Serologic and PCR testing of persons with chronic fatigue syndrome in the United States shows no association with xenotropic or polytropic murine leukemia virus-related viruses

Abstract:

In 2009, a newly discovered human retrovirus, xenotropic murine leukemia virus (MuLV)-related virus (XMRV), was reported by Lombardi et al. in 67% of persons from the US with chronic fatigue syndrome (CFS) by PCR detection of gag sequences. Although six subsequent studies have been negative for XMRV, CFS was defined more broadly using only the CDC or Oxford criteria and samples from the US were limited in geographic diversity, both potentially reducing the chances of identifying XMRV positive CFS cases. A seventh study recently found polytropic MuLV sequences, but not XMRV, in a high proportion of persons with CFS. Here we tested blood specimens from 45 CFS cases and 42 persons without CFS from over 20 states in the United States for both XMRV and MuLV. The CFS patients all had a minimum of 6 months of post-exertional malaise and a high degree of disability, the same key symptoms described in the Lombardi et al. study. Using highly sensitive and generic DNA and RNA PCR tests, and a new Western blot assay employing purified whole XMRV as antigen, we found no evidence of XMRV or MuLV in all 45 CFS cases and in the 42 persons without CFS. Our findings, together with previous negative reports, do not suggest an association of XMRV or MuLV in the majority of CFS cases.

 

Source: Satterfield BC, Garcia RA, Jia H, Tang S, Zheng H, Switzer WM. Serologic and PCR testing of persons with chronic fatigue syndrome in the United States shows no association with xenotropic or polytropic murine leukemia virus-related viruses. Retrovirology. 2011 Feb 22;8:12. doi: 10.1186/1742-4690-8-12. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3050813/ (Full article)

 

Comparison of adaptive pacing therapy, cognitive behaviour therapy, graded exercise therapy, and specialist medical care for chronic fatigue syndrome (PACE): a randomised trial

Abstract:

BACKGROUND: Trial findings show cognitive behaviour therapy (CBT) and graded exercise therapy (GET) can be effective treatments for chronic fatigue syndrome, but patients’ organisations have reported that these treatments can be harmful and favour pacing and specialist health care. We aimed to assess effectiveness and safety of all four treatments.

METHODS: In our parallel-group randomised trial, patients meeting Oxford criteria for chronic fatigue syndrome were recruited from six secondary-care clinics in the UK and randomly allocated by computer-generated sequence to receive specialist medical care (SMC) alone or with adaptive pacing therapy (APT), CBT, or GET. Primary outcomes were fatigue (measured by Chalder fatigue questionnaire score) and physical function (measured by short form-36 subscale score) up to 52 weeks after randomisation, and safety was assessed primarily by recording all serious adverse events, including serious adverse reactions to trial treatments. Primary outcomes were rated by participants, who were necessarily unmasked to treatment assignment; the statistician was masked to treatment assignment for the analysis of primary outcomes. We used longitudinal regression models to compare SMC alone with other treatments, APT with CBT, and APT with GET. The final analysis included all participants for whom we had data for primary outcomes. This trial is registered at http://isrctn.org, number ISRCTN54285094.

FINDINGS: We recruited 641 eligible patients, of whom 160 were assigned to the APT group, 161 to the CBT group, 160 to the GET group, and 160 to the SMC-alone group. Compared with SMC alone, mean fatigue scores at 52 weeks were 3·4 (95% CI 1·8 to 5·0) points lower for CBT (p = 0·0001) and 3·2 (1·7 to 4·8) points lower for GET (p = 0·0003), but did not differ for APT (0·7 [-0·9 to 2·3] points lower; p = 0·38). Compared with SMC alone, mean physical function scores were 7·1 (2·0 to 12·1) points higher for CBT (p = 0·0068) and 9·4 (4·4 to 14·4) points higher for GET (p = 0·0005), but did not differ for APT (3·4 [-1·6 to 8·4] points lower; p=0·18). Compared with APT, CBT and GET were associated with less fatigue (CBT p = 0·0027; GET p = 0·0059) and better physical function (CBT p=0·0002; GET p<0·0001). Subgroup analysis of 427 participants meeting international criteria for chronic fatigue syndrome and 329 participants meeting London criteria for myalgic encephalomyelitis yielded equivalent results. Serious adverse reactions were recorded in two (1%) of 159 participants in the APT group, three (2%) of 161 in the CBT group, two (1%) of 160 in the GET group, and two (1%) of 160 in the SMC-alone group.

