Why has 'persistent enteroviral infection' been dropped as a research strand in ME/CFS? (Jen Brea asking)

[Guest 102]

I wish everyone would read Melvin Ramsay's text from 1986, The Saga of Royal Free Disease - it has a great summary of all the epidemic outbreaks pre-1980s (available from ME Association) - and Peter Behan, who diagnosed me, wrote the preface. Dr Ramsay himself said other viruses were causing almost identical illness, not all down to enterovirus. He saw little clinical difference between epidemic and endemic. As someone who has proven Coxsackie trigger to ME (others were getting ill from Coxsackie in west Scotland at this time, but not all of us developed ME) I am of course interested in the role of enterovirus, but am certainly not wedded it to being the sole cause. Too many patients nowadays have severe ME from other viruses. Not sure this is where I want research to be focused. Revisiting old ground.

 

[chrisb]

www.ncbi.nlm.nih.gov/pmc/articles/PMC2425322/?page=1

This paper by Parish describes the phenomenon at p713

 

[Mithriel]

Dr Ian Richardson from Newcastle was one of the last polio experts. He believed polio affected one part of the brain and ME another. (I lost all my old documents changing computers so have nothing to refer to so relying on memory) The experts on enteroviruses have gone.

The biopsies found enteroviruses in patients but not healthy controls. There is no suggestion that it is found in healthy people, just that that is where it lives. They are curious viruses because they do not lyse the cell but multiply within it invisible to the immune system but damaging the function. They also do not replicate true to evade the immune system. Very interesting biology.

There is a political dimension to the work. Because the symptoms they cause are so widespread (and because ME was reconsidered as "fatigue) too many samples were being sent into labs. It was a complicated test and was costing too much so the test was dropped. Restricting it to people with PEM may have given useful results.

"Our own blinded studies using PCR found no enterovirus RNA in the sera or other specimens from patients or control subjects."" My husband, a microbiologist, hates PCR. Yes, it can be useful but it is not the straightforward test people believe it to be. Also it only finds what you're looking for. For example for many years there was a category of Non A/ Non B hepatitis. They knew something was there and eventually Hep C was discovered. It would never have happen if the test had been PCR.

 

[Jonathan Edwards]

This is the ME- pedia link about it but I think Ramsay said more in his book, which I no longer have. I shall see what I can find. I think Acheson may also have mentioned it.

http://me-pedia.org/wiki/1948-49_Akureyri_outbreak

Thanks. Acheson does also mention much the same material. I am not sure one can make much of the various observations, especially when we have no idea if the same virus was involved in the different outbreaks, as NMJ points out.

Reading Acheson the thing that strikes me most is that what stood out for him as the pattern of illness in these outbreaks bears pretty little relation to the illness that most people with ME seem to have now. There is a focus on local neurological symptoms that seem to peter out fairly quickly. The acute illness seems to be the main problem. I increasingly tend to think that the Acheson/Ramsay concept of ME is a red herring.

ME, as something that makes life a struggle for people here and people I meet in relation to the charities and stakeholder meetings, and is defined by long term PEM, is to my mind a very real illness. Royal Free and Iceland diseases in comparison look like historical oddities that are not well documented enough clinically and pathologically to know quite what to make of.

 

[chrisb]

The feeling that I have about this is that there are quite a few of us here who started out with an illness very like the Ramsay defined ME, but whose illness has morphed, over the years, into something rather different. There are others, equally ill, whose illness followed a different course. The difficulty is that we have little idea of the outcomes for the original epidemic patients at twenty or thirty years and whether a proportion of them were similar at the same stage of the illness.

I think it will be difficult to persuade some of us who had an acute onset with an unidentified virus and who have ben unwell ever since that the virus is not responsible. The difficulty was created in the early 1990s by the BPS brigade saying that everyone was probably exposed to half a dozen viruses a year and that the virus was merely associated with onset rather than being causative. They really do have contempt for our intelligence..

 

[Jonathan Edwards]

The feeling that I have about this is that there are quite a few of us here who started out with an illness very like the Ramsay defined ME, but whose illness has morphed, over the years, into something rather different. There are others, equally ill, whose illness followed a different course. The difficulty is that we have little idea of the outcomes for the original epidemic patients at twenty or thirty years and whether a proportion of them were similar at the same stage of the illness.

