS) patients showed evidence of systemic mycoplasmal infections, and their blood tested positive using a polymerase chain reaction assay for at least one of the four following Mycoplasma species: M. fermentans, M. hominis, M. pneumoniae or M. penetrans. Consistent with previous results, patients in the current study (n=200) showed a high prevalence (overall 52%) of mycoplasmal infections. Using forensic polymerase chain reaction we also examined whether these same patients showed evidence of infections with Chlamydia pneumoniae (overall 7.5% positive) and/or active human herpes virus-6 (HHV-6, overall 30.5% positive). Since the presence of one or more infections may predispose patients to other infections, we examined the prevalence of C. pneumoniae and HHV-6 active infections in mycoplasma-positive and -negative patients. Unexpectedly, we found that the incidence of C. pneumoniae or HHV-6 was similar in Mycoplasma-positive and -negative patients, and the converse was also found in active HHV-6-positive and -negative patients. Control subjects (n=100) had low rates of mycoplasmal (6%), active HHV-6 (9%) or chlamydial (1%) infections, and there were no co-infections in control subjects. Differences in bacterial and/or viral infections in CFS patients compared to control subjects were significant. Severity and incidence of patients' signs and symptoms were compared within the above groups. Although there was a tendency for patients with multiple infections to have more severe signs and symptoms (p<0.01), the only significant differences found were in the incidence and severity of certain signs and symptoms in patients with multiple co-infections of any type compared to the other groups (p<0.01). There was no correlation between the type of co-infection and severity of signs and symptoms. The results indicate that a large subset of CFS patients show evidence of bacterial and/or viral infection(s), and these infections may contribute to the severity of signs and symptoms found in these patients." [Abstract]

Nijs J, Nicolson GL, De Becker P, Coomans D, De Meirleir K.
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 2002 Nov 15;34(3):209-14
"Prevalence of Mycoplasma species infections in chronic fatigue syndrome (CFS) has been extensively reported in the scientific literature. However, all previous reports highlighted the presence of Mycoplasmas in American patients. In this prospective study, the presence of Mycoplasma fermentans, M. penetrans, M. pneumoniae and M. hominis in the blood of 261 European CFS patients and 36 healthy volunteers was examined using forensic polymerase chain reaction. One hundred and seventy-nine (68.6%) patients were infected by at least one species of Mycoplasma, compared to two out of 36 (5.6%) in the control sample (P<0.001). Among Mycoplasma-infected patients, M. hominis was the most frequently observed infection (n=96; 36.8% of the overall sample), followed by M. pneumoniae and M. fermentans infections (equal frequencies; n=67; 25.7%). M. penetrans infections were not found. Multiple mycoplasmal infections were detected in 45 patients (17.2%). Compared to American CFS patients (M. pneumoniae>M. hominis>M. penetrans), a slightly different pattern of mycoplasmal infections was found in European CFS patients (M. hominis>M. pneumoniae, M. fermentansz.Gt;M. penetrans)." [Abstract]

Vojdani A, Choppa PC, Tagle C, Andrin R, Samimi B, Lapp CW.
Detection of Mycoplasma genus and Mycoplasma fermentans by PCR in patients with Chronic Fatigue Syndrome.
FEMS Immunol Med Microbiol 1998 Dec;22(4):355-65
"Mycoplasma fermentans and other Mycoplasma species are colonizers of human mucosal surfaces and may be associated with human immunodeficiency virus infection. While many infectious agents have been described in different percentages of patients with Chronic Fatigue Syndrome (CFS), little is known about the prevalence of mycoplasmas and especially M. fermentans in CFS patients. A polymerase chain reaction (PCR)-based assay was used to detect Mycoplasma genus and M. fermentans genomes in peripheral blood mononuclear cells (PBMC) of CFS patients. Blood was collected from 100 patients with CFS and 50 control subjects. The amplified products of 717 bp of Mycoplasma genus, and 206 bp of M. fermentans were detected in DNA purified from blood samples in 52% and 34% of CFS samples, respectively. In contrast, these genomes were found in only 14% and 8% of healthy control subjects respectively (P < 0.0001). All samples were confirmed by Southern blot with a specific probe based on internal sequences of the expected amplification product. Several samples, which were positive for Mycoplasma genus, were negative for M. fermentans indicating that other Mycoplasma species are involved. A quantitative PCR was developed to determine the number of M. fermentans genome copies present in 1 microg of DNA for controls and CFS patients. Mycoplasma copy numbers ranging from 130 to 880 and from 264 to 2400 were detected in controls and CFS positive subjects, respectively. An enzyme immunoassay was applied for the detection of antibodies against p29 surface lipoprotein of M. fermentans to determine the relationship between M. fermentans genome copy numbers and antibody levels. Individuals with high genome copy numbers exhibited higher IgG and IgM antibodies against M. fermentans specific peptides. Isolation of this organism by culture from clinical specimens is needed in order to demonstrate specificity of signal detected by PCR in this study." [Abstract]

