Why did antivirals (valcyte, etc) for SEIDs fail?

[Wishful]

Which rapid switching are you referring to? Do you mean the switch between healthy and getting ME/CFS?

No, I meant the temporary remissions. I've had the baseline symptoms for years, then triggered temporary remission within hours, felt totally healthy again and bouncing with energy, then some more hours later, abruptly switched back to baseline ME symptoms. To me that doesn't match viral population change. I think it's more likely a switch in something, maybe RNA transcription of some protein, with a cascade reaction that affects the whole body. My guess is that it's in some system that controls major systems, perhaps a hormone gland. The immune system may have the means for switching into an activated state body-wide, but I'm not sure if it has that quick or general of a 'all immune cells return to normal function' function.

The temporary remissions have also been triggered by different drugs or chemicals, which again doesn't really fit a viral cause for ME symptoms. I very much doubt that T2, prednisone, and cuminaldehyde are all going to have similar abrupt on/off effects on a chronic viral infection.

 

[Hip]

No, I meant the temporary remissions. I've had the baseline symptoms for years, then triggered temporary remission within hours, felt totally healthy again and bouncing with energy, then some more hours later, abruptly switched back to baseline ME symptoms. To me that doesn't match viral population change.

Those temporary remissions are intriguing, and many long-term ME/CFS patients have experienced them at least once. But remember that the symptoms of ME/CFS probably arise from the immune response to any infection, rather than the infection itself. That may explain for example why PEM can often be temporarily be eliminated by corticosteroids, which wind down the immune response.

So these occasional remissions may relate to some momentary aberration of the immune response, rather than any change in viral populations.

 

[Wishful]

More often, a course of antivirals (usually lasting for a year or so) will improve the ME/CFS state, but not cure it. For example, antivirals may improve a severe ME/CFS patient such that they are now only moderate or mild.

To me that fits the hypothesis of chronic viruses worsening ME symptoms through elevated immune activation, or possibly through altered cell function. I'm sure there are plenty of other diseases that are worsened by chronic infections, whether viral, other microbial, or parasitic. There are probably a few cases where additional infections, such as those parasitic worms (I forget the name right now) might reduce the symptoms of a disease.

So yes, I agree that treating a chronic infection might reduce ME symptoms. I just disagree with statements claiming that viral infections are the root cause of ME. I think you could wipe out all viruses in someone with ME, and they'd still be suffering from ME, possibly with a reduction in severity of some symptoms.

 

[Wishful]

So these occasional remissions may relate to some momentary aberration of the immune response, rather than any change in viral populations.

Yes, that's a valid argument. However, if it were true, then adding another viral infection should be continuing the same immune response (producing certain cytokines, depleting TRP in cells, etc), and so shouldn't affect overall symptoms strongly, which I've observed that it does. A cold, or viral meningitis, strongly increased my ME symptoms.

If the symptoms were from the immune response to a chronic viral infection, I'd expect more fluctuations in severity, particularly when taking some drugs or foods that affect the immune response. Cyclosporin (strong immunosuppressant) had no effect on my symptoms. Maybe cyclosporin doesn't affect that specific cytokine or whatever that gets triggered in temporary remission, according to your hypothesis, but that seems an unlikely coincidence. I'd also expect more immunosupressants to work on symptoms if they were due to immune response to chronic infections.

 

[Hip]

However, if it were true, then adding another viral infection should be continuing the same immune response (producing certain cytokines, depleting TRP in cells, etc), and so shouldn't affect overall symptoms strongly, which I've observed that it does. A cold, or viral meningitis, strongly increased my ME symptoms.

That does not always have to be the case, as different infections can elicit different immune responses.

And also, the same pathogen as it infects different people can infect different organs, and thus lead to different symptoms and different diseases.

One relative of mine caught the same coxsackievirus B4 infection which appeared to trigger my ME/CFS. I developed ME/CFS after this virus caused a brain infection. Whereas this relative later went on to develop type 1 diabetes, which is linked to CVB4 infection of the pancreas.

Several other friends and family who caught my virus were hit by viral myocarditis, which is where a virus infects the heart muscle.

