Category: Viruses

A chronic “postinfectious” fatigue syndrome associated with benign lymphoproliferation, B-cell proliferation, and active replication of human herpesvirus-6

Abstract:

A 17-year-old, previously healthy woman developed an acute “mononucleosis-like” illness with an associated “atypical” pneumonitis, followed by years of debilitating chronic fatigue, fevers, a 10-kg weight loss, night sweats, and neurocognitive symptoms. Thereafter, her sister developed a similar but less severe illness.

The patient developed marked, chronic lymphadenopathy and splenomegaly, with associated persistent relative lymphocytosis and atypical lymphocytosis and with thrombocytopenia. After 3 years of illness, a splenectomy was performed, which resulted in some symptomatic improvement, prompt weight gain, and resolution of all hematologic abnormalities. Serial immunologic studies revealed a strikingly elevated number of activated B lymphocytes and a T lymphopenia, which improved but did not return to normal postsplenectomy. No causal association was found with any of several infectious agents that could produce such a lymphoproliferative illness.

However, both the patient and her sister had evidence of active infection with the recently discovered human herpesvirus-6. Seven years after the onset of the illness, the patient and her sister remain chronically ill.

 

Source:  Buchwald D, Freedman AS, Ablashi DV, Sullivan JL, Caligiuri M, Weinberg DS, Hall CG, Ashley RL, Saxinger C, Balachandran N, et al. A chronic “postinfectious” fatigue syndrome associated with benign lymphoproliferation, B-cell proliferation, and active replication of human herpesvirus-6. J Clin Immunol. 1990 Nov;10(6):335-44. http://www.ncbi.nlm.nih.gov/pubmed/1964694

 

Clinical and laboratory findings in the Paul-Bunnell negative glandular fever-fatigue syndrome

Abstract:

Forty-one patients with recurrent fatigue were studied for evidence of symptom clustering, abnormal laboratory findings and infection with novel viruses. Symptom enquiry and investigations were repeated 4 months later.

Four patients were found to have diseases compatible with their symptoms. In those remaining, an initial acute onset of symptoms was associated with an intermittent course, tender glands and a raised number of T suppressor lymphocytes. Raised numbers of T suppressor lymphocytes at follow-up correlated with resolution of symptoms. Antibodies to human herpesvirus 6 (HHV-6) were found in 75% of the patients as compared to 53% of a control group and more patients than controls were strongly seropositive.

Some patients with chronic fatigue have a pattern of illness which suggests glandular fever, although acute infection with Epstein-Barr virus (EBV) is not demonstrated. Primary or reactivation infection with HHV-6 may have a role in this syndrome.

 

Source:  Read R, Larson E, Harvey J, Edwards A, Thomson B, Briggs M, Fox J. Clinical and laboratory findings in the Paul-Bunnell negative glandular fever-fatigue syndrome. J Infect. 1990 Sep;21(2):157-65. http://www.ncbi.nlm.nih.gov/pubmed/2172387

 

Chronic fatigue syndrome

Abstract:

Reports on conditions of chronic fatigue associated with other somatopsychic symptoms after acute viral infections have led to the hypothesis of a “chronic fatigue syndrome” (CFS). Historical disease descriptions, like e.g. “myalgic encephalomyelitits”, were updated by means of modern virological diagnostic techniques and data analysis.

Several viral agents like enteroviruses, Epstein-Barr virus, Human-Herpesvirus 6 and other herpesviruses have been implicated for possible underlying infections. A preliminary disease definition by the Center for Disease Control (CDC) seeks to provide a rational basis for further etiological studies. In fact, there is growing consensus that the syndrome comprises various separate disease entities and causative agents.

Today we can tentatively differentiate a “chronic mononucleosis” after infection with Epstein-Barr virus, an etiologically undetermined “postviral fatigue syndrome” and a fatigue syndrome of the myalgic type after Coxsackie-B virus infection. Furthermore, a valid diagnosis of CFS must be based on the exclusion of defined other diseases and the awareness of dealing with a hypothetical concept. As a result, current knowledge does not yet allow specific therapeutic recommendations.

 

Source: Ewig S, Dengler HJ. Chronic fatigue syndrome. Klin Wochenschr. 1990 Aug 17;68(16):789-96. [Article in German] http://www.ncbi.nlm.nih.gov/pubmed/2170741

 

Chronic fatigue. A prospective clinical and virologic study

Abstract:

To evaluate the clinical and virologic course of patients with chronic fatigue who had elevated Epstein-Barr virus (EBV) titers, we prospectively followed up 26 patients with serial cultures for EBV in blood and saliva and serial EBV serologic and clinical and psychiatric evaluations, and we compared these results with those for healthy controls.

