Category: Viruses

Clinical correlates of infection with human herpesvirus-6

Abstract:

Human herpesvirus-6 is a lymphotropic virus which infects susceptible individuals during the first year of life and usually causes life-long latency. In a variable percentage primary infections are followed by a short acute disease, exanthema subitum. Older individuals may suffer from infectious mononucleosis-like illnesses or from Kikuchi-Fujimoto’s disease. In addition, there is a fairly wide spectrum of lymphoid and hematopoietic diseases or autoimmune disorders, which are associated with elevated titers of HHV-6 antibody, and from which replicating virus may be isolated. Such diseases include atypical polyclonal lymphoproliferation, Hodgkin’s disease, chronic fatigue syndrome and systemic lupus erythematosus. The present article reviews the current knowledge of such associations.

 

Source: Krueger GR, Klueppelberg U, Hoffmann A, Ablashi DV. Clinical correlates of infection with human herpesvirus-6. In Vivo. 1994 Jul-Aug;8(4):457-85. http://www.ncbi.nlm.nih.gov/pubmed/7893974

 

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

 

Studies on enterovirus in patients with chronic fatigue syndrome

Abstract:

A large study on 121 patients with the chronic fatigue syndrome (CFS) that examined muscle biopsy samples for enterovirus by means of polymerase chain reaction analysis was carried out. The results were compared with those obtained from 101 muscle biopsy specimens from patients with a variety of other neuromuscular disorders (OND), including neurogenic atrophies, dystrophies, and mitochondrial, metabolic, and endocrine myopathies.

Thirty-two (26.4%) of the biopsy specimens from the group of patients with CFS were positive, compared with 20 (19.8%) from the group of patients with OND, a difference that was not significant.

This finding is in contrast to those of our previous smaller study in which significantly more patients with CFS than control subjects (53% [32 of 60] vs. 15% [6 of 41]) had enterovirus RNA sequences in their muscle. It was concluded that it is unlikely that persistent enterovirus infection plays a pathogenetic role in CFS, although an effect in initiating the disease process cannot be excluded.

 

Source: Gow JW, Behan WM, Simpson K, McGarry F, Keir S, Behan PO. Studies on enterovirus in patients with chronic fatigue syndrome. Clin Infect Dis. 1994 Jan;18 Suppl 1:S126-9. http://www.ncbi.nlm.nih.gov/pubmed/8148439

 

Lack of evidence for infection with known human and animal retroviruses in patients with chronic fatigue syndrome

Abstract:

We investigated 21 patients with chronic fatigue syndrome who were identified through the surveillance system of the Centers for Disease Control and Prevention (CDC) in Atlanta for the presence of several human and animal retroviruses. In addition, we evaluated 21 CDC employee controls matched with the patients for age (+/- 5 years), gender, and race.

The viruses tested included human T-lymphotropic viruses types I and II; human spuma retrovirus; simian T-lymphotropic virus type I; simian retroviruses types 1, 2, and 3; bovine leukemia virus; feline leukemia virus; and gibbon ape leukemia virus.

Samples of peripheral blood lymphocytes and leukocytes from patients and controls were analyzed in a blinded fashion for retroviral sequences; polymerase chain reaction (PCR) amplification assays and Southern blot hybridization to 32P-labeled internal oligoprobes were used. All PCR assays were optimized for maximal sensitivity on respective infected cell lines or plasmids, and sensitivity controls were included in each experiment.

All samples from patients and controls were negative for the tested retroviral sequences. Our data indicate that none of these retroviruses plays an etiologic role or is a cofactor in the chronic fatigue syndrome illnesses of our study population.

 

Source: Heneine W, Woods TC, Sinha SD, Khan AS, Chapman LE, Schonberger LB, Folks TM. Lack of evidence for infection with known human and animal retroviruses in patients with chronic fatigue syndrome. Clin Infect Dis. 1994 Jan;18 Suppl 1:S121-5. http://www.ncbi.nlm.nih.gov/pubmed/8148438

 

Viral studies of chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) has many characteristics suggesting persistent fatigue following a viral illness. At least nine different RNA and DNA viruses have been considered to be associated with this disease, but none of these viruses has been found to be the etiologic agent. Immunologic studies have demonstrated activated CD8+ cells and reduced function of natural killer cells suggesting a host response to an infection that has led to persistent immune disorders. Some of the symptoms of CFS may be due to cytokines produced by this hyperactive immune response to a virus that is still present in the host or that has been eliminate but leaves abnormal immunologic sequelae. These possibilities offer directions for future studies of CFS and therapeutic approaches to this condition.

 

Source: Levy JA. Viral studies of chronic fatigue syndrome. Clin Infect Dis. 1994 Jan;18 Suppl 1:S117-20. http://www.ncbi.nlm.nih.gov/pubmed/8148437

 

Prevalence of human herpesvirus 6 variants A and B in patients with chronic fatigue syndrome

Abstract:

 

Peripheral blood mononuclear cells collected from 13 patients with chronic fatigue syndrome and 13 healthy controls were analyzed for the presence of human herpesvirus 6 (HHV-6) DNA by variant-specific polymerase chain reaction and dot blot hybridization. HHV-6 DNA was detected in 7 of 13 (53%) patients, and of those 7 patients, 4 were positive for HHV-6 variant A DNA and 3 were for variant B. No HHV-6 DNA was detected in the controls. Serum antibody titers to the late antigen and antibody prevalence to the early antigen of HHV-6 were significantly higher in the patient group. These results suggest active replication of HHV-6 in patients with chronic fatigue syndrome.