INTERPRETATION: CBT and GET can safely be added to SMC to moderately improve outcomes for chronic fatigue syndrome, but APT is not an effective addition.

FUNDING: UK Medical Research Council, Department of Health for England, Scottish Chief Scientist Office, Department for Work and Pensions.

Copyright © 2011 Elsevier Ltd. All rights reserved.

Comment in:

 

Source: White PD, Goldsmith KA, Johnson AL, Potts L, Walwyn R, DeCesare JC, Baber HL, Burgess M, Clark LV, Cox DL, Bavinton J, Angus BJ, Murphy G, Murphy M, O’Dowd H, Wilks D, McCrone P, Chalder T, Sharpe M; PACE trial management group. Collaborators (19). Comparison of adaptive pacing therapy, cognitive behaviour therapy, graded exercise therapy, and specialist medical care for chronic fatigue syndrome (PACE): a randomised trial. Lancet. 2011 Mar 5;377(9768):823-36. doi: 10.1016/S0140-6736(11)60096-2. Epub 2011 Feb 18. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3065633/ (Full article)

 

Fatigue In Teenagers on the interNET–the FITNET Trial. A randomized clinical trial of web-based cognitive behavioural therapy for adolescents with chronic fatigue syndrome: study protocol

Abstract:

BACKGROUND: Chronic Fatigue Syndrome (CFS) is increasingly recognized as a cause of disability and inactivity in adolescents in the Netherlands. CFS is characterized by unexplained fatigue lasting more than 6 months. Cognitive Behavioural Therapy (CBT) has proven to be effective. However, CBT availability for adolescents with CFS is limited and requires special therapeutic skills not always readily available. An alternative to the face-to-face CBT is FITNET, a web-based therapeutic program designed specifically for adolescents diagnosed with CFS, and their parents. This new CBT approach appeals to the modern youth, who grow up with internet as their main source of information. A web-based program offers the opportunity to lower thresholds for the acceptance and realization of healthcare. This treatment can be activated at any chosen time. The communication between patient and therapist can elapse asynchronously. If effective, this web-based program would greatly increase the therapeutic accessibility.

METHODS/DESIGN: A randomized clinical trial is currently conducted. One-hundred-forty adolescents aged 12-18 years diagnosed with CFS will be recruited and randomized to one of two groups: FITNET or usual care. After 6 months, the usual care group will have access to the FITNET program. Outcomes will be assessed at baseline, post intervention, and at 6 months follow-up. Primary outcome measures are school presence, fatigue severity, and physical functioning.

DISCUSSION: The FITNET study is the first randomized clinical trial which evaluates the effect of web-based CBT versus usual care in adolescents with CFS. The intervention is based on a theoretical existing model of CBT for patients with CFS. The results of this study will provide information about the possibility and efficacy of web-based CBT for adolescents with CFS and will reveal predictors of efficacy.

TRIAL REGISTRATION: ISRCTN: ISRCTN59878666 and ClinicalTrials.gov: NCT00893438.

 

Source: Nijhof SL, Bleijenberg G, Uiterwaal CS, Kimpen JL, van de Putte EM. Fatigue In Teenagers on the interNET–the FITNET Trial. A randomized clinical trial of web-based cognitive behavioural therapy for adolescents with chronic fatigue syndrome: study protocol. [ISRCTN59878666]. BMC Neurol. 2011 Feb 19;11:23. doi: 10.1186/1471-2377-11-23. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3049137/ (Full article)

 

Chronic fatigue syndrome: more than fatigue

Abstract:

Chronic fatigue syndrome (CFS) is a disease recognized by all international medical organizations and WHO, and is classified under the code G93.3 of the International Classification of Diseases. Its prevalence is estimated around 2.54% being more common in women than in men (8/2) aged between 20 and 40 Is defined as a chronic new description characterized by the presence of subjective feeling of fatigue and exhaustion long disabling of more than 6 months duration that is not relieved by rest. It is a multisystem disorder that often presents a significant number of comorbid phenomena.