Ramsay's definition looked a bit open ended last time I looked at it but that was a while back. What strikes me about Acheson's account is that he refers to ME as 'a paralytic illness'. He gives the features as
All the outbreaks shared the following characteristics: (1) headache; (2) myalgia; (3) paresis; (4) symptoms or signs other than paresis suggestive of damage to the brain, spinal cord or peripheral nerves; (5) mental symptoms; (6) low or absent fever in most cases; (7) no mortality.

As far as I am aware few if any people with ME, as now defined as a long term condition with exertion intolerance or PEM, have these features in bold, which are really the only specific features in Acheson's list. If people with ME had actual paralysis or signs indicating damage to brain or spinal cord every medic would know about it and would probably have come across someone arriving at A/E with it during their internship or residency. This is not the ME this website spends its time discussing as far as I can see.

There are reports of follow up and although limited they all seem to suggest that most people got better - which again is not like ME.

 

[duncan]

@Jonathan Edwards, relative to your two bolded items, I have to disagree. Paresis doesn't only refer to paralysis, it also refers to a more or less permanent muscle weakness, which I have seen many pwME describe. Individuals with periodic paralysis - also characterized USUALLY with PMW or permanent muscle weakness - I think can overlap with us by default misdiagnosis, at least in some cases, and most think they should all be paralysed, but of course they are not, so the confusion relative to muscle weakness vs paralysis isn't unique to pwME.

As for symptoms or signs other than paresis suggestive of damage to the brain etc, one need look little farther than balance issues, which could be rooted in the 8th cranial nerve. Many of us also have peripheral neuropathies. There are more examples, but I suspect some of those can be accounted for by simply erasing the false plurality between Acheson's damage to the brain and mental issues. I am sure I am forgetting other examples.

 

[Amw66]

Ramsay's definition looked a bit open ended last time I looked at it but that was a while back. What strikes me about Acheson's account is that he refers to ME as 'a paralytic illness'. He gives the features as
All the outbreaks shared the following characteristics: (1) headache; (2) myalgia; (3) paresis; (4) symptoms or signs other than paresis suggestive of damage to the brain, spinal cord or peripheral nerves; (5) mental symptoms; (6) low or absent fever in most cases; (7) no mortality.

As far as I am aware few if any people with ME, as now defined as a long term condition with exertion intolerance or PEM, have these features in bold, which are really the only specific features in Acheson's list. If people with ME had actual paralysis or signs indicating damage to brain or spinal cord every medic would know about it and would probably have come across someone arriving at A/E with it during their internship or residency. This is not the ME this website spends its time discussing as far as I can see.

There are reports of follow up and although limited they all seem to suggest that most people got better - which again is not like ME.

There are some who have paralysis sporadically. A child the same age as my daughter had paralysis for a few days at onset, for 2 months following HPV vaccine ( these were both legs), and scarily yesterday almost total paralysis - only able to speak some words and move eyebrows for 12 hours following emotional upset.

I think @Jenny TipsforME had a thread involving paralysis some time ago

 

[adambeyoncelowe]

Ramsay's definition looked a bit open ended last time I looked at it but that was a while back. What strikes me about Acheson's account is that he refers to ME as 'a paralytic illness'. He gives the features as
All the outbreaks shared the following characteristics: (1) headache; (2) myalgia; (3) paresis; (4) symptoms or signs other than paresis suggestive of damage to the brain, spinal cord or peripheral nerves; (5) mental symptoms; (6) low or absent fever in most cases; (7) no mortality.

As far as I am aware few if any people with ME, as now defined as a long term condition with exertion intolerance or PEM, have these features in bold, which are really the only specific features in Acheson's list. If people with ME had actual paralysis or signs indicating damage to brain or spinal cord every medic would know about it and would probably have come across someone arriving at A/E with it during their internship or residency. This is not the ME this website spends its time discussing as far as I can see.

There are reports of follow up and although limited they all seem to suggest that most people got better - which again is not like ME.

I think Acheson's description is quite a lot vaguer than Ramsay's. The latter seems much more precise:

Disease in chronic state
Once the syndrome is fully established the patient presents a multiplicity of symptoms which can most conveniently be described in three groups.

