Epstein-Barr virus (EBV) and the chronic fatigue syndrome: normal virus load in blood and normal immunologic reactivity in the EBV regression assay

Abstract:

The etiology of chronic fatigue syndrome (CFS) is unknown. Some patients have high antibody titers to viral capsid antigen (VCA) and early antigen (EA) of Epstein-Barr virus (EBV), suggesting that reactivation of EBV is involved. We investigated virus load (spontaneous transformation) and immunologic regression of EBV-induced transformation in peripheral blood mononuclear cells (PBMCs) from 10 selected patients with CFS who had high antibody titers to VCA and EA. The outcome was compared with that for nine healthy controls and one patient with severe chronic active EBV infection (SCAEBV). There were no significant differences in viral load between patients and healthy controls. Immunologic regression of in vitro-transformed PBMCs was also equally efficient in patients and controls. The SCAEBV-infected patient and two controls, who were all seronegative for EBV, showed impaired regression. In conclusion, we were unable to demonstrate a role for reactivation of EBV in CFS, even in selected patients with high titers of antibody to VCA and EA of EBV.

 

Source: Swanink CM, van der Meer JW, Vercoulen JH, Bleijenberg G, Fennis JF, Galama JM. Epstein-Barr virus (EBV) and the chronic fatigue syndrome: normal virus load in blood and normal immunologic reactivity in the EBV regression assay. Clin Infect Dis. 1995 May;20(5):1390-2. http://www.ncbi.nlm.nih.gov/pubmed/7620030

 

Cytomegalovirus and Epstein-Barr Virus Infection as a Cause of Chronic Fatigue Syndrome in Travelers to Tropical Countries

Although for research purposes the clinical definition of the chronic fatigue syndrome (CFS) is well established, many aspects of this illness such as its etiology, pathogenesis, and treatment are still unknown. Even the clinical definition is subject to controversy, and although much effort has been expended in the investigation of the clinical aspects of the syndrome, little is known about its epidemiology.

This article considers a cohort of 14 cases that meet the criteria of CFS.The signs and symptoms of CFS in these cases manifested during, or shortly after, a trip to a tropical country.These signs and symptoms appeared to be related to cytomegalovirus (MV) or Epstein-Barr virus infection (EBV).

You can read the full article here: http://jtm.oxfordjournals.org/content/jtm/2/1/41.full.pdf

 

Source: Gascón J, Marcos T, Vidal J, Garcia-Forcada A, Corachán M. Cytomegalovirus and Epstein-Barr Virus Infection as a Cause of Chronic Fatigue Syndrome in Travelers to Tropical Countries. J Travel Med. 1995 Mar 1;2(1):41-44. http://www.ncbi.nlm.nih.gov/pubmed/9815359

 

Case control study of chronic fatigue in pediatric patients

Abstract:

OBJECTIVE: To determine the demographic characteristics, medical features, psychological profile, and natural history of children with chronic fatigue.

DESIGN: Case control study.

SETTING: Pediatric Infectious Diseases Clinic of Kosair Children’s Hospital, 1990 to 1992.

PARTICIPANTS: Forty-four patients referred for persistent fatigue were evaluated. Twenty patients participated in a psychological study; 20 healthy controls of similar age and gender were recruited from community pediatric practices and 20 matched depressed controls were recruited from university psychiatry services (subjects were treated as groups in the analyses).

MEASURES: Demographic data were obtained for all referred patients. Those with fatigue for at least 2 months and no alternative diagnosis received a detailed history, physical, and battery of laboratory tests (complete blood count, sedimentation rate, chemistry panel, chest X-ray thyroid stimulating hormone, thyroxine, anti-nuclear antibodies, urinalysis, immunoglobulins, and Epstein-Barr virus (EBV), toxoplasma, and cytomegalovirus serologies). Psychological study participants completed the following: background structured interview; Kaufman Brief Intelligence Test; Children’s Depression Inventory; Child Behavior Checklist; Youth Self Report; Diagnostic Interview for Children and Adolescents-Revised; mail-in follow-up survey.

RESULTS: The median age of fatigue patients was 14.3 years; 60% were female, 96% white, and 87% from the mid/upper socioeconomic status (SES). Fatigue patients were demographically similar to 21 patients referred for infectious mononucleosis (IM) but were older than other clinic patients (P < .0001). White race (P = .0568) and mid/upper SES (P = .0403) were over-represented among fatigue patients compared to patients referred for other diagnoses. Of 36 patients meeting criteria for further study, 5 had an IM-like illness including evidence of recent EBV infection. For the remaining 31 patients, clinical and laboratory evaluations were unrevealing. Psychological study subjects reported marked declines in quality-of-life and scored high on measures of internalizing, withdrawal, and social isolation. Nine met diagnostic criteria for depression, although depressive symptoms were not as prominent as those reported by depressed controls. Fatigue subjects scored higher on somatization than both control groups. The follow-up survey indicated symptomatic improvement in most patients.

