Tag: EBV

Antibodies to Epstein-Barr virus in patients with chronic fatigue

Abstract:

To clarify the role of Epstein-Barr virus (EBV) infection and the value of EBV antibody testing in evaluating patients with chronic fatigue, we studied 200 consecutive patients with chronic fatigue (mean duration, 9 years).

Complete EBV serologic panels were obtained for 154 patients, 35 (23%) of whom met serologic or clinical criteria for chronic or reactivated EBV infection. We compared these patients with chronic EBV infection (CEBV cases) to 35 age- and sex-matched patients who were selected from the same cohort of fatigued patients but who did not meet the criteria (CEBV control subjects).

We found few differences between groups in demographic characteristics, clinical features, and symptoms; CEBV cases were more likely to meet criteria for the proposed chronic fatigue syndrome (14% vs 0%), and to report that they suffered from an influenza-like illness at the onset of their fatigue syndrome (34% vs 12%), that they lost their job because of their fatigue (37% vs 11%), and that their fatigue was improved by recreational activity (26% vs 3%).

Physical examination and laboratory testing showed few abnormalities in either group. Psychiatric morbidity was common in both groups, including mood disorders (63% of CEBV cases vs 54% of CEBV controls), anxiety (11% vs 9%) and somatization disorder (9% in each group).

We conclude that EBV serologic patterns have little clinical usefulness in evaluating patients with chronic fatigue.

 

Source: Matthews DA, Lane TJ, Manu P. Antibodies to Epstein-Barr virus in patients with chronic fatigue. South Med J. 1991 Jul;84(7):832-40. http://www.ncbi.nlm.nih.gov/pubmed/1648795

 

Postinfectious chronic fatigue syndrome: case history of thirty-five patients in Germany

Abstract:

Thirty-five patients with chronic fatigue syndrome according to the criteria of Holmes were followed for periods of up to eight years. The most frequent symptoms were severe fatigue, arthralgias and myalgias, recurrent oropharyngitis and various psychiatric disorders.

More than half of the patients suffered from neuropathy, lymphadenopathy, gastrointestinal complaints and recurrent low-grade fever. Recurrent or persistent activity of human herpesvirus -6 infection was seen in 73% of the patients and of Epstein-Barr virus in 34.4%. In addition, various other infections were diagnosed at lower frequency.

Initial routine immunologic screening revealed various types of deficiencies, these were yet inconsistent and variable when different patients were compared with each other. Tentative treatments included in immunoglobulins, nonspecific immunostimulation and virostatic drugs. No consistently positive results were obtained with any treatment schedule although immunoglobulins appeared the most efficient measure. In addition, psychologic care of the patients is indicated, since disturbances in the psycho-neuroimmunologic regulation may play a significant role in the pathogenesis of the disease.

 

Source: Hilgers A, Krueger GR, Lembke U, Ramon A. Postinfectious chronic fatigue syndrome: case history of thirty-five patients in Germany. In Vivo. 1991 May-Jun;5(3):201-5. http://www.ncbi.nlm.nih.gov/pubmed/1893076

 

Frequent double infection with Epstein-Barr virus and human herpesvirus-6 in patients with acute infectious mononucleosis

Abstract:

Clinical infectious mononucleosis (IM) represents a benign self-limited form of lymphoproliferative disease which is usually caused by infection with Epstein-Barr virus (EBV). Microscopic characteristics of this lymphoproliferative disorder, however, are not ultimately specific for EBV infection, but can also be seen in infections with other lymphotropic viruses, especially of the herpesvirus family.

Human herpesvirus-6 (HHV-6) infection can apparently be associated with a number of diseases also seen in EBV infection. Also, postinfectious chronic fatigue syndrome (PICFS) which may follow IM is in more than 60% of the cases accompanied by persistent active HHV-6 infection.

