Tag: enteroviruses

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

 

Enteroviruses and postviral fatigue syndrome

Abstract:

Postviral fatigue syndrome (PFS) occurs both in epidemics and sporadically. Many of the original epidemics were related to poliomyelitis outbreaks which either preceded or followed them.

The core clinical symptoms are always the same: severe fatigue made worse by exercise, myalgia, night sweats, atypical depression and excessive sleep. The other common symptoms include dysequilibrium disorders and irritable bowel syndrome.

We have detected enteroviral genome sequences in muscle biopsies from cases of PFS, using specific enteroviral oligonucleotide primers in the polymerase chain reaction (PCR). In addition, whole virus particles can be demonstrated in PCR-positive muscle, using solid-phase immuno-electron microscopy.

An increase in the number and size of muscle mitochondria was found in 70% of PFS cases, suggesting an abnormality in metabolic function. Evidence of hypothalamic dysfunction was present, particularly involving 5-hydroxytryptamine metabolism.

A putative model of PFS, based on persistent enteroviral infection in laboratory mice, revealed resolving inflammatory lesions in muscle with, however, a marked increase in the production of certain cytokines in the brain. This model may help to explain the pathogenesis of PFS.

 

Source: Behan PO, Behan WM, Gow JW, Cavanagh H, Gillespie S. Ciba Found Symp. 1993;173:146-54; discussion 154-9. http://www.ncbi.nlm.nih.gov/pubmed/8387908

 

Chronic fatigue syndrome and virus infection: human herpesvirus 6 (HHV-6) infection

Abstract:

Chronic fatigue syndrome (CFS) is newly-recognized disease characterized by chronic and debilitating fatigue. It has been suggested that viral infection may be involved in this syndrome from the results of clinical examination, including increased activity of 2′,5′-synthetase in leukocytes of patients. The following viruses have been reported as etiologic agents of this disease. First, many studies have found elevated levels of IgG to viral capsid antigen and early antigens to Epstein-Barr virus (EBV), but low titer or absence of antibody to EBV-associated nuclear antigen. Second, the enteroviruses have also been implicated as possible causative agent of CFS, because virus could be isolated from patients. Recently it was also reported that antibodies to human T-lymphotropic virus (HTLV) and HTLV type II (HTLV-II) gag sequence were detectable in patients. Finally several reports state that human herpesvirus 6 (HHV-6) could be isolated from CFS patients in the high frequency. In conclusion, it is still early to identify the etiologic agent from these reports, and more effort is needed.

 

Source: Yamanishi K. [Chronic fatigue syndrome and virus infection: human herpesvirus 6 (HHV-6) infection]. Nihon Rinsho. 1992 Nov;50(11):2612-6. [Article in Japanese] http://www.ncbi.nlm.nih.gov/pubmed/1337558

 

Chronic fatigue syndrome: a joint paediatric-psychiatric approach

Comment on: Chronic fatigue syndrome: a joint paediatric-psychiatric approach. [Arch Dis Child. 1992]

 

SIR,-While agreeing that physical, psychological, and social factors must all be taken into account in the management of this complex and controversial syndrome I would disagree with Dr Margaret Vereker’s statement that no organic pathology can be detected to account for any of the symptoms. This conclusion has been made without reference to a number of research papers describing persisting viral infection, neuromuscular abnormalities in both structure and function, and immune system dysfunction.

Gow et al using polymerase chain reaction techniques, have been able to demonstrate the presence of enteroviral genome in muscle biopsies from a significant number of patients (53%) compared with controls (15%). None of the healthy control group in this study had evidence of viral particles in their muscle, this was only found in those with colonic or breast malignancies. Precisely what cytopathological effect this intracellular virus is having within muscle remains open to debate. However, Behan et al have published electron microscopic evidence of structural damage to the muscle mitochondria along with type II fibre atrophy; this is a finding which is not normally considered to be consistent with simple disuse.

You can read the rest of this letter here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1793782/pdf/archdisch00632-0102a.pdf

 

Source: Shepherd C. Chronic fatigue syndrome: a joint paediatric-psychiatric approach. Arch Dis Child. 1992 Nov;67(11):1410. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1793782/

 

Epstein-Barr virus serology in the chronic fatigue syndrome

Abstract:

The antibody profiles against Epstein-Barr virus were studied in 136 patients presenting with chronic fatigue syndromes. These profiles were compared with a panel of sera from blood donors. The patients exhibited higher titres in a combined assay for antibodies to the Restricted (R) and Diffuse (D) components of the Early Antigen complex than controls (P less than 0.001) but titres against these antigens were not useful on an individual patient basis. The patients who displayed elevated titres of antibodies to Early Antigens did not differ clinically from those displaying titres in the control range. Four of nine patients who had increased antibodies to Early Antigens also had evidence of active enterovirus infection.