CONCLUSIONS: Chronic fatigue was a common reason for referral, with over-representation of white children from mid/upper SES. After exclusion of EBV-associated IM, screening laboratory tests were not helpful in establishing specific organic diagnoses. Whereas the natural history was favorable, chronic fatigue resulted in major quality-of-life changes and was associated with significant levels of psychosocial distress.

IMPLICATIONS: Psychological evaluation is warranted in these patients, as some may have treatable psychological conditions. Given the absence of proved medical therapies, psychosocial interventions to improve quality-of-life should be studied.

 

Source: Carter BD, Edwards JF, Kronenberger WG, Michalczyk L, Marshall GS. Case control study of chronic fatigue in pediatric patients. Pediatrics. 1995 Feb;95(2):179-86. http://www.ncbi.nlm.nih.gov/pubmed/7838632

 

Antibody responses to Epstein-Barr virus, human herpesvirus 6 and human herpesvirus 7 in patients with chronic fatigue syndrome

Abstract:

To test for an association between chronic fatigue syndrome (CFS) and infections with Epstein-Barr virus (EBV), human herpesvirus 6 (HHV-6) and human herpesvirus 7 (HHV-7), antibodies to these viruses were tested in the serum from three groups of individuals: (1) 10 CFS patients with chronic fatigue beginning with a clinical pattern of acute infectious mononucleosis [IM; true chronic IM (CIM)]; (2) 10 CFS patients whose illness did not start with acute IM (non-CIM), and (3) healthy controls.

High EBV antibody titers were demonstrated in most patients. Antibodies to ZEBRA, a product of the immediate early EBV gene BZLF1, were detected in the serum of CFS patients at a higher frequency than in healthy controls. Antibody titers to HHV-6 and HHV-7 were also higher in the patients with CFS than in the controls. These results are consistent with the view that CFS patients may have reactivations of EBV, HHV-6 and HHV-7.

 

Source: Sairenji T, Yamanishi K, Tachibana Y, Bertoni G, Kurata T. Antibody responses to Epstein-Barr virus, human herpesvirus 6 and human herpesvirus 7 in patients with chronic fatigue syndrome. Intervirology. 1995;38(5):269-73. http://www.ncbi.nlm.nih.gov/pubmed/8724857

 

High titers of anti-Epstein-Barr virus DNA polymerase are found in patients with severe fatiguing illness

Abstract:

Forty-one patients with chronic fatigue syndrome (CFS), 76 healthy controls matched with the patient group for age range, sex, race, and socioeconomic class, and 22 symptomatic patients with seasonal affective disorder (SAD) had serum sampled for antibodies against 2 Epstein-Barr virus (EBV) replicating enzymes.

Abnormal titers of antibodies were found twice as often in CFS patients as controls (34.1% vs. 17.1%), with SAD patients having an intermediate frequency (27.3%). Stratifying for disease severity sharpened the differences considerably, with the sicker CFS and SAD patients having 52% and 50% abnormal tests, respectively; more mildly afflicted CFS and SAD patients had a frequency of abnormal tests in the normal range.

Antibodies to EBV DNA polymerase (DNAP) were the more sensitive of the two tests in that they were positive in all cases but one. These findings suggest that antibodies against EBV DNAP may be a useful marker in delineating a subset of patients with severe fatiguing illness for appropriate treatment trials and for monitoring their outcomes.

 

Source: Natelson BH, Ye N, Moul DE, Jenkins FJ, Oren DA, Tapp WN, Cheng YC. High titers of anti-Epstein-Barr virus DNA polymerase are found in patients with severe fatiguing illness. J Med Virol. 1994 Jan;42(1):42-6. http://www.ncbi.nlm.nih.gov/pubmed/8308519

 

Chronic fatigue syndrome: a novel disorder with cutaneous manifestations

Abstract:

Persistent and disabling fatigue associated with low-grade fever and other constitutional symptoms, without any known disorder that accounts for it, is recognized as chronic fatigue syndrome (CFS). Skin lesions occur in 10-35% of patients, but their description is inaccurate. Recurrent aphthous stomatitis or persistent Epstein-Barr virus (EBV)-related erythema multiforme have also been reported. Patients may be diagnosed as having CFS only when they fulfill at least 2 major and 8 minor criteria. Major criteria are the presence of debilitating fatigue persisting or recurring for at least 6 months and the absence of any other medical disorder that may explain it. Although different viral or nonviral etiologies have been documented, evidence implicating EBV is gaining support.

