Elevated EBV, HHV 6 -- what does this mean?

[Eeyore]

What about epstein barr virus?

This is one of the most widely studied viruses in ME patients, yet no study has shown any significant differences. Same rates of seropositivity, same antibody titers, etc. And we know for a fact that many cases of ME begin with a virus that is not a herpes virus. There just is no evidence that EBV is any different in ME patients.

 

[Eeyore]

Even with respect to endoplasmic reticulum stress, if you have a virus and don't factor that in, you will most likely be unsuccessful in dealing with your issues. Actually, you could even make your issues worse.

If a virus is important to the pathology, then it would be important to consider that when devising a treatment. However, we don't have any evidence that any particular virus plays an important role, especially the herpes viruses, which have been so widely studied and just don't show up as interesting. If anything, there's the most evidence for enteroviruses - and even that I consider relatively weak in terms of long term disease propagation. I think they often play a major role in triggering - and in my case I suspect it was in fact an enterovirus that started it all.

Dr. A. Melvin Ramsay, MD, who named ME and was one of the first to describe it in detail, thought it was somehow related to poliovirus (which is an enterovirus). Dr. Byron Hyde explains how it's impossible for herpesviruses to cause epidemic ME due to the incubation period. Enteroviruses could, however.

 

[Violeta]

Okay, but what do you think about people having good results from treating viruses? If I tell you I am having good results from treating viruses and improving my immune system, does that count?

 

[Eeyore]

Sure, if you tell me that you feel better, I will assume you are telling the truth. Placebo effect is possible, but so is genuine improvement. I think as adult patients, we should be able to make our own decisions on what to take, although I think we should listen to doctors' warnings as well and take them seriously. When I was a good deal younger, I tried antivirals - high dose valtrex (4g/d) for 6 months. Dropped all my titers to nothing. Had no clinical effect at all whatsoever. It substantially lightened my wallet (valtrex wasn't generic yet!)

I don't think we should just take patients' words for it - we should be doing high quality, double blind, placebo controlled trials. However, in the absence of that, if I were a doc, I would go on what patients were telling me unless medically it was not possible - although I'd be cautious with dangerous meds. Valcyte is pretty scary, and even valtrex can be bad in higher doses (not always, but sometimes). All drugs have risks, but ME is a serious illness and I do not advocate doing nothing while we wait for a perfect understanding - especially considering how poorly funded and poorly understood it is.

 

[Violeta]

This is one of the most widely studied viruses in ME patients, yet no study has shown any significant differences. Same rates of seropositivity, same antibody titers, etc. And we know for a fact that many cases of ME begin with a virus that is not a herpes virus. There just is no evidence that EBV is any different in ME patients.

What would be an outward sign of Epstein Barr Virus?

 

[Violeta]

Sure, if you tell me that you feel better, I will assume you are telling the truth. Placebo effect is possible, but so is genuine improvement. I think as adult patients, we should be able to make our own decisions on what to take, although I think we should listen to doctors' warnings as well and take them seriously. When I was a good deal younger, I tried antivirals - high dose valtrex (4g/d) for 6 months. Dropped all my titers to nothing. Had no clinical effect at all whatsoever. It substantially lightened my wallet (valtrex wasn't generic yet!)

I don't think we should just take patients' words for it - we should be doing high quality, double blind, placebo controlled trials. However, in the absence of that, if I were a doc, I would go on what patients were telling me unless medically it was not possible - although I'd be cautious with dangerous meds. Valcyte is pretty scary, and even valtrex can be bad in higher doses (not always, but sometimes). All drugs have risks, but ME is a serious illness and I do not advocate doing nothing while we wait for a perfect understanding - especially considering how poorly funded and poorly understood it is.

I don't take meds.

I take herbal antivirals, herbal immune boosters, colostrum for it's immune enhancement. There are so many alternatives, I guess you're not into alternatives.

 

[Mij]

That's interesting, @Mij , did it happen after the transfer factor, or not until after the Immunovir? I am specifically wondering because I have a friend that's taking transfer factor with no improvement.

I wonder what happened?

I relapse after taking TF for 2.5 months. The symptoms were building for one month (very sore upper back), but I didn't attribute it to TF so I continued to take it. Then it hit me one day, I went out to do some errands and within a few hours I could no longer walk or stand. I was stuck on a busy downtown street.

I recovered somewhat 3 months later, but never went back to base.

I went to see a virologist 1.5yrs later and he rx'd Imunovir, but within 3 weeks I started experiencing neurological symptoms and felt weak, I discontinued out of fear I would get worse.

The virologist told me that this was an immune inflammatory response.
https://en.wikipedia.org/wiki/Immune_reconstitution_inflammatory_syndrome

I agree with the OP, studying the inflammation process makes more sense than trying to treat viruses.