Not known until specific tests to confirm the diagnosis, nor is there a cure to solve this health problem definitively. The strongest evidence is based on the multidisciplinary approach for the symptomatic treatment of pain, sleep disorders, neurocognitive dysfunction, autonomic and control of depression and anxiety. The specific contribution of nursing to care for the person who lives and live with the SFC should be developed primarily in the field of health education and supportive care, support and assistance to help the patient and their relatives are an adaptive response to changes in health.

 

Source: Royes B, Alvarez C, Lalinde S, Vidal L, Martín A. Chronic fatigue syndrome: more than fatigue. Rev Enferm. 2010 Dec;33(12):16-9. [Article in Spanish] https://www.ncbi.nlm.nih.gov/pubmed/21322184

 

Characteristics of chronic fatigue syndrome in a Japanese community population : chronic fatigue syndrome in Japan

Abstract:

This study seeks to estimate the prevalence of chronic fatigue syndrome (CFS) and assess the characteristics of CFS in a community population in Japan using laboratory tests and questionnaires for lifestyle, fatigue states, and depression states. The design of this study is a cross-sectional observational study. The setting of this study is a medical health checkup program in a general hospital.

This study was conducted with 1,430 Japanese (867 men and 563 women), 20 to 78 years of age. We classified participants who complained of fatigue according to the case definition of CFS proposed by the Centers for Disease Control and Prevention in the USA in 1994. Alcohol, caffeine, catechin and total polyphenol consumption, smoking status, sleep duration, and physical activity were evaluated using questionnaires.

The prevalence of CFS was 1.0% (95% CI 0.5-1.6%) of a community population in Japan. Although various lifestyle factors of the participants with CFS were similar to those without chronic fatigue, average sleep duration was significantly shorter among the participants with CFS (5.5 ± 0.8 h) compared to those without chronic fatigue (6.3 ± 0.9 h, P < 0.001). Proportion at subjects having average sleep duration of less than 6 h was 64.3% among the participants with CFS in contrast to only 15.0% in those without chronic fatigue (P < 0.001).

Among the eight case-defining symptoms, “Unrefreshing sleep” had high sensitivity and high specificity for screening CFS in Japanese population (92.9% and 87.8%, respectively). The average sleep duration was notably shorter in Japanese suffering from CFS. Further longitudinal study is needed to evaluate the possibility of extreme short sleep duration as a major cause of CFS in Japan.

 

Source: Hamaguchi M, Kawahito Y, Takeda N, Kato T, Kojima T. Characteristics of chronic fatigue syndrome in a Japanese community population : chronic fatigue syndrome in Japan. Clin Rheumatol. 2011 Jul;30(7):895-906. doi: 10.1007/s10067-011-1702-9. Epub 2011 Feb 8. https://www.ncbi.nlm.nih.gov/pubmed/21302125

 

Cognitive deficits in patients with chronic fatigue syndrome compared to those with major depressive disorder and healthy controls

Abstract:

OBJECT: Chronic fatigue syndrome (CFS) patients report usually cognitive complaints. They also have frequently comorbid depression that can be considered a possible explanation for their cognitive dysfunction. We evaluated the cognitive performance of patients with CFS in comparison with a control group of healthy volunteers and a group of patients with MDD.

PATIENTS AND METHODS: Twenty-five patients with CFS, 25 patients with major depressive disorder (MDD), and 25 healthy control subjects were given standardized tests of attention, working memory, and verbal and visual episodic memory, and were also tested for effects related to lack of effort/simulation, suggestibility, and fatigue.

RESULTS: Patients with CFS had slower phasic alertness, and also had impaired working, visual and verbal episodic memory compared to controls. They were, however, no more sensitive than the other groups to suggestibility or to fatigue induced during the cognitive session. Cognitive impairments in MDD patients were strongly associated with depression and subjective fatigue; in patients with CFS, there was a weaker correlation between cognition and depression (and no correlation with fatigue).

CONCLUSIONS: This study confirms the presence of an objective impairment in attention and memory in patients with CFS but with good mobilization of effort and without exaggerated suggestibility.

Copyright © 2011 Elsevier B.V. All rights reserved.