So the organs infected may dictate which disease ensues.

If the symptoms were from the immune response to a chronic viral infection, I'd expect more fluctuations in severity, particularly when taking some drugs or foods that affect the immune response.

The immune response has many different departments, and an immunosuppressive drug may target one department — but that may not be the right area to reduce ME/CFS symptoms. Obviously the potently immunosuppressive corticosteroid drugs are targeting the right immune areas, as corticosteroids can allow ME/CFS patients to push themselves well beyond their normal exertional envelope, but not experience PEM.


While we are talking about corticosteroids, these may indirectly provide proof of a viral role in ME/CFS: corticosteroids work great for ME/CFS in the short term if you take them for one or two days in order to avoid PEM. But tellingly, ME/CFS patients who try long term corticosteroids (for weeks or months) usually become much worse.

How can corticosteroids help so much in the short term, but cause damage in the long term? Well, a simple answer may be that in the long term, they allow underlying viral infections to proliferate, thus making ME/CFS worse.

To me that fits the hypothesis of chronic viruses worsening ME symptoms through elevated immune activation, or possibly through altered cell function.

No doubt additional infections can worsen some ME/CFS symptoms. I have a recurrent urinary tract infection, and each time this infection flares up, I get a lot more fatigue. My UTI is not the basis of my ME/CFS (because I had it before my ME/CFS was virally triggered), but it does increase the fatigue.

One idea that occurred to me is similar to yours: that the ME/CFS triggering infection could both over-sensitize the immune response (perhaps by infecting critical organs of the body involved in immunity) AND as an ongoing low-level infection, might also constitute the main target of the over-sensitized immune response.

 

[Wishful]

But tellingly, ME/CFS patients who try long term corticosteroids (for weeks or months) usually become much worse.

I did two trials of prednisone, the second only a few days after the first one tapered off. I forget what the standard length of the trial is (one week or two?). I didn't feel worse after the second one; I just returned to my baseline ME. I tried it a couple of times after that (months or years), but it had no effect on my ME those times, and the last trial was at double the regular dosage.

Cyclosporin doesn't cross the BBB easily, so from its failure, I deduced that the part of my immune system involved in ME was in my brain, probably the microglial cells.

 

[Hip]

I did two trials of prednisone, the second only a few days after the first one tapered off. I forget what the standard length of the trial is (one week or two?). I didn't feel worse after the second one; I just returned to my baseline ME.

Have you been tested for chronic active viral infections using the right tests?

Dr Chia says two ME/CFS patients who took prednisone daily for two weeks improved remarkably; but when they tapered off they got much worse, and ended up in the hospital. He believes such extended use of corticosteroids allows enterovirus to proliferate.

 

[Wishful]

Have you been tested for chronic active viral infections using the right tests?

I'm pretty sure that any viral tests were standard. All I recall is that I had the EBV antibodies, but not active infection.

Prednisone triggered remission while I was on it (took 5 days to trigger the first time, 2 the second), and just went back to baseline after tapering off. After the second trial tapered off, I discovered that cumin (Cuminum cyminum) worked just as well as the prednisone, and a week or two later I realized that it had stopped working at some point (gradual return to baseline). I'm pretty sure that I didn't feel worse than baseline during that period. Nothing made me think: "Hey, does this feel like enteroviruses have proliferated?"

 

[Hip]

I'm pretty sure that any viral tests were standard.

So you were tested using antibody blood tests for EBV, CMV, HHV-6 (and not by PCR, which is not normally useful in ME/CFS for herpesviruses or enterovirus); and your coxsackievirus B and echovirus were done using Dr Chia's recommended ARUP Lab micro-neutralization antibody tests?

 

[Wishful]

So you were tested using antibody blood tests for EBV, CMV, HHV-6 (and not by PCR, which is not normally useful in ME/CFS for herpesviruses or enterovirus); and your coxsackievirus B and echovirus were done using Dr Chia's recommended ARUP Lab micro-neutralization antibody tests?

