Dr. John Chia and Enterovirus. Old hat? Nope - a key.

Recently, the 12th Invest in ME conference in London ended. This ME/CFS conference is three days of serious research discussion and presentations. It is one of the best conferences on difficult diseases. The sponsors Richard and Pia Simpson exert an extreme effort to put on this conference, a conference which expands in scope every year. These two individuals are extraordinary people.

One wonders, with all the comprehensive research at this conference, if Dr. Chia and his Enteroviral research were even mentioned at the Invest in ME conference conversations this year?

Is it possible that the low level of response to his research will continue indefinitely? Let's hope not.

Dr. John Chia knows that enteroviruses are a cause of ME/CFS.

I first met Dr. John Chia at the Invest in ME conference many years ago. Dr. Chia made a presentation on enterovirus and ME/CFS. He has made several other presentation at Invest in ME and I have written about him before, here and here and here and here.

Recently I came upon the NIH RFI request sent out this spring. Various people responded and the publication of responses can be found here. Dr. Chia's is the third response down, talking about his subject - enteroviral involvement in ME/CFS. The real question is if anyone - specifically the NIH - will pick up the thread.

Dr. Chia made a three-hour presentation on Enteroviruses at the IACFS/ME conference in the fall of 2016. In it, he makes the case that he has been making for many years now.

Dr. Chia keeps working on enteroviruses involvement in ME/CFS. He is undeterred and is committed to continue until there is a solution. In the meantime, Dr. Chia treats patients with oxymatrine. A certain percentage respond. He also uses Epivir in some cases. More recently he recommends dihydroquercitin and specifically Swanson's Russian Rejuvenator. Dihydroquercitin appears to inhibit coxsackie b4 virus and stabilizes mast cells. It has various other activities - anti-inflammatory, neuroprotective, combats oxidative stress - that you can read about online. It suppresses the release of histamine.

Dr. Chia has no problem with the recent metabolome data coming from Naviaux, seeing it as a step in the process of ME/CFS. He believes that a number of drugs might modulate the cellular function in the brain but eventually the viral replication or related mechanisms will have to be inhibited. This will come with anti-virals against coxsackie B and Echo viruses. It is known that two European companies are working on a anti-viral coxsackie drug, but they keep their work very quiet. The companies working on this have extra motivation now, knowing that their market for this drug is greater than originally thought.

By sheer chance, my daughter started doing the ARUP coxsackie antibody test in 2005. Only in 2007 did I hear Dr. Chia state the importance of doing this specific test. My daughter's antibodies to CVB4 and CVB3 have been at the top of the range for ten years. To me this means something, as opposed to many other test results, which are indeterminate. I know a lot of people with ME/CFS - and a good number of doctors who try to treat it. To all of them I urge doing the coxsackie antibody test via neutralization at ARUP. Amazingly, I have yet to convince one patient or one doctor to do this test. This in itself says something - and it is not good. It appears that they just do not want to know.

More can be read on Dr. Chia and enteroviruses on the Phoenix Rising forum and another one on PR here.

There are a number of interesting responses in the NIH RFI cited above. For instance check out Dr. William Weir's response. It is the second one from the top.

More on Enteroviruses and ME/CFS

A few recent comments on the history of research into enteroviral involvement in ME/CFS are worth highlighting. These comments come from Dr. Charles Shepherd and from Hip, of the Phoenix Rising forums. Hip contributes multiple, important observations to the Phoenix Rising forum and his ideas are always insightful.

From Charles Shepherd:

"I have now met and listened to Dr. Chia on several occasions and I was at the IACFS/ME conference in San Francisco - where he again presented his findings relating to persisting enteroviral infection. I agree with Tony Komaroff that these findings cannot simply be dismissed and we do need another independent group of virologists to see if they can replicate these findings. I have made these points in my own detailed summary of the conference - which is now being prepared for publication. At present, the balance of evidence (much of which was done in the UK by Professor John Gow and colleagues in Glasgow) relating to persisting enteroviral infection in ME/CFS is against any such link. But I think we should adopt a position of 'the jury is still out' on persistent enteroviral infection in ME/CFS until someone has tried to replicate what is a very thorough and interesting piece of virology research."