Choppa PC, Vojdani A, Tagle C, Andrin R, Magtoto L.
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 1998 Oct;12(5):301-8
"A multiplex polymerase chain reaction (PCR) was initially developed to detect the presence of mycoplasma genus DNA sequences in cell cultures and to differentiate between three human pathogenic mycoplasma species simultaneously. The assay in turn, proved to be a useful tool for the detection of mycoplasma infection in human DNA samples. One set of oligonucleotide primers which are specific for a highly conserved region among all members of the genus mycoplasma along with three other primer sets which are specific for Mycoplasma fermentans, Mycoplasma hominis andMycoplasma penetrans species were used in this assay. The sensitivity of detection was determined by infecting peripheral blood mononuclear cells (PBMC) of healthy individuals with known bacterial copy numbers from each species, extracting the DNA, and subjecting 1 microgram of DNA from each sample to 40 cycles of amplification. By using agarose gel electrophoresis the detection level was determined to be 7, 7, 9 and 15 mycoplasma cells per microgram of human genomic DNA for M. genus,M. fermentans, M. hominis and M. penetrans, respectively. The assay was applied to DNA extracted from the PBMCs of individuals suffering from chronic fatigue syndrome (CFS) (n=100) as determined by the Center for Disease Control (CDC) criteria, and compared to healthy individuals (n=100). The percentage of M. genus infection was found to be 52% in CFS patients and only 15% in healthy individuals.Mycoplasma fermentans, M. hominis andM. penetrans were detected in 32, 9 and 6% of the CFS patients while they were detected in 8, 3 and 2% of the healthy control subjects, respectively. This assay provides a rapid and cost efficient procedure to screen either cell cultures or clinical samples for the presence of three potentially pathogenic species of mycoplasma with a high level of sensitivity and specificity." [Abstract]

Aristo Vojdani, Ph.D., M.T.

"We emphasize that M. fermentans is not the etiologic agent for Chronic Fatigue Syndrome. It may serve as a cofactor in the induction of cytokines and other immune abnormalities found in CFS. These abnormalities may compromise the immune system, allowing other agents, whether they be biological, chemical, or both, to exert an effect resulting in symptomatology shown in CFIDS. Therefore, if the genome of this bacteria is detected in the blood cells of patients with chronic illnesses, treatment with antibiotics may be the logical step for its elimination from the blood."

Prof. Garth L. Nicolson
Chronic Infections in Fibromyalgia Syndrome: Sources of Morbidity and Illness Progression

Shmuel Razin

Is Fibromyalgia caused by a Mycoplasmal Infection?