 

Source: Rebora A, Drago F. Chronic fatigue syndrome: a novel disorder with cutaneous manifestations. Dermatology. 1994;188(1):3-5. http://www.ncbi.nlm.nih.gov/pubmed/8305753

 

Chronic fatigue syndrome

Abstract:

The authors followed up for a period of 1-14 years 52 patients with CFS who met the criteria outlined by Holmes. The group comprised 10 men and 42 women. In 15% of these patients after a mean period of 5.5 years thyroiditis was diagnosed. Complete recovery was recorded in 20%, improvement in 32% of the patients, on average after 7 years. In the course of treatment mainly immunomodulating preparations were used. Indication of these drugs was individual based on immunological examinations. The success was only partial. The clinical condition of the patients did not correlate with serological findings of IgM, IgA and IgG antibodies against VCA nor with antibodies against EA of the EBV virus.

 

Source: Fucíková T, Petanová J. Chronic fatigue syndrome. Vnitr Lek. 1993 Oct;39(10):995-1002. [Article in Czech] http://www.ncbi.nlm.nih.gov/pubmed/8236872

 

Chronic fatigue syndrome–study of 51 cases treated at the Second Tokyo National Hospital

Abstract:

Fifty-one patients with chronic fatigue syndrome (CFS) were studied. Tender points, which are a characteristic clinical feature of fibromyalgia, were found in all but two of the patients at 11.4 points (mean) per patient. IgG antibody titers to EB virus viral capsid antigen were more elevated in the CFS patient group compared to that of the control (p < 0.0015). IgG antibody titers to HHV-6 were not higher in the patient group. NK cell activity was not more decreased in the patient group, whereas, the mean number of NK cells was lower (p < 0.005) in the patient group, when CD57 was used as the NK cell marker. Viral infections and/or disorders in cellular immunity may be important factors in the pathogenesis of CFS.

 

Source: Nishikai M. Chronic fatigue syndrome–study of 51 cases treated at the Second Tokyo National Hospital. Nihon Rinsho. 1992 Nov;50(11):2641-7. [Article in Japanese] http://www.ncbi.nlm.nih.gov/pubmed/1337560

 

Viral infection and its causative role for chronic fatigue syndrome

Abstract:

Patients with chronic fatigue syndrome (CFS), of unknown etiology, have been increasingly reported. This syndrome is characterized by debilitating fatigue, lymphadenopathy, and fever. Herein, I focus on and review this syndrome from the view point of the causative role of viral infection. Since the symptoms of CFS are similar to those of chronic infectious mononucleosis (CIM) or chronic Epstein-Barr virus infection (CEBV), the role of EBV has been intensively studied. The etiological relationship between EBV and CFS, however, is questioned, like other lymphotropic viruses, including human retroviruses, adenoviruses and human herpesvirus 6. Additionally, severe chronic active EBV infection syndrome (SCAEBV) is also discussed in this review because symptoms of this disorder are similar to those of CFS but more severe in degree. Currently, the cause(s) and treatment of CFS are enigmatic and require further research and multidisciplinary study.

 

Source: Okano M. Viral infection and its causative role for chronic fatigue syndrome. Nihon Rinsho. 1992 Nov;50(11):2617-24. [Article in Japanese] http://www.ncbi.nlm.nih.gov/pubmed/1337559

 

Chronic fatigue syndrome and virus infection: human herpesvirus 6 (HHV-6) infection

Abstract:

Chronic fatigue syndrome (CFS) is newly-recognized disease characterized by chronic and debilitating fatigue. It has been suggested that viral infection may be involved in this syndrome from the results of clinical examination, including increased activity of 2′,5′-synthetase in leukocytes of patients. The following viruses have been reported as etiologic agents of this disease. First, many studies have found elevated levels of IgG to viral capsid antigen and early antigens to Epstein-Barr virus (EBV), but low titer or absence of antibody to EBV-associated nuclear antigen. Second, the enteroviruses have also been implicated as possible causative agent of CFS, because virus could be isolated from patients. Recently it was also reported that antibodies to human T-lymphotropic virus (HTLV) and HTLV type II (HTLV-II) gag sequence were detectable in patients. Finally several reports state that human herpesvirus 6 (HHV-6) could be isolated from CFS patients in the high frequency. In conclusion, it is still early to identify the etiologic agent from these reports, and more effort is needed.

 

Source: Yamanishi K. [Chronic fatigue syndrome and virus infection: human herpesvirus 6 (HHV-6) infection]. Nihon Rinsho. 1992 Nov;50(11):2612-6. [Article in Japanese] http://www.ncbi.nlm.nih.gov/pubmed/1337558