The frequency of isolating EBV in blood or demonstrating EBV infection by in situ hybridization in blood lymphocytes or in saliva was similar in patients and controls. The prevalence and titers of antibody to human herpesvirus type 6 were also similar in the two populations. Patients with chronic fatigue did demonstrate higher in vitro natural killer activity and lower in vitro interleukin 2 production than controls, and patients had a high frequency of DSM-III depressive illness. Over 50% of patients with chronic fatigue improved over the course of follow-up. Improvement was not associated with any discernible change in titers of EBV proteins.

No evidence of ongoing EBV infection with either transforming or nontransforming strains was demonstrated in this population of patients with chronic fatigue. Clinically, most patients gradually improve over time.

 

Source: Gold D, Bowden R, Sixbey J, Riggs R, Katon WJ, Ashley R, Obrigewitch RM, Corey L. Chronic fatigue. A prospective clinical and virologic study. JAMA. 1990 Jul 4;264(1):48-53. http://www.ncbi.nlm.nih.gov/pubmed/2162397

 

Post-viral fatigue syndrome, viral infections in atopic eczema, and essential fatty acids

Abstract:

Three clinical observations relating to viral infections are well-known but poorly understood. These are: the susceptibility of people with atopic eczema to viral infections; the occasional precipitation of an atopic syndrome by viral infections; the occurrence of a fatigue syndrome following viral infections.

A unifying hypothesis is presented which explains these observations in terms of the interactions between viral infections and essential fatty acid (EFA) metabolism. Key elements of the hypothesis are the facts that interferon requires 6-desaturated EFAs in order to exert its anti-viral effects, that people with atopic eczema have low levels of 6-desaturated EFAs, and that viruses, as part of their attack strategy, may reduce the ability of cells to make 6-desaturated EFAs.

The hypothesis has practical implications for the treatment of patients with viral infections.

 

Source: Horrobin DF. Post-viral fatigue syndrome, viral infections in atopic eczema, and essential fatty acids.  Med Hypotheses. 1990 Jul;32(3):211-7.  http://www.ncbi.nlm.nih.gov/pubmed/2204789

 

Myalgic encephalomyelitis–a persistent enteroviral infection?

Abstract:

Myalgic encephalomyelitis is a common disability but frequently misinterpreted. Amongst 6,000 patients referred for general microbiological diagnosis between 1975 and 1987, 420 cases were recognized.

Coxsackie B neutralization tests, in 205 of these, demonstrated significant titres in 103/205 (50%), while of 124 additionally investigated for enteroviral IgM, 38/124 (31%) were positive. This illness is distinguished from a variety of other post-viral states by an unique clinical and epidemiological pattern characteristic of enteroviral infection.

Prompt recognition and advice to avoid over-exertion is mandatory. Routine diagnosis, specific therapy and prevention, await further technical advances.

 

Source:  Dowsett EG, Ramsay AM, McCartney RA, Bell EJ. Myalgic encephalomyelitis–a persistent enteroviral infection? Postgrad Med J. 1990 Jul;66(777):526-30. http://www.ncbi.nlm.nih.gov/pubmed/2170962

Note: You can read the full article here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2429637/

 

Persistence of enteroviral RNA in chronic fatigue syndrome is associated with the abnormal production of equal amounts of positive and negative strands of enteroviral RNA

Abstract:

A subgenomic restriction fragment from cDNA prepared from Coxsackie B2 virus (CVB2) RNA was subcloned into a riboprobe vector allowing the production of enteroviral group-specific RNA probes complementary to either the positive (genomic) or negative (template) strand of enteroviral RNA. These riboprobes were used to follow productive infection of cultured cells by CVB2; as expected, positive strand RNA was synthesized in approximately 100-fold excess over negative strand.

RNA was extracted from muscle biopsy samples from patients with chronic fatigue syndrome and probed for the presence of enteroviral RNA. In cases where enteroviral RNA was detected the amounts of positive and negative strands of enteroviral RNA were approximately equal, in contrast to the situation in lytic infection of cultured cells.

This suggests that enterovirus persistence in muscle is due to a defect in control of viral RNA synthesis.