I don't know. The tests were possibly a decade or so ago, and I'm sure the doctor didn't explain the details of what method was used. I expect it was whatever was standard for seeing if the patient has an active infection.

If my ME was severe, I'd probably want to get the detailed test to find any hard to find chronic infections. Since it isn't severe, I'm not sure there's a point in bothering, unless it's important for research.

 

[Hip]

If my ME was severe, I'd probably want to get the detailed test to find any hard to find chronic infections. Since it isn't severe, I'm not sure there's a point in bothering, unless it's important for research.

Well at any level of ME/CFS severity, the main reason for viral testing is because of the treatment opportunities. For example, if you have enterovirus, then oxymatrine helps some people. If you have herpesviruses, then Valcyte is often effective.

 

[Wishful]

Yes, but from what I've read, the antivirals tend to be expensive, require a long time to have an effect, and have a risk of unpleasant side effects. It's a cost/benefits issue. A patient with severe symptoms can hope for significant benefits. Someone with mild symptoms might not even notice a reduction in severity. Do chronic enteroviruses cause strong ME symptoms without showing any symptoms from the viruses (or immune response to them) themselves? If all it does is save me from a cold sore or two a year, it's not worth it.

 

[Hip]

from what I've read, the antivirals tend to be expensive, require a long time to have an effect, and have a risk of unpleasant side effects. It's a cost/benefits issue.

Valcyte unfortunately is very expensive, with the cheapest generics still costing about $14 per day, and you may need to be on Valcyte for a year. By contrast oxymatrine, Dr Chia's treatment for enterovirus, costs as little as $40 for a two month course.

A patient with severe symptoms can hope for significant benefits. Someone with mild symptoms might not even notice a reduction in severity.

That's not the way it works with antivirals: antivirals will often move a patient up one level on the ME/CFS scale of: very severe, severe, moderate, mild, remission.

So if you are severe, then if you are lucky, antivirals may move you up 1 level, to the position of moderate. And if you are mild, then antivirals may move you up 1 level to the position of remission.

At any level of ME/CFS severity, if you can move up one level on that scale, it is a major achievement.

Do chronic enteroviruses cause strong ME symptoms without showing any symptoms from the viruses (or immune response to them) themselves?

Depends how you define symptoms of viruses. When I first caught the Coxsackie B4 virus which later triggered my ME/CFS, the first symptom was a sore throat that would never quite go away, and well as chronic nasal inflammation. Then a few months later as the virus spread to other areas of my body, it started causing stomach aches, flatulence, paresthesias. Finally it started affecting my brain, causing anxiety and anhedonia. These were all viral symptoms that were present before my ME/CFS started.

Once the ME/CFS started, many of the above symptoms remained and continued for years, although some eventually cleared up after about 5 years.

 

[lukesirde]

Hip, may I ask your views on coxsackie and it's long term effects on the hearts of sufferers; particularly those of us with ME who have a chronic not acute presentation. I can't get any doctor to pursue investigations as I don't present any acute symptoms (even though I am bedridden and exertion intolerant!).
I fear if I eventually manage to get further testing/treatment it will be too late and any damage will be irreversible.

Sorry if I have hijacked a thread out of turn, but I am wet behind the ears. Big fan by the way . . . !
Best wishes

 

[Hip]

Hip, may I ask your views on coxsackie and it's long term effects on the hearts of sufferers; particularly those of us with ME who have a chronic not acute presentation.

Coxsackievirus B can cause myocarditis, and is linked to sudden heart attacks, dilated cardiomyopathy, and heart valve disease.

The coxsackievirus B4 I caught which triggered my ME/CFS also infected over 30 of my family an friends, and when it did so caused 4 sudden heart attacks in previously healthy people, a few cases of myocarditis, and some years later, mitral valve prolapse (a heart valve disease) appeared in one infected person. See this post for more info.

I don't think there is a way to predict in advance who gets these heart diseases from a virus circulating in their body, and I don't think there is much you can do to prevent it (though selenium can help reduce coxsackievirus B virulence in myocarditis). Mitral valve prolapse is more common in ME/CFS.