From Hip:

"Hi Charles Shepherd,

I believe Professor John Gow primarily looked for enteroviruses in the muscles of ME/CFS patients. However, generally speaking, muscle symptoms such as muscle pain are not that common in ME/CFs, whereas gut and of course especially neurological symptoms (e.g. brain fog, sound sensitivity) are the norm. Thus unless you look for enteroviruses in the areas where the symptoms exist, i.e. gut and nervous system or brain, you may not find much evidence for these viruses. Dr. Chia looked in the gut, and found a strong association between ME/CFS and enterovirus infection; but ideally I think you would want to look in the brain and nervous system (in postmortem studies), because neurological symptoms are really the core of ME/CFS. It is known that when enteroviruses like coxsackie virus B enter the brain, they form a persistent infection of the astrocyte cells and the neural progenitor cells. So these perhaps are the areas where we should be looking for enteroviruses in ME/CFS. Two brain autopsies on deceased ME/CFS patients did indeed find enterovirus in the brain.
See:
Viral Isolation from Brain in Myalgic Encephalomyelitis (A Case Report) 2001 J. Richardson www.oocities.org/vitamvas/viralfm.html 
Enterovirus in the Chronic Fatigue Syndrome 1994. McGarry F, Gow J, Behan PQ. www.ncf-net.org/library/enterovirusincfs.htm

Also, it is now known that enteroviruses such as coxsackie virus B form two distinct types of infections in the body: first the normal lytic enterovirus infection, and second the noncytolytic enterovirus infection.  The latter resides purely within human cells, and is not easily detected. Nevertheless, Dr. Chia, and other researchers such as Dr. Nora Chapman, suggest these hard to detect noncytolytic enteroviruses may play a significant role in ME/CFS. Thus ME/CFS studies need to search for both lytic and noncytolytic enteroviruses in ME/CFS patients.

Hi Charles Shepherd,

Also, if you look at the list of enterovirus studies by British researchers from 1983 to 2001 (which includes Prof. Gow's studies), these all found a pretty strong association between ME/CFS and enteroviruses such as coxsackie virus B. This list of enterovirus studies can be found here.

As far as I can see, there seems to be solid and consistent evidence over several decades for the role of enteroviruses in ME/CFS."

Thanks again to Hip and Dr. Charles Shepherd

"ad astra per aspera" - Dr. John Chia's ideas taking hold

("ad astra per aspera" - "a rough road leads to the stars")

Several summaries have emerged of the IACFS/ME conference, for those who are interested in the details. The first is the transcription of Dr. Komaroff's summary at the end of the conference. We have Patricia Carter of ME/CFS forums to thank for this. Another summary is by Dr. Charles Lapp. It can be found here. 

Several paragraphs in each summary caught my interest and both deal with a favorite subject of mine: Dr. John Chia and his research into Enterovirus and ME/CFS.

From Patricia Carter's transcription of Dr. Komaroff:

"Dr Chia reported again at this meeting, as he has in the past, the expansion, the latest summary of data from a remarkable report and a remarkable amount of work, Enterovirus Antigen and nucleic acid found in biopsy samples from stomach in cases and control subjects. Finding very marked differences in the frequency of both antigen and nucleic acid in CFS patients compared with controls. He then also reported that when you took the biopsy specimens that these tests suggested contained enterovirus and injected them into mice that, in fact, you found when you sacrificed the mice, evidence of enteroviral infection, a virus in the mouse, indicating that this thing lit up looking like it might be an infectious agent of the biopsy tissue actually produced an infection in another animal. 

To me, these results are very impressive, but it's also depressing to see that, to my knowledge, no academic enterovirologists have sought to try to reproduce this, not even in bulk, to take the samples that already have been collected at enormous effort by Dr. Chia and test them themselves to see if they get the same results that Dr. Chia does. It's a great shame and I hope it changes." 

In fact two of the infected mice died over a weekend, one on a Friday, one on a Monday. "If they do not believe in death, then what do they believe in?" At least one enterovirologist, and perhaps two,  have worked with Dr. Chia's samples.

