List of enterovirus infection studies

In this list of studies looking for evidence of enterovirus infection in ME/CFS patients ➕ indicates a positive study (one finding enterovirus much more commonly in ME/CFS patients than healthy controls) and ➖ indicates a negative study (no difference between patients and healthy controls). 

Early ME/CFS enterovirus research

This early period of enterovirus research from 1970 to 2003 comprises mainly British studies.

	Study Title	Date	Details
➕	Encephalomyelitis Resembling Benign Myalgic Encephalomyelitis Innes SGB	1970	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 antibody testing.
➕	Sporadic myalgic encephalomyelitis in a rural practice Keighley BD, Bell EJ	1983	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 Fegan KG, Behan PO, Bell EJ	1983	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 Calder BD, Warnock PJ	1984	This study found high antibody titers 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 Gray JA	1984	Discussion of coxsackievirus B and echovirus in relation to ME/CFS.
➕	A study of Coxsackie B virus infections, 1972-1983 Bell EJ, McCartney RA	1984	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 Bell EJ, McCartney RA, Riding MH	1988	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 Cunningham L, Bowles NE, Lane RJ, Dubowitz V, Archard LC	1990	Normally in enterovirus infection, in the cell positive strand enteroviral RNA is 100 times more common than negative strand enterovirus RNA (the negative strand is the template which creates hundreds of positive strand copies). But this study found in ME/CFS patients, intriguingly there were equal amounts of both. This study was the first to demonstrate an unusual viral phenomenon in ME/CFS that would later be understood as a non-cytolytic enterovirus infection (also called non-cytopathic or defective enterovirus infection).
➕	Myalgic encephalomyelitis--a persistent enteroviral infection? Dowsett EG, Ramsay AM, McCartney RA, Bell EJ	1990	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	1991	This study of 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	1991	This study of 60 ME/CFS patients 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	1991	This study of 140 ME/CFS patients found enteroviral RNA in 24% of their muscle biopsy samples, and Epstein-Barr virus DNA in a further 9% of these biopsy samples (though no ME/CFS patient had both enterovirus and EBV in their muscle biopsies). No enterovirus RNA was detected in any of the 152 control samples of human muscle.
➕	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	1993	This study of 158 ME/CFS patients found enteroviral RNA in 26% of the patients' 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	1994	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 sound, firstly because persistent enterovirus is associated with a wide range of diseases, including chronic inflammatory myopathy, and thus might be playing a role in these other neuromuscular disorders as well; and secondly because persistent enterovirus infections are also found in other organs in ME/CFS patients, such as the brain and stomach, and it is possible ME/CFS might in fact be caused by an enterovirus brain infection, rather than (or in addition to) a muscle infection.
➕	Enterovirus in the chronic fatigue syndrome McGarry F, Gow J, Behan PO	1994	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. See also: post-mortem brain studies.
➖	Enteroviruses and the chronic fatigue syndrome Swanink CM, Melchers WJ, van der Meer JW, Vercoulen JH, Bleijenberg G, Fennis JF, Galama JM	1994	This study, conducted by some of the psychologists at the Nijmegen Group in the Netherlands did not find any difference between the blood and stool samples of 76 ME/CFS patients and 76 healthy controls.
➕	Detection of enterovirus-specific RNA in serum: the relationship to chronic fatigue Clements GB, McGarry F, Nairn C, Galbraith DN	1995	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	1995	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.
➖	Investigation by polymerase chain reaction of enteroviral infection in patients with chronic fatigue syndrome McArdle A, McArdle F, Jackson MJ, Page SF, Fahal I, Edwards RH	1996	This study examined 34 muscle biopsies from ME/CFS patients and 10 muscle biopsies from healthy controls, but did not detect enterovirus RNA in the patient or control muscle tissues. But commenting on the differences between their negative and the positive results found in Gow 1991, the authors say: "The difference in findings between our study and that of Gow et al. may be due to the population of CFS patients studied. Although the diagnostic criteria of both groups was broadly similar, the patients used in the study of Gow et al. all reported that the illness had an acute onset after a feverish illness, whereas only 58% of patients in our study reported a viral infection before the onset of their illness. Another possible explanation comes from the work of Galbraith et al. Direct sequencing of PCR products from enterovirus-positive serum samples of patients with CFS by these authors has suggested the presence of distinct novel enterovir- uses. These viruses are thus unclassified and their site of replication is unknown. Thus, the different findings of different studies may reflect the nature of the samples examined. "
➖	No findings of enteroviruses in Swedish patients with chronic fatigue syndrome Lindh G, Samuelson A, Hedlund KO, Evengård B, Lindquist L, Ehrnst A	1996	This Swedish study examined 29 muscle biopsies from ME/CFS patients, but could not detect enterovirus RNA in the tissues.
➕	Viral Isolation from Brain in Myalgic Encephalomyelitis(A Case Report) Richardson J	2001	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. See also: post-mortem brain studies.
➕	Enterovirus related metabolic myopathy: a postviral fatigue syndrome Lane RJ, Soteriou BA, Zhang H, Archard LC	2003	This study of 48 patients with ME/CFS found enteroviral sequences by reverse transcription nested polymerase chain reaction (RT-NPCR) in 20.8% of the patients' muscle biopsy samples, while all the 29 control samples were negative for such sequences.