Coxsackievirus B is also linked to type 1 diabetes, Sjogren's, ALS and Parkinson's. And of course ME/CFS. This virus most likely causes a ton of human diseases, yet for some reason there is very little interest in creating a vaccine.

 

[lukesirde]

Coxsackievirus B can cause myocarditis, and is linked to sudden heart attacks, dilated cardiomyopathy, and heart valve disease.

The coxsackievirus B4 I caught which triggered my ME/CFS also infected over 30 of my family an friends, and when it did so caused 4 sudden heart attacks in previously healthy people, a few cases of myocarditis, and some years later, mitral valve prolapse (a heart valve disease) appeared in one infected person. See this post for more info.

I don't think there is a way to predict in advance who gets these heart diseases from a virus circulating in their body, and I don't think there is much you can do to prevent it (though selenium can help reduce coxsackievirus B virulence in myocarditis). Mitral valve prolapse is more common in ME/CFS.

Coxsackievirus B is also linked to type 1 diabetes, Sjogren's, ALS and Parkinson's. And of course ME/CFS. This virus most likely causes a ton of human diseases, yet for some reason there is very little interest in creating a vaccine.

I think what I'm really asking is, is dysfunction/damage with regards to the heart (possibly from enteroviral infection) an irreversible condition, or like Dr Myhill postulates, more of a mitochondrial dysfunction/impairment that can greatly improve given appropriate protocols?
Reason I ask is I am sure I am in the enteroviral cardiomyopathy bracket and it scares the crap out of me. Especially considering I have found it impossible to get any help or recognition of my situation, regardless of how ill I become.

Many thanks for your energy.

 

[Hip]

I think what I'm really asking is, is dysfunction/damage with regards to the heart (possibly from enteroviral infection) an irreversible condition

Do you mean would the cardiomyopathy reverse if someone developed a potent antiviral which eliminates enterovirus infection from the body? It might well do, but we've never been in situation to check, as we do not have these sort of antivirals. Though a potent new anti-coxsackievirus B drug is expected to come to market in a year or two (search this forum for Rega Compound), which will be interesting.

Some German research suggested that a lot of the problem with viral heart disease is the development of virally-induced autoantibodies which target the ANT protein in the mitochondria, impairing energy production in the heart muscle. So it looks like the presence of the virus in the heart is causing an immune attack on mitochondria. But I've seen no replication of their research elsewhere, so I am not sure how valid the research is.

 

[lukesirde]

I saw that post of yours. I find your insights extremely helpful. Your contributions surely can't be overlooked. If researchers aren't using your obvious talents, there is something seriously wrong!
Hopefully my heart symptoms will ease. I'm currently unable to exert myself in nearly any way. No elevated troponin and no irregularities on an ECG, but I know this isn't a massive help.
I'll continue to keep my eye out on here, and if I have the energy, I'll keep my fingers crossed . . .

 

[Hip]

I saw that post of yours.

I did actually write more than once to two of the German researchers of those ANT autoantibody studies, asking them whether these autoantibodies might potentially explain ME/CFS, but they never replied.


Have you been tested positive for elevated antibodies to coxsackie B virus, @lukesirde? We unfortunately do not have in the UK any blood tests which are sensitive enough to detect CVB antibodies in the chronic infections of ME/CFS. Only the neutralization-type antibody tests are sensitive enough. But there are labs in Germany and Greece that provide inexpensive antibody neutralization tests for CVB.

 

[lukesirde]

I've only had run of the mill tests; EBV, CMV and alike. My test results always show I am a picture of health. I catch every bug (not good with a 5 year old daughter) and always feel ill and deathly. I have an immunologist referal in the pipeline and I can hopefully ask GP for a cardiologist referal when I'm well enough to leave the house.
I always mention that when I'm well enough to exert myself in any way, I have some kind of crash that feels like something is going after my heart. This crash can last month's, but this time around the heart symptoms persist. I've never had any joy with doctors. In fact my most recent visit to a new GP is the ONLY time I have been given any time to talk an attemptto put my concerns across.
I'm pretty stuck, if I'm honest . . .