Journal of Chronic Fatigue Syndrome: Volume 11, Issue 2, 2003

Titles and abstracts for the Journal of Chronic Fatigue Syndrome, Volume 11, Issue 2, 2003.

Volume 11, Issue 2, 2003

• Editorial by Kenny De Meirleir & Neil McGregor
• Evidence for Bacterial (Mycoplasma, Chlamydia) and Viral (HHV-6) Co-Infections in Chronic Fatigue Syndrome Patients

  "Abstract - Using the blood of 100 CFS patients and forensic polymerase chain reaction we have found that a majority of Chronic Fatigue Syndrome (CFS) patients show evidence of multiple, systemic bacterial and viral infections (OR = 18.0, 95%CL 8.5–37.9, P >0.001) that could play an important role in CFS morbidity. CFS patients had a high prevalence (51%) of one of four Mycoplasma species (OR = 13.8, 95%CL 5.8–32.9, P >0.001) and often showed evidence of co-infections with different Mycoplasma species, Chlamydia pneumoniae (OR = 8.6,95%CL 1.0–71.1, P >0.01) and/or active Human Herpes Virus-6 (HHV-6) (OR = 4.5,95%CL 2.0–10.2, P >0.001). We found that 8% of the CFS patients showed evidence of C. pneumoniae and 31% of active HHV-6 infections. Since the presence of one or more chronic systemic infections may predispose patients to other infections, we examined the prevalence of C. pneumoniae and active HHV-6 infections in mycoplasma-positive and -negative patients. The incidence of C. pneumoniae or HHV-6 was similar in mycoplasma-positive and -negative patients, suggesting that such infections occur independently in CFS patients. Also, the incidence of C. pneumoniae in active HHV-6-positive and -negative patients was similar. Control subjects (N = 100) had low rates of mycoplasma (6%), active HHV-6 (9%) or chlamydia (1%) infections, and there were no coinfections in control subjects. Differences in bacterial and/or viral infections in CFS patients compared to control subjects were significant. The results indicate that a relatively large subset of CFS patients show evidence of bacterial and viral co-infections."

• High Prevalence of Mycoplasma Infections in Symptomatic (Chronic Fatigue Syndrome) Family Members of Mycoplasma-Positive Gulf War Illness Patients

  "Abstract - Immediate family members of veterans diagnosed with Gulf War Illnesses (GWI) often complain of fatiguing illnesses, and upon analysis they report similar signs and symptoms as their veteran family members. Since a relatively common finding in Gulf War illness patients is a bacterial infection due to Mycoplasma spp., we examined military families (149 patients: 42 veterans, 40 spouses, 32 other relatives and 35 children with at least one family complaint of illness) selected from a group of 110 veterans with Gulf War illness who tested positive (∼41%) for at least one of four Mycoplasma spp.: M. fermentans, M. hominis, M. pneumoniae or M. genitalium. Consistent with previous results, over 80% of Gulf War illness patients who were positive for blood mycoplasma infections had only one Mycoplasma spp. (Odds ratio = 9.0, 95%CL 3.3–24.3, P >.0.001), in particular M. fermentans (Odds ratio = 17.9, 95%CL 4.1–78.1, P >.0.001). In healthy control subjects the incidence of mycoplasma infection was ∼8.5% and none were found to have multiple mycoplasma species (Multiple species Odds ratio >25, Chi2 = 8.1, P >.0.004). In 107 family members of mycoplasma-positive Gulf War illness patients there were 57 patients (53%) that had essentially the same signs and symptoms as the veterans and were diagnosed with Chronic Fatigue Syndrome (CFS) and/or Fibromyalgia Syndrome. Most of these CFS patients also had mycoplasma infections compared to the few non-symptomatic family members (Odds ratio = 16.9, 95%CL 6.0–47.6, P >.0.001), and the most common species found was M. fermentans (Odds ratio = 40.3, 95%CL 8.7–186.4, P >.0.001). In contrast, in the few non-symptomatic family members that tested mycoplasma-positive, the Mycoplasma spp. were often different from the species found in the Gulf War illness patients. The results suggest that a subset of Gulf War illness patients have mycoplasma infections, possibly obtained as contaminants from multiple vaccines given during deployment, and these infections can be transmitted to immediate family members who subsequently display similar signs and symptoms and are diagnosed with CFS and/or Fibromyalgia Syndrome."

• Deregulation of the 2,5A Synthetase RNase L Antiviral Pathway by Mycoplasma spp. in Subsets of Chronic Fatigue Syndrome

  "Abstract - The deregulation of the 2,5A synthetase RNase L antiviral pathway and the prevalence of Mycoplasma spp. in subsets of Chronic Fatigue Syndrome (CFS) have been separately reported in the scientific literature. We hypothesised that a comorbid pathophysiological mechanism involving infection by Mycoplasma spp. and the deregulation of the 2,5A synthetase/RNase L antiviral pathway may exist in CFS. Therefore, 186 consecutive CFS patients were enrolled. Mycoplasma detection was performed using forensic polymerase chain reaction. For RNase L determination, a radioactive probe was used to label 2,5A binding proteins in unfractionated peripheral blood mononuclear cell extracts. Mycoplasma-infected CFS patients presented with significantly elevated RNase L-ratio, compared to non-infected age- and sex-matched patients (p = 0.016). These results suggest that mycoplasma infections may cause deregulation of the 2,5A synthetase RNase L antiviral pathway in patients with CFS."

