The Enterovirus Theory of Disease Etiology in ME/CFS: A Critical Review (O'Neal and Hanson, 2021)

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The full article is finally published and is freely available!

The Enterovirus Theory of Disease Etiology in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Critical Review
https://www.frontiersin.org/articles/10.3389/fmed.2021.688486/full

Now we can finally begin, er... I mean continue this discussion! ;)
That fits my worsening 100%. Croatia with one week of diarrhea , lots of stress as a lawyer... Back home mild-> moderate within one day. I also have Coxsackie B4.
4434A6A7-EDDD-4846-887D-D8988384E20F.jpeg
 

msf

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It's quite clear that many different organisms can trigger ME. Giardia is well established in the literature. The trigger in my case was Yersinia (classic symptoms + IgA positivity). The Dubbo study showed EBV, Q fever, and Ross River virus, along with unidentified pathogens:

The medical, psychiatric, and laboratory assessments of the 29 provisional cases of post-infective fatigue syndrome at six months led to exclusion of one participant on medical grounds and none on psychiatric grounds. The 28 cases of chronic fatigue syndrome, termed here confirmed post-infective fatigue syndrome, included 14 men and 14 women with a mean age of 37 (range 17-63) years, including five participants with confirmed Epstein-Barr virus infection, three with Q fever, 13 with Ross River virus, and eight with unconfirmed infection

Now it seems that Coronavirus can cause ME as well. So it would not be surprising if some cases of ME are caused by Enterovirus. The key thing at this point would be trying to determine if several triggers all end with the same basic pathology, which should then become the focus in terms of trying to find a treatment for 'ME.' The literature and my own experience suggests that it will also be important to identify and treat the triggering infection,
 
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It's quite clear that many different organisms can trigger ME. Giardia is well established in the literature. The trigger in my case was Yersinia (classic symptoms + IgA positivity). The Dubbo study showed EBV, Q fever, and Ross River virus, along with unidentified pathogens:

The medical, psychiatric, and laboratory assessments of the 29 provisional cases of post-infective fatigue syndrome at six months led to exclusion of one participant on medical grounds and none on psychiatric grounds. The 28 cases of chronic fatigue syndrome, termed here confirmed post-infective fatigue syndrome, included 14 men and 14 women with a mean age of 37 (range 17-63) years, including five participants with confirmed Epstein-Barr virus infection, three with Q fever, 13 with Ross River virus, and eight with unconfirmed infection

Now it seems that Coronavirus can cause ME as well. So it would not be surprising if some cases of ME are caused by Enterovirus. The key thing at this point would be trying to determine if several triggers all end with the same basic pathology, which should then become the focus in terms of trying to find a treatment for 'ME.' The literature and my own experience suggests that it will also be important to identify and treat the triggering infection,
And stress… so it doesn’t need an infection … reminds me of autoimmunity
 

perrier

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Just a personal detail: our family member did test positive (double positive) for enterovirus on a biopsy. Dr. Chia just told me to try a little equilabrant. This was a telephone consult. This supplement apparently doesn't work that well for females. But is it accurate to say that treatment possibilities are still not reliable? Dr. Hanson is in close contact with Dr. Ron Davis. I have to wonder what OMF is speculating in this regard? Does anyone know? Dr. Chia has been a sort of loner for a long time. I hope he is brought into the picture more. Thanks for this interesting discussion.
 
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Just a personal detail: our family member did test positive (double positive) for enterovirus on a biopsy. Dr. Chia just told me to try a little equilabrant. This was a telephone consult. This supplement apparently doesn't work that well for females. But is it accurate to say that treatment possibilities are still not reliable? Dr. Hanson is in close contact with Dr. Ron Davis. I have to wonder what OMF is speculating in this regard? Does anyone know? Dr. Chia has been a sort of loner for a long time. I hope he is brought into the picture more. Thanks for this interesting discussion.
Only thing I know is that Ron is sceptical that we all have infections and that this is the cause of the illness. But they also look into it. They didn’t give that up! That’s a big misunderstanding… if I remember right Ron himself said that they do further investigations bc it looks like an ongoing virus. But I’m not so sure, I was severely ill when watching the video.
 

