Enterovirus Followup Study?

[halcyon]

That's very interesting. @halcyon, you always have these interesting nuggets of information! Where did you come across that one, may I ask?

Dr. Chia mentioned it during my appointment. I stupidly forgot to ask if I could record the appointment, he had about a million other interesting anecdotes that I have since forgotten.

Though is it possible to test in vitro (in cell lines) for the Th1/Th2 immunomodulatory effects of oxymatrine, because presumably you haven't got the full immune system present in cell lines? The Th1/Th2 immunomodulatory effects of oxymatrine may be the main way oxymatrine fights off enteroviral infections.

Yeah, that's an interesting point. Testing in a cell culture will only stimulate the cell mediated immune effects. Oxymatrine stimulates cells to release interferon and interferon is the triggering ligand that kicks off all the interferon stimulated gene antiviral pathways. If this is ineffective against certain enteroviruses, there must be more to it than just that. Oxymatrine itself must directly interfere with the virus in some way. But as you say, this ignores the impact that other immune cells have on the infection. I believe this is the purpose of some of the other compounds in Equilibrant. For example, astragalus is known to help activate macrophages.

 

[halcyon]

It turns out there is a CDC CFS conference call coming up on Monday, including a Q&A segment. I will submit a question regarding the status of this.

According to Dr. Unger of the CDC, their Picornavirus lab (not part of their CFS program) received the 30 patient samples in September 2014. Apparently the Picornavirus lab has been fully occupied with EV D68 testing since that time, but they anticipate that they will initiate testing of Dr. Chia's samples in March 2015. The results of their testing will be released directly to Dr. Chia.

 

[Never Give Up]

Dr. Chia just told us that last week they positively identified enterovirus RNA in the brain of a deceased patient and that this is the first independent replication of similar British findings from decades ago. Go Dr. Chia!

 

[halcyon]

Dr. Chia just told us that last week they positively identified enterovirus RNA in the brain of a deceased patient and that this is the first independent replication of similar British findings from decades ago. Go Dr. Chia!

Interesting, "they" being the CDC or someone else?

 

[Never Give Up]

Interesting, "they" being the CDC or someone else?

He actually used the pronoun "we". Not sure exactly who "we" is though. I would guess that it might be his lab. He said it was very difficult to tease out the tiny RNA from the giant protein. He said they found it all over the brain and had previously found it in muscles and tissues all over the body of this same deceased patient.

I would be curious to know if these same techniques applied to a healthy control would yield the same or different results.

 

[Hip]

Dr. Chia just told us that last week they positively identified enterovirus RNA in the brain of a deceased patient and that this is the first independent replication of similar British findings from decades ago. Go Dr. Chia!

Wow that's amazing. I look forward to reading that study. I guess his brain autopsy findings will be published in due course. It will be particularly interesting to see if Dr Chia has determined the types of cells in the brain where he found the enterovirus RNA, and whether this matches up to the 2001 study by the late Dr John Richardson, which found enteroviruses in the glial cells of the brain.

I would be curious to know if these same techniques applied to a healthy control would yield the same or different results.

In this 1994 brain autopsy study, the they used as controls four patients who died of cerebrovascular diseases, and none of these four control showed any evidence of enteroviral RNA in their brains; enteroviral RNA was only found in the brain of the deceased ME/CFS patient.

According to Dr. Unger of the CDC, their Picornavirus lab (not part of their CFS program) received the 30 patient samples in September 2014. Apparently the Picornavirus lab has been fully occupied with EV D68 testing since that time, but they anticipate that they will initiate testing of Dr. Chia's samples in March 2015. The results of their testing will be released directly to Dr. Chia.

That is certainly going to interesting. I wonder if this CDC testing of Chia's samples will be considered as a replication study? Replication of Dr Chia's results is much needed.



By the way, @halcyon did you see this info I posted on non-cytolytic enteroviruses recently (it's about the two rival views of the nature of non-cytolytic viruses)? I just wondered if you have any insight into this; I am wondering if this has any import for ME/CFS.

 

[halcyon]

By the way, @halcyon did you see this info I posted on non-cytolytic enteroviruses recently (it's about the two rival views of the nature of non-cytolytic viruses)? I just wondered if you have any insight into this; I am wondering if this has any import for ME/CFS.

I did see that and I've been meaning to take a look at it but haven't had a chance yet.

 

[Hip]

I did see that and I've been meaning to take a look at it but haven't had a chance yet.

What I have been considering lately is whether there might be ways to prevent or inhibit the creation the non-cytolytic dsRNA in these chronic enteroviral infections. Prevention is the other side of the coin to considering how to destroy the viral dsRNA in cells after it is created.

One area that might be worth examining is RNA interference (RNAi). In the RNAi process, endogenous human dsRNA is created and also broken down by the dicer enzyme. I was trying to read a bit about RNAi, but it is quite complex.

 

[halcyon]

What I have been considering lately is whether there might be ways to prevent or inhibit the creation the non-cytolytic dsRNA in these chronic enteroviral infections. Prevention is the other side of the coin to considering how to destroy the viral dsRNA in cells after it is created.

Again, I regret not recording my appointment with Dr. Chia because it was difficult to follow him at the time, but he did discuss a bit the idea behind using Epivir and inosine. I believe he said that Epivir acts as a viral chain terminator and should inhibit viral replication and thus the maintenance of large amounts of dsRNA. The presence of inosine encourages a-to-i RNA editing which inhibits the genetic material in some way. One or both of these things helps make the viral genome more susceptible to enzymatic dicing.

