I am also not aware of any good study relating chronic coxsackie infection to ME.
What do you make of these studies? (via
@Hip)
Epidemiological aspects of an outbreak of encephalomyelitis at the Royal Free Hospital, London, in the summer of 1955
Nuala Crowley, Merran Nelson, and Sybille Stovin.
J Hyg (Lond). 1957 March; 55(1): 102–122.
An Outbreak of Encephalomyelitis in the Royal Free Hospital Group, London, in 1955
The Medical Staff Of The Royal Free Hospital.
Br Med J. 1957 October 19; 2(5050): 895–904.
In the Royal Free outbreak, coxsackievirus B was suspected, but at that time no serological evidence was obtained.
ME/CFS Enterovirus Research:
Encephalomyelitis Resembling Benign Myalgic Encephalomyelitis
S.G.B. Innes.
The Lancet.
1970 May; 1(7654): 969-971.
➤ This study examined 4 cases of ME. In the cerebrospinal fluid they found coxsackievirus B2 in one case and echovirus 3 in another. In the sera of the two other cases they found elevated coxsackievirus B2 and elevated coxsackievirus B5 titers via neutralization testing.
Sporadic myalgic encephalomyelitis in a rural practice
B. D. Keighley and E. J. Bell.
J R Coll Gen Pract. 1983 June; 33(251): 339–341.
➤ This study found elevated coxsackievirus B titers in 16 of of 20 patients in an ME/CFS outbreak in Ayrshire, UK.
Myalgic encephalomyelitis—report of an epidemic
K. G. Fegan, P. O. Behan, and E. J. Bell.
J R Coll Gen Pract. 1983 June; 33(251): 335–337.
➤ This study found elevated coxsackievirus B titers in 18 out of 20 patients in an ME/CFS outbreak in Ayrshire, UK.
Coxsackie B infection in a Scottish general practice
B. D. Calder and P. J. Warnock.
J R Coll Gen Pract. Jan 1984; 34(258): 15-16, 18-19.
➤ This study found significant antibody titres to coxsackievirus B in 38 out of 81 patients who experienced a syndrome with many of the features of myalgic encephalomyelitis.
Some long-term sequelae of Coxsackie B virus infection
J. A. Gray.
J R Coll Gen Pract. 1984 January; 34(258): 3–5.
➤ Discussion of coxsackievirus B and echovirus in relation to ME/CFS.
A study of Coxsackie B virus infections, 1972-1983
Bell EJ and McCartney RA. J Hyg (Lond).
1984 Oct;93(2):197-203
➤ Found that in well-documented cases of ME/CFS, 41% of patients had elevated neutralizing antibody titers, compared to 4% of healthy controls.
Coxsackie B viruses and myalgic encephalomyelitis
E J Bell, R A McCartney, and M H Riding.
J R Soc Med. 1988 June; 81(6): 329–331.
➤ This study on 290 adults and 47 children with ME/CFS found 37% and 38% respectively were IgM positive for coxsackievirus B, compared to 9% in 500 healthy adult controls.
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 (full text
here).
Cunningham L, Bowles NE, Lane RJ, Dubowitz V, Archard LC.
J Gen Virol. 1990 Jun;71 ( Pt 6):1399-402.
➤ This study found that normally, positive strand enterovirus RNA is 100-fold more common over negative strand enterovirus RNA; but in ME/CFS patients, equal amount of both were found. This study was the very first to demonstrate a persistent
non-cytolytic enterovirus infection (aka:
defective enterovirus infection) in ME/CFS patients.
Myalgic encephalomyelitis--a persistent enteroviral infection?
Dowsett EG, Ramsay AM, McCartney RA, Bell EJ.
Postgrad Med J. 1990 Jul;66(777):526-30.
➤ This study found that out of 420 cases of ME/CFS, 205 had significant titers to coxsackievirus B.
Enteroviral RNA sequences detected by polymerase chain reaction in muscle of patients with postviral fatigue syndrome
Gow JW, Behan WM, Clements GB, Woodall C, Riding M, Behan PO.
BMJ. 1991 Mar 23;302(6778):692-6.
➤ This study on 60 ME/CFS patients found 20% had high titers to coxsackievirus B, compared to 14% of healthy controls. Furthermore, 53% of these ME/CFS patients had enteroviral RNA sequences in their muscles, compared to 15% for healthy controls.
Amplification and identification of enteroviral sequences in the postviral fatigue syndrome
Gow JW1, Behan WM. Br Med Bull.
1991 Oct;47(4):872-85.
➤ This study found that ME/CFS patients were 6.7 times more likely to have enteroviral RNA in their muscle tissue, compared to healthy controls.
Persistent virus infection of muscle in postviral fatigue syndrome
Cunningham L, Bowles NE, Archard LC.
Br Med Bull. 1991 Oct;47(4):852-71.
➤ This study found enteroviral RNA in 24% of ME/CFS patients' muscle biopsy samples, and Epstein-Barr virus DNA in a further 9% of these biopsy samples.