 

[Eeyore]

@Violeta - EBV's classic manifestation is glandular fever or infectious mononucleosis. There are other less common manifestations too though.

I would only consider alternative therapies if there were studies to prove that they worked, and that they worked better than available pharmaceuticals and/or were safer. Prescription pharmaceuticals, supplements, whatever - they're all just chemicals that may or may not do much in our bodies. Neither class is automatically safer. The advantage of pharmaceuticals is that they've been rigorously tested and have higher quality control in production. So generally I do prefer to go with well tested scientifically validated treatments and work with a doctor.

 

[IreneF]

Show me some evidence that ME patients have higher titers to herpes viruses - I haven't seen any.

The virology community seems to be moving more toward the idea that herpes viruses are always active at a low level. Infected cells are probably always producing some low level of virus. So far this has been best studied with VZV and also with the HSV's.

Titers to herpes viruses actually tend to increase with time, not decrease, as the viruses always chronically reactivate and continue to prime the immune system. Higher avidity antibodies are also selected. However, over longer time periods, old age causes a reduction in immunity. So having it longer means higher titers normally, but getting old means lower titers - so for most people titers will increase for a long time then start to taper off as age becomes more relevant. That's why high dose VZV vaccines are given to older people. It's probably not relevant until well into old age, without major differences throughout most of adulthood. Teens have very strong antibody responses.

I thought that immunities faded over time, but in an unvaccinated population people would be repeatedly stimulated by exposure to the disease (usually in children)--which is why shingles has gotten to be a problem. We have a generation of young people who were all vaccinated, so there is no longer a continous source of immune stimulation.

 

[IreneF]

My point with the VZV was mostly in response to @Valentijn, that at least in a few cases (HHV6 / VZV), I produce normal antibodies to herpes viruses. I would expect the general population to show similar results to mine. @Valentijn makes an interesting point though about whether it's possible that someone like me has EBV but isn't producing antibodies anymore - I suppose it's possible.

I don't believe there is anything really unique about us and herpes viruses. I think we just have the same viruses with the same frequency as everyone else.

My VZV titers didn't drop as far as I know - it's not something I've tested that much. They were normal though (although lab would say abnormal in that they indicate exposure to the virus, and "normal" would be no exposure, which by my age is almost unheard of).

My own belief is that herpes viruses are just red herrings for ME patients and have nothing to do with our illness. I think there are a few factors that led to this happening. First, I think it goes back to Dr. Strauss at the NIH not wanting to accept he had a brain tumor and experiencing seizures, instead trying to blame his CFS on EBV - he later died of that brain tumor though (read Byron Hyde's personal accounts of this).

The other factor is that we get a lot of blood tests. Most come back normal. The first things that will usually jump out as abnormal (and be flagged as such by the lab) are elevated titers for common herpes viruses like VZV and HHV6. As a result, patients think this is really abnormal, when what would be more abnormal is to have no evidence of exposure to VZV or HHV6 (although the lab would mark this as normal).

Lastly, EBV has long been associated with prolonged fatigue (with mono / glandular fever) lasting months after infection, and because our disease was so unfortunately named, many docs jumped to EBV as being the case of fatigue. It was a reasonable hypothesis, but over time, studies failed to show any connection with ME. Ultimately we must think scientifically and toss out theories that are scientifically refuted. Holding on to bad theories just hurts us because we can't get to the root of the problem.

In summary, I don't think herpes viruses are important to ME pathogenesis, other than that they, like other infectious and non-infectious causes, can serve as the initial trigger. I feel we've wasted too much time and too many resources hunting for a mystery pathogen that is not there.

None of the testing I've had has done me any good. I'm still sick. I think Stanford might be doing so much testing because it is a research university, and the tests could have research potential.

Montoya says the cytokine profile of CFS/ME patients is closest to that of sepsis patients. I guess it's like a cytokine breeze instead of a cytokine storm. A cytokine storm, (including sepsis) is a case of the immune system over-reacting to any one of a number of triggers, at least as I understand it.

 

[heapsreal]

No one is saying herpes viruses is a cause of cfsme but more a consequences of a dysfunctional immune system and treating this can help people improve.

to say herpes viruses isnt a factor is just being blind to all the research that has shown high viral titres and the many clinicians that find these issues.

this isnt an issue for everyone with cfsme, but this is why subgrouping is mentioned.

low nk function commonly found in cfsme seems to play a role in these viruses being an issue. One just has to look at the role of natural killer cells to see that if they dont work well than iinfections can become a problem.

To be ignorant of this is to be ignorant of previous research and drs such as lerner, peterson, klimas etc

some dont seem to think one can have more than one issue at once such as immune dysfunction as well as infections .

 

[msf]

Sounds like Montoya is slowly coming over to the dark side (Lyme, that is). He must at least suspect bacterial involvement now if he thinks ME looks like sepsis.