We thus screened serologically 215 cases of acute IM for evidence for infection with EBV, HHV-6 and CMN. Patients were tentatively grouped into those having primary infection or reactivated (probably non-primary) infections. Cases were followed for two years to monitor changes in titers.

Of all 215 cases, 211 (98.1%) were positive for EBV, 137 (63.7%) for primary infections, 21 (9.8%) for reactivated infection, and 53 (24.6%) for latent EBV. Thirty-three (15.3%) cases had primary HHV-6 infection, 63 (29.3%) active or reactivated HHV-6 infection, and 71 (33.9%) latent HHV-6. Double active EBV and HHV-6 infection, including primary and reactivated infections, amounted to 89 (39.5%) cases. Cytomegalovirus (CMV) antibody titers were found in 81 (37%) cases, 48 (22.3%) of which indicated latent infection and 33 (15.3%) active infection. Only two cases had evidence of active CMV infection alone, 1 cases of active CMV and HHV-6 infection. Serologic titers in 12 (5.6%) cases indicated combined active infection with CMV, EBV and HHV-6.

(ABSTRACT TRUNCATED AT 250 WORDS)

 

Source: Bertram G, Dreiner N, Krueger GR, Ramon A, Ablashi DV, Salahuddin SZ, Balachandram N. Frequent double infection with Epstein-Barr virus and human herpesvirus-6 in patients with acute infectious mononucleosis. In Vivo. 1991 May-Jun;5(3):271-9. http://www.ncbi.nlm.nih.gov/pubmed/1654150

 

Enteroviral RNA sequences detected by polymerase chain reaction in muscle of patients with postviral fatigue syndrome

Abstract:

OBJECTIVE: To determine the presence of enteroviral sequences in muscle of patients with the postviral fatigue syndrome.

DESIGN: Detection of sequences with the polymerase chain reaction in a well defined group of patients with the syndrome and controls over the same period.

SETTING: Institute of Neurological Sciences, Glasgow.

SUBJECTS: 60 consecutive patients admitted to the institute with the postviral fatigue syndrome who had undergone extensive investigation to exclude other conditions. 41 controls from the same catchment area without evidence of fatigue, all undergoing routine surgery.

MAIN OUTCOME MEASURES: Routine investigations, serological screen for antibodies to a range of viruses, and presence of enteroviral RNA sequences in muscle biopsy specimens.

RESULTS: 15 (25%) patients and 10 (24.4%) controls had important serological findings. 12 patients had neutralising antibody titres of greater than or equal to 256 to coxsackieviruses B1-5 (six positive for enteroviral RNA sequences, six negative); three were positive for Epstein-Barr virus specific IgM (two positive, one negative). Six controls had similar neutralising antibody titres to coxsackieviruses (all negative); one was positive for Epstein-Barr virus specific IgM (negative); and three had titres of complement fixing antibody greater than or equal to 256 to cytomegalovirus (all negative). Overall, significantly more patients than controls had enteroviral RNA sequences in muscle (32/60, 53% v 6/41, 15%; odds ratio 6.7, 95% confidence interval 2.4 to 18.2). This was not correlated with duration of disease, patient and age, or to raised titres of antibodies to coxsackieviruses B1-5.

CONCLUSIONS: Persistent enteroviral infection of muscle may occur in some patients with postviral fatigue syndrome and may have an aetiological role.

Comment in: Postviral fatigue syndrome. [BMJ. 1991]

 

Source: Gow JW, Behan WM, Clements GB, Woodall C, Riding M, Behan PO. Enteroviral RNA sequences detected by polymerase chain reaction in muscle of patients with postviral fatigue syndrome. BMJ. 1991 Mar 23;302(6778):692-6. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1669122/ (Full article)

 

Chronic fatigue syndrome: I. Epstein-Barr virus immune response and molecular epidemiology

Abstract:

Patients with chronic fatigue syndrome were compared to healthy seropositive control subjects in an open study and a case-control study analyzing spontaneous transformation rates of peripheral blood lymphocytes, EBV viral genome characteristics as determined by DNA restriction fragment polymorphisms, and antibody production by Western blot analysis.

