Karius Dx CFS/ME and Plasma NGS for Pathogen Detection

[Pgrovetom]

I was curious if anyone had heard of any effort or studies for CFS/ME that utilized Next Generation Metagenomic Shotgun Sequencing of Blood or Plasma for in hunting for underlying infections that might be causing an individual's CFS/ME symptoms?

I know there has been many attempts to find any underlying infections in CFS/ME and I'm sure many individual's doctors have run many of the usual pathogen antibody or PCR tests to look for an underlying infection. Until recently,a doctor or ID doctor had to make a guess as to a likely pathogen and run one test per guess or in some cases use a fixed pathogen panel to cover the 10 guesses made by the lab who developed the panel.

A panels example might be the Luminex GI Pathogen Panel.
https://www.luminexcorp.com/gastrointestinal-pathogen-panel/

White Paper : https://www.luminexcorp.com/?wpdmdl=13681

If someone is in the intensive care unit with a life threatening suspected infection, the doctor(s) throw multiple antimicrobials at the patient and guess as to what to test for. If they are wrong, the patient might die. Recently both UCSF and a company Karius Dx have been offering NGS sequencing of blood or Serum to critically ill patients in hospitals and are able to detect free DNA of anything in their body. They report levels that are above background noise that "might" be an infection with astounding success. Their testing is both state of the art and held in high regard in both the scientific and medical communities but the ID doctors to date have convinced them to restrict the offering to hospital patients with serious suspected infections and not allowing testing of chronic conditions such as CFS/ME.

They describe their test as: A quantitative next-generation sequencing test to help clinicians rapidly diagnose infectious diseases. Our analytically validated assay identifies microbial cell-free DNA in plasma from bacteria, DNA viruses, fungi, molds and protozoa.

You can read about Karius Dx here:
https://kariusdx.com/products/karius-test

This is there currently validated list of pathogens they detect:
https://kariusdx.com/pathogenlist/3.4

UCSF has no less than 3 labs pursuing the same approach:
https://nextgendiagnostics.ucsf.edu/our-research/

The cost of the Karius Dx test to the hospital is $2000 but this would the cost of about 3-4 wrong guesses for PCR pathogen tests or similar to a panel mentioned earlier. The beauty is that the doctor does not need to make any guesses based on symptoms or history and can simply screen for anything leaving free DNA in the bloodstream. An infection most anywhere in your body will "leak" broken down free DNA into your blood as the pathogen complete its life cycle, dies and enters the bloodstream for removal. The test will detect any microbial DNA so the doctor must be able to look at the report and eliminate things like reactivated Herpes.

Its a shame that the ID doctors are controlling how Karius Dx offers its test. It seems obvious to me that this would be a no-brainer study for CFS/ME. I would consider funding such a study under the right circumstances. I suspect Karius will eventually open this testing up to chronic conditions but didn't want to rock the boat for now. That just pushes patients and doctors to use less reputable labs with no validation. I notice the UCSF labs also require permission by UCSF ID so appear to have the same restrictions.

 

[Carl#1]

Do not was your time because it can be either bacterial, yeast or fungi which causes CFS/Me/Fibro and it is not in the blood. It is in the digestive system which causes Increased Digestive Permeability with destruction of part of the pituitary and hypothalamus by the micro-organisms effect on the vagus nerve in the location it attacks. There can be a thousand different micro-organisms responsible. They are also biofilm protected so antimicrobials might not be able to destroy them with their biofilm intact because it promotes their adaption.

It is the IDP which causes the immune system dysfunction which can cause viral proliferation. People think that the cause of their CFS is viral when it is not, it is the result of their immune system dysfunction caused by raised cytokines. That also affects ATP mitochondrial energy production and a heavy detox load with extreme nutrient requirements.

I am working on destroying them when I can get around to it with other things to deal with. I have previously eliminated their biofilm but so far what I have tried has not destroyed them. I did destroy a large part of another closely related infection with Reduced Colloidal Silver without eliminating their biofilm, which reduced my IDP. I certainly felt that because it was quite uncomfortable until it healed. IBS is all related to this.


