Are Infections Just a Trigger of ME/CFS, or an Ongoing Cause of ME/CFS?
- Thread starter Eeyore
- Start date
According to the CAA, 75.6% of patients developed ME after an infection. If we trust that statistic, and if we trust Dr. Edwards' assertion that infections don't trigger autoimmune disease, then the majority of patients likely have more in common with the epidemic patients than not. This would put the insidious onset patients in the minority.
I don't think there is a bias in diagnosis either and I agree that males with this disease will go to the doctor just as often as females. As I mentioned above, I worry more about the supposed large majority of patients that are undiagnosed. I also worry about misdiagnosis. As you mentioned, autoimmune disease is more prevalent in women. How many women included in your statistic have a CFS diagnosis but actually have an undiagnosed autoimmune disease as the true cause of their illness? Without a biomarker I will never be 100% confident in the reported prevalence.
I don't think there is a bias in diagnosis either and I agree that males with this disease will go to the doctor just as often as females. As I mentioned above, I worry more about the supposed large majority of patients that are undiagnosed. I also worry about misdiagnosis. As you mentioned, autoimmune disease is more prevalent in women. How many women included in your statistic have a CFS diagnosis but actually have an undiagnosed autoimmune disease as the true cause of their illness? Without a biomarker I will never be 100% confident in the reported prevalence.
Yes thanks for that . I thought it was standard knowledge that nk cells were known as cd56 unless otherwise stated. It was the nk cd56 bright cells that were found to function low compared to healthy controls. The nk cd56 dim cells wete said to be normal when compared to healthy controls.
sorry @Eeyore I just didnt understand what u were saying.
also the bright and dim nk cells are commonly being studied in cfs at bond/griffith university in australia. Researching their work may help you understand this better.
Yes, a lack of finding, apart from, of course, this finding: http://www.ncbi.nlm.nih.gov/pubmed/18396793
It's not that hard to google De Meirleir K on Pubmed!
It's not that hard to google De Meirleir K on Pubmed!
Right, but the point is that healthy people that clear the infection don't end up with non-cytolytic virus left behind producing these proteases.
I still believe that it's the infections themselves that are possibly causing the immune dysfunction. Recall that a number of the suspected ME triggering pathogens infect immune cells themselves. What happens when an enterovirus in a lymphocyte interferes with STAT1 signalling? Will that lymphocyte be able to operate properly? Obviously they only infect a small percentage of cells but it seems possible that this could cause some sort of dysfunction.
I still believe that it's the infections themselves that are possibly causing the immune dysfunction. Recall that a number of the suspected ME triggering pathogens infect immune cells themselves. What happens when an enterovirus in a lymphocyte interferes with STAT1 signalling? Will that lymphocyte be able to operate properly? Obviously they only infect a small percentage of cells but it seems possible that this could cause some sort of dysfunction.
Undoubtedly these infections do cause some immune dysfunction or weakness, as all infectious pathogens employ immune evasion tactics to thwart or disrupt the immune system. Immune evasion is part of a pathogen's survival strategy in the body.
However, if we are going try to identify the possible immune dysfunctions or weaknesses that might help explain why ME/CFS patients cannot clear non-cytolytic enterovirus infections, I would think we need to look at dysfunctions or weaknesses which are specific to ME/CFS patients.
When people catch an enterovirus, or any other pathogen for that matter, enterovirus immune evasion techniques (such as the 2A protease, 3C protease, etc, or down-regulating of the MHC to make infected cells invisible to the immune system) will be found in the infection acute phase in both people who did not succumb to a chronic infection but cleared the virus, as well as people who did succumb to a chronic infection, and developed ME/CFS. So it is not clear how the built-in immune evasion techniques of a virus can explain the difference between clearing the virus and succumbing to a chronic infection.
Though certainly some good antivirals that targeted and disabled these various enterovirus immune evasion tactics, like the 2A protease, could help fight or eliminate a chronic infection.
However, if we are going try to identify the possible immune dysfunctions or weaknesses that might help explain why ME/CFS patients cannot clear non-cytolytic enterovirus infections, I would think we need to look at dysfunctions or weaknesses which are specific to ME/CFS patients.