Endresen GK.
Mycoplasma blood infection in chronic fatigue and fibromyalgia syndromes.
Rheumatol Int. 2003 Sep; 23(5): 211-5. Epub 2003 Jul 16.
"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." [Abstract]

Sack J, Zilberstein D, Barile MF, Lukes YG, Baker JR Jr, Wartofsky L, Burman KD.
Binding of thyrotropin to selected Mycoplasma species: detection of serum antibodies against a specific Mycoplasma membrane antigen in patients with autoimmune thyroid disease.
J Endocrinol Invest 1989 Feb;12(2):77-86
"Radiolabeled human (hTSH) and bovine (bTSH) thyroid stimulating hormone was shown to bind to five species of Mycoplasma, the wall-less prokaryotes. The maximum binding capacity of 125I-bTSH to these five species was about 7.9 x 10(-13) moles-1.4 x 10(-12) moles for 50-100 micrograms protein with dissociation constants of approximately 1.7 to 2.2 x 10(-7)M. Approximately 50% of the 125I-bTSH binding was displaced by excess, unlabeled bTSH or hTSH, but labeled bTSH was not effectively displaced by growth hormone, LH, FSH, prolactin, or the beta subunit of hTSH, FSH and LH. Antisera prepared against Mycoplasma gallisepticum and Mycoplasma pneumoniae bound to human thyroid membranes and guinea pig fat cells, suggesting that receptors on human thyroid tissues and on Mycoplasma cells may have similarities in antigenicity. These findings were substantiated by the occurrence of TSH binding to Mycoplasma antisera. Further, sera from three of six patients with Graves' disease containing antibodies to thyroid tissues also reacted to a 108 Kd polypeptide of Mycoplasma gallisepticum." [Abstract]

Yirmiya R, Weidenfeld J, Barak O, Avitsur R, Pollak Y, Gallily R, Wohlman A, Ovadia H, Ben-Hur T.
The role of brain cytokines in mediating the behavioral and neuroendocrine effects of intracerebral mycoplasma fermentans.
Brain Res 1999 May 22;829(1-2):28-38
"Intracerebral administration of Mycoplasma fermentans (MF), a small microorganism that has been found in the brain of some AIDS patients, induces behavioral and neuroendocrine alterations in rats. To examine the role of tumor necrosis factor-alpha (TNFalpha) and interleukin-1 (IL-1) in mediating these effects we measured MF-induced expression of TNFalpha and IL-1beta mRNA in various brain regions, and the effects of TNFalpha synthesis blockers and IL-1 receptor antagonist (IL-1ra) on MF-induced sickness behavior and adrenocortical activation. Intracerebroventricular (i.c.v.) administration of heat-inactivated MF induced the expression of both TNFalpha and IL-1beta mRNA in the cortex, dorsal hippocampus, amygdala, and hypothalamus. Pre-treatment of rats with either TNFalpha synthesis blockers, pentoxifylline or rolipram, or with IL-1ra did not attenuate MF-induced anorexia, body weight loss, and suppression of social behavior. However, simultaneous administration of both pentoxifylline and IL-1ra markedly attenuated MF-induced anorexia and body weight loss, but had no effect on the suppression of social behavior. Pre-treatment with pentoxifylline, but not with IL-1ra, significantly attenuated MF-induced corticosterone (CS) secretion. Together, these findings indicate that both TNFalpha and IL-1 participate, in a complementary manner, in mediating some of the behavioral effects of MF, whereas only TNFalpha, but not IL-1, is involved in mediating MF-induced adrenocortical activation. We suggest that cytokines within the brain are involved in mediating at least some of the neurobehavioral and neuroendocrine abnormalities that may be produced by MF in AIDS patients." [Abstract]

Marwan Nasralla, Ph.D., Joerg Haier, M.D., Ph.D. and Garth L. Nicolson, Ph.D.
Mycoplasmal Infections in Blood from Patients with Chronic Fatigue Syndrome, Fibromyalgia Syndrome or Gulf War Illness
International CFS Conference, Sydney, Australia, 1998 [Full Text]