 

[Sing]

Wow that's amazing. I look forward to reading that study. I guess his brain autopsy findings will be published in due course. It will be particularly interesting to see if Dr Chia has determined the types of cells in the brain where he found the enterovirus RNA, and whether this matches up to the 2001 study by the late Dr John Richardson, which found enteroviruses in the glial cells of the brain.




In this 1994 brain autopsy study, the they used as controls four patients who died of cerebrovascular diseases, and none of the four showed any evidence of enteroviral RNA in their brains; enteroviral RNA was only found in the brain of the deceased ME/CFS patient.




That is certainly going to interesting. I wonder if this CDC testing of Chia's samples will be considered as a replication study? Replication of Dr Chia's results is much needed.



By the way, @halcyon did you see this info I posted on non-cytolytic enteroviruses recently (it's about the two rival views of the nature of non-cytolytic viruses)? I just wondered if you have any insight into this; I am wondering if this has any import for ME/CFS.

From the call today with Dr. Unger and Dr. Montoya, I vaguely recall the idea that the CDC testing of Dr. Chia's samples may count as a replication study.

 

[Never Give Up]

In this 1994 brain autopsy study, the they used as controls four patients who died of cerebrovascular diseases, and none of the four showed any evidence of enteroviral RNA in their brains; enteroviral RNA was only found in the brain of the deceased ME/CFS patient.

Fabulous! Thank you for the information, Hip!

 

[halcyon]

I vaguely recall the idea that the CDC testing of Dr. Chia's samples may count as a replication study.

Unfortunately neither the CDC nor Dr. Chia has officially commented on the nature of this exchange as far as I know, so there's no way to know. Is it simply a sanity check, to verify that he really is finding viral protein and RNA? Are they digging deeper into the nature of the genomic material present to see if there is something special or different about it versus wildtype virus from non ME patients? If I have the time during my next appointment with Dr. Chia, I will try to ask him exactly what the purpose was.

 

[Wally]

FYI - I am not a patient of Dr. Chia, but I met him at the IACFSME Conference last March. He so graciously took his time to talk to me and seemed genuinely interested in wanting to know my history with this illness. When hearing that I had come down with this illness after vacationing in Tahoe (in Incline Village circa 1991), he suggested I might want to get samples taken from my gastrointestinal tract (from a planned endoscopy/colonoscopy) and examined for enteroviruses. This was not something that my gastroenterologist was that familiar with, but when I showed him Dr. Chia's work and that I could have samples tested by his lab, I found he was open to the idea. I believe others may be familiar with how this testing can be done and run through Dr. Chia's lab, but if not I thought I would just mention it in case anyone else might be undergoing similar gastrointestinal procedures in the future.

Since I just love being a specimen for research, Dr. Kogelnik (my infectious disease doctor) also received samples for research purposes. It cost me about $25o for the testing at Dr. Chia's lab, nothing extra for my gastroenterologist to take a couple of extra steps to collect samples. The pathology department at the hospital where the procedures were done ended up not charging me anything to make up the slides and send them off to two different locations. They had originally said I would be charged about $100 for this service, but in the end no charges were ever billed.

The most difficult part of the process was getting everything coordinated between Dr. Chia's lab, my gastroenterologist, and the hospital's pathology department. It took lots of phone calls and making sure all the instructions were provided prior to the procedures, carried with me to the operating room at the time of the procedure, faxed again to the pathology department the same day as the procedures and a final closing of the loop to make sure that the samples and report were received by both sets of doctors who wanted to do further research. I have no idea if my samples are some of those specimens waiting for further testing at the CDC, but I figure at least I am happily sharing my illness with as many takers as I can find.

Bottom line for me is that Dr. Chia's lab did find that I have enteroviruses. While healthy individuals may also show up with enteroviruses, I am hoping that whatever was found will someday help me or someone else to see whether this is a piece of the puzzle that is needed to treat/solve this illness.

 

[Gingergrrl]

@Wally Good for you for undergoing all that extra effort to get the biopsy to both doctors. I have no doubt those results will help many others down the line.

You mentioned that Dr. Chia was concerned b/c you were in Tahoe around 1991 and it made me wonder, what were the years that it was considered dangerous to be in Tahoe? I was there in 2012 a few months after I had believed to be recovered from mono but I am sure this is not relevant in my case.

 

[Wally]

@gingergirl,
I don't know that there was a date other than the "cluster outbreaks" around that region (including some in nearby Sacramento, CA or other small towns in CA and Nevada), which occurred during the 1980's (Incline Village outbreak I believe was in 1984 - ?). Perhaps someone with more recall than my brain has right now can add some more information about the known cluster outbreaks in that region.

If I remember my conversation with Dr. Chia correctly, I believe he mentioned something about the idea of possible ingestion of protozoa found in the water. I didn't get the impression that this potential trigger would just be limited to Incline Village, but could be seen in other areas under the right conditions. I was in Incline Village during the first week of July in 1991.

I grew up spending time at Lake Tahoe in both the winter and summer months for over thirty years before I got sick, but most of my visits were on the opposite side of the Lake. Incline Village is considered to be on the North Shore and I spent most of my time near the South Shore. All the same body of water, but the Lake is quite large, so water and contaminants can feed into the area from many different locations around the lake.

 

[Gingergrrl]

@Wally thanks and I was just curious b/c I thought the Tahoe outbreaks were in the 80's but when you said Dr. Chia was concerned about 1991, it made me wonder. I was in Tahoe both North & South shore in 2012 but am fairly sure it is not relevant in my case and it was also after I had mono vs. before.