When people catch an enterovirus, or any other pathogen for that matter, enterovirus immune evasion techniques (such as the 2A protease, 3C protease, etc, or down-regulating of the MHC to make infected cells invisible to the immune system) will be found in the infection acute phase in both people who did not succumb to a chronic infection but cleared the virus, as well as people who did succumb to a chronic infection, and developed ME/CFS. So it is not clear how the built-in immune evasion techniques of a virus can explain the difference between clearing the virus and succumbing to a chronic infection.
Though certainly some good antivirals that targeted and disabled these various enterovirus immune evasion tactics, like the 2A protease, could help fight or eliminate a chronic infection.
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I don't believe there is going to be a consistent immune dysfunction present in all ME patients before onset. I think some may have acquired or inborn immune deficiencies that are present both before and after ME onset, and others had temporary immune deficiency due to some other factor at time of ME onset, but the deficiency in these patients might go away after onset as it only reflected a temporary situation.
You're right, I don't believe that the immune evasion tactics have anything to do with development of ME. There is no difference between the enterovirus that infects a healthy person and someone that goes on to develop ME. The difference is in the host response to the virus. Those that develop ME likely had a deficient immune response that allowed the virus to escape immune containment in the GI tract and seeded the muscles and CNS with persisting virus.
You're right, I don't believe that the immune evasion tactics have anything to do with development of ME. There is no difference between the enterovirus that infects a healthy person and someone that goes on to develop ME. The difference is in the host response to the virus. Those that develop ME likely had a deficient immune response that allowed the virus to escape immune containment in the GI tract and seeded the muscles and CNS with persisting virus.
Sorry if I didn't understand this statement correctly, but you are deducing then that 75.6% people have ME/CFS due to infection as the root cause? I don't know if @Jonathan Edwards has ever said it openly here on PR but from his posts I believe he is skeptical of this, and so am I.
It is possible that the infection just might be something that happens as a side effect of the underlying autoimmunity that looks to be causal because it happens at the time as the ME/CFS onset, but in actuality the infection might not have anything to do with bring on the disease.
It is possible that the infection just might be something that happens as a side effect of the underlying autoimmunity that looks to be causal because it happens at the time as the ME/CFS onset, but in actuality the infection might not have anything to do with bring on the disease.
That's what is implied. I don't think it's contentious that a large majority of patients develop ME after a flu-like illness, I thought this was pretty well established.They didn't name it post-viral fatigue syndrome for nothing. Of course there's no easy way to prove it, but I think it's a strong correlation and is the obvious place to start.
Sure it's possible, but why would the autoimmune condition be present with no symptoms until the infection came along? If the infection hadn't come along, would symptoms of ME still develop? If not, doesn't this imply that the infection caused the disease?
Sure it's possible, but why would the autoimmune condition be present with no symptoms until the infection came along? If the infection hadn't come along, would symptoms of ME still develop? If not, doesn't this imply that the infection caused the disease?
A lot of patients and ME/CFS experts including myself feel that the "sudden onset" isn't always so sudden as people believe, that it's just was a tipping point and if one closely paid attention many sudden onset patients actually had symptoms and other issues building before the big flu. This is what I believe happened to me and only in hindsight once the symptoms exploded did I realize that I was having mild versions that slowly got worse I think for months to years before. I thought it was just me getting older.
My daughter was hospitalised with what seemed to be appendicitis but which wasn't. The acute pains resolved but the MECFS symptoms stayed. I was well while my daughter was in hospital. Around two weeks later, my son and I had similar illnesses involving abdominal pain. The MECFS symptoms stayed with us too.
There might have been other precipitating factors and certainly an underlying susceptibility. But Ockham's Razor would point to the acute illness being a precipitating factor.
It is possible that there were some very mild MECFS symptoms in all of three of us prior to the acute illness. But, basically we were healthy and active.
I think the Dubbo study that followed all patients turning up at several clinics with EBV, Ross River Virus and Q fever did not find the patients who developed MECFS symptoms were different health-wise prior to the acute illness from the patients who didn't develop MECFS symptoms. From memory, the only predictive factor was the severity of the acute illness.
There might have been other precipitating factors and certainly an underlying susceptibility. But Ockham's Razor would point to the acute illness being a precipitating factor.
It is possible that there were some very mild MECFS symptoms in all of three of us prior to the acute illness. But, basically we were healthy and active.