• Muscle phenomena
  • [Fatiguability]: Muscle fatigability, whereby, even after a minor degree of physical effort, three, four or five days, or longer, elapse before full muscle power is restored and constitutes the sheet anchor of diagnosis. Without it I would be unwilling to diagnose a patient as suffering from ME, but it is most important to stress the fact that cases of ME or mild or even moderate severity may have normal muscle power in a remission. In such cases, tests for muscle power should be repeated after exercise.
  • [Pain:] In severe cases of ME, muscle spasms and twitchings are a prominent feature and give rise to swollen bands of tissue which are acutely tender. In less severe cases, muscle tenderness may not be so readily elicited but careful palpation of the trapezii and gastrocnemii (the muscle groups most commonly involved) with the tip of the forefinger should enable the examiner to detect minute foci or exquisite tenderness.
  • [Clumsiness:] In the aftermath of the disease patients frequently fumble with relatively simple manoevres such as turning a key in a lock or taking the cork of a bottle.

• Circulatory impairment. Most cases of ME complain of
  • Cold extremities and
  • Hypersensitivity to climactic change . . .
  • Ashen-grey facial pallor, some twenty or thirty minutes before the Patient complains of feeling ill

• Cerebral dysfunction. The cardinal features:
  • Impairment of memory
  • Impairment of powers of concentration and
  • Emotional lability
  • [Other] common deviations from normal cerebral function:
    • Failure to recall recent or past events,
    • Difficulty in completing a line of thought . . .
    • Becoming tongue-tied in the middle of a sentence, and a
    • Strong inclination to use wrong words, saying door when they mean table or hot when they mean cold . . .
    • Complete inability to comprehend a paragraph even after re-reading it
    • Bouts of uncontrollable weeping . . .
    • Alterations of sleep rhythm or vivid dreams, or both . . .
• [Accompanying] features [that] can only be attributed to involvement of the Autonomic nervous system:
  • Frequency of micturition (urination)
  • Hyperacusis (hypersensitivity to noise)
  • Episodic sweating
  • Orthostatic tachycardia . . .

Variability and fluctuation of both symptoms and physical findings in the course of a day is a constant feature in the clinical picture of myalgic encephalomyelitis.

An alarming tendency to become chronic. [Added in the 2nd edition, 1988][3]​

This is from here: http://me-pedia.org/wiki/Ramsay_definition (fully referenced), and it's the same criteria in Ramsay's white book. I've bolded a few of the symptoms that appear in other criteria and definitely resemble the illness we're talking about today. The only difference is that fatigue isn't the central feature, but rather is implied by some of the other symptoms.

With its focus on delayed recovery (PEM?), pain, cognitive problems (brain fog), temperature problems, sleep problems and OI, it's actually very close to the CCC and ICC. Like those criteria, neuro symptoms are included too, although they appear optional in all three cases.

The IoM criteria are also not a million miles away, with their focus on PEM, pain and either sleep problems or OI. Again, though, fatigue is a defining feature here.

In fact, Ramsay's criteria also have significant overlap with the pick 'n' mix symptom lists of Fukuda and the NICE criteria, except that it makes it very clear that the muscle problems are essential in Ramsay's definition, while PEM is optional for those criteria. Again, they focus more on fatigue as opposed to muscle fatiguability.

Ramsay's criteria also includes more mention of the neurological symptoms, although these symptoms also appear in the CCC and ICC, and appear to be optional in all cases.

So the biggest difference, really, is the concept of 'muscle fatiguability' versus either PEM, fatigue or both.

 

[Jonathan Edwards]

Paresis doesn't only refer to paralysis, it also refers to a more or less permanent muscle weakness, which I have seen many pwME describe.

Acheson was referring to 'paralytic illness'. To a physician paresis means paralysis - inability to contract a muscle from muscle or motor neuron problems. If muscle cannot be contracted because of pain or other inhibiting factors we do not call that paresis.

As for symptoms or signs other than paresis suggestive of damage to the brain etc, one need look little farther than balance issues, which could be rooted in the 8th cranial nerve. Many of us also have peripheral neuropathies.

I am afraid I just do not buy that. Vestibular nerve damage gives very particular signs that can be diagnosed and I have no reason to think PWME have vestibular nerve damage. I have also not seen any indication that PWME have peripheral neuropathies more than the rest of the population. If they did there would be papers on it. Neurologists love writing papers on peripheral neuropathy.

To me ME as a long term condition that makes it impossible to lead a normal life is far more important than possible minutiae about neurological lesions that nobody has documented. Even in Acheson's review it is made clear that most of the time signs were not recorded systematically.

 

[adambeyoncelowe]

I think Acheson's description is quite a lot vaguer than Ramsay's. The latter seems much more precise:

Disease in chronic state
Once the syndrome is fully established the patient presents a multiplicity of symptoms which can most conveniently be described in three groups.