And then there is this from Dr. Lapp:

"Dr John Chia is an infectious disease specialist and pathologist from Lomita CA. He and his son contracted CFS/ME and were found to have enterovirus infections in their stomachs (see his article in the Journal of Clinical Pathology, Jan 2009. After treatment with a Chinese herbal called oxymatrine (there is no other known therapy for EV) both have recovered and stayed well. Dr. Chia reported to us on further EV studies from his lab. To demonstrate the infectiousness of EV, Chia injected the lysate (Osterized tissue or homogenate) from 24 EV-positive human stomach biopsies into immune deficient SCID mice. When the mice were later sacrificed, 13 out of 20 were positive for EV in their spleens, but only 1 of 10 control mice were positive. However, Chia could not culture the virus from any of the spleens suggesting that although the infections were transferred, incomplete viruses were formed in the receiving mice. In a second study, Chia obtained pathology specimens from 27 women with CFS/ME who had undergone total hysterectomy or salpingo-oophorectomy for chronic pelvic pain. 24 or 27 specimens stained positive for EV, whereas none of 15 healthy control specimens were positive. Three SCID mice were injected from EV-positive specimens and the mice were sacrificed at either 2 or 5 weeks. Spleens and fallopian tubes stained positive for EV at both 2 and 5 weeks, although spleen stain was less obvious at 5 weeks. Western blot studies of all mouse fallopian tubes demonstrated enteroviral proteins. (Ed. note (Lapp) Dr. Chia is making a strong case for enterovirus as a common trigger for CFS/ME, and these studies imply that the infection is transferable. I found it interesting that chronic pelvic pain was localized to the infected fallopian tube in his patients, and that surgery relieved the pain. Sadly, no one else has taken on the task of confirming Dr. Chia's studies. Also there is no known antiviral therapy for EV - just an ill tolerated herbal preparation. Hopefully someone with Chia's expertise will investigate this further and confirm these important findings!)"

It has been seven long years since Dr. Chia's important paper of potential enteroviral involvement in ME/CFS. No one has significantly picked up on his study. As the backbone of his work, Dr. Chia has studied and revisited the history of ME especially in the UK. He has personally re-ignited important and forgotten associations. Dr.Chia is not coming out of nowhere on this. 

"We need to declare EV as one of the causes of ME/CFS. It has been 30 years!"

"Enteroviruses need to be accepted as one of the causes of this illness this year, or else we will wait another ten or more years before a drug will be available for this disease. You need to ask the researchers at Stanford and at the meeting why they are not working on enteroviruses."

I personally have witnessed several virologists flatten Dr. Chia's work. A prominent virologist (regarding Dr. Chia's work, which I had sent him) gave this blunt assessment: "It's crap". There is evidence that this prominent virologist might have altered his views - and perhaps might be willing to help.

We need to move on beyond these attitudes and find out what Dr. Chia is finding. Dr. Chia himself says: "I have spent considerable time trying to convince that I am right. Now it is time for others to prove that I am wrong."

After this IACFS/ME conference it seems that things are turning in a more positive direction for Dr. Chia's stupendous efforts in trying to get at this nasty illness. For those interested, there is more information on Patrick W. Calvins' Quixotic blog. 

And then there is the recent very exciting news regarding new drugs for Hep C. One drug, Sovaldi, from Gilead was approved by the FDA and is both well tolerated and extremely successful in treating Hep C. Two more amazing Hep C drugs are in the pipeline, one from Abbot and another from Bristol-Myers. There is some hope that one of these drugs might be effective against enteroviruses. "If this proves true, it will make all the difference in the world".

So there is some urgency here, and some real hope - but only if Dr. Chia's work is followed up on. 

IACFS/ME - and then Mission Delores

At the end of this year's IACFS/ME meeting I headed out on foot to the Mission District and to visit an old favorite: Mission Delores. Over the years, I have come here often, as well as many of the other missions up and down the coast of California. (The mission system was sort of the CDC of the late 18th and early 19th centuries)

Mission Delores and its cemetery are featured in a mistily mysterious scene in Hitchcock's "Vertigo" - one of my favorite films. I am going to watch it again when I get home.

The day was sunny and warm and the sweet smell of dope wafted through the air in the Mission District - as the locals were seeking their medicinal or medical improvements. Crowds of people flocked to a local park to see a concert of the Rollin' Snows or the Scoobie Doos.