I think the Dubbo study that followed all patients turning up at several clinics with EBV, Ross River Virus and Q fever did not find the patients who developed MECFS symptoms were different health-wise prior to the acute illness from the patients who didn't develop MECFS symptoms. From memory, the only predictive factor was the severity of the acute illness.
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I don't think there is much doubt that in most cases, there is an infectious illness that heralds the arrival of ME. The question is really just regarding the mechanism of propagation. Everyone acknowledges that most of us had a viral illness and never really recovered (although not all - about 25% or so don't have any such illness they can recall).
I developed ME/CFS shortly after meeting my wife but I'd be VERY wary about suggesting any causal link 
Occam's razor might suggest a causal link between reported viral onset and ME/CFS and this scenario has dominated one major strand of research but it could also be a red herring which has left us looking in entirely the wrong place (and also hasn't yielded anything definitive).
Alternative interpretations which have already been discussed are that an acute infection (or other stressor) 'un-masks' the pre-existing disorder whatever that may be or that it 'nudges' the disorder into a aggravated and chronic state (the final straw etc).
Occam's razor might suggest a causal link between reported viral onset and ME/CFS and this scenario has dominated one major strand of research but it could also be a red herring which has left us looking in entirely the wrong place (and also hasn't yielded anything definitive).
Alternative interpretations which have already been discussed are that an acute infection (or other stressor) 'un-masks' the pre-existing disorder whatever that may be or that it 'nudges' the disorder into a aggravated and chronic state (the final straw etc).
But if a couple of your close friends, a whole lot of people on Phoenix Rising and a collection of people in Dubbo also developed MECFS shortly after meeting your wife, perhaps even you would have to look at your wife a bit suspiciously?
Yes, of course there must be something else other than that initial illness that results in some people getting MECFS and others recovering from their acute illness.
But this idea
doesn't feel right for me.
Yes, of course there must be something else other than that initial illness that results in some people getting MECFS and others recovering from their acute illness.
But this idea
doesn't feel right for me.
Standard operating procedure
I am quite skeptical of many claims of sudden onset. When you question the patient in more detail it often turns out they had issues in the months or years leading up to the "sudden onset" but these were not interpreted as signs of disease at the time. Patients usually consider their onset to be when obvious disease and disability started but upon further questioning you often uncover a long history of irritable bowel syndrome, allergies, migraine, menstrual problems, anxiety, depression etc.
I wouldn't be surprised if a subclinical state of ME existed in many of us long before acute illness. I do, however, believe that the illness brings on full blown ME. I suspect that ultimately it is a failure to resolve the inflammatory response after acute stress.
@Sidereal
But probably if you questioned any selection of healthy people, there will be histories of these common health issues.
e.g.
Aug 2, 2012 - Number of people in the U.S. who have either allergy or asthma symptoms: one in five. Percentage of the U.S. population that tests positive to one or more allergens: 55%.
Lifetime prevalence of depression in the US - 17%
I don't think I or my children have remarkable health histories apart from my one year of MECFS at age 10.
You could be right that there is less sudden onset than is claimed. And I think it is quite possible that PWME have a higher incidence of autoimmune-type conditions prior to illness onset.
But, our health status before and after the acute illness was markedly different. Something changed and it changed at the time of this acute illness. As it did for the people in epidemics.
But probably if you questioned any selection of healthy people, there will be histories of these common health issues.
e.g.
Aug 2, 2012 - Number of people in the U.S. who have either allergy or asthma symptoms: one in five. Percentage of the U.S. population that tests positive to one or more allergens: 55%.
Lifetime prevalence of depression in the US - 17%
I don't think I or my children have remarkable health histories apart from my one year of MECFS at age 10.
You could be right that there is less sudden onset than is claimed. And I think it is quite possible that PWME have a higher incidence of autoimmune-type conditions prior to illness onset.
But, our health status before and after the acute illness was markedly different. Something changed and it changed at the time of this acute illness. As it did for the people in epidemics.
Yes, that's a model of infectious onset ME/CFS I think is quite plausible: that temporary immune weaknesses during the critical acute phase of the infection may allow the virus to breach into deeper tissue compartments (such as the central or peripheral nervous system) that it normally does not reach. Once in these tissue compartments, the virus seeds a chronic infection, because these tissue compartments are more amendable to supporting a chronic infection than others.