• Muscle phenomena
  • [Fatiguability]: Muscle fatigability, whereby, even after a minor degree of physical effort, three, four or five days, or longer, elapse before full muscle power is restored and constitutes the sheet anchor of diagnosis. Without it I would be unwilling to diagnose a patient as suffering from ME, but it is most important to stress the fact that cases of ME or mild or even moderate severity may have normal muscle power in a remission. In such cases, tests for muscle power should be repeated after exercise.
  • [Pain:] In severe cases of ME, muscle spasms and twitchings are a prominent feature and give rise to swollen bands of tissue which are acutely tender. In less severe cases, muscle tenderness may not be so readily elicited but careful palpation of the trapezii and gastrocnemii (the muscle groups most commonly involved) with the tip of the forefinger should enable the examiner to detect minute foci or exquisite tenderness.
  • [Clumsiness:] In the aftermath of the disease patients frequently fumble with relatively simple manoevres such as turning a key in a lock or taking the cork of a bottle.

• Circulatory impairment. Most cases of ME complain of
  • Cold extremities and
  • Hypersensitivity to climactic change . . .
  • Ashen-grey facial pallor, some twenty or thirty minutes before the Patient complains of feeling ill

• Cerebral dysfunction. The cardinal features:
  • Impairment of memory
  • Impairment of powers of concentration and
  • Emotional lability
  • [Other] common deviations from normal cerebral function:
    • Failure to recall recent or past events,
    • Difficulty in completing a line of thought . . .
    • Becoming tongue-tied in the middle of a sentence, and a
    • Strong inclination to use wrong words, saying door when they mean table or hot when they mean cold . . .
    • Complete inability to comprehend a paragraph even after re-reading it
    • Bouts of uncontrollable weeping . . .
    • Alterations of sleep rhythm or vivid dreams, or both . . .
• [Accompanying] features [that] can only be attributed to involvement of the Autonomic nervous system:
  • Frequency of micturition (urination)
  • Hyperacusis (hypersensitivity to noise)
  • Episodic sweating
  • Orthostatic tachycardia . . .

Variability and fluctuation of both symptoms and physical findings in the course of a day is a constant feature in the clinical picture of myalgic encephalomyelitis.

An alarming tendency to become chronic. [Added in the 2nd edition, 1988][3]​

This is from here: http://me-pedia.org/wiki/Ramsay_definition (fully referenced), and it's the same criteria in Ramsay's white book. I've bolded a few of the symptoms that appear in other criteria and definitely resemble the illness we're talking about today. The only difference is that fatigue isn't the central feature, but rather is implied by some of the other symptoms.

With its focus on delayed recovery (PEM?), pain, cognitive problems (brain fog), temperature problems, sleep problems and OI, it's actually very close to the CCC and ICC. Like those criteria, neuro symptoms are included too, although they appear optional in all three cases.

The IoM criteria are also not a million miles away, with their focus on PEM, pain and either sleep problems or OI. Again, though, fatigue is a defining feature here.

In fact, Ramsay's criteria also have significant overlap with the pick 'n' mix symptom lists of Fukuda and the NICE criteria, except that it makes it very clear that the muscle problems are essential in Ramsay's definition, while PEM is optional for those criteria. Again, they focus more on fatigue as opposed to muscle fatiguability.

Ramsay's criteria also includes more mention of the neurological symptoms, although these symptoms also appear in the CCC and ICC, and appear to be optional in all cases.

So the biggest difference, really, is the concept of 'muscle fatiguability' versus either PEM, fatigue or both.

Reading this back now, in fact, it really is a lot like the CCC and ICC criteria, which likewise group symptoms up into categories like this. The immunological symptoms are sort of scattered throughout the Ramsay definition, rather than having a category of their own, and the circulatory issues are categorised differently (neuro-endocrine and autonomic, mostly).

 

[duncan]

Acheson was referring to 'paralytic illness'. To a physician paresis means paralysis - inability to contract a muscle from muscle or motor neuron problems. If muscle cannot be contracted because of pain or other inhibiting factors we do not call that paresis.

I cannot speak to what Acheson was referring to, but I can tell you that neurologists have a whole category of illness called Periodic Paralsys which in most of its patients does not refer to paralysis most of the time, but instead can be characterized by permanent muscle weakness that episodically waxes and wanes, and revolves around channelopathies.

I am afraid I just do not buy that. Vestibular nerve damage gives very particular signs that can be diagnosed and I have no reason to think PWME have vestibular nerve damage.

I have it. I have been diagnosed with ME/CFS by no less the three worlclass ME/CFS experts. My vestibular damage was confirmed at the NIH in a six-hour test.