Thirty percent of patients versus 8% of control subjects underwent spontaneous transformation in the two studies. Viral genome patterns were overall similar to one another, with polymorphisms frequently present in BamHI B’, K, H, and Y fragments. Only one line was found with the EBNA-2B genotype.

Nineteen lines were found to contain viral DNA in the linear form suggesting active lytic replication. Western blot studies suggested that ill subjects made antibodies to lytic proteins more frequently than did healthy control subjects. Lack of control of EBV outgrowth in vitro is correlated with antibody evidence of active infection in vivo in some patients with chronic fatigue syndrome.

 

Source: Jones JF, Streib J, Baker S, Herberger M. Chronic fatigue syndrome: I. Epstein-Barr virus immune response and molecular epidemiology. J Med Virol. 1991 Mar;33(3):151-8. http://www.ncbi.nlm.nih.gov/pubmed/1679118

 

Infectious mononucleosis, Epstein-Barr virus, and chronic fatigue syndrome: a prospective case series

Abstract:

Epstein-Barr viral infection, specifically infectious mononucleosis, typically has a more protracted course than other acute viral illnesses. Some recent observers have additionally suggested the possibility that Epstein-Barr virus (EBV) is the etiologic infectious agent in chronic fatigue syndrome, based on the finding of higher proportions of elevated antibodies to the EBV early antigen in some patients complaining of chronic fatigue.

Straus et al reported on 23 patients with chronic fatigue, 83% of whom exhibited persistently elevated antibodies in modest titer to the early antigen. Ten of these patients had never fully recovered from an episode of acute infectious mononucleosis. Other studies had noted similar associations between persistently elevated antibodies to EBV-specific antigens and chronic symptoms in patients who presented with chronic symptoms after mononucleosis.

Three important antigen complexes, demonstrable by immunofluorescence procedures, are expressed in EBV-infected cells. The early antigen is thought to function perhaps in early replication of viral DNA. A late antigenic complex, the viral capsid antigen, may represent, in addition to structural capsid proteins, components of the viral enzymatic machinery for late phases of replication or transformation. The Epstein-Barr nuclear antigen is felt to function in viral transformation of host cells.

 

Source: Fark AR. Infectious mononucleosis, Epstein-Barr virus, and chronic fatigue syndrome: a prospective case series. J Fam Pract. 1991 Feb;32(2):202, 205-6, 209. http://www.ncbi.nlm.nih.gov/pubmed/1846641

 

Chronic fatigue syndrome in northern Nevada

Abstract:

The clinical and laboratory findings from studies of patients with chronic fatigue syndrome (CFS) from northern Nevada are summarized. Physicians caring for these patients have estimated that greater than 400 patients with CFS from northern Nevada and nearby communities in California were identified between 1984 and 1988.

As a result of these studies, a cluster of clinical and laboratory features associated with the illness in moderately to severely affected patients has been identified: profound fatigue of prolonged duration; cervical lymphadenopathy; recurrent sore throat and/or symptoms of influenza; loss of cognitive function manifested by loss of memory and loss of ability to concentrate; myalgia; impairment of fine motor skills; abnormal findings on magnetic resonance imaging brain scan; depressed level of antibody to Epstein-Barr virus (EBV) nuclear antigen; elevated level of antibody to EBV early antigen restricted component; elevated ratio of CD4 helper to CD8 suppressor cells; and strong evidence of association of this syndrome with infection with human herpesvirus 6.

More-serious and longer-lasting neurologic impairments, including seizures, psychosis, and dementia, have also been observed in some of these patients.

