Please, update re: HHV6?

[NilaJones]

Hi folks,!

I would be so grateful if some of you could update me on the current thinking regarding patients who have high levels of antibodies to HH6, but are negative on PCR or T cell tests, and whether valcyte is warranted

Back when I saw Dr deMierlier, 10 or 15 years ago, he said that he thought our immune systems were making huge numbers of malformed antibodies for unknown reason, but that we did not have an actual active infection

(Of course, I understand that everyone has dormant HH6)

But I have no idea what the current thinking is, and my long covid doctor wants to know

I'm having computer difficulties and unable to use search

Thank you so much, anyone who can help!

 

[Hip]

I heard that Stanford stopped treating ME/CFS patients with Valcyte due to the low success rate.

That said, there are some anecdotes of Valcyte making a major difference for some ME/CFS patients; you can see these success stories in the first post of this thread.

 

[NilaJones]

I heard that Stanford stopped treating ME/CFS patients with Valcyte due to the low success rate.

That said, there are some anecdotes of Valcyte making a major difference for some ME/CFS patients; you can see these success stories in the first post of this thread.

Thank you, @Hip !

Is there any current theory about why some of us have high antibodies, but are negative for indicators of active infection?

 

[Hip]

Is there any current theory about why some of us have high antibodies, but are negative for indicators of active infection?

One theory is that the viral infection is located in the tissues, not in the blood. So if you take a blood sample, and test with PCR, you often do not find the virus. But because there may be an infection in the tissues, antibodies remain high.

Not much research has been done for herpesvirus tissue infections, but in the case of enterovirus ME/CFS, there have been lots of studies which took tissue biopsies from the muscles or gut, and found enterovirus there. So in the case of enterovirus ME/CFS, there is a correlation between the virus found in the tissues, and the high antibodies.

 

[gbells]

Back when I saw Dr deMierlier, 10 or 15 years ago, he said that he thought our immune systems were making huge numbers of malformed antibodies for unknown reason, but that we did not have an actual active infection

The only people who make excess autoimmune antibodies are patients with lupus or other autoimmune diseases. CFS could be another kind of autoimmunity disease. CFS patients usually have a history of viral infections. Most likely CFS patients are making antibodies to try to destroy the virally infected cells (CMV, HHV-6/7, EBV, CMV, enterovirus, Herpes Zoster) but apoptosis is blocked so they can't bind to the cell receptors and get used up so they are in excess. The more tissues the viruses infect, the larger the response will be, so it should worsen over time. Immunosuppressant therapy controls the effects but doesn't stop the underlying cause.

 

[gbells]

I heard that Stanford stopped treating ME/CFS patients with Valcyte due to the low success rate.

Bhupesh Prusty PhD made a comment about this a few months ago. He said that the problem was that the viral DNA transcription blockers like valganciclover don't the production of the MRNA that causes the mitochondral fragmentation behind the fatigue. He recommended that drug companies simply make MRNA blockers and said they would be very effective and would turn CFS into a treatable disease.

 

[Garz]

there is a lot of cross reactivity between antibodies to antigens on herpes family viruses and those on bacteria in the proteobacteria class - and a few notable others

a lot of these bacteria are difficult to diagnose - slow growing and have poor response to antibiotics - so rather than our typical idea of bacterial infections as acute puss filled eruptions - they can result in slow dragging fatiguing illnesses that perfectly fit CFS - as in my case.

very high viral antibodies but no corresponding PCR positive test for that would tend to point away from it being an active viral infection - and instead a disturbance in the immune system caused by something else - quite possibly one of these infections

symptoms patterns can give some indications - but there is a lot of crossover with CFS
reactions to abx - often feeling worse - occasionally slightly better afterwards - is another indication
occupational or recreational exposures can give some clues
testing is available but problematic - mainly due to poor sensitivity

 

[Judee]

I do think and have read that these viruses can be stealthy and can hide in B-cells, tissues and organs. I don't know enough about PCR testing though to know if it would detect them still esp if it's a plasma test if they are hiding. ??