I have also not seen any indication that PWME have peripheral neuropathies more than the rest of the population. If they did there would be papers on it. Neurologists love writing papers on peripheral neuropathy.

I'd wager this is wrong. Besides, how many neurologists are looking at our population besides Natelson? I can count on one hand the number that study PP with any sort of regularity or expertise. Neurologists don't like unsafe topics, imo, and there are few that are less safe than ME/CFS.

 

[Jonathan Edwards]

I think Acheson's description is quite a lot vaguer than Ramsay's. The latter seems much more precise:

Yes, looking at Ramsay's list there, it is certainly much more like ME as we generally understand it. I was trying to make the point that focusing on the features of the outbreaks may be a red herring - which Acheson seems to do much more than Ramsay. And it was Acheson who coined the term myalgic encephalomyelitis if I remember rightly. He seems to have wanted to invent a 'sister of polio' disease and I think that may be wildly off target.

Ramsay is certainly more detailed. On the other hand Acheson is 'less vague' in the sense that he requires objective neurological deficit. Pretty much all of Ramsay's list is symptomatic. He mentions loss of muscle power but that is a very subjective thing to test and would not normally be taken on its own as an objective physical sign by a neurologist without other features like reflex changes. And although Ramsay certainly fits much better with what seems to be the current concept of ME an awful lot of the features are very open to interpretation - which I think is what i meant by open-ended. The list does not lend itself to a set of criteria suitable for research study, which is presumably why it has been superseded.

 

[Jonathan Edwards]

I cannot speak to what Acheson was referring to, but I can tell you that neurologists have a whole category of illness called Paralytic Paralsis which in most of its patients does not refer to paralysis most of the time, but instead can be characterized by permanent muscle weakness that episodically waxes and wanes, and revolves around channelopathies.

I think you are referring to periodic paralysis, which comes under paralysis because abnormalities in cation levels or movements make the muscle paretic.

Vestibular damage is very common. I have no vestibular function on the right since my mid thirties at least (when I had a typical attack of 'vestibular neuronitis') and I do not have ME. It might be worth running an unselected cohort of PWME through vestibular tests with matched controls but until we have data from that I don't think we have reason to think PWME have more vestibular problems than others. The unsteadiness people describe does not sound vestibular to me.

 

[duncan]

Yes, periodic paralysis (thank you, I have corrected my earlier post). But I believe in most cases of periodic paralysis, there usually is little to no paralysis, just permanent muscle weakness (albeit frequently profound, debilitating weakness). There are many that have paralysis, some pretty much complete, but I'm thinking not most. I use the term "most" guardedly since this is not a well-studied population.

 

[duncan]

Vestibular damage is very common. I have no vestibular function on the right since my mid thirties at least and I do not have ME. It might be worth running an unselected cohort of PWME through vestibular tests with matched controls but until we have data from that I don't think we have reason to think PWME have more vestibular problems than others. The unsteadiness people describe does not sound vestibular to me.

I think you need to factor in degree. And I only threw in vestibular damage as an example of brain damage. I did not mean for it to be interpreted as definitive. I think there are many examples of brain damage in pwME, as well as damage to the peripheral system. POTS, for instance, could be rooted in brain stem damage.

You realize I can go on and on. To say something is not studied enough is not the same as to say it does not exist.

 

[chrisb]

This comment by Acheson is interesting:

"What then is the link between this article (the 1959 one) and the present monograph? The key lies in the "protracted debility" which was a feature of a minority of patients in almost all the outbreaks and which persisted for months and, in a few cases, for years. It was noted that:

convalescence has been prolonged by fatigue and recurring myalgia but recovery has usually been complete within three months. In a proportion, which varies from outbreak to outbreak, a well defined state of chronic ill-health has developed characterised by fluctuating myalgia and paresis, partial remissions exacerbations and depression, emotional lability and lack of concentration.

…...I am glad that the British Medical Bulletin has decided to use the term" postviral fatigue syndrome" rather than "myalgic encephalomyelitis". Since the description benign myalgic encephalomyelitis was proposed in 1956, no pathological evidence has emerged to support the view that the symptoms are due to inflammatory changes in the central nervous system. Rather such evidence as there is suggests that in some cases there may be persistence of infection in muscle. Until definite evidence is forthcoming a more general, such as "postviral fatigue syndrome" is more appropriate."



So, by 1991 Acheson's views had evolved.

