Comparison of coxsackie B neutralisation and enteroviral PCR in chronic fatigue patients

Abstract:

Coxsackie B enteroviruses have been implicated repeatedly as agents associated with chronic fatigue syndrome (CFS). The objective of this study was to compare the serological evidence for the presence of Coxsackie B virus neutralising antibody, with the polymerase chain reaction (PCR) detecting a portion of the 5′ nontranslated region (NTR) of the enterovirus genome.

Serum samples from 100 chronic fatigue patients and from 100 healthy comparison patients were used in this study. In the CFS study group, 42% patients were positive for enteroviral sequences by PCR, compared to only 9% of the comparison group. Using the neutralisation assay, 34% of study patients were positive, compared to 41% of comparison patients.

In the study group, 66/100 patient results correlated, i.e., they were either positive/positive or negative/negative for both tests. Of those that did not correlate, the majority were PCR-positive/Coxsackie B antibody-negative (21/34).

In the comparison group, 58/100 patient results correlated. Of those that did not, the majority were PCR-negative/Coxsackie B antibody-positive (37/42).

The Coxsackie B antibody neutralisation assay was not able to differentiate the CFS study group from the healthy comparison group, and thus the clinical relevance of this assay may be questioned. The PCR assay did differentiate the two groups with significantly more CFS patients having evidence of enterovirus than the comparison group.

Source: Nairn C, Galbraith DN, Clements GB. Comparison of coxsackie B neutralisation and enteroviral PCR in chronic fatigue patients. J Med Virol. 1995 Aug;46(4):310-3. http://www.ncbi.nlm.nih.gov/pubmed/7595406

 

African green monkey origin of the atypical cytopathic ‘stealth virus’ isolated from a patient with chronic fatigue syndrome

Abstract:

BACKGROUND: A cytomegalovirus-like ‘stealth virus’ had previously been isolated from a patient with the chronic fatigue syndrome (CFS).

OBJECTIVE: To determine the original derivation of this virus.

STUDY DESIGN: DNA sequencing of cloned regions of the virus was performed and the sequences were compared using BLASTN and FASTA analyses against the entire GenBank database. Viral sequences were also used to design primers for the polymerase chain reaction (PCR).

RESULTS: DNA and amino acid sequence comparisons showed that the stealth virus was more closely related to the Colburn strain of simian cytomegalovirus (SCMV) than to CMV of either human or rhesus monkey origin or to any other sequenced herpesvirus. Similarity, but non-identity, between the stealth virus and SCMV, was confirmed using PCR.

CONCLUSION: The findings implicate the African green monkey as the probable source of the virus isolated from this CFS patient.

 

Source: Martin WJ, Ahmed KN, Zeng LC, Olsen JC, Seward JG, Seehrai JS. African green monkey origin of the atypical cytopathic ‘stealth virus’ isolated from a patient with chronic fatigue syndrome. Clin Diagn Virol. 1995 Jul;4(1):93-103. http://www.ncbi.nlm.nih.gov/pubmed/15566831

 

Human herpesvirus 6 and human herpesvirus 7 in chronic fatigue syndrome

Abstract:

We analyzed lymphocytes of patients with chronic fatigue syndrome (CFS) for the presence of human herpesvirus 6 (HHV-6) and HHV-7 DNA. HHV-7 was present in over 80% of CFS patients and healthy controls, while the prevalence of HHV-6 variant A increased significantly in CFS cases (22 versus 4%; P = 0.05).

 

Source: Di Luca D, Zorzenon M, Mirandola P, Colle R, Botta GA, Cassai E. Human herpesvirus 6 and human herpesvirus 7 in chronic fatigue syndrome. J Clin Microbiol. 1995 Jun;33(6):1660-61. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC228240/pdf/331660.pdf (Full article)

 

The disease associations of the antibody response against the Epstein-Barr virus transactivator protein ZEBRA can be separated into different epitopes

Abstract:

The BamHI-Z-encoded Epstein-Barr virus (EBV) replication activator (ZEBRA) is a key mediator of the switch from latency to productive cycle in EBV virus. Antibodies against ZEBRA are a marker of EBV reactivation and are regularly found among patients with infectious mononucleosis (IM) or nasopharyngeal carcinoma (NPC), but are only rarely found among healthy EBV-seropositive donors.

In order to define the serologically reactive epitopes in the ZEBRA protein, we synthesized a set of overlapping peptides and tested them for reactivity with serum samples from EBV-seronegative persons, patients with NPC, IM, chronic fatigue syndrome, lymphoma or from healthy donors. Three major EBV-specific epitopes were found.

These epitopes were further defined and optimized using substitution or truncation analogues of the peptides. Reactivity with epitope number 22 was found in 63% of NPC patients’ sera, with < 2% of healthy donors’ sera being positive. Serological reactivity with epitope number 19 was associated with IM (57% positive, 5% healthy donors positive).

Serum antibodies against epitope 1 were found among healthy donors, but were significantly elevated among patients with NPC, IM or lymphomas. In conclusion, different serologically reactive epitopes in the ZEBRA protein associate with different EBV-associated diseases.