 

Source: Constant EL, Adam S, Gillain B, Lambert M, Masquelier E, Seron X. Cognitive deficits in patients with chronic fatigue syndrome compared to those with major depressive disorder and healthy controls. Clin Neurol Neurosurg. 2011 May;113(4):295-302. doi: 10.1016/j.clineuro.2010.12.002. Epub 2011 Jan 20. https://www.ncbi.nlm.nih.gov/pubmed/21255911

 

The role of changes in activity as a function of perceived available and expended energy in nonpharmacological treatment outcomes for ME/CFS

Abstract:

Nonpharmacological interventions for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) often emphasize gradual increases in activity to promote improvement in physical functioning and fatigue. The energy envelope theory may provide a framework for understanding the relationship between changes in activity level and outcomes for patients with ME/CFS. This study examined the relationship between energy envelope and changes in activity after nonpharmacological interventions in a sample of 44 adults with ME/CFS.

Results showed that those who were within their energy envelope before treatment showed more improvement in physical functioning and fatigue compared with those outside of their energy envelope. These findings suggest that an assessment of perceived available and expended energy could help guide the development of individualized nonpharmacological interventions for people with ME/CFS.

© 2010 Wiley Periodicals, Inc.

 

Source: Brown M, Khorana N, Jason LA. The role of changes in activity as a function of perceived available and expended energy in nonpharmacological treatment outcomes for ME/CFS. J Clin Psychol. 2011 Mar;67(3):253-60. doi: 10.1002/jclp.20744. Epub 2010 Oct 25. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3164291/ (Full article)

 

The economic impact of chronic fatigue syndrome in Georgia: direct and indirect costs

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) is a debilitating chronic illness affecting at least 4 million people in the United States. Understanding its cost improves decisions regarding resource allocation that may be directed towards treatment and cure, and guides the evaluation of clinical and community interventions designed to reduce the burden of disease.

METHODS: This research estimated direct and indirect costs of CFS and the impact on educational attainment using a population-based, case-control study between September 2004 and July 2005, Georgia, USA. Participants completed a clinical evaluation to confirm CFS, identify other illnesses, and report on socioeconomic factors. We estimated the effect of CFS on direct medical costs (inpatient hospitalizations, provider visits, prescription medication spending, other medical supplies and services) and loss in productivity (employment and earnings) with a stratified sample (n = 500) from metropolitan, urban, and rural Georgia. We adjusted medical costs and earnings for confounders (age, sex, race/ethnicity, education, and geographic strata) using econometric models and weighted estimates to reflect response-rate adjusted sampling rates.

RESULTS: Individuals with CFS had mean annual direct medical costs of $5,683. After adjusting for confounding factors, CFS accounted for $3,286 of these costs (p < 0.01), which were driven by increased provider visits and prescription medication use. Nearly one-quarter of these expenses were paid directly out-of pocket by those with CFS. Individuals with CFS reported mean annual household income of $23,076. After adjustment, CFS accounted for $8,554 annually in lost household earnings (p < 0.01). Lower educational attainment accounted for 19% of the reduction in earnings associated with CFS.

CONCLUSIONS: Study results indicate that chronic fatigue syndrome may lead to substantial increases in healthcare costs and decreases in individual earnings. Studies have estimated up to 2.5% of non-elderly adults may suffer from CFS. In Georgia, a state with roughly 5.5 million people age 18-59, illness could account for $452 million in total healthcare expenditures and $1.2 billion of lost productivity.

 

Source: Lin JM, Resch SC, Brimmer DJ, Johnson A, Kennedy S, Burstein N, Simon CJ. The economic impact of chronic fatigue syndrome in Georgia: direct and indirect costs. Cost Eff Resour Alloc. 2011 Jan 21;9(1):1. doi: 10.1186/1478-7547-9-1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3033815/ (Full article)

 

Heterologous immunity: immunopathology, autoimmunity and protection during viral infections