Persistence of enterovirus RNA in muscle biopsy samples suggests that some cases of chronic fatigue syndrome result from a previous, inflammatory viral myopathy
Bowles NE, Bayston TA, Zhang HY, Doyle D, Lane RJ, Cunningham L, Archard LC.
J Med. 1993;24(2-3):145-60.
➤ This study of 158 ME/CFS patients found enteroviral RNA in 26% of the patient's muscle biopsy samples, compared to only 1% in healthy controls.
Studies on enterovirus in patients with chronic fatigue syndrome
Gow JW, Behan WM, Simpson K, McGarry F, Keir S, Behan PO.
Clin Infect Dis. 1994 Jan;18 Suppl 1:S126-9.
➤ This study of 121 patients with ME/CFS found enteroviral RNA in 26.4% of the patients' muscle biopsy samples, and found enteroviral RNA in 19.8% the muscle biopsies of patients other neuromuscular disorders. From these results the authors 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."
However, this conclusion may not be a logical, firstly because persistent enterovirus is associated with a wide range of diseases, including chronic inflammatory myopathy, and thus might also be playing a role in these other neuromuscular disorders; and secondly because persistent enterovirus infection are found in other organs in ME/CFS patients, such as the brain and stomach (although this fact was not known at the time of publication).
Enterovirus in the chronic fatigue syndrome (full text
here)
McGarry F, Gow J, Behan PO.
Ann Intern Med. 1994 Jun 1;120(11):972-3.
➤ This study details an autopsy of a deceased ME/CFS patient. Enteroviral RNA was found in the heart, muscles, hypothalamus and brainstem of this patient, and this RNA showed an 83% similarity to coxsackievirus B3. Control tissue samples taken from four patients who died of cerebrovascular diseases, and another four who had depression and committed suicide, showed no evidence of enteroviral RNA.
Detection of enterovirus-specific RNA in serum: the relationship to chronic fatigue
Clements GB, McGarry F, Nairn C, Galbraith DN.
J Med Virol. 1995 Feb;45(2):156-61.
➤ This study of 88 ME/CFS patients found enteroviral RNA in the serum of 41% of patients, compared to 2% of healthy controls.
Phylogenetic analysis of short enteroviral sequences from patients with chronic fatigue syndrome
Galbraith DN, Nairn C, Clements GB.
J Gen Virol. 1995 Jul;76 ( Pt 7):1701-7.
➤ This study found that ME/CFS patients with persistent enteroviral infections nearly always have viruses with a different genetic makeup compared to enteroviruses found in acute, self-limiting infections in healthy controls. This is strong evidence for enteroviruses playing a causal role in ME/CFS, and indicates that the enteroviruses which may cause ME/CFS are different in nature to the enteroviruses in general circulation.
Viral Isolation from Brain in Myalgic Encephalomyelitis (A Case Report)
Richardson, J.
Journal of Chronic Fatigue Syndrome, Vol. 9(3/4) 2001, pp. 15-19.
➤ This study examined the brain of an ME patient who died through suicide, and found enteroviral VP1 protein in the fibroblasts of small blood vessels in the cerebral cortex, plus some patchy distribution of enteroviral VP1 protein in a small fraction of glial cells.
Enterovirus related metabolic myopathy: a postviral fatigue syndrome
Lane RJ, Soteriou BA, Zhang H, Archard LC.
J Neurol Neurosurg Psychiatry. 2003 Oct;74(10):1382-6.
➤ This study of 48 patients with ME/CFS found enteroviral sequences by RT-NPCR in 20.8% of patients' muscle biopsy samples, while all the 29 control samples were negative for such sequences.
Just for completeness, Dr John Chia's ME/CFS enterovirus studies are these:
The role of enterovirus in chronic fatigue syndrome.
Chia JK.
J Clin Pathol. 2005 Nov;58(11):1126-32.
Chronic fatigue syndrome is associated with chronic enterovirus infection of the stomach.
Chia JK, Chia AY.
J Clin Pathol. 2008 Jan;61(1):43-8. Epub 2007 Sep 13. Full paper
here.
➤ This study of 165 ME/CFS patients found enterovirus VP1 protein in 82% of stomach tissue samples from patients, compared to 20% in healthy controls. 37% of the ME/CFS patient stomach tissue samples tested positive for enterovirus RNA, compared to less than 1% for healthy controls.
Acute enterovirus infection followed by myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and viral persistence.
Chia J, Chia A, Voeller M, Lee T, Chang R.
J Clin Pathol. 2010 Feb;63(2):165-8. doi: 10.1136/jcp.2009.070466.
➤ This study followed patients who were hospitalized for acute enterovirus infections, and found that in the next few years subsequent to the acute infections, symptoms consistent with ME/CFS emerged in some patients.
In addition to the above, three separate
brain autopsies on deceased ME/CFS patients found enterovirus / coxsackievirus B infection in the brain tissues. See
here.