John Chia's ME/CFS enterovirus research

John Chiain California: his research papers on enterovirus in ME/CFS from 2005 to present

	The role of enterovirus in chronic fatigue syndrome Chia J	2005	A review paper summarizing experimental and clinical evidence supporting the role of enterovirus in chronic fatigue syndrome.
➕	Chronic fatigue syndrome is associated with chronic enterovirus infection of the stomach Chia JK, Chia AY	2008	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 also 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	2010	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 3 patients.
➕	Chronic enterovirus infection in a patient with myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) – clinical, virologic and pathological analysis John Chia, David Wang, Andrew Chia, Rabiha El-Habbal	2015	This brain autopsy on a deceased ME/CFS patient found evidence of enterovirus infection in various areas of the brain. See also: post-mortem brain studies.

enterovirus A genus of RNA viruses which typically enter the body through the respiratory or gastrointestinal systems and sometimes spread to the central nervous system or other parts of the body, causing neurological, cardiac, and other damage. Since the first reports of myalgic encephalomyelitis (ME), enteroviruses have been suspected as a cause of ME. Enteroviruses have also been implicated as the cause of Type I diabetes, congestive heart failure, and other conditions. Enteroviruses include poliovirus, coxsackieviruses, and many others. New enteroviruses and new strains of existing enteroviruses are continuously being discovered. (Learn more: viralzone.expasy.org)

myalgic encephalomyelitis (M.E.) - A disease often marked by neurological symptoms, but fatigue is sometimes a symptom as well. Some diagnostic criteria distinguish it from chronic fatigue syndrome, while other diagnostic criteria consider it to be a synonym for chronic fatigue syndrome. A defining characteristic of ME is post-exertional malaise (PEM), or post-exertional neuroimmune exhaustion (PENE), which is a notable exacerbation of symptoms brought on by small exertions. PEM can last for days or weeks. Symptoms can include cognitive impairments, muscle pain (myalgia), trouble remaining upright (orthostatic intolerance), sleep abnormalities, and gastro-intestinal impairments, among others. An estimated 25% of those suffering from ME are housebound or bedbound. The World Health Organization (WHO) classifies ME as a neurological disease.

serum The clear yellowish fluid that remains from blood plasma after clotting factors have been removed by clot formation. (Blood plasma is simply blood that has had its blood cells removed.)

antibodies Antibody/immunoglobulin refers to any of a large number of specific proteins produced by B cells that act against an antigen in an immune response.

