Tag: EBV

Acyclovir treatment of the chronic fatigue syndrome. Lack of efficacy in a placebo-controlled trial

Abstract:

Twenty-seven adults with a diagnosis of the chronic fatigue syndrome were enrolled in a double-blind, placebo-controlled study of acyclovir therapy. The patients had had debilitating fatigue for an average of 6.8 years, accompanied by persisting antibodies to Epstein-Barr virus early antigens (titers greater than or equal to 1:40) or undetectable levels of antibodies to Epstein-Barr virus nuclear antigens (titers less than 1:2) or both.

Each course of treatment consisted of intravenous placebo or acyclovir (500 mg per square meter of body-surface area) administered every eight hours for seven days. The same drug was then given orally for 30 days (acyclovir, 800 mg four times daily). There were six-week observation periods before, between, and after the treatments. Three patients had acyclovir-induced nephrotoxicity and were withdrawn from the study.

Of the 24 patients who completed the trial, similar numbers improved with acyclovir therapy and with placebo (11 and 10, respectively). Neither acyclovir treatment nor clinical improvement correlated with alterations in laboratory findings, including titers of antibody to Epstein-Barr virus or levels of circulating immune complexes or of leukocyte 2′,5′-oligoadenylate synthetase. Subjective improvement correlated with various measures of mood.

We conclude that acyclovir, as used in this study, does not ameliorate the chronic fatigue syndrome. We believe that the clinical improvement observed in most patients reflected either spontaneous remission of the syndrome or a placebo effect.

 

Source: Straus SE, Dale JK, Tobi M, Lawley T, Preble O, Blaese RM, Hallahan C, Henle W. Acyclovir treatment of the chronic fatigue syndrome. Lack of efficacy in a placebo-controlled trial. N Engl J Med. 1988 Dec 29;319(26):1692-8. http://www.ncbi.nlm.nih.gov/pubmed/2849717

 

Epstein-Barr virus and the chronic fatigue syndrome: a short review

Abstract:

Chronic Fatigue Syndrome (CFS), previously known as neuroasthenia is often considered to be due to psychiatric causes. Evidence for a possible role for the Epstein-Barr virus in CFS is summarized. A plea is made for physicians to accept CFS as a non-psychiatric chronic illness to encourage further research into a clear definition of the syndrome.

 

Source: Jones JF. Epstein-Barr virus and the chronic fatigue syndrome: a short review. Microbiol Sci. 1988 Dec;5(12):366-9.  http://www.ncbi.nlm.nih.gov/pubmed/2856301

 

Chronic fatigue syndrome: a working case definition

Abstract:

The chronic Epstein-Barr virus syndrome is a poorly defined symptom complex characterized primarily by chronic or recurrent debilitating fatigue and various combinations of other symptoms, including sore throat, lymph node pain and tenderness, headache, myalgia, and arthralgias.

Although the syndrome has received recent attention, and has been diagnosed in many patients, the chronic Epstein-Barr virus syndrome has not been defined consistently. Despite the name of the syndrome, both the diagnostic value of Epstein-Barr virus serologic tests and the proposed causal relationship between Epstein-Barr virus infection and patients who have been diagnosed with the chronic Epstein-Barr virus syndrome remain doubtful.

We propose a new name for the chronic Epstein-Barr virus syndrome–the chronic fatigue syndrome–that more accurately describes this symptom complex as a syndrome of unknown cause characterized primarily by chronic fatigue. We also present a working definition for the chronic fatigue syndrome designed to improve the comparability and reproducibility of clinical research and epidemiologic studies, and to provide a rational basis for evaluating patients who have chronic fatigue of undetermined cause.

 

Source: Holmes GP, Kaplan JE, Gantz NM, Komaroff AL, Schonberger LB, Straus SE, Jones JF, Dubois RE, Cunningham-Rundles C, Pahwa S, et al. Chronic fatigue syndrome: a working case definition. Ann Intern Med. 1988 Mar;108(3):387-9. http://www.ncbi.nlm.nih.gov/pubmed/2829679

 

“Chronic Epstein-Barr virus infection” syndrome and polymyalgia rheumatica

Abstract:

Twenty-three patients with polymyalgia rheumatica (PMR) followed in an academic rheumatology practice frequently reported symptoms commonly found in the recently described “chronic fatigue syndrome” or “chronic Epstein-Barr infection syndrome.” These symptoms persisted for months after treatment had reduced the severity of the myalgias and lowered the sedimentation rate: periodically disabling fatigue (33%), recurrent pharyngitis (30%), sleep disorder (65%) and arthralgias (70%). However, antibody titers to Epstein-Barr virus in the patients with PMR were not significantly different from those in age and sex matched control subjects.