 

[halcyon]

Sounds like Montoya is slowly coming over to the dark side (Lyme, that is). He must at least suspect bacterial involvemelooksnt now if he thinks ME looks like sepsis.

He didn't say it looks like sepsis he said it looks like SIRS, which sepsis is a form of.

 

[Eeyore]

I thought that immunities faded over time, but in an unvaccinated population people would be repeatedly stimulated by exposure to the disease (usually in children)--which is why shingles has gotten to be a problem. We have a generation of young people who were all vaccinated, so there is no longer a continous source of immune stimulation.

Normally, when the immune system is exposed to a pathogen, it creates a "memory" and responds faster the next time. It continually produces a certain level of antibodies to that pathogen. Over time, in the absence of more stimulation, the response fades - faster for some pathogens than others.

It's very different when you are talking about viruses that are persistent. Some examples would include HIV, HTLV-1/2 (also retroviruses), human herpesviruses (including VZV - chicken pox / shingles), and (sometimes) hepatitis b or c (although these may not always be chronic). Because the viruses are not eliminated entirely, the immune system continues to be stimulated, and over time, the body makes better and better antibodies against them (it selects for those that work best). Titers tend to rise over time to persistent infectious agents. People with herpes simplex tend to have very severe first outbreaks, followed by outbreaks of decreasing severity and frequency over time as the body makes more and better antibodies and learns to control the infection.

Shingles occurs only (to the best of my knowledge) in unvaccinated people who were exposed to wild type varicella virus and first developed chicken pox, and later, due to aging, the immune system starts to become less effective and the virus is able to break through. I don't think we really know how the vaccine works, although I may be wrong on this. My understanding is that there are multiple possibilities. It may be that the live, attenuated virus establishes a long term infection, which continues to offer immunity. It may be that it only primes the body to react more quickly to vzv when it encounters the wild type version, which then establishes a long term infection. It may be that no long term infection occurs - although I doubt this. It's also possible both strains coexist.

I believe the VZV strain used is not replication defective, just attenuated and less pathogenic. If it were a replication defective live virus, then it would not establish any infection.

There is currently some controversy in the development of vaccines against EBV, CMV, and the herpes simplex viruses. Some argue that even live attenuated is too dangerous, although we already use it in VZV. It does seem to produce a much more robust response than VLP glycoprotein based vaccines, and the VZV vax appears quite safe.

 

[Eeyore]

@heapsreal - Can you show me a published study that proves that ME patients have higher titers on average against any herpes virus?

I agree with you that there are subclasses and that we are not all the same. I could even believe that there are people with more issues with herpes viruses, or particular herpes viruses, I'm just not convinced that this group is overrepresented among ME patients. i.e. I'm not sure it makes any more sense to treat ME patients with antivirals than non-ME patients.

 

[Violeta]

@Violeta - EBV's classic manifestation is glandular fever or infectious mononucleosis. There are other less common manifestations too though.

I would only consider alternative therapies if there were studies to prove that they worked, and that they worked better than available pharmaceuticals and/or were safer. Prescription pharmaceuticals, supplements, whatever - they're all just chemicals that may or may not do much in our bodies. Neither class is automatically safer. The advantage of pharmaceuticals is that they've been rigorously tested and have higher quality control in production. So generally I do prefer to go with well tested scientifically validated treatments and work with a doctor.

@Eeyore Is not EBV classic long term manifestation fatigue?

 

[msf]

I was responding to a comment by a patient of his that seemed to be quoting him.

 

[halcyon]

I was responding to a comment by a patient of his that seemed to be quoting him.

It was most recently mentioned in the Stanford 2015 newsletter:

In a separate cytokine-related study carried out in partnership with the Human Immune Monitoring Center, we found that several cytokines, chemokines, and cell factors clearly correlated with the severity of ME/CFS. This data contradicts claims that ME/CFS is not an inflammatory disease. Not only does inflammation exist in these patients, but also our study opened the door for using anti-inflammatory drugs or biologics to treat ME/CFS. Further analysis of mRNA gene expression, in a study led by Dr. Lipkin and Dr. Mady Hornig, showed that the disease with the closest resemblance to ME/CFS is Systemic Inflammatory Response Syndrome (SIRS). These two studies provide objective evidence that that ME/CFS is indeed an inflammatory disease.

 

[IreneF]

He didn't say it looks like sepsis he said it looks like SIRS, which sepsis is a form of.

Right. At least someone here can remember things!

 

[IreneF]

Sounds like Montoya is slowly coming over to the dark side (Lyme, that is). He must at least suspect bacterial involvement now if he thinks ME looks like sepsis.

No, that doesn't follow. He was looking at the cytokine profiles, which can be triggered by bacterial infection, but also by other things.

I'm sorry if I was unclear.