Lo SC, Levin L, Ribas J, Chung R, Wang RY, Wear D, Shih JW.
Lack of serological evidence for Mycoplasma fermentans infection in army Gulf War veterans: a large scale case-control study.
Epidemiol Infect 2000 Dec;125(3):609-16
"Mycoplasma firmentans is suspected in the development of 'Gulf War illness' in veterans of Operation Desert Storm. We conducted a matched case-control study for the prevalence of M. firmentans-specific antibodies before and after the operation, as well as seroconversion rates in veterans with and without complaints of 'Gulf War illness'. Cases consisted of Gulf War veterans, who complained of various illnesses and were enrolled in the second phase of the health evaluation by the Army Comprehensive Clinical Examination Program (CCEP). Controls were selected from Gulf War veterans who did not participate in the registry and did not request a health evaluation by the CCEP. Before operation deployment, 34 out of 718 of the cases (48%) and 116 out of 2233 of the controls (5.2%) tested positive for M. fermentans-specific antibodies. There was no difference in rates of seroconversion between cases and controls (1.1 vs. 1.2%) to M. fermentans during Operation Desert Storm. Thus, there is no serological evidence that suggests infectionby M. fermentans is associated with development of 'Gulf War illness'." [Abstract]

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Recent Mycoplasma and Fibromyalgia/Chronic Fatigue Syndrome Research

1) Cassisi G, Sarzi-Puttini P, Cazzola M
Chronic widespread pain and fibromyalgia: could there be some relationships with infections and vaccinations?
Clin Exp Rheumatol. 2011 Nov-Dec;29(6 Suppl 69):S118-26.
Chronic widespread pain (CWP) is a common symptom within the community, and may be part of or arise as a result of various diseases or conditions. Fibromyalgia (FM) is probably the most common and best known disease whose cardinal symptom is CWP. Many authors, however, indistinctively describe pain as 'widespread', 'diffuse' or 'generalised', and this may lead to misunderstandings about true clinical or scientific significance. Widespread pain has been variously defined, over the years, beginning from the American College of Rheumatology (ACR) classification criteria for FM in 1990, and the CWP Manchester definition in 1996. A comprehensive and brief core sets for CWP was developed in 2003, by the WHO International Classification of Functioning Consensus Conference, and finally, the ACR proposed new preliminary diagnostic criteria for FM in 2010. Research into CWP and/or FM is therefore difficult and can lead to conflicting results. CWP and (particularly) FM are multifactorial disorders. There is increasing evidence that they may be triggered by environmental factors, and many authors have highlighted a relationship with various infectious agents and some have suggested that vaccinations may play a role. This review analyses the available data concerning the relationships between FM and widespread pain (in its various meanings) with infections and vaccinations, from the earliest report to the most recent contributions. Considering all scientific papers, various levels of possible associations emerge. There is no clear-cut evidence of FM or CWP due to infections or vaccinations, no correlations with persistent infection, and no proven relationship between infection, antimicrobial therapies and pain improvement. A higher prevalence of FM and chronic pain has been found in patients with Lyme disease, and HIV or HCV infection, and, perhaps, also in patients with mycoplasmas, HBV, HTLV I, and parvovirus B19 infections. Some unconfirmed evidence and case reports suggest that vaccinations may trigger FM or chronic pain. [PubMed Citation] [Order full text from Infotrieve]

2) Liu CL, Tian GS, He Y, Zhou P, Wang CW, Wang ZY, Sun SQ, Zhou Y, Sun Y, Sun Y, Zhang HW, Li L
[A family associated outbreak of Mycoplasma pneumoniae infection in a hospital ward].
Zhonghua Liu Xing Bing Xue Za Zhi. 2011 Nov;32(11):1110-3.
[PubMed Citation] [Order full text from Infotrieve]

3) Sairenji T, Nagata K
[Viral infections in chronic fatigue syndrome].
Nihon Rinsho. 2007 Jun;65(6):991-6.
Chronic fatigue syndrome (CFS) is a heterogeneous illness in which patients can have different, overlapping signs and symptoms. No single underlying cause has been established for all CFS patients. Epidemiological studies reveal that a flu-like sickness precedes the onset in the majority of cases. The major hypothesis of the pathogenesis of CFS is that infectious agents such as viruses, may trigger and lead to chronic activation of the immune system with abnormal regulation of cytokine production. Many studies have been performed to identify the possible microbial triggers and to understand the epidemiological microbial agents. We have summarized the recent progressive literature of virus, rickettsia, and mycoplasma implicated in the pathogenesis of CFS. [PubMed Citation] [Order full text from Infotrieve]