 

Source: Buchwald D, Sullivan JL, Leddy S, Komaroff AL. “Chronic Epstein-Barr virus infection” syndrome and polymyalgia rheumatica. J Rheumatol. 1988 Mar;15(3):479-82. http://www.ncbi.nlm.nih.gov/pubmed/2837573

 

Chronic fatigue syndromes: relationship to chronic viral infections

Abstract :

Chronic fatigue syndrome (CFS) is a newly-recognized clinical entity characterized by chronic, debilitating fatigue lasting longer than six months. Common associated findings are chronic and recurrent fever, pharyngitis, myalgias, adenopathy, arthralgias, difficulties in cognition and disorders of mood. In the majority of patients, the illness starts suddenly with an acute, ‘flu-like’ illness.

The following abnormalities are seen with some frequency although none are seen in all patients: lymphocytosis, atypical lymphocytosis, monocytosis, elevation of hepatocellular enzymes, low levels of antinuclear antibodies, low levels of immune complexes.

Clinical and serologic studies suggest an association of CFS with all of the human herpesviruses, particularly Epstein-Barr virus (EBV) and the recently-discovered human B-lymphotropic virus (HBLV) or human herpesvirus-6; neither EBV nor HBLV has yet been shown to play a causal role in the illness.

 

Source: Komaroff AL. Chronic fatigue syndromes: relationship to chronic viral infections. J Virol Methods. 1988 Sep;21(1-4):3-10. http://www.ncbi.nlm.nih.gov/pubmed/2846619

 

Chronic fatigue syndrome and the diagnostic utility of antibody to Epstein-Barr virus early antigen

Abstract:

Antibody to Epstein-Barr virus (EBV) early antigen has been said to be the most specific indicator of symptomatic chronic EBV infection. We studied the clinical utility of this serologic test in the evaluation of patients with chronic fatigue.

Thirty patients with chronic fatigue and highly elevated titers of antibody to early antigen (greater than or equal to 1:160) were compared with 30 age- and sex-matched controls with no antibody to early antigen.

There were no significant differences noted between patients and controls at the initial evaluation (symptoms, physical examination, laboratory data). Follow-up information, available for 15 matched pairs, showed no differences in outcome between patients and controls. We conclude that the antibody to EBV early antigen is not helpful in the clinical evaluation of patients with chronic fatigue.

 

Source: Hellinger WC1, Smith TF, Van Scoy RE, Spitzer PG, Forgacs P, Edson RS. Chronic fatigue syndrome and the diagnostic utility of antibody to Epstein-Barr virus early antigen. JAMA. 1988 Aug 19;260(7):971-3. http://www.ncbi.nlm.nih.gov/pubmed/2840523

 

Antibodies to Epstein-Barr virus-specific DNase and DNA polymerase in the chronic fatigue syndrome

Abstract:

In an attempt to examine further the association between active Epstein-Barr virus (EBV) infection and the chronic fatigue syndrome (chronic EBV syndrome, or chronic or atypical mononucleosis), antibodies acting against EBV-specific DNase and DNA polymerase, which are expressed only during virus replication, were assayed.

Serum samples from 25 healthy EBV-seropositive individuals neutralized 3.5 +/- 5.1 U (mean +/- SD) of DNase activity and 14.7 +/- 8.5 U of DNA polymerase activity. From these values were selected upper limits of anti-EBV enzyme activity of 17.9 and 31.3 U neutralized in normal individuals, respectively (representing the 95% confidence limit). Serum samples from six groups of subjects representing a variety of EBV-related illnesses were then studied.

Only patients with notably elevated anti-EBV antibody titers to viral capsid antigen (VCA) (greater than 10,000) had elevated levels of anti-EBV DNase (38 to 56 U neutralized) and anti-EBV DNA polymerase (72 to 106 U neutralized). Three additional patients and two geriatric controls with average anti-EBV early antigen/VCA titers had slightly elevated levels of antibody to EBV DNA polymerase. IgA anti-VCA, anti-early antigen antibodies, or both, were also detected in the same patients who had high EBV DNase and polymerase antibody levels.

These antibody profiles are similar to those in patients with nasopharyngeal carcinoma. Since three of the six patients with elevated anti-EBV enzyme antibody levels developed fatal lymphomas, patients with chronic EBV and this antibody profile might be in another illness category at risk for malignant disease.

