Ron Davis and Trypanosomes

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Hi all, I'm also interested to hear whether there are any updates on the possible Trypanosome connection mentioned by Dr Ron Davis.

A couple of related questions (though these are perhaps for tropical diseases specialists): does anyone know: (i) whether there's a way to test for a low-level trypanosome infection, i.e. an infection that persists at below the level that would reliably appear on blood results? (ii) What the best/latest drug and dosing treatment regime is for chronic African Trypanosomiasis (sleeping sickness)? CDC information seems to suggest suramin, melarsoprol, eflornithine, or nifurtimox used in combination with eflornithine (see: https://www.cdc.gov/parasites/sleepingsickness/treatment.html), but I'm not familiar with any of these. I've also seen articles on Fexinidazole, (again, not familiar) while another forum member posted separately on a novel approach based on extracting an antibiotic from Acremonium egyptiacum -https://www.sciencedaily.com/releases/2019/04/190404094909.htm - but I'm not sure whether this has yet been commercialised?

Look forward to any thoughts. Thanks in advance.
 

nