#OMFScienceWednesdays-The hunt for elusive pathogens in ME/CFS, by Jaime Seltzer, M.S

[Ben H]

Hi guys,


Do infections lead to lasting changes in immune or metabolic function that lead to symptoms, or is the pathogen still present? This #ScienceWednesday, OMF discusses recently funded research into addressing this central question in ME/CFS.

Do infections lead to lasting changes in immune or metabolic function that lead to symptoms, is the pathogen still present, or could it be both? OMF recently funded research into addressing this central question in ME/CFS pathology.

Some viruses replicate using RNA, while other viruses replicate using DNA instead. Several pathogens that have been associated with ME/CFS onset are DNA viruses, including herpesviruses (HHV6, HHV7, EBV), cytomegalovirus, parvovirus B19, and adenovirus. While there is good evidence that these viruses can trigger ME/CFS, studies are inconsistent as to whether the pathogens persist past onset.

The Stanford Genome Technology Center under Dr Ron Davis partnered with Dr Eric Delwart at the Blood Systems Research Institute to examine patients’ blood for microorganisms.
By comparing the DNA sequences of the microorganisms they found to the DNA of all known microorganisms, the researchers could find if patients had elevated levels of any known microbe. Scientists can even identify organisms no one has ever studied before, finding close DNA relatives to microorganisms by scanning for partial matches. However, they found no unusual microorganisms, or evidence that there was a significant difference in microorganism population between patients and healthy controls.

Next, the scientists looked for cell-free DNA. Cell-free DNA is genetic material that once belonged to a patient’s own cells, or DNA that used to belong to bacteria, fungi, or viruses. When pathogens die and break down in the patient’s body, fragments of their DNA are released into the bloodstream to be eliminated. Some pathogens are challenging to detect if the infection is mostly confined to a particular organ or tissue; however, by relying only on fragments and not on whole, healthy pathogens, cell-free DNA analysis can identify an infection growing anywhere in the body.

When the scientists looked for DNA viruses, there was no difference in overall levels of DNA viruses in patients and controls.

Examining cell-free RNA to look for RNA viruses, such as enterovirus -- notably studied by John Chia in association with ME/CFS onset -- is more challenging, due to the fact that cell-free RNA is less stable. The Stanford Genome Technology Center is currently developing technology that will allow them to look for RNA viruses in the ME/CFS population.

If the analysis of microorganisms reveals a particular pattern of common pathogens, it may be possible to employ as part of a diagnostic algorithm. If a lingering infection is causing or contributing to ME/CFS symptoms in a subset of patients, it may be possible to address with targeted therapies.

Read our previous post about viruses in ME/CFS:
https://www.omf.ngo/2016/09/09/viruses-and-cfs-statement-by-ron-davis-and-bob-naviaux/

Would you like to learn more about pathogens in ME/CFS? What’s a topic you’d like to see more about in a future post? Let us know in the comments below!


Thanks,


B

 

[Diwi9]

@Ben H - My big question in all of this virus hunting is: what kinds of cells are being looked at? Do we expect certain viruses to be camped out in specific cell types (i.e. nerve cells, muscle cells, immune cells)? What are the current limitations in examining specific cell types? You've posted some great primers in the past...so something that discusses why we look at specific cells would be of interest to me. Maybe there is already a post on it and someone will direct me if that is the case.

Thank you!

 

[AdamS]

Thanks for posting Ben, very interesting as usual.

One area that i’d like to see OMF expand on is circulation issues in ME/CFS, it seems that some of us benefit from vasodilators, hot weather, while others fare better with vasoconstrictors, Midodrine etc. Also for many of us, using our arms makes us crash much quicker than using our legs...these seem to be clues that appear regularly on PR but i’m not sure if docs/researchers are aware.

I remember @Murph coming up with some fantastic ideas around circulatory issues recently but I can’t find the thread. Perhaps the circlulatory issues mentioned above link to the sticky blood finding too?

 

[Alesh]

Many European patients are helped by amisulpride. Amisulpride among other things blocks 5-HT2. This receptor is the entry point of JC polyomavirus to the cell. Can it play any role?

 

[ljimbo423]

Would you like to learn more about pathogens in ME/CFS? What’s a topic you’d like to see more about in a future post? Let us know in the comments below!

Great article Ben! Do you know if they have any plans to test for bacterial DNA blood levels after an exercise challenge?

I know of at least one study that found significantly elevated levels of bacterial DNA in the blood of CFS patients over controls that remained elevated for 72 hours post exercise challenge, from a leaky gut.

Linking the increased level of bacterial DNA in the blood to PEM.....

These findings suggest a role for an altered gut microbiome and increased bacterial translocation following exercise in ME/CFS patients that may account for the profound post-exertional malaise experienced by ME/CFS patients.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4684203/#sec011title

Jim

 

[Murph]

I have basically been closed off to the pathogen theory. Until now.

A close friend of mine was dating a girl with me/cfs. They broke up. Now, six months later, he's telling me that he feels dizzy in the garden, and if he goes for a run he can't get off the couch the next day. He's been kicked around a whole set of doctors who are telling him he's fine.... It's a very familiar tale.

This is a guy with an incredible stamina. The kind of guy whose furniture is in pristine condition because he's never home. He's out every night of the week doing things.

And now this seems to be happening to him... I have to wonder if he somehow caught it off his partner.

(I also really overdid things recently while skipping some of my best supplements, and had chronic sore throat reactivation for about two weeks. That hasn't happened for years. This further makes me wonder if something pathogenic is lurking within.)

 

[Diwi9]

@Murph - The thought of contagion scares the crap out of me. But, I still wonder if it is just not normal infections that others can deal with that people with certain susceptibility cannot. This illness has been around for far too long for us to not have these answers sorted out. I'm not a conspiracy theorist, but then, the CDC has done nothing to even try to understand this illness, rather...they actively avoid doing so. We don't have answers because some people in power do not want answers...it's so much easier if we can all be classified as nut jobs. Outlaw-funded science may finally be the ticket to get this sorted...thank you to OMF and all donors.

 

[Alesh]

My ME started like an infection, it feels like an infection (of the brain in my case) and if you exercise with an infection, say a flu, you get PEM. I am not an expert but it seems to me that the source could be contaminated tap water since I and my two brothers fell ill after we moved to a different town. On the other hand during the 20 years of my illness none of my partners got ME. But honestly I don't know since at the begining doctors told me that it is a mono.

 

[Diwi9]

My ME started like an infection, it feels like an infection (of the brain in my case) and if you exercise with an infection, say a flu, you get PEM. I am not an expert but it seems to me that the source could be contaminated tap water since I and my two brothers fell ill after we moved to a different town. On the other hand during the 20 years of my illness none of my partners got ME. But honestly I don't know since at the begining doctors told me that it is a mono.

So after all these years, is it not amazing that there is no official source that can tell us whether or not this is contagious? Rather, we must infer it from the lack of official information and from sharing personal stories on internet forums.

 

[Mel9]

Hi guys,


Do infections lead to lasting changes in immune or metabolic function that lead to symptoms, or is the pathogen still present? This #ScienceWednesday, OMF discusses recently funded research into addressing this central question in ME/CFS.

Do infections lead to lasting changes in immune or metabolic function that lead to symptoms, is the pathogen still present, or could it be both? OMF recently funded research into addressing this central question in ME/CFS pathology.

Some viruses replicate using RNA, while other viruses replicate using DNA instead. Several pathogens that have been associated with ME/CFS onset are DNA viruses, including herpesviruses (HHV6, HHV7, EBV), cytomegalovirus, parvovirus B19, and adenovirus. While there is good evidence that these viruses can trigger ME/CFS, studies are inconsistent as to whether the pathogens persist past onset.

The Stanford Genome Technology Center under Dr Ron Davis partnered with Dr Eric Delwart at the Blood Systems Research Institute to examine patients’ blood for microorganisms.
By comparing the DNA sequences of the microorganisms they found to the DNA of all known microorganisms, the researchers could find if patients had elevated levels of any known microbe. Scientists can even identify organisms no one has ever studied before, finding close DNA relatives to microorganisms by scanning for partial matches. However, they found no unusual microorganisms, or evidence that there was a significant difference in microorganism population between patients and healthy controls.

Next, the scientists looked for cell-free DNA. Cell-free DNA is genetic material that once belonged to a patient’s own cells, or DNA that used to belong to bacteria, fungi, or viruses. When pathogens die and break down in the patient’s body, fragments of their DNA are released into the bloodstream to be eliminated. Some pathogens are challenging to detect if the infection is mostly confined to a particular organ or tissue; however, by relying only on fragments and not on whole, healthy pathogens, cell-free DNA analysis can identify an infection growing anywhere in the body.

When the scientists looked for DNA viruses, there was no difference in overall levels of DNA viruses in patients and controls.

Examining cell-free RNA to look for RNA viruses, such as enterovirus -- notably studied by John Chia in association with ME/CFS onset -- is more challenging, due to the fact that cell-free RNA is less stable. The Stanford Genome Technology Center is currently developing technology that will allow them to look for RNA viruses in the ME/CFS population.

If the analysis of microorganisms reveals a particular pattern of common pathogens, it may be possible to employ as part of a diagnostic algorithm. If a lingering infection is causing or contributing to ME/CFS symptoms in a subset of patients, it may be possible to address with targeted therapies.

Read our previous post about viruses in ME/CFS:
https://www.omf.ngo/2016/09/09/viruses-and-cfs-statement-by-ron-davis-and-bob-naviaux/

Would you like to learn more about pathogens in ME/CFS? What’s a topic you’d like to see more about in a future post? Let us know in the comments below!


Thanks,


B

Very interesting thanks Ben . So it seems that there is no elevated viral or bacterial DNA in the severely ill cell-free serum? How Was that tested?

 

[Sing]

My view is that it isn’t the bug, or a bug, that causes this long term (endless) illness or “condition” (Cheney), but rather the body’s response to it which gets locked in. So far I am of the Naviaux and Cheney persuasion. The overall symptom picture, certainly mine, is of a downturn across many of the body’s systems, a general state of hypo.

I have been frustrated and tired of all the money, time and resources which have gone into looking for the hypothetical first cause and sustaining cause, in terms of a bug. That is an idée fixe which has greatly slowed down progress on understanding and treatment.

The only research so far that has helped us, in my view, has been the kind that looks at what is actually going on once this illness or condition is established.

 

[msf]

It would seem that along with the RNA, there also needs to be a way of checking other areas of the body for microorganisms. Since Lyme, Q fever, and various GI pathogens have been suspected in ME, I would like to think this would be a high priority. If this is too difficult, looking for bacterial cell free DNA in the blood would be a good start.

 

[perrier]

My ME started like an infection, it feels like an infection (of the brain in my case) and if you exercise with an infection, say a flu, you get PEM. I am not an expert but it seems to me that the source could be contaminated tap water since I and my two brothers fell ill after we moved to a different town. On the other hand during the 20 years of my illness none of my partners got ME. But honestly I don't know since at the begining doctors told me that it is a mono.

Dear Alesh
Very interesting comment about using new tap water; Dr Chia says less Chinese people have cfs, and he thinks it is because they drink more tea. At least, I seem to recall reading this point.

 

[me/cfs 27931]

I'd love to see Enterovirus D68 tested for, if that's possible.

https://www.sciencedaily.com/releases/2018/02/180226122534.htm
http://www.thelancet.com/journals/laninf/article/PIIS1473-3099(18)30094-X/abstract

 

[msf]

Dear Alesh
Very interesting comment about using new tap water; Dr Chia says less Chinese people have cfs, and he thinks it is because they drink more tea. At least, I seem to recall reading this point.

Hmm, I think we might need to see the stats on that one.

 

[jpcv]

Thanks for posting Ben, very interesting as usual.

One area that i’d like to see OMF expand on is circulation issues in ME/CFS, it seems that some of us benefit from vasodilators, hot weather, while others fare better with vasoconstrictors, Midodrine etc. Also for many of us, using our arms makes us crash much quicker than using our legs...these seem to be clues that appear regularly on PR but i’m not sure if docs/researchers are aware.