They did find viral antibodies for these viruses in saliva too though the only one it sounds like they tested by PCR was Sars-CoV-2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9630598/ (Wonder why they didn't also test the others that way. )

 

[NilaJones]

Wow, thank you folks so much! You are amazing!

@Hip @gbells @Garz @Judee

 

[Garz]

@NilaJones - i just noticed that your signature mentions mast cell syndromes and EDS

borrelia burgdorferi (the causative agent of lyme disease) is one of the organisms known to cause cross reactive antibodies with herpes family viruses

quite a large proportion of people with diagnosed Lyme disease develop EDS symptoms and are often misdiagnosed with EDS - when in fact the infection breaks down collagen in the musculoskeletal system which can cause EDS like symptoms - there may be a genetic predisposition to which patients get which symptoms - every one with lyme disease long term gets some kind of collagen deterioration - but not everyone gets EDS

lastly - MCAS is also very common in the chronic Lyme disease patient group - and in those with some of the common co-infections, like bartonella, it is even more prevalent.

i have confirmed chronic bartonellelosis. but for 6 years i was told i had CFS - and indeed my symptoms were a perfect match for CFS - but after being sick for 6 years, starting to treat the infection has allowed me to recover around 60% so far -and i am still in treatment and improving

i suspect a significant portion of people who have been told they have CFS actually have infections such as these - the tests are very poor and the symptoms do overlap - so its understandable. but in my case my partner and i became ill at the same time with the same symptoms - so i had trouble accepting two fit health people would suddenly get CFS or post viral fatigue - and pushed for more answers.

 

[Garz]

I heard that Stanford stopped treating ME/CFS patients with Valcyte due to the low success rate.

That said, there are some anecdotes of Valcyte making a major difference for some ME/CFS patients; you can see these success stories in the first post of this thread.

it costs approx. $50M to bring a new drug to market through FDA approval in the USA ( i assume a similar or higher number in Europe )
so, when they are looking for new drugs, for instance to treat stubborn infections, one of the ways to find drugs that could be available sooner and cheaper is to screen already FDA approved drugs ( there are around 3500 of them) for their antimicrobial activity against whatever your target organism is

in such trials antivirals do pop up as having sometimes v potent anti-bacterial properties - sometimes more than the standard of care drugs given forthat infection

so while these things were developed to target specific viruses - they find they often have off target effects that are just as powerful against something else.
the same thing has happened with some anti-fungals

examples of both in this paper
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6628006/

see table 1 - where Lopinavir/ritonavir was 2-4x more potent than the usual antibiotics used
and clotrimazole (an antifungal) was similarly potent

​

so we really often do not know what these things are hitting - even if they are effective in improving symptoms - its not necessarily a virus - even if antivirals help symptoms

 

[Hip]

so we really often do not know what these things are hitting - even if they are effective in improving symptoms - its not necessarily a virus - even if antivirals help symptoms

Yes, many drugs have multiple effects in the body, and so if benefits manifest, it is not always clear which mechanism of action of the drug is responsible.


However, one piece of evidence that suggests it is the viruses in ME/CFS which are the issue is the interferon trial results. A course of interferon therapy can often often make dramatic improvements in enterovirus ME/CFS patients — like bedbound to back-to-work improvements — since interferon has potent antiviral effects against enterovirus.

(Unfortunately patients relapse after about 4 to 12 months, and there are reasons why you cannot keep giving further courses of interferon).

Now you could argue that interferon may have some off-target effects nothing to do with viruses, which might also explain why it results in great improvements in ME/CFS.

But here's the thing: interferon only seems to work for enterovirus ME/CFS patients, not for herpesvirus ME/CFS. If it were the off-target effects that caused the dramatic improvements, you would expect those improvements to manifest irrespective of the virus that the ME/CFS patient has.