 

Source: Yalcin S1, Kuratsune H, Yamaguchi K, Kitani T, Yamanishi K. Prevalence of human herpesvirus 6 variants A and B in patients with chronic fatigue syndrome. Microbiol Immunol. 1994;38(7):587-90. http://onlinelibrary.wiley.com/doi/10.1111/j.1348-0421.1994.tb01827.x/pdf (Full article)

 

Chronic fatigue syndrome: immune dysfunction, role of pathogens and toxic agents and neurological and cardial changes

Abstract:

375 patients with chronic fatigue syndrome (CFS) were examined using a standardized questionnaire and subsequent interview on 11 risk factors and 45 symptoms. Additionally immunologic, serologic, toxicologic, neuroradiologic, neurophysiologic and cardiologic investigations were performed.

Immunologic tests showed cellular immunodeficiences particularly in functional regard (pathological lymphocyte stimulation in 50% of the patients, disorders of granulocyte function in 44%). Furthermore variable deviations were found in the lymphocyte subpopulations (CD3, CD4, CD8, CD19, DR, Leu 11 + 19).

In the humoral part tendencies to low IgG-3- and IgG-1-subclass-levels occurred (59% respectively 11% of the patients) also as decreases in complement system (CH50, C3, C4, C1-esterase-inhibitor). In the group of activation markers and cytokines 42% of the investigated patients had circulating immune complexes (CIC), 47% increases of tumor-necrosis-factor (TNF-a) and 21% increases of soluble interleukin-2-receptor (IL-2-R).

The increased occurrence of autoantibodies in the CFS-patients (specially antinuclear anti-bodies [ANA], microsomal thyroid antibodies) suggest, that CFS is associated with or the beginning of manifest autoimmune disease.

Under the pathogens 78% of the patients had a striking serological constellation of Epstein-Barr-Virus (EBV-EA positive, low EBNA-titers), in the HHV-6-Virus 47% showed increased antibody-titers. Tests on further herpes viruses and on Borreliae, Chlamydiae, Candida and Amoebae were positive in 8 to 36% of the examined patients. Furthermore there were found variable deficits of vitamins and trace elements also as hormonal disturbances.

In 26% of the patients there were hints of pollutants (e.g. wood preservatives), in 32 patients blood-levels of pentachlorphenol (PCP) and gamma-hexachlorcyclohexan (γ-HCH, lindan) were measured, which showed vanable increases.

178 (83%) of 225 investigated patients showed disturbances of perfusion in cerebral SPECT imaging, 65 (29%) of 218 patients cerebral punctuate signal changes in cranial magnetic resonance imaging (MRI).

Neurophysiologic measurements (motor evoked potentials, MEP) showed in about 50% of 112 patients prolonged central motor conduction times. 62 patients were additionally investigated by myocardial SPECT-imaging, which was abnormal under exercise in 73%. Our data confirm the concept, that CFS must be considered as a complex psycho-neuro-immunological disorder.

 

Source: Hilgers A, Frank J. Chronic fatigue syndrome: immune dysfunction, role of pathogens and toxic agents and neurological and cardial changes. Wien Med Wochenschr. 1994;144(16):399-406.[Article in German] http://www.scopus.com/record/display.uri?eid=2-s2.0-0027940724&origin=inward&txGid=0

and http://www.ncbi.nlm.nih.gov/pubmed/7856214

 

 

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

 

Detection of Epstein-Barr virus and cytomegalovirus in patients with chronic fatigue

Abstract:

Patients with chronic fatigue as a major complaint frequently present with recurrent sore throat, and on physical examination they have hyperemia and lymphoid hyperplasia of the pharyngeal area.

Pharyngeal scrapings were obtained from 41 such patients and analyzed for Epstein-Barr virus or cytomegalovirus DNA by colorimetric in situ hybridization. Results were compared with healthy control subjects matched for age and sex. Epstein-Barr virus-DNA was detected more frequently in male patients, 5/9 (55.6%), than controls, 0/6 (0%), but there was no difference in frequency in female patients, 4/32 (12.5%), than control subjects, 1/29 (3.4%).

Cytomegalovirus-DNA was detected infrequently in patients and controls, 13% versus 22% respectively. The presence of EBV-DNA did not correlate with antibody titers nor with the complaint of sore throat. Four of the five males who had positive EBV-DNA in the pharyngeal smears have now recovered.

 

Source: Wray BB, Gaughf C, Chandler FW Jr, Berry SS, Latham JE, Wood L, DuRant RH. Detection of Epstein-Barr virus and cytomegalovirus in patients with chronic fatigue. Ann Allergy. 1993 Sep;71(3):223-6. http://www.ncbi.nlm.nih.gov/pubmed/8396863