 

[duncan]

Assuming enterovirises play a role (as well as other pathogens?), some of the confusion over inconsistencies in patient experience could be due to the course the disease runs. I do not know if enteroviruses are tissue-tropic, or if the virus spreads uniformly through-out the body. If it does not, then some hit may have more brain signs and symptoms, some more gastro-intestinal, and so on and so forth.

It would be the overall pattern that would matter, the symptom cluster, not the specific manifestations that could be peculiar to a given pwME.

 

[JenB]

I have not heard of that. Is it recorded somewhere?

Take a look at:

http://me-pedia.org/wiki/Epidemic_myalgic_encephalomyelitis
http://me-pedia.org/wiki/Poliovirus

EDIT: Let me just copy and paste from the Epidemic ME page as I've posted a lot of links and I'm sure not everyone has dug in!


Prior to the poliovirus vaccine, several outbreaks of what later came to be called myalgic encephalomyelitis coincided with confirmed outbreaks of poliomyelitis including the 1934 Los Angeles outbreak, the 1948 Akureyri, Iceland outbreak, and 1949 outbreak in Adelaide, Australia.[4] Many outbreaks were initially misinterpreted as clusters of poliomyelitis or abortive poliomyelitis, hence one of ME's earliest names, atypical polio. It is not known whether there is a direct relationship between polio outbreaks and ME or if outbreaks of ME were more likely to be reported when public health authorities were already mobilized for an earlier crisis.

No serological evidence of polio was ever found in these outbreaks and the ultimate pattern of the outbreaks differed in significant ways, chief among them the higher attack rate, the tendency to affect adults rather than children, and the higher morbidity than poliomyelitis but no mortality.[2][10] Findings in several outbreaks seemed to suggest that symptoms were caused by an enterovirus distinct from but related to polio: findings of mild, diffuse peripheral nervous system damage in monkeys infected with the virus; a stronger response to polio vaccination in children who had been in epidemic areas; and seasonal patterns of infection resembling polio, i.e., the rise in cases during summer months.[2][10]

There is indirect evidence of cross-immunity between poliovirus and the unidentified virus or viruses in epidemic myalgic encephalomyelitis outbreaks. After the Akureyri outbreak, children in areas that had been affected responded to poliomyelitis vaccination with higher antibody titres, as if these children had already been exposed to an agent immunologically similar to the poliovirus.[2][23] During the outbreak in Adelaide, cases of classic poliomyelitis dropped by 43%.[24]

And from the polio page:

Cross-immunity[edit | edit source]
It is theorized that exposure to one enterovirus may confer partial immunity or improved immune response to another enteroviruses. One study compared schoolchildren in Estonia, who were inoculated with the Sabin, live attenuated virus polio vaccine, to Finnish schoolchildren, who were inoculated with the Salk, inactivated vaccine.[4] Estonian children had stronger T cell responses to coxsackievirus B4 and poliovirus type 1, and stronger expression of IFN-γ when exposed to poliovirus challenge as compared to Finnish children. Finnish children have weaker cellular immunity against enteroviruses at the age of 9 months compared with Estonian children at the same age. (Finland has a rate of Type 1 diabetes three times the rate of Estonia. Coxsackie B4 has been associated with Type 1 diabetes.) An unintended consequence of widespread polio vaccination may have been impaired immunity to other enteroviruses, such as Coxsackie and echoviruses.

There is indirect evidence of cross-immunity between Akureyri outbreak in Iceland, children in areas that had been affected responded to poliomyelitis vaccination with higher antibody titres, as if these children had already been exposed to an agent immunologically similar to poliomyelitis virus.[3][5] During the 1949-1953 outbreak in Adelaide, cases of classic poliomyelitis dropped by 43%.[6]




The individual outbreak pages go into more detail. The Iceland observation re: stronger immune response to vaccine is interesting. So is the drop in poliomyelitis in Adelaide/South Australia (when rates had risen in nearly every other state).

I'm still reading my way through, so will post more if I find anything that stands out.

 

[Adrian]

If a virus is not interfering with cell function then it is hard to see why it should cause any symptoms.

As far as I am aware the same standards apply to trying to understand ME as any other condition. The absence of fever presumably means that whatever produces ME symptoms does not stimulate fever pathways. There is no particular reason why it should. Lots of chronic diseases occur without fever.

Could a virus be creating some sort of proteins that act as a signal and cause particular responses (say with the metabolic processes) without the virus really doing much in terms of damage to the tissue? Even if this was at quite a low level of infection?