I remember @Murph coming up with some fantastic ideas around circulatory issues recently but I can’t find the thread. Perhaps the circlulatory issues mentioned above link to the sticky blood finding too?

That´s me, using my arms to pick up thing, hang clothes, eveng shooting a small pistol at the range can cause me a crash.

 

[jpcv]

So after all these years, is it not amazing that there is no official source that can tell us whether or not this is contagious? Rather, we must infer it from the lack of official information and from sharing personal stories on internet forums.

IT is infectious, if one studies the patterns of many outbreaks the conclusion is there is no way it can not be infectious.
Qfever, EBV, Enterovirus, Herpes vírus ,Giardia, there are cases of diferente infectious diseases leading to ME/CFS
the question is : does a infectious agent start a process that later on becomes chronic and progressive or the pathogen not only starts but perpetuates the disease?
I think it´s a crucial question because it has profound impications for the treatment of the patients.
Maybe for some pathogens it´s the first alternative, maybe for others it´s the second one.

 

[jpcv]

I have basically been closed off to the pathogen theory. Until now.

A close friend of mine was dating a girl with me/cfs. They broke up. Now, six months later, he's telling me that he feels dizzy in the garden, and if he goes for a run he can't get off the couch the next day. He's been kicked around a whole set of doctors who are telling him he's fine.... It's a very familiar tale.

This is a guy with an incredible stamina. The kind of guy whose furniture is in pristine condition because he's never home. He's out every night of the week doing things.

And now this seems to be happening to him... I have to wonder if he somehow caught it off his partner.

(I also really overdid things recently while skipping some of my best supplements, and had chronic sore throat reactivation for about two weeks. That hasn't happened for years. This further makes me wonder if something pathogenic is lurking within.)

Very intersting pattern, and a familiar one also...that scares me because I fear my kid might get infected too...
my girlfriend has been under lots of stress lately, from long working hours and also from a judicial dispite with her ex husband.
lately she´s been complaining of body pain and worsening fatigue, I tell her to slow down, work less a rest more but she doesn´t listen....

 

[jpcv]

My view is that it isn’t the bug, or a bug, that causes this long term (endless) illness or “condition” (Cheney), but rather the body’s response to it which gets locked in. So far I am of the Naviaux and Cheney persuasion. The overall symptom picture, certainly mine, is of a downturn across many of the body’s systems, a general state of hypo.

I have been frustrated and tired of all the money, time and resources which have gone into looking for the hypothetical first cause and sustaining cause, in terms of a bug. That is an idée fixe which has greatly slowed down progress on understanding and treatment.

The only research so far that has helped us, in my view, has been the kind that looks at what is actually going on once this illness or condition is established.

but have you considered that the presence of a bug might be the reason why this response gets locked in?

 

[heapsreal]

I dont think medicine can detect most chronic active infections unless its an overwhelming infection causing septic shock etc. So my first point is accurately testing and detecting active infections in different tissues not just blood.

Most treatments to actively treat an infection either dont directly kill the infection or they weaken an infection enough for the immune system to clean up the rest. So if there is immune dysfunctions going on, then it wont clean up whats left over from different antivirals and antibiotics used to treat certain infections.

Its also very possible that once the immune dysfunction starts even if theres one initial infection, that other infections could be picked up along the way as well as some latent infections will reactivate . Makes it extremely hard to find the initial triggering infection but also the other ongoing infections that occur and what to actually treat.

Theres a horse or the cart scenario that may feed into itself. As well as a hit and run scenario where the initial infection leaves behind alot of damage and the trigger is gone.

When you look at the small number of reported autopsies on cfsme people reported most seem to show evidence of inflammation and infection within the brain and spinal cord that wasnt detected in previous testing these patients had when they were alive. Many told something like ebv and such infections arent present after 3 months etc.

So researchers are obviously missing things maybe because technology isnt advanced enough. I also think alot of past research is narrow in finding the one cause or one infection??

I think we all agree that theres not enough research into cfsme compared to other disorders of similar severity.