 

[hapl808]

it costs approx. $50M to bring a new drug to market through FDA approval in the USA ( i assume a similar or higher number in Europe )

I believe in the USA the $50m is about right for the cost of the clinical trial itself, but the overall average cost to bring a drug to market these days from start to finish is usually cited at over $1b. At $50m, some charities or well meaning people could do it themselves. The app Signal that allows free encrypted chats was started with an individual $50m grant from one of the founders of WhatsApp.

At $1b with no guarantee of success, only huge pharma companies can do it. And that's why they have to milk it for every dollar. Pfizer views their vaccines as making up for every drug they ever failed on, so there's no amount of profit where they will ever say that's enough.

https://publichealth.jhu.edu/2018/c...w-drug-FDA-approval-are-fraction-of-total-tab

 

[Garz]

yep - i think that's right - the 50M is more just for the FDA trials . approval process

 

[Garz]

Yes, many drugs have multiple effects in the body, and so if benefits manifest, it is not always clear which mechanism of action of the drug is responsible.


However, one piece of evidence that suggests it is the viruses in ME/CFS which are the issue is the interferon trial results. A course of interferon therapy can often often make dramatic improvements in enterovirus ME/CFS patients — like bedbound to back-to-work improvements — since interferon has potent antiviral effects against enterovirus.

(Unfortunately patients relapse after about 4 to 12 months, and there are reasons why you cannot keep giving further courses of interferon).

Now you could argue that interferon may have some off-target effects nothing to do with viruses, which might also explain why it results in great improvements in ME/CFS.

But here's the thing: interferon only seems to work for enterovirus ME/CFS patients, not for herpesvirus ME/CFS. If it were the off-target effects that caused the dramatic improvements, you would expect those improvements to manifest irrespective of the virus that the ME/CFS patient has.

fair points, but interferons are indeed heavily involved in bacterial infections also - all pathogens in fact - not just viruses
and i don't think we know enough about how chronic bacterial or chronic viral infections work to determine what exactly the response to interferons in some patients means

but to clarify where i am coming from - i don't think all CFS/ME patients are suffering from an undiagnosed stealth bacterial infection - but it would be entirely consistent with what i have seen so far, in my 8 years of digging in and around this topic if at least a significant fraction were. i am after all one of them.

its likely in my view that there only a certain number of pathways and mechanisms in the human body that can be activated - and get stuck in a loop / new homeostasis - and so anything that activates the same ones will present with much the same pattern of symptoms regardless of the root cause.

so i think what we call CFS today is likely to be a syndrome or constellation of symptoms caused by a number of different and distinct root causes that all result in the same - or many of the same - switches being thrown - and then the symptoms are v similar indeed.
this is a long way from the one infection one symptoms picture / old model - and one which would fit with the consternation of the current medical system in terms of figuring it out
and perhaps why no one biomarker or criteria seems to fit all cases well.

There are those that work in this sphere that think the chronic / stealth infections patients are actually suffering a kind of immune system inversion - where instead of the immune system being in charge and keeping all these viruses and bacteria in check and under control - stress, trauma, a viral infection etc had temporarily suppressed the immune system - the microbes ( pathogenic bacteria, fungi, protozoa in some cases ) have got the upper hand and keep the immune system dysregulated and ineffective - and this state keeps the hosts sick.

if that is true - the viruses - if real and actually replicating in a CFS sufferer (ie. not a serologic anomaly via cross reactivity ) - and not controlled like they normally are in everyone else - are in fact a downstream effect of a dysregulated and ineffective immune system - rather than the cause......

there is a general heavy overreliance on serology for diagnosing infectious disease - and yet it is well known that serologic testing is deeply flawed when it comes to detecting infections that have been present for more than 6 months - ie all chronic infections. ( and many of these organisms are undetectable via serology at any point post infection)
all of my infectious disease tests came back negative but with this rider at the bottom when i was tested 12 months into my illness at Portland Down - so its a recognised phenomenon in conventional infectious disease science.

however, this fact is currently comfortably ignored because most western doctors believe such chronic infections are rare

and since you cannot teach a person something they already know - despite the mounting evidence to the contrary - they continue to believe that - and it becomes somewhat circular.