Pyrrhus

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The key thing at this point would be trying to determine if several triggers all end with the same basic pathology, which should then become the focus in terms of trying to find a treatment for 'ME.' The literature and my own experience suggests that it will also be important to identify and treat the triggering infection,
That sounds eminently reasonable.

But is it accurate to say that treatment possibilities are still not reliable?
I believe it is accurate to say that.

From what I can recall they didn’t look for RNA viruses yet, just DNA. Please correct me if I‘m wrong.
It is certainly accurate to say that.
 

halcyon

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So, a couple of things I noticed. I had forgotten that the antibody titers are maxed out at >=1:640
Not all of the serotype tests max out at 1:640. Coxsackie B4 for some reason produces a larger humoral response than other enteroviruses and can produce effective antibody concentrations at the 1:1024 dilution.

Don't make the mistake of treating this microneutralization assay as being quantitative in any way. It's a measure of viral neutralization effect in vitro, which then provides an indirect measure of neutralizing antibody concentrations in the blood sample. It can't really inform how much actual viral load is present in the body at any one time.

The presence or absence of enterovirus RNA in those samples at various time periods from the study are much more direct and interesting to look at.
 
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Not all of the serotype tests max out at 1:640. Coxsackie B4 for some reason produces a larger humoral response than other enteroviruses and can produce effective antibody concentrations at the 1:1024 dilution.

Don't make the mistake of treating this microneutralization assay as being quantitative in any way. It's a measure of viral neutralization effect in vitro, which then provides an indirect measure of neutralizing antibody concentrations in the blood sample. It can't really inform how much actual viral load is present in the body at any one time.

The presence or absence of enterovirus RNA in those samples at various time periods from the study are much more direct and interesting to look at.
The problem is to detect those RNA as the virus can completely disappear from blood and cerebral fluid … not every doc will do a stomach biopsy based on those results and the Hanson study. So what are your options then? Leave everything as it is, especially when you’re very severe? Try to treat it? What do you think?
 

halcyon

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However, we also have to consider the possibility that Dr. Chia doesn't want to disrupt the cash flow he get from Equilibrant.
I can't know what's in another persons heart, but having been a patient of his for over 6 years I am extremely confident he is not motivated by profit in any way. Not in his medical practice, nor in selling Equilibrant. He could very easily be like any number of other CFS practitioners that I won't name here that don't bill insurance and sell marked up supplements, but he doesn't. He's well into the age where he could retire but he's not because he is motivated to cure his patients (not to mention that he still busts his ass doing hospital rounds and has continued to do so throughout the COVID-19 epidemic). He sells Equilibrant as a courtesy to patients so they don't have to navigate importing bulk oxymatrine of unknown quality from China themselves, which is how it had to be done before.
 

halcyon

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Giardia is well established in the literature.
Unless I missed something, there is only one instance (and perhaps multiple papers if I recall) where G. lamblia was associated with CFS, so I wouldn't call that "well established". It was highlighted in that outbreak because it was unusual (G. lamblia not being endemic in the part of northern Europe where the outbreak occurred), and what it indicated was that the people that were infected were infected through human sewage contamination into the water supply, which obviously would have also contained other water stable enteric pathogens such as enteroviruses. Correlation, of course, is not causation.
 
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halcyon

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The problem is to detect those RNA as the virus can completely disappear from blood and cerebral fluid … not every doc will do a stomach biopsy based on those results and the Hanson study. So what are your options then? Leave everything as it is, especially when you’re very severe? Try to treat it? What do you think?
That's not entirely true. It's difficult, but not impossible. Again look at the graphs from the Chia interferon study I was replying about. Enterovirus RNA was detected in the samples at various points (and disappeared with treatment).

What I hope is discussed in the paper this thread is about (I haven't read it yet) is that the methods used to date in a lot of studies are severely lacking. RNA is extremely fragile, doubly so floating free in serum where things like RNase will make short work of it. Blood samples have to be drawn into an RNA preservative and processed and tested very quickly before what little RNA that may be present can degrade. The other problem is that for a long time people have probably been completely throwing out the blood fraction (or at least not testing it) that actually does contain virus in it, the buffy coat. Take a look at the study I linked previously. The virus (or genome fragments thereof) can end up in leukocytes which are present in the blood. Co-culturing those leukocytes with permissive cell lines can produce a nice, natural amplification effect and can ease RNA detection. It's not something that will be used anytime soon clinically I imagine, but it's something ME researchers should be paying attention to for sure.