 

Source: Daugherty SA, Henry BE, Peterson DL, Swarts RL, Bastien S, Thomas RS. Chronic fatigue syndrome in northern Nevada. Rev Infect Dis. 1991 Jan-Feb;13 Suppl 1:S39-44. http://www.ncbi.nlm.nih.gov/pubmed/1850542

 

Serologic and immunologic responses in chronic fatigue syndrome with emphasis on the Epstein-Barr virus

Abstract:

Although patients with chronic fatigue syndrome (CFS) can be diagnosed by clinical criteria, the lack of specific laboratory criteria delays or prevents the diagnosis and contributes to the quasi-disease status of the syndrome.

A resurgence of interest in the syndrome has followed reports suggesting that CFS may be associated with chronic active infection due to the Epstein-Barr virus. Analysis of reports to date shows that the mean titers of antibodies to viral capsid antigen and to early antigen are greater for patients with CFS than for healthy individuals; this is particularly evident in cases for which serial samples were tested.

However, these differences do not prove the cause of CFS. Cell-mediated immune responses in patients with CFS vary from study to study, and the number and function of natural killer cells in those patients are the most variable factors. Rates of isolation of virus from saliva do not differ, but in one comparison study with a large number of subjects, more lymphocytes that contained virus were isolated from patients than from controls.

Other viruses, such as the Coxsackie B virus, have been implicated as causes of CFS in studies from Great Britain. The use of a working definition of CFS and standardized tests to address abnormalities revealed by laboratory tests among homogeneous populations should allow determination of useful tests for the diagnosis of CFS and studies of its mechanisms.

 

Source:  Jones JF. Serologic and immunologic responses in chronic fatigue syndrome with emphasis on the Epstein-Barr virus. Rev Infect Dis. 1991 Jan-Feb;13 Suppl 1:S26-31. http://www.ncbi.nlm.nih.gov/pubmed/1850541

 

Serologic and virologic epidemiology of Epstein-Barr virus: relevance to chronic fatigue syndrome

Abstract:

Patients considered to have chronic fatigue syndrome (CFS) have been reported to exhibit an increased antibody response to Epstein-Barr virus (EBV) early antigen complex and capsid antigen, findings that suggest some relationship between EBV and CFS.

However, the serologic findings have not been totally consistent among different study groups, and the antibody patterns in asymptomatic individuals may be similar. Moreover, patients with symptomatology indicative of CFS do not appear to have an abnormal burden of EBV in body fluids and manifest only a variable, mild degree of EBV-specific cell-mediated responses.

The evidence is growing that the serologic findings of an enhanced EBV state in individuals with CFS-like manifestations, as well as the subsequent reports of increased antibody titers to other viruses, reflect a generalized underlying immunologic dysfunction in these patients.

Future studies with criteria-defined CFS study groups in which determinations are made of antibody responses to newly identified EBV-associated nuclear antigen components and distinct EBV proteins in addition to specific virologic and immunologic analyses of EBV may be worthwhile as a means of clarifying the association between EBV and CFS.

 

Source: Sumaya CV. Serologic and virologic epidemiology of Epstein-Barr virus: relevance to chronic fatigue syndrome. Rev Infect Dis. 1991 Jan-Feb;13 Suppl 1:S19-25. http://www.ncbi.nlm.nih.gov/pubmed/1850540

 

Detection of Epstein-Barr virus with molecular hybridization techniques

Abstract:

The cord-blood transformation assay remains the standard method for detecting Epstein-Barr virus (EBV) in secretions. However, newer methods are much faster and more sensitive, although most are still regarded as research procedures. The most useful of these are Southern blot hybridization, particularly the variation that employs terminal genomic probe analysis; in situ cytohybridization; and polymerase chain reaction analyses. Use of these methods alone or in combination should disclose the infected cell type, whether the infection is productive or latent, and the presence of multiple strains of EBV. Such information may help establish whether EBV is a causal agent in chronic fatigue syndrome.

 

Source: Pagano JS. Detection of Epstein-Barr virus with molecular hybridization techniques. Rev Infect Dis. 1991 Jan-Feb;13 Suppl 1:S123-8. http://www.ncbi.nlm.nih.gov/pubmed/1850538