Chronic Fatigue Syndrome Linked To Stomach Virus

Chronic fatigue syndrome, also known as ME (myalgic encephalitis), is linked to a stomach virus, suggests research published ahead of print in Journal of Clinical Pathology.

The researchers base their findings on 165 patients with ME, all of whom were subjected to endoscopy because of longstanding gut complaints.

Endoscopy involves the threading of a long tube with a camera on the tip through the gullet into the stomach.

Specimens of stomach tissue were also taken to search for viral proteins and compared with specimens taken from healthy people and patients with other gut diseases none of whom had been diagnosed with ME.

Patients with ME often have intermittent or persistent gut problems, including indigestion and irritable bowel syndrome.

And viral infections, such as Epstein Barr virus (glandular fever), cytomegalovirus, and parvovirus, among others, produce many of the symptoms associated with chronic fatigue syndrome.

Enteroviruses, which infect the bowel, cause severe but short lasting respiratory and gut infections.

There are more than 70 different types, and they head for the central nervous system, heart and muscles.

Most of the biopsy specimens from patients with gut problems showed evidence of mild long term inflammation, although few were infected with Helicobacter pylori, a common bacterial infection associated with inflammation.

But more than 80% of the specimens from the ME patients tested positive for enteroviral particles compared with only seven of the 34 specimens from healthy people.

In a significant proportion of patients, the initial infection had occurred many years earlier.

 

Source: BMJ Specialty Journals. (2007, September 17). Chronic Fatigue Syndrome Linked To Stomach Virus. ScienceDaily. Retrieved March 4, 2017 from  https://www.sciencedaily.com/releases/2007/09/070913132933.htm

 

Acute enterovirus infection followed by myalgic encephalomyelitis/chronic fatigue syndrome(ME/CFS) and viral persistence

Abstract:

AIMS: Enteroviruses are well-known causes of acute respiratory and/or gastrointestinal infections and non-specific flu-like illness. Although enterovirus protein, RNA and non-cytopathic viruses have been demonstrated in the stomach biopsies of patients with myalgia encephalomyelitis/chronic fatigue syndrome (ME/CFS), causality for chronic diseases is difficult to establish without having well-documented cases of acute enterovirus infections. The aim of this study was to link acute enteroviral infection to viral persistence in patients with ME/CFS.

METHOD: Patients admitted to the hospital with acute febrile illnesses were screened for enteroviral infections. Acutely infected patients were followed longitudinally, and those who developed symptoms of ME/CFS underwent oesophagogastroduodenoscopy and biopsies of the antrum to document viral persistence by immunoperoxidase staining for viral protein and viral RNA assay.

RESULTS: Three representative patients with different manifestations of acute enterovirus infections progressed to have chronic symptoms of ME/CFS. Persistent viral infection was demonstrated in the antrum years later.

CONCLUSION: After acute infections, enteroviruses can persist in patients resulting in manifestation of ME/CFS. Chronic enterovirus infection in an immunocompetent host may be an example of a stalemate between attenuated, intracellular viruses and an ineffective immune response.

 

Source: Chia J, Chia A, Voeller M, Lee T, Chang R. Acute enterovirus infection followed by myalgic encephalomyelitis/chronic fatigue syndrome(ME/CFS) and viral persistence. J Clin Pathol. 2010 Feb;63(2):165-8. doi: 10.1136/jcp.2009.070466. Epub 2009 Oct 14. https://www.ncbi.nlm.nih.gov/pubmed/19828908

 

The role of enterovirus in chronic fatigue syndrome

Abstract:

Two and a half decades after coining of the term chronic fatigue syndrome (CFS), the diagnosis of this illness is still symptom based and the aetiology remains elusive. Enteroviruses are well known causes of acute respiratory and gastrointestinal infections, with tropism for the central nervous system, muscles, and heart.

Initial reports of chronic enteroviral infections causing debilitating symptoms in patients with CFS were met with skeptism, and had been largely forgotten for the past decade. Observations from in vitro experiments and from animal models clearly established a state of chronic persistence through the formation of double stranded RNA, similar to findings reported in muscle biopsies of patients with CFS.

Recent evidence not only confirmed the earlier studies, but also clarified the pathogenic role of viral RNA through antiviral treatment. This review summarises the available experimental and clinical evidence that supports the role of enterovirus in chronic fatigue syndrome.

 

Source: Chia JK. The role of enterovirus in chronic fatigue syndrome. J Clin Pathol. 2005 Nov;58(11):1126-32. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1770761/ (Full article)

 

Enteroviruses in chronic fatigue syndrome: “now you see them, now you don’t”

Comment on: Enterovirus related metabolic myopathy: a postviral fatigue syndrome. [J Neurol Neurosurg Psychiatry. 2003]

 

In the paper by Lane et al(see pp 1382– 1386)1 an association was found between abnormal exercise lactate response and enterovirus sequences in the muscle of some patients with chronic fatigue syndrome (CFS). The paper rekindles the old saga of enteroviruses, muscle inflammation, and fatigue.

You can read the rest of this comment here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1757390/pdf/v074p01361.pdf

 

Source: Dalakas MC. Enteroviruses in chronic fatigue syndrome: “now you see them, now you don’t”. J Neurol Neurosurg Psychiatry. 2003 Oct;74(10):1361-2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1757390/  (Full article)

 

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

 

Immune responsiveness in chronic fatigue syndrome

Comment on: Immune responsiveness in chronic fatigue syndrome. [Postgrad Med J. 1991]

 

Sir, The paper by Milton and colleagues (1) challenges the hypothesis that patients with postviral fatigue syndrome (myalgic encephalomyelitis) have a persisting viral infection along with consequent immune dysregulation. The protocol employed in the study suggests that their conclusions may not be valid.

Firstly, the 31 patients were selected from a group attending a ‘muscle clinic’ who complained of ‘unexplained chronic fatigue’. Of these only 15 had a clear history of a precipitating viral illness – a key diagnostic feature of postviral fatigue syndrome. Secondly, although other research groups have also demonstrated that raised levels of Coxsackie B virus IgG and IgM antibodies are not diagnostic of the syndrome, (2) these findings cannot be used to exclude the possibility of persisting viral infection within either muscle or the central nervous system.

As far as muscle is concerned, Gow and colleagues( 3) have recently detected enteroviral RNA sequences in muscle biopsies of 53% of patients with a well-defined postviral fatigue syndrome compared to 15% in a control group, and Archard et al. (4) have shown that this persisting enterovirus is poorly replicating.

Demonstrating the presence of persisting virus within the central nervous system is obviously far more difficult without autopsy material. However, Daugherty et al. (5) in America have published the results of MRI scans and cognitive function tests on 20 patients (with age and sex matched healthy controls) showing abnormalities consistent with an organic brain syndrome similar to that seen in patients who are positive for human immunodeficiency virus.

You can read the rest of this letter here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2399327/pdf/postmedj00061-0069a.pdf

 

Source: Shepherd C. Immune responsiveness in chronic fatigue syndrome. Postgrad Med J. 1992 Jan;68(795):66-7. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2399327/

 

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)

 

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 herehttp://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