Nasralla M, Haier J, Nicolson GL.
infections detected in blood of patients with chronic fatigue syndrome and/or
Eur J Clin Microbiol Infect Dis 1999
"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]
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.
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]
J, Nicolson GL, De Becker P, Coomans D, De Meirleir K.
of Mycoplasma infections among European chronic fatigue syndrome patients. Examination
of four Mycoplasma species in blood of chronic fatigue syndrome patients.
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.
A, Choppa PC, Tagle C, Andrin R, Samimi B, Lapp CW.
Mycoplasma genus and Mycoplasma fermentans by PCR in patients with Chronic Fatigue
FEMS Immunol Med Microbiol 1998 Dec;22(4):355-65
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]
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.
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]
Vojdani, Ph.D., M.T.
FACTS VERSUS FICTION
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."
Garth L. Nicolson
Infections in Fibromyalgia Syndrome: Sources of Morbidity and Illness Progression
caused by a Mycoplasmal Infection?
blood infection in chronic fatigue and fibromyalgia syndromes.
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."
J, Zilberstein D, Barile MF, Lukes YG, Baker JR Jr, Wartofsky L, Burman KD.
of thyrotropin to selected Mycoplasma species: detection of serum antibodies against
a specific Mycoplasma membrane antigen in patients with autoimmune thyroid disease.
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."
R, Weidenfeld J, Barak O, Avitsur R, Pollak Y, Gallily R, Wohlman A, Ovadia H,
The role of brain cytokines in mediating the behavioral
and neuroendocrine effects of intracerebral mycoplasma fermentans.
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]
Nasralla, Ph.D., Joerg Haier, M.D., Ph.D. and Garth L. Nicolson, Ph.D.
Infections in Blood from Patients with Chronic Fatigue Syndrome, Fibromyalgia
Syndrome or Gulf War Illness
International CFS Conference,
Sydney, Australia, 1998 [Full
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.
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]