There is a strong association between infection-related cell-mediated immunity and autoimmune diseases such as diabetes, multiple sclerosis (MS), rheumatoid arthritis (RA) and lupus erythematosis (SLE)1. Infections have also been associated with unusual immunopathologies of unknown origin, such as Wegner granulomatosis, sarcoidosis, colitis, panniculitis, bronchiolitis obliterans and even chronic fatigue syndrome. Despite exhaustive efforts, a definitive link between one particular pathogen and any of one these pathologies has never been found. More often several pathogens have become associated with each of these conditions. For instance multiple sclerosis has been associated with Epstein Barr virus (EBV), measles virus, HHV-6, varicella-zoster virus, and Picornaviruses2-6. Panniculitis in the form of erythema nodosum and bronchiolitis obliterans have both been associated with unusual cell-mediated immune responses that occur following non-specified viral or intracellular bacterial infections 7-9. Erythema nodosum, which has also been associated with Crohn’s disease8, is a very painful condition, where nodules of inflamed subcutaneous fat often on the shins and forearms persist for months. There is no known therapy. Bronchiolitis obliterans is a lethal condition in humans where the bronchioles become occluded with immune cells and fibrinous material, with no known cause or treatment9.

Chronic fatigue syndrome (CFS) is another unusual multisystem disease which is thought to be associated with immune dysregulation. Over the past two decades millions of patients world wide have suffered from a clinical syndrome of disabling fatigue, myalgias, palpitations and cognitive dysfunction that lasts longer than 6 months. In 50% of cases it develops after a mild viral illness. Cases may appear sporadically or in clusters10,11. Many attempts have been made to define the syndrome on the basis of an etiologic agent. These agents have included Epstein-Barr virus10, Brucella12, Candida albicans13, Borrelia burgdorferi, and human herpesvirus-614,15. More recently it has been associated with enteroviruses and xenoretroviruses 16-18. The general conclusion has been that it is unlikely that the syndrome is caused by a single etiologic agent. The mechanisms mediating CFS are poorly understood, and there are few well designed studies examining its cause. The symptoms of CFS are similar to those experienced during viral infections such as infectious mononucleosis or influenza or in the setting of therapy with cytokines such as interferon or interleukin-2. It has been speculated that some or all the symptoms are reflective of an altered immune response to some pathogen with over production of one or more cytokines. An alternative hypothesis suggests that a number of infectious agents are involved and result in a regulatory imbalance of cytokines and the patient with CFS is unable to reestablish the appropriate balance of cytokines. These theories have been supported by reports of immune deficiency seen associated with CFS19.

 

Source: Selin LK, Wlodarczyk MF, Kraft AR, Nie S, Kenney LL, Puzone R, Celada F. Heterologous immunity: immunopathology, autoimmunity and protection during viral infections. Autoimmunity. 2011 Jun;44(4):328-47. doi: 10.3109/08916934.2011.523277. Epub 2011 Jan 20. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3633594/ (Full article)

 

Effect of Tuina on oxygen free radicals metabolism in patients with chronic fatigue syndrome

Abstract:

OBJECTIVE: To explore the mechanism of Tuina for treatment of chronic fatigue syndrome.

METHODS: A total of 90 patients were randomly divided into a Tuina group, a Taijiquan (take exercise) group and a Fluoxetine group, 30 cases in each group. They were treated with Tuina, Taijiquan and Fluoxetine, respectively. After a month, the therapeutic effects and the changes of malondialdehyde (MDA) content and the activity of serum superoxide dismutases (SOD) and serum glutathione peroxidase (GSH-Px) were observed.

RESULTS: The total effective rate of 93.3% (28/30) in the Tuina group was better than 80.0% (24/30) in the Taijiquan group and 73.3% (22/30) in the Fluoxetine group (both P < 0.05). After treatment, MDA contents in the three groups were all decreased (P < 0.01, P < 0.05), and the activity of SOD. GSH-Px in both the Tuina group and the Fluoxetine group were increased (P < 0.01, P < 0.05), and especially in the Tuina group with a significant difference as compared with the other two groups (P < 0.05, P < 0.01).

CONCLUSION: The therapeutic effect of the Tuina group is superior to that of the Taijiquan group and the Fluoxetine group. Tuina can regulate oxygen free radicals metabolism and clean superfluous oxygen free radicals to alleviate fatigue, which may be one of the mechanisms of Tuina in treating chronic fatigue syndrome.

 

Source: Liu CZ, Lei B. Effect of Tuina on oxygen free radicals metabolism in patients with chronic fatigue syndrome. Zhongguo Zhen Jiu. 2010 Nov;30(11):946-8. [Article in Chinese] https://www.ncbi.nlm.nih.gov/pubmed/21246855