Quorum Sensing Inhibitors, Efflux Pump Inhibitors, Enzymes+EDTA, Antimicrobials are needed but the micro-organism that I believe could be responsible based upon a prime symptom I have not yet managed to find a suitable EPI to make destroying them easier. That concerns me greatly.

BTW Hip is treating the wrong location which will never fix his problems because the problem is not in the colon but the colon is affected. Specifically the Right Transverse Colon is affected which is where IBS originates in CFS and in the Transverse Colon in most cases of IBS outside CFS. But that is not where the infection resides. It's all about the Vagus nerve and how the human nervous system functions which science, medicine and researchers know very little about.

 

[Pgrovetom]

I should have said something about the context of my post.

"Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is diagnosed after ruling out all other diseases that may explain the symptoms presented. The diagnosis relies upon a set of symptoms presented according to the type of criteria used."

My understanding is that depending on the criteria used, there are somewhere between .5 and 4 million Americans that have been diagnosed with CFS/ME. The cause is almost certainly not the same. The cause could be anywhere in the system. It could be hormonal, the nervous system, metabolic, an infection etc.. or some combination.

That strongly suggests that CFS/ME is most likely a group of overlapping conditions with any number of causes that result in a similar presentation and resulting diagnosis. There have been a variety of people diagnosed with CFS/ME that have recovered after treatment for a suspected cause. An example of this would be the recent article here on spinal stenosis that appeared to be one actual cause. Another example would be the treatment with Valcyte that led to remission. There are many examples like this.

So when a person presents with the symptoms of CFS/ME, a doctor should eliminate as many possible treatable causes as is practical. This seems obvious but is rarely done in a consistent or systematic manner. I know this from experience.

One category that is obvious and needs to be eliminated is some kind of chronic infection that is perturbing the persons entire system. I use the term infection loosely since it could range from a gut dysbiois or actual gut bacterial/viral/fungal/parasitic infection to a disseminated infection to a Herpes infection in the nervous system or a chronic spirochetal infection or any of many possible microbes.

Typically each "suspected" microbe requires one expensive test. Many antibody tests are species or strain sensitive making detection very unreliable. Just testing the top 20 suspected microbes would cost thousands of dollars. That leaves a few thousand untested possibilities. That also assumes the test is reliable. Many people are familiar with the Lyme ELISA/Western Blot 2 tired test which is known to fail if the species of spirochete is too distant from the the one used in developing the test. This species strain reliability problem exists in may microbe tests. NGS sequencing does not suffer from this problem.

So I would want to know if there are any suspicious microbes "living" in the persons body. I would want to "look" into the 2 most obvious places initially to determine if any of the microbes are suspicious. The first would be the gut and the second would be the blood.

The Karius Dx test is the obvious choice for "looking" at the blood since most infections in the body would leave some free DNA of the microbe in the blood. That free DNA would most likely exist in quantities higher than the background noise. Karius Dx filters out what appears to be background noise DNA. That DNA would also be persistent over time such that repeat testing could eliminate transient microbe DNA from an ongoing infection source.

The DNA reported may due to the actual cause of the symptoms or be an unrelated infection such as a could virus, Flu virus, a bacterial or fungal sinus infection, an HSV reactivation etc.. It would be the doctors role to sort through the reported DNA and determine if its suspicious or not. Further specific antibody or PCR testing could be used to zero in on a specific suspicious microbe once its known.

If for example, the doctors saw the DNA from something like a parasite that should not exist in a human, then it would seem like an empiric course of an antiparasitic would be justified. If the DNA of the spirochete Borrelia Miyamotoi was found, that might justify empiric spirochete treatment. There are many examples like this where the microbe DNA found "should not" be in your body and it should be investigated.

If a specific suspicious microbe DNA appeared in repeat testing and or was further confirmed through targeted PCR or antibody testing, then empiric treatment could be used to either treat or eliminate this microbe as the cause or one of the causes.

The same could be applied to gut based metagenomic stool testing with some additional complications. Most of the bacteria found in the stool whether it be pathogenic or not would be an unlikely cause. There are some bacteria which produce toxins that if "leaked" into the blood would cause havoc with the immune system. The problem in this case is likely gut permeability and the treatment path would involve finding its cause rather than trying to treat the microbe. If in the case of Karius Dx blood or similar testing, a large amount and variety of bacterial DNA was found. it might suggest a gut permeability problem that is allowing bacterial "junk" and toxins to get into the blood.

There are microbes such as virus's and parasites that should not be living in the gut that would stand out and could be considered for pursuing. A gut parasitic infection could either disseminate or be the cause of the gut permeability mentioned earlier. Treating a known pathogenic parasite empirically would make sense.

The point I was making with regard to the Karius Dx or similar testing was that it fulfilled an obvious step in eliminating infection or microbial possible causes for a condition like CFS/ME or any chronic illness. I'm not trying to suggest CFS/ME has one microbial cause but rather suggesting infections and microbial cause elimination should be a standard part in any differential diagnostic process.

I suspect some portion or people diagnosed with CFS/ME or FM do have an infection cause. That proportion is unknown since testing like the Darius Dx has never been used systematically on CFS/ME or any other chronic illness. I'm suggesting it would be smart to utilize this testing to investigate and try and rule out or in, infections as part of any diagnosis process. Never before has this kind of microbe testing been available where the doctor does not need to make assumptions or guesses. It was previously impossible to test for "everything" at once for a reasonable cost. Now its possible.

I do suspect Infectious Doctors will be fearful of this type of testing since it will make them less important on diagnosis side of most infections. They will be relegated to the cases where the NGS sequencing was unable to find the cause. They will still be needed on the difficult treatment side.

UCSF's Dr Chiu is a leading proponent who runs a microbiology NGS sequencing lab at UCSF and has a number papers and videos on his lectures and presentations on the use of NGS sequencing and Infectious Disease. Take a look. Its fascinating.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6345613/

 

[Carl#1]

Do not waste your time because it can be either bacterial, yeast or fungi which causes CFS/Me/Fibro and it is not in the blood. It is in the digestive system which causes Increased Digestive Permeability with destruction of part of the pituitary and hypothalamus by the micro-organisms effect on the vagus nerve in the location it attacks. There can be a thousand different micro-organisms responsible. They are also biofilm protected so antimicrobials might not be able to destroy them with their biofilm intact because it promotes their adaption.

It is the IDP which causes the immune system dysfunction which can cause viral proliferation. People think that the cause of their CFS is viral when it is not, it is the result of their immune system dysfunction caused by raised cytokines. That also affects ATP mitochondrial energy production and a heavy detox load with extreme nutrient requirements.

I am working on destroying them when I can get around to it with other things to deal with. I have previously eliminated their biofilm but so far what I have tried has not destroyed them. I did destroy a large part of another closely related infection with Reduced Colloidal Silver without eliminating their biofilm, which reduced my IDP. I certainly felt that because it was quite uncomfortable until it healed. IBS is all related to this.


Quorum Sensing Inhibitors, Efflux Pump Inhibitors, Enzymes+EDTA, Antimicrobials are needed but the micro-organism that I believe could be responsible based upon a prime symptom I have not yet managed to find a suitable EPI to make destroying them easier. That concerns me greatly.

BTW Hip is treating the wrong location which will never fix his problems because the problem is not in the colon but the colon is affected. Specifically the Right Transverse Colon is affected which is where IBS originates in CFS and in the Transverse Colon in most cases of IBS outside CFS. But that is not where the infection resides. It's all about the Vagus nerve and how the human nervous system functions which science, medicine and researchers know very little about.

Correction of my post, for some reason I wrote was instead of waste. Not sure what happened there.......

 

[Issie]

I agree with you on this. Dr. Stephen Fry has similar testing at Fry Labs. He can run studies such as this. He found a type fungus that should not be in humans in our blood and organs (my thyroid biopsy). It forms biofilms and clogs veins and forms tumors. I have been using the same approach as you for years now. It has made a difference. The biggest key is the combination of breaking biofilm down while killing fungal, bacteria and protozoa that lives in them. Yet trying to not disrupt the good things we want to keep at too high a level. Binders are necessary so as to not recirculate these things and eliminate them. There also seems to be a piece my Functional doc and I missed.....retrovirus and virus. We have recently added to my protocol to address this and I'm making gains. Feel we are on the right track now.