The treatment options right now are not good, to say the least. Lamivudine and tenofovir, if you can get it, can be helpful for some (likely acting through indirect effects rather than actual chain termination of the enterovirus replication IMO), hardcore immune modulation as with type I interferon is really not recommended. That leaves at home immune modulation with things like the plant compounds in Equilibrant, inosine, etc. This can just as easily make you feel worse as it can make you feel better, it's really individual. I'd encourage folks to check out Chia's talk at the upcoming IACFS conference later this year, he may or may not have some updates on future avenues to explore regarding treatment.
 
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That's not entirely true. It's difficult, but not impossible. Again look at the graphs from the Chia interferon study I was replying about. Enterovirus RNA was detected in the samples at various points (and disappeared with treatment).

What I hope is discussed in the paper this thread is about (I haven't read it yet) is that the methods used to date in a lot of studies are severely lacking. RNA is extremely fragile, doubly so floating free in serum where things like RNase will make short work of it. Blood samples have to be drawn into an RNA preservative and processed and tested very quickly before what little RNA that may be present can degrade. The other problem is that for a long time people have probably been completely throwing out the blood fraction (or at least not testing it) that actually does contain virus in it, the buffy coat. Take a look at the study I linked previously. The virus (or genome fragments thereof) can end up in leukocytes which are present in the blood. Co-culturing those leukocytes with permissive cell lines can produce a nice, natural amplification effect and can ease RNA detection. It's not something that will be used anytime soon clinically I imagine, but it's something ME researchers should be paying attention to for sure.

The treatment options right now are not good, to say the least. Lamivudine and tenofovir, if you can get it, can be helpful for some (likely acting through indirect effects rather than actual chair termination of the enterovirus replication IMO), hardcore immune modulation as with type I interferon is really not recommended. That leaves at home immune modulation with things like the plant compounds in Equilibrant, inosine, etc. This can just as easily make you feel worse as it can make you feel better, it's really individual. I'd encourage folks to check out Chia's talk at the upcoming IACFS conference later this year, he may or may not have some updates on future avenues to explore regarding treatment.
This is what the Enterovirus Foundation says

„ After the acute phase of an infection, enteroviruses can disappear from the blood and cerebrospinal fluid completely, but can remain in organs and other tissues. This makes it difficult to diagnose enterovirus infections without a biopsy, and even then, the tests are limited.”

And what means tested quickly? I'm 100% bedridden and can’t visit a lab.

Sorry I’m too severe to read a whole study you linked. Hope my finance can.
 

halcyon

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This is what the Enterovirus Foundation says

„ After the acute phase of an infection, enteroviruses can disappear from the blood and cerebrospinal fluid completely, but can remain in organs and other tissues. This makes it difficult to diagnose enterovirus infections without a biopsy, and even then, the tests are limited.”
It's a reasonable statement, but the functional word is "can", not "always". Chia knows how to do it, he's done it in his studies, it's just not something he's equipped to do at scale on a clinical basis. Others have as well (I linked two previous studies that found enterovirus RNA in spinal fluid, not important to read if you are too sick to, just be aware they exist). I can't give you a figure on how quickly, but for example in Chia's previous studies he mentioned he would literally have to take the blood immediately after having it drawn and drive it back to the lab to spin down and process, and even doing so would net very very low copy numbers with qPCR. No commercial or nationalized health system that I'm aware of will use RNA preservatives in the tubes when they draw your blood/CSF for PCR testing, nor will they be guaranteed to process it with any rapidity, nor are you guaranteed that there happened to be any meaningful quantity of cell-free RNA in the few ml of blood they drew.

If enough interest and evidence can build around this idea, I really hope that there will be improvements in clinical testing of enteroviruses so it can be dragged out of the 20th century ideology behind the testing that's barely available even today.