myalgic encephalomyelitis (M.E.) - A disease often marked by neurological symptoms, but fatigue is sometimes a symptom as well. Some diagnostic criteria distinguish it from chronic fatigue syndrome, while other diagnostic criteria consider it to be a synonym for chronic fatigue syndrome. A defining characteristic of ME is post-exertional malaise (PEM), or post-exertional neuroimmune exhaustion (PENE), which is a notable exacerbation of symptoms brought on by small exertions. PEM can last for days or weeks. Symptoms can include cognitive impairments, muscle pain (myalgia), trouble remaining upright (orthostatic intolerance), sleep abnormalities, and gastro-intestinal impairments, among others. An estimated 25% of those suffering from ME are housebound or bedbound. The World Health Organization (WHO) classifies ME as a neurological disease.

enterovirus A genus of RNA viruses which typically enter the body through the respiratory or gastrointestinal systems and sometimes spread to the central nervous system or other parts of the body, causing neurological, cardiac, and other damage. Since the first reports of myalgic encephalomyelitis (ME), enteroviruses have been suspected as a cause of ME. Enteroviruses have also been implicated as the cause of Type I diabetes, congestive heart failure, and other conditions. Enteroviruses include poliovirus, coxsackieviruses, and many others. New enteroviruses and new strains of existing enteroviruses are continuously being discovered. (Learn more: viralzone.expasy.org)

enterovirus A genus of RNA viruses which typically enter the body through the respiratory or gastrointestinal systems and sometimes spread to the central nervous system or other parts of the body, causing neurological, cardiac, and other damage. Since the first reports of myalgic encephalomyelitis (ME), enteroviruses have been suspected as a cause of ME. Enteroviruses have also been implicated as the cause of Type I diabetes, congestive heart failure, and other conditions. Enteroviruses include poliovirus, coxsackieviruses, and many others. New enteroviruses and new strains of existing enteroviruses are continuously being discovered. (Learn more: viralzone.expasy.org)

enterovirus A genus of RNA viruses which typically enter the body through the respiratory or gastrointestinal systems and sometimes spread to the central nervous system or other parts of the body, causing neurological, cardiac, and other damage. Since the first reports of myalgic encephalomyelitis (ME), enteroviruses have been suspected as a cause of ME. Enteroviruses have also been implicated as the cause of Type I diabetes, congestive heart failure, and other conditions. Enteroviruses include poliovirus, coxsackieviruses, and many others. New enteroviruses and new strains of existing enteroviruses are continuously being discovered. (Learn more: viralzone.expasy.org)

brainstem Region of the midbrain in adults, includes midbrain, pons, and medulla oblongata and develops.

enterovirus A genus of RNA viruses which typically enter the body through the respiratory or gastrointestinal systems and sometimes spread to the central nervous system or other parts of the body, causing neurological, cardiac, and other damage. Since the first reports of myalgic encephalomyelitis (ME), enteroviruses have been suspected as a cause of ME. Enteroviruses have also been implicated as the cause of Type I diabetes, congestive heart failure, and other conditions. Enteroviruses include poliovirus, coxsackieviruses, and many others. New enteroviruses and new strains of existing enteroviruses are continuously being discovered. (Learn more: viralzone.expasy.org)

serum The clear yellowish fluid that remains from blood plasma after clotting factors have been removed by clot formation. (Blood plasma is simply blood that has had its blood cells removed.)

enterovirus A genus of RNA viruses which typically enter the body through the respiratory or gastrointestinal systems and sometimes spread to the central nervous system or other parts of the body, causing neurological, cardiac, and other damage. Since the first reports of myalgic encephalomyelitis (ME), enteroviruses have been suspected as a cause of ME. Enteroviruses have also been implicated as the cause of Type I diabetes, congestive heart failure, and other conditions. Enteroviruses include poliovirus, coxsackieviruses, and many others. New enteroviruses and new strains of existing enteroviruses are continuously being discovered. (Learn more: viralzone.expasy.org)

cerebral 1. of or relating to the brain or the intellect 2. of, relating to, affecting, or being the cerebrum.

BMJ The BMJ (previously the British Medical Journal) is a weekly peer-reviewed medical journal.