 

Source: Tedeschi R, Foong YT, Cheng HM, dePaoli P, Lehtinen T, Elfborg T, Dillner J. The disease associations of the antibody response against the Epstein-Barr virus transactivator protein ZEBRA can be separated into different epitopes. J Gen Virol. 1995 Jun;76 ( Pt 6):1393-400. http://www.ncbi.nlm.nih.gov/pubmed/7540196

Note: You can read the full study HERE.

 

Absence of parvovirus B19 infection in chronic fatigue syndrome

Abstract:

OBJECTIVE: To evaluate the presence of infection with parvovirus B19 in patients with chronic fatigue syndrome (CFS) who also had rheumatologic symptoms and mild hematologic abnormalities.

METHODS: Seven patients meeting the Centers for Disease Control and Prevention working case definition for CFS who also had mild leukopenia, thrombocytopenia, or anemia were studied. Bone marrow was aspirated from each patient, and examined for morphologic abnormalities, including features seen in marrow infections with parvovirus B19, as well as for parvoviral DNA, using polymerase chain reaction (PCR) amplification. Serum obtained at the time of marrow aspiration was also evaluated for parvoviral DNA, using the PCR method, and was examined for the presence of IgM and IgG antibodies to the virus.

RESULTS: No evidence of marrow involvement with parvovirus B19 was found in any patient. One patient had antibody evidence of a transient parvoviral infection, during which time an underlying thrombocytopenia worsened.

CONCLUSION: Despite examining a selected group of patients thought most likely to have parvoviral infection, based on clinical and hematologic measures, no evidence of clinically important parvoviral infection was noted. Thus, it seems unlikely that parvovirus B19 plays a role in CFS, even though it has been associated with fibromyalgia, a clinically similar syndrome.

 

Source: Ilaria RL Jr, Komaroff AL, Fagioli LR, Moloney WC, True CA, Naides SJ. Absence of parvovirus B19 infection in chronic fatigue syndrome. Arthritis Rheum. 1995 May;38(5):638-41. http://www.ncbi.nlm.nih.gov/pubmed/7748220

 

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

 

Chronic Fatigue Syndrome

Abstract:

Despite its new name, chronic fatigue syndrome is not a new disease. This chapter reviews current definitions, emphasizing that chronic fatigue syndrome is a diagnosis of exclusion. The author also discusses viral infections that are associated with CFS, including Epstein-Barr virus, cytomegalovirus, herpesvirus type 6, enteroviruses, and retroviruses.

 

Source: Glover DM. Chronic Fatigue Syndrome. Adolesc Med. 1995 Feb;6(1):101-114. http://www.ncbi.nlm.nih.gov/pubmed/10358305

 

Detection of enterovirus-specific RNA in serum: the relationship to chronic fatigue

Abstract:

The serum of 88 chronic fatigue patients was screened for enteroviral specific sequences by polymerase chain reaction (PCR) assay. The PCR method used was “nested” PCR targetting the 5′ nontranslated region of the enteroviral genome which yielded a final fragment length of 264 base pairs. Samples were obtained from patients during 1990-1991.

In addition, buffy coat specimens and stool specimens were examined in some patients. Samples from two cohorts of comparison individuals were also obtained. The comparison groups were firstly, acutely ill individuals with symptoms consistent with a presumed enteroviral infection (matched by age, sex, and date of receipt of specimen) and secondly, healthy individuals (matched by age and date of receipt of specimen).

Enteroviral specific sequences were detected in 36 of 88 serum samples from chronic fatigue patients, 22 of 82 acutely ill individuals, and 3 of 126 healthy individuals. The enteroviral PCR positivity did not correlate with any one particular feature of chronic fatigue nor did it reflect any history of illness at onset of fatigue, duration of fatigue, or age of patient.

These results provide new evidence for the presence of enteroviral specific sequences in serum, buffy coat, and stool samples in many patients with chronic fatigue. This may reflect a persistent enterovirus infection in a proportion of chronic fatigue patients.

 

Source: Clements GB, McGarry F, Nairn C, Galbraith DN. Detection of enterovirus-specific RNA in serum: the relationship to chronic fatigue. J Med Virol. 1995 Feb;45(2):156-61. http://www.ncbi.nlm.nih.gov/pubmed/7775934

 

Acute encephalopathy induced in cats with a stealth virus isolated from a patient with chronic fatigue syndrome

Abstract:

A simian cytomegalovirus-related stealth virus, isolated from a patient with the chronic fatigue syndrome, induced an acute neurological illness when inoculated into cats. Histological examination of brain tissue showed foci of cells with cytoplasmic vacuolization and an absence of any inflammatory reaction. Electron microscopy confirmed the presence of herpes-like viral particles and viral-like products in the brain of an inoculated animal. These findings support the role of stealth viruses in the pathogenesis of human neurological diseases and provide an animal model to evaluate potential antiviral therapy.

 

Source: Martin WJ, Glass RT. Acute encephalopathy induced in cats with a stealth virus isolated from a patient with chronic fatigue syndrome. Pathobiology. 1995;63(3):115-8. http://www.ncbi.nlm.nih.gov/pubmed/8821627