The IACFS/ME conference ended Sunday afternoon. The IACFS/ME conference was four, very long days, running March 20-23. Always I find this conference too long - and too broad in its reach. I suppose I understand why the planners do this, as they have a large constituency to please or honor - but they include so many items that I consider to be auxiliary. To me parts of this conference are like watching a bad movie over and over - or falling to one's death off a very tall building.

I come to these conferences as an observer - to watch and listen. I don't think of myself as a participant, but more of an outsider or outlier. I am in the process of my own illness discovery. I figure that I represent my daughter, who cannot be here.

Over time I have learned to be very selective in going to lectures. This time I think that I went to five. I am happier just looking at the poster papers, and talking to old and new friends. This is my fourth IACFS/ME, and it functions as a touchstone of sorts. I just wish it were more focused. I have learned what a focused conference can be. I saw it at the Stanford Conference, I see it at Mt. Sinai, and I see it every year at the Invest in ME conference in London.

Am I giving a mixed message here? Yes I am giving a mixed message.

Dr. John Chia delivered two important talks. It has been seven years since Dr. Chia's pivotal paper was published showing enterovirus protein found in stomach tissue of ME/CFS patients. No one has followed up with this paper. It just sits there with its weight of ME history leaning on it. Meanwhile Dr. Chia continues his superb research - on his own, in virtual isolation. Dr. Chia gave two talks in a section on "Virology Research", chaired by Dr. Jose Montoya. (I hope that Dr. Montoya was listening.) The first talk was entitled "Chronic pelvic pain (CPP) in patients with ME/CFS is associated with chronic enterovirus infection of ovarian tubes" and the second was entitled "Pathogenesis of chronic enterovirus infection in ME/CFS - in vitro and in vivo studies of infected stomach tissue". Regarding the second study, "Of 24 mice injected with VP1+, and RNA+ stomach biopsies, 2 died in two weeks and13/20 (66%) spleen specimens tested positive for VP1 where 1 of 10 controls tested positive for VP1 by immunoperoxidase staining."

("If they do not believe in death, then what do they believe in?"). Of course there is the possibility that these mice died of sneezing fits - or committed suicide.

There was considerable interest during the question period and Dr. Chia answered a host of questions. He also made a hard-nosed presentation, and defense, of his research over the years, stating that "I have spent considerable time trying to convince people that I am right. Now it is time for others to prove that I am wrong". Perhaps soon we will finally be able to answer this question, whether Dr. Chia is right or wrong. I am betting on his being right.

Dr. Maureen Hanson's team gave a talk, "Plasma cytokines in ME/CFS patients and controls before and after a cardiopulmonary exercise test." Dr. Sonya Marshall-Gradisnik's team gave a presentation on NK cells. There has been a string of exciting research coming out of this lab.  Dr. Gradisnik will also be making a presentation in May at the Invest in ME conference.

It seemed a great oversight that Dr. Carmen Scheibenbogen was not giving a talk or a poster paper. I don't think she was even here. I could say the same about other UK or European researchers. Nothing was presented or mentioned about Dr. Joseph Brewer's recent work in mycotoxins. This seemed a slight oversight. Dr. Brewer made a recent presentation at the Lyme conference in October and will follow up at the next ILADS conference. So someone besides myself must know of his existence?

Where were research concerns involving gut ecology, the metabolome, mitochondria, lipid membranes (Yes, it was great to see Dr. Garth Nicholson's poster paper), mycotoxins and a host of important subjects? What world do these people live in? What illness are they studying?

The strength of this conference lies in its poster papers. This year there were several exciting presentations. I took note of Dr. Maureen Hanson's gut biome study in ME/CFS. Dr. Hanson will be giving a talk at the Invest in ME conference this May. She will be able to trade notes with Dr. Simon Carding, who is also working on a gut biome study in ME/CFS. Dr. Hanson reminded me that her colleague, Dr. Ruth Ley, works mostly in the gut biome arena. Incidentally, there seems to be a percolating effort to have ME/CFS patients do their biome study through Ubiome. The objective would be to publish their own biome study. Is this a good idea or what? - and it all sounds vaguely familiar.

There was another study out of Griffith University of the team of Dr. Sonya Marshall Gradisnik. Nancy Klimas and her group had an entire host of poster papers. I hope these poster papers become readily available.