4) Ablin JN, Shoenfeld Y, Buskila D
Fibromyalgia, infection and vaccination: two more parts in the etiological puzzle.
J Autoimmun. 2006 Nov;27(3):145-52.
As the pathogenesis of fibromyalgia continues to raise debate, multiple putative triggers have been implicated. The current review summarizes the available data linking fibromyalgia to either infection or vaccination. Multiple infectious agents have been associated with the development of either full-blown fibromyalgia (e.g. hepatits C), or with symptom complexes extensively overlapping with that syndrome (e.g. chronic Lyme disease). The cases of Lyme disease, mycoplasma, hepatits C and HIV are detailed. Despite the described associations, no evidence is available demonstrating the utility of antibiotic or anti-viral treatment in the management of fibromyalgia. Possible mechanistic links between fibromyalgia and HIV are reviewed. Associations have been described between various vaccinations and symptom complexes including fibromyalgia and chronic fatigue syndrome. The case of Gulf War syndrome, a functional multisystem entity sharing many clinical characteristics with fibromyalgia is discussed, with emphasis on the possibility of association with administration of multiple vaccinations during deployment in the Persian Gulf and the interaction with stress and trauma. Based on this example a model is proposed, wherein vaccinations function as co-triggers for the development of functional disorders including fibromyalgia, in conjunction with additional contributing factors. [PubMed Citation] [Order full text from Infotrieve]

5) Nijs J, Van de Velde B, De Meirleir K
Pain in patients with chronic fatigue syndrome: does nitric oxide trigger central sensitisation?
Med Hypotheses. 2005;64(3):558-62.
Previous studies have provided evidence supportive of the clinical importance of widespread pain in patients with chronic fatigue syndrome (CFS): pain severity may account for 26-34% of the variability in the CFS patient's activity limitations and participation restrictions. The etiology of widespread pain in CFS remains to be elucidated, but sensitisation of the central nervous system has been suggested to take part of CFS pathophysiology. It is hypothesised that a nitric oxide (NO)-dependent reduction in inhibitory activity of the central nervous system and consequent central sensitisation accounts for chronic widespread pain in CFS patients. In CFS patients, deregulation of the 2',5'-oligoadenylate synthetase/RNase L pathway is accompanied by activation of the protein kinase R enzyme. Activation of the protein kinase R and subsequent nuclear factor-kappaB activation might account for the increased production of NO, while infectious agents frequently associated with CFS (Coxsackie B virus, Epstein-Barr Virus, Mycoplasma) might initiate or accelerate this process. In addition, the evidence addressing behavioural changes in CFS patients fits the central sensitisation-hypothesis: catastrophizing, avoidance behaviour, and somatization may result in, or are initiated by sensitisation of the central nervous system. [PubMed Citation] [Order full text from Infotrieve]

6) Marrie TJ, Beecroft M, Herman-Gnjidic Z, Poulin-Costello M
Symptom resolution in patients with Mycoplasma pneumoniae pneumonia.
Can Respir J. 2004 Nov-Dec;11(8):573-7.
[PubMed Citation] [Order full text from Infotrieve]

7) Donta ST, Engel CC, Collins JF, Baseman JB, Dever LL, Taylor T, Boardman KD, Kazis LE, Martin SE, Horney RA, Wiseman AL, Kernodle DS, Smith RP, Baltch AL, Handanos C, Catto B, Montalvo L, Everson M, Blackburn W, Thakore M, Brown ST, Lutwick L, Norwood D, Bernstein J, Bacheller C, Ribner B, Church LW, Wilson KH, Guduru P, Cooper R, Lentino J, Hamill RJ, Gorin AB, Gordan V, Wagner D, Robinson C, DeJace P, Greenfield R, Beck L, Bittner M, Schumacher HR, Silverblatt F, Schmitt J, Wong E, Ryan MA, Figueroa J, Nice C, Feussner JR
Benefits and harms of doxycycline treatment for Gulf War veterans' illnesses: a randomized, double-blind, placebo-controlled trial.
Ann Intern Med. 2004 Jul 20;141(2):85-94.
[PubMed Citation] [Order full text from Infotrieve]