In the case of enterovirus, we know that non-cytolytic enterovirus infections are only hosted in cells which are non-dividing and quiescent, such as brain cells (neurons and astrocytes). So tissue compartments containing quiescent cells that enterovirus is able to infect should be amendable to supporting a chronic infection.
Perhaps if there is immune weaknesses during the acute enterovirus infection phase, this gives the virus enough leeway to break into deeper tissue compartments containing quiescent which it can infect, and from there on, the infection becomes chronic, developing into ME/CFS.
Dr Chia's, observation that immune-weakening corticosteroids given during an acute enterovirus infection are a recipe for creating ME/CFS would seem to support this idea.
And this corticosteroid connection might, incidentally, help explain why stressful events have been linked to the onset of ME/CFS: stress increases cortisol levels.
It is interesting that quiescent cells (G0 phase cells) include the nervous systems cells and the heart muscle cells — these are two places where enterovirus is known to create chronic infections: chronic coxsackievirus B myocarditis in the case of the heart muscles, and quite possibly ME/CFS in the case of the nervous system (certainly brain autopsies of ME/CFS patients have shown there is an enterovirus infection in the brain).
So it might be that if, during an acute enterovirus infection, the immune response is not robust enough to prevent the virus from entering either the nervous system or heart muscle tissues, you get a chronic non-cytolytic infection leading to chronic myocarditis, or perhaps to ME/CFS.
However, although breaking into a tissue compartment containing quiescent cells may be a necessary condition to set up a chronic non-cytolytic enterovirus infection, it does not seem to be a sufficient condition, at least in the case of coxsackievirus B myocarditis. This is because some people can catch an coxsackievirus B, develop acute myocarditis from it, but the acute myocarditis resolves, and never turns into chronic myocarditis.
But then in other people, the acute coxsackievirus B myocarditis (heart muscle infection) turns into chronic myocarditis. If we knew the exact mechanics of why a certain subset of acute CVB myocarditis turns into chronic CVB myocarditis, this may throw light on the chronic enterovirus infections which Dr Chia found in 82% of ME/CFS patients.
In the case of enterovirus, we know that non-cytolytic enterovirus infections are only hosted in cells which are non-dividing and quiescent, such as brain cells (neurons and astrocytes). So tissue compartments containing quiescent cells that enterovirus is able to infect should be amendable to supporting a chronic infection.
Perhaps if there is immune weaknesses during the acute enterovirus infection phase, this gives the virus enough leeway to break into deeper tissue compartments containing quiescent which it can infect, and from there on, the infection becomes chronic, developing into ME/CFS.
Dr Chia's, observation that immune-weakening corticosteroids given during an acute enterovirus infection are a recipe for creating ME/CFS would seem to support this idea.
And this corticosteroid connection might, incidentally, help explain why stressful events have been linked to the onset of ME/CFS: stress increases cortisol levels.
It is interesting that quiescent cells (G0 phase cells) include the nervous systems cells and the heart muscle cells — these are two places where enterovirus is known to create chronic infections: chronic coxsackievirus B myocarditis in the case of the heart muscles, and quite possibly ME/CFS in the case of the nervous system (certainly brain autopsies of ME/CFS patients have shown there is an enterovirus infection in the brain).
So it might be that if, during an acute enterovirus infection, the immune response is not robust enough to prevent the virus from entering either the nervous system or heart muscle tissues, you get a chronic non-cytolytic infection leading to chronic myocarditis, or perhaps to ME/CFS.
However, although breaking into a tissue compartment containing quiescent cells may be a necessary condition to set up a chronic non-cytolytic enterovirus infection, it does not seem to be a sufficient condition, at least in the case of coxsackievirus B myocarditis. This is because some people can catch an coxsackievirus B, develop acute myocarditis from it, but the acute myocarditis resolves, and never turns into chronic myocarditis.
But then in other people, the acute coxsackievirus B myocarditis (heart muscle infection) turns into chronic myocarditis. If we knew the exact mechanics of why a certain subset of acute CVB myocarditis turns into chronic CVB myocarditis, this may throw light on the chronic enterovirus infections which Dr Chia found in 82% of ME/CFS patients.
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