• Immunophenotyping Predictive of Mycoplasma Infection in Patients with Chronic Fatigue Syndrome?

  "Abstract - An impaired immune system and opportunistic infections are considered important characteristics in the pathophysiology of Chronic Fatigue Syndrome (CFS). Using immunofluorescence we examined healthy subjects (N = 35) and two subsets of CFS patients: those without evidence of Mycoplasma (N = 55) and those with evidence of a Mycoplasma infection in their blood (N = 131). Using monoclonal antibodies and forensic polymerase chain reaction for detection of M. hominis, M. fermentans, M. pneumoniae and M. penetrans, we examined leukocytes in peripheral blood samples. Both patient groups presented with significantly elevated CD25+ (activated) cells as compared to healthy volunteers. CFS patients without evidence of mycoplasma infection(s) had increased amounts of CD5+ B-cells. Stepwise discriminant analysis indicated the number of activated cells, number of memory CD4+ cells and percentage of suppressor T-cells (lower in Mycoplasma+ patients as compared to Mycoplasma- patients) as the discriminant variables. A classification tree, for predicting the presence of Mycoplasma species in CFS patients, was constructed. Taken together, these data confirm earlier reports on immune activation among CFS patients, but this does not appear to be specific for Mycoplasma-infected CFS patients."

• Clinical Improvement in Chronic Fatigue Syndrome Is Associated with Enhanced Natural Killer Cell-Mediated Cytotoxicity: The Results of a Pilot Study with Isoprinosine®

  "Abstract - Chronic fatigue syndrome is associated with systemic and cognitive symptoms and with several immune abnormalities. The clinical impact of Isoprinosine® was evaluated in sixteen CFS patients, followed for 28 weeks in a single-blind, placebo controlled trial. Patients were also monitored for various immune parameters. Improvement based on clinical staging was observed in six of ten treated patients (60%). Clinically improved patients showed significantly enhanced natural killer (NK) cell activity, which correlated with the duration of Isoprinosine treatment (p >0.03). Treatment with Isoprinosine resulted in significantly increased numbers of CD4+ T helper cells (p >0.03). Treatment with Isoprinosine for 12 weeks did not appreciably influence the in vitro production of IFN-y, IL-1oc, IL-10 or IL-12. However, IL-12 was significantly increased at week 28 (p >0.02) in patients who improved after treatment with Isoprinosine. These results suggest that taking Isoprinosine may benefit a subgroup of patients with CFS, and this clinical improvement is associated with enhanced NK cell function and IL-12 levels. Further trials to evaluate the use of Isoprinosine in the treatment of CFS patients are warranted."

• RNase L in Health and Disease-What Did We Learn Recently?

  "Abstract - The 2′,5′-oligoadenylate-dependent ribonuclease L (RNase L) is central to the innate cellular defense mechanism induced by type I interferons during intracellular infection. The protein, activated by 2′,5′-oligoadenylates, precludes the replication of the infectious agent by cleaving single-stranded RNA and, along with the double-stranded RNA-dependent protein kinase, its spreading by inducing the cell to undergo suicide (apoptosis). In absence of infection, the protein remains dormant. Recent evidence indicates, however, that the protein is activated in absence of infection and may play a role in cell differentiation, immune activation, and act as a tumor-suppressor. A deregulation in this pathway has been documented in immune cells of chronic fatigue syndrome patients which involves the presence of a catalytically active truncated RNase L. This protein escapes the normal regulation which implies the development of a cascade of unwanted cellular events. The present article reviews our current understanding of this deregulation, enlightens its relevance in the pathological process and proposes new targets for therapeutic development."

• Critical Reviews and Comments on Current Research

CELLULAR IMMUNITY IN MONOZYGOTIC TWINS DISCORDANT FOR CHRONIC FATIGUE SYNDROME. Sabath DE, Barcy S, Koelle DM, Zeh J, Ashton S, BuchwaldD. The Journal of Infectious Diseases 2002; 185: 828-32.

MARKERS OF VIRAL INFECTION IN MONOZYGOTIC TWINS DISCORDANT FOR CHRONIC FATIGUE SYNDROME. Koelle DM, Barcy S, Huang M-L, Ashley RL, Corey L, Zeh J, Ashton S, BuchwaldD. Clinical Infectious Diseases 2002; 35: 518–525.

MAXIMAL OXYGEN UPTAKE AND LACTATE METABOLISM ARE NORMAL IN CHRONIC FATIGUE SYNDROME. Sargent C, Scroop GC, Nemeth PM, Burnet RB, Buckley JD. Med Sci Sports Exerc 2002; 34: 51–6.

• Current Papers in ME/CFS
• In Memoriam - John Richardson, Physician, 6th February 1915–18th July 2002

See also

• Journal of Chronic Fatigue Syndrome for other Issues