 

Source: Woodward CG, Cox RA. Epstein-Barr virus serology in the chronic fatigue syndrome. J Infect. 1992 Mar;24(2):133-9. http://www.ncbi.nlm.nih.gov/pubmed/1314860

 

Amplification and identification of enteroviral sequences in the postviral fatigue syndrome

Abstract:

Evidence from several sources has long suggested that enteroviruses might play a role in the postviral fatigue syndrome (PVFS).

We used the most sensitive molecular virological method available at present, the polymerase chain reaction (PCR) amplification technique, to look for enteroviral copies in peripheral blood leucocytes and muscle from a well-defined group of patients. We demonstrated that our PCR method amplified a sequence common to a wide range of enteroviral serotypes. A highly significant number of the muscle biopsies (53%: P = less than 0.001) from the patients were positive for enteroviral sequences. With regard to the leucocyte samples, 16% in both patient and control were positive.

The PCR results on the peripheral blood leucocytes were in keeping with serological findings, in showing that the level of exposure to enteroviruses seemed to be the same in patients and controls: it was therefore of the greatest interest that patients were 6.7 times more likely to have enteroviral genome in their muscle.

We conclude that persistent enteroviral infection plays a role in the pathogenesis of PVFS, also providing preliminary evidence that severe mitochondrial injury is one of the mechanisms involved.

 

Source: Gow JW, Behan WM. Amplification and identification of enteroviral sequences in the postviral fatigue syndrome. Br Med Bull. 1991 Oct;47(4):872-85. http://www.ncbi.nlm.nih.gov/pubmed/1665380

 

Persistent virus infection of muscle in postviral fatigue syndrome

Abstract:

Nucleic acid was extracted from muscle biopsy samples from a series of highly selected patients suffering from chronic muscle fatiguability following a viral infection (Postviral Fatigue Syndrome: PVFS).

Samples were examined for the presence of enteroviral RNA sequences or Epstein-Barr (EBV) virus DNA sequences by molecular hybridisation as these two agents have been implicated by retrospective serology in the aetiology of PVFS. We found enteroviral RNA in 24% of biopsy samples and EBV DNA in a further 9% of biopsy samples: no biopsy was positive for both enteroviral RNA and EBV DNA.

In addition, in the case of enteroviruses we found that the persisting virus is defective in control of RNA replication as both strands of enteroviral RNA are present in similar amounts: this is unlike the asymmetric synthesis of genomic RNA seen in a productive, cytolytic enterovirus infection. The implications of these data in relation to mechanisms of viral persistence and muscle dysfunction are discussed.

 

Source: Cunningham L, Bowles NE, Archard LC. Persistent virus infection of muscle in postviral fatigue syndrome. Br Med Bull. 1991 Oct;47(4):852-71. http://www.ncbi.nlm.nih.gov/pubmed/1665379

 

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)

 

Coxsackie B virus and postviral fatigue syndrome

Comment on: Antibody to Coxsackie B virus in diagnosing postviral fatigue syndrome. [BMJ. 1991]

 

SIR,-Dr N A Miller and colleagues highlight the difficulty of associating a virus (coxsackie B virus) with a disease (postviral fatigue syndrome) when the virus in question is common in the general population.’ In a recent serological survey of the family members of children with insulin dependent diabetes mellitus we also found a high prevalence of IgM antibody specific to enterovirus: 14% of children with recently diagnosed insulin dependent diabetes mellitus, 8% of unaffected siblings, and 18% of parents had the antibody at the time of entry into the study. Serum samples were collected between 1985 and 1987. These seroprevalence figures are higher than those reported among control populations in earlier studies in the United Kingdom-5 5% in children during 19822 and 3-5% in adults during 1979-80.3 Because the assay used in these studies was the same as that used by Dr Miller and colleagues this indicates that enterovirus was endemic during 1985-7, which covers the period of the study of Dr Miller and colleagues.

You can read the rest of this comment here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1675464/pdf/bmj00117-0062c.pdf

 

Source: Muir P, Nicholson F, Banatvala JE, Bingley PJ. Coxsackie B virus and postviral fatigue syndrome. BMJ. 1991 Mar 16;302(6777):658-9. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1675464/

 

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