 

Source: Jones JF, Williams M, Schooley RT, Robinson C, Glaser R. Antibodies to Epstein-Barr virus-specific DNase and DNA polymerase in the chronic fatigue syndrome. Arch Intern Med. 1988 Sep;148(9):1957-60. http://www.ncbi.nlm.nih.gov/pubmed/2843138

 

Chronic mononucleosis syndrome

Abstract:

We present data on 14 patients with chronic symptoms of disabling fatigue in association with serologic evidence of active Epstein-Barr virus (EBV) infection. Two thirds were women, and the average age at onset was 29.6 years. Forty-three percent were known to have had previous infectious mononucleosis, but the usual criteria for that diagnosis were not helpful with the present syndrome.

Eighty-six percent had serologic evidence of cytomegalovirus (CMV) infection. Profound immunodeficiency was not present, but 71% had partial hypogammaglobulinemia, and minor abnormalities of T cell subsets were noted in six of seven patients studied.

Fifty-seven percent achieved temporary serologic and symptomatic remission after an average duration of 33 months. Only one patient has a sustained remission.

Comparison is made with other reported chronic, recurrent, and persistent EBV syndromes, and tentative diagnostic criteria for chronic mononucleosis syndrome are presented. Recently available EBV serologic techniques allow for identification of patients who have reactivated EBV infection, and this reactivation may be related to symptoms.

 

Source: DuBois RE, Seeley JK, Brus I, Sakamoto K, Ballow M, Harada S, Bechtold TA, Pearson G, Purtilo DT. Chronic mononucleosis syndrome. South Med J. 1984 Nov;77(11):1376-82.  http://www.ncbi.nlm.nih.gov/pubmed/6093268

 

A cluster of patients with a chronic mononucleosis-like syndrome. Is Epstein-Barr virus the cause?

Abstract:

A cluster of 134 patients who had undergone Epstein-Barr virus (EBV) serological testing because of suspected chronic EBV syndrome was investigated in Nevada.

Fifteen case-patients were identified who had severe, persistent fatigue of undetermined etiology for more than two months. When compared with the remaining 119 patients who had less severe illnesses and with 30 age-, sex-, and race-matched control-persons, these 15 patients had significantly higher antibody titers against various components of EBV and against cytomegalovirus and herpes simplex and measles viruses. Epstein-Barr virus serology could not reliably differentiate individual case-patients from the others, and the reproducibility of the tests within and among laboratories was poor.

As a group, the case-patients appear to have had a syndrome that is characterized by chronic fatigue, fever, sore throat, and lymphadenopathy. The relationship of this fatigue syndrome to EBV is unclear; further studies are needed to determine its etiology.

 

Source: Holmes GP, Kaplan JE, Stewart JA, Hunt B, Pinsky PF, Schonberger LB. A cluster of patients with a chronic mononucleosis-like syndrome. Is Epstein-Barr virus the cause? JAMA. 1987 May 1;257(17):2297-302. http://www.ncbi.nlm.nih.gov/pubmed/3033337

 

Frequency of ‘chronic active Epstein-Barr virus infection’ in a general medical practice

Abstract:

Twenty-one percent of 500 unselected patients, aged 17 to 50 years, seeking primary care for any reason were found to be suffering from a chronic fatigue syndrome consistent with “chronic active Epstein-Barr virus (EBV) infection,” They had been experiencing “severe” fatigue, usually cyclic, for a median of 16 months (range, six to 458 months), associated with sore throat, myalgias, or headaches; 45% of the patients were periodically bedridden; and 25% to 73% reported recurrent cervical adenopathy, paresthesias, arthralgias, and difficulty in concentrating or sleeping.

The patients had no recognized chronic “physical” illness and were not receiving psychiatric care. While antibody titers to several EBV-specific antigens were higher in patients than in age- and sex-matched controls subjects, the differences generally were not statistically significant.

A chronic fatigue syndrome consistent with the chronic active EBV infection syndrome was prevalent in our primary care practice. However, our data offer no evidence that EBV is causally related to the syndrome. Indeed, we feel that among unselected patients seen in a general medical practice currently available EBV serologic test results must be interpreted with great caution.

 

Source: Buchwald D, Sullivan JL, Komaroff AL. Frequency of ‘chronic active Epstein-Barr virus infection’ in a general medical practice. JAMA. 1987 May 1;257(17):2303-7. http://www.ncbi.nlm.nih.gov/pubmed/3033338