The most interesting poster papers were two by Dr. Paul Cheney. Dr. Cheney has always contributed one or two important poster papers. One yearns for Dr. Cheney to be given a chunk of time to make a full presentation of his ideas. Dr. Cheney does best in three-hour slots of time, so he could have a morning session, a break for him to rest for a half-hour (but does he need it?), and then an afternoon session. This could go on for two or three days. And then maybe we could have a comprehensive conversation of what might be happening in this illness. But, of course, this is not going to happen. Instead we have to content ourselves with Dr. Cheney's self-published studies, and with Dr. Cheney's riveting explanations in front of his poster paper. He gives it willingly and repeatedly.

Asked what he does for his patients, Dr. Cheney says that "he stabilizes them".

I witnessed a few snippy engagements and comments, which are always interesting to me - and which I will keep to myself. I watched old adversaries be cordial and even respectful to each other.

The conference awards dinner had an especially good feeling to it. Nancy Klimas got a top award, which she certainly deserves. Dan Peterson gave the Keynote Address and took us on a stroll down memory lane. He described the history of IACFS/ME meetings, in the process recognizing many individuals in the audience, including Hillary Johnson, the gifted writer. Dr. Peterson showed a short video with 1990's video snippets of the early heroes in this struggle - Komaroff, Cheney, Bell, Klimas and Peterson himself. It was a hoot to see Nancy Klimas as a young clinician/researcher. This video was a lot of fun. Dr. Peterson has a special skill, either natural or developed, of getting the flow going in a positiive direction.

I was surprised, really surprised - and pleasantly surprised - to see Pia and Richard Simpson of Invest in ME receive an award. Never were there two people who have less interest in awards. Instead, they are interested in science - and money to fuel research. So if you have extra money, after giving to John Chia's EV Med Research, write a big check to Pia and Richard Simpson and Invest in ME.

Now that Richard and Pia have been recognized by IACFS/ME for their stupendous efforts, maybe the steering committee of the IACFS/ME group can select a group of "Important People" to actually make the journey to the upcoming Invest in ME conference - and thus learn a bit about how to organize a meaningful conference.

One thing that always, always irritates me about this IACFS/ME conference is the lack of attention to the severely ill. In fact, I have trouble connecting the severity of my daughter's illness with anything that happens at this conference. I do not think that most of the people who attend this conference have the slightest clue as to the true nature of this illness. They look at the half-sick, always at peak times, and draw their conclusions - if they only did a little more exercise.

And it is my belief that they do not want to know. I have observed the displeasure incurred by Dr. Kenny De Meirleir at an Invest in ME conference for presenting videos of very seriously ill patients from Norway, and for the testimony of a young woman who lived in the same house with a severely ill sister and had not seen her sister for four years. And then there is the whole anxiety about showing Voices from the Shadows. It is a very profound and great video, but it is seen as a downer. Well, this illness is a downer.

There is something so frightening about the core of this illness - from which almost everyone turns away. A little of this "ground zero"can be seen in Natalie Boulton's and Josh Bigg's extraordinary film. Dr. Montoya had the wisdom, the courage to show "Voices" at the Stanford Conference. (Dr. Montoya understands, he has learned this.) These totally isolated human beings hold the key - or a key - to the essential nature of this strange and devastating illness. Why are they not studied? Why does everyone turn away? Can we move forward if we are a bunch of cowards? If one is careful, blood, urine, saliva and feces can be removed from these patients (in some cases). If one wants to know what tests to do, I and others can tell you.

The efforts here at the conference and elsewhere to engage or embrace the severe ME patient is pathetic - really pathetic - and this means something.

Maybe this is all an age-related problem? Maybe I am just unable to see all the connecting parts at this conference and put them together? I will have to ask others, back in NY, like Jay Spero, if this is the problem, if this is my problem. In the meantime, I am in a hurry. I am not interested in the one-hundred year fix. I am less interested in stasis and more interested in dynamism, as reflected perhaps in what Dr. Skip Pridgen announced yesterday. Was Dr. Pridgen at this conference?

A number of serious clinicians did not go to this conference - Dr Eric Gordon, Dr. Kenny De Meirleir, Dr. Ritchie Shoemaker, Dr Derek Enlander, and Dr. Joseph Brewer. One has to ask why?