 

Source: Cunningham L, Bowles NE, Lane RJ, Dubowitz V, Archard LC. Persistence of enteroviral RNA in chronic fatigue syndrome is associated with the abnormal production of equal amounts of positive and negative strands of enteroviral RNA. J Gen Virol. 1990 Jun;71 ( Pt 6):1399-402. http://www.ncbi.nlm.nih.gov/pubmed/2161907

 

Isolation of human herpesvirus-6 from clinical specimens using human fibroblast cultures

Abstract:

The isolation and characterization of human herpesvirus-6 (HHV-6) has been hindered by the lack of cell lines useful for its rapid propagation. Recently, we have reported that the MRC-5 cell line (human diploid lung fibroblasts) was susceptible for HHV-6 infection.

In this study, we report on the isolation of HHV-6 from the peripheral blood or buffy coat of three chronic fatigue syndrome patients, one post-liver transplant patient, and one severe chronic active Epstein-Barr virus syndrome patient using the MRC-5 cell line.

Additionally, it was observed by Southern blot hybridization studies that four of five isolates had different restriction enzyme fragment patterns than the isolate obtained from the National Institutes of Health with Eco RI.

These data suggest the usefulness of the MRC-5 cell line in the isolation and characterization of HHV-6 from various patients.

 

Source: Luka J, Okano M, Thiele G. Isolation of human herpesvirus-6 from clinical specimens using human fibroblast cultures. J Clin Lab Anal. 1990;4(6):483-6. http://www.ncbi.nlm.nih.gov/pubmed/2178187

 

Severe chronic active Epstein-Barr virus infection syndrome and adenovirus type-2 infection

Abstract:

Four patients from 4 to 24 years of age (3 males, 1 female) with generalized lymphadenopathy, hepatosplenomegaly, and intermittent fever associated with chronic active Epstein-Barr virus (EBV) infection were investigated.

Laboratory data showed polyclonal gammopathy and a tendency for bone marrow suppression. Noteworthy were the extremely elevated immunoglobulin G (IgG) antibody titers to Epstein-Barr viral capsid antigen (VCA) (range, 10,240-81,920) and early antigen (EA) (range, 1,280-40,960). All patients had IgA antibodies to VCA and EA. Subtle, heterogeneous immune functional defects were observed in all four patients. Another unusual feature was our inability to establish spontaneous or B95-8 EBV-immortalized lymphoblastoid cell lines (LCLs) due to a marked cytopathic effect (CPE). Thus, we investigated for other viruses.

Both IgG and IgM antibodies to adenovirus type-2 (Ad-2) were positive by enzyme-linked immunosorbent assay (ELISA) and immunofluorescence (IF) test, suggesting recent or activated Ad-2 infection had occurred. Dual active EBV and Ad-2 infections were likely etiologic in this severe chronic active EBV infection syndrome.

 

Source: Okano M, Thiele GM, Purtilo DT. Severe chronic active Epstein-Barr virus infection syndrome and adenovirus type-2 infection. Am J Pediatr Hematol Oncol. 1990 Summer;12(2):168-73. http://www.ncbi.nlm.nih.gov/pubmed/2165745

 

Postviral syndrome–how can a diagnosis be made? A study of patients undergoing a Monospot test

Abstract:

Eighty-nine of 150 patients having a Monospot test filled out a questionnaire about their illness, and the General Health Questionnaire. They completed a follow-up questionnaire 6 months later.

Twelve (8%) had a positive Monospot. Twenty-eight of 83 serum samples tested (34%) were positive for VP1 enteroviral antigen. Forty of the patients had a self limiting illness, 13 had a definite diagnosis (excepting glandular fever), 14 had a possible postviral syndrome, 10 had recurrent sore throats/flu, and 12 had a chronic non-specific illness.

Patients with a specific diagnosis were less likely to complain of aching muscles/joints, sore throat, tiredness or loss of concentration. Their GHQ scores were lower, although this just failed to reach significance (P = 0.08), and they scored significantly lower on the somatic symptoms subscale (P = 0.022). Overall 72% scored above the GHQ threshold for ‘psychological caseness’ which is higher than in other studies. Sixty-five per cent of the sample questioned at 6 months felt that their illness started with a viral infection.

The methodological problems involved in making a diagnosis of postviral syndrome are discussed.

 

Source:  Bowman SJ, Brostoff J, Newman S, Mowbray JF. Postviral syndrome–how can a diagnosis be made? A study of patients undergoing a Monospot test. J R Soc Med. 1989 Dec;82(12):712-6. http://www.ncbi.nlm.nih.gov/pubmed/2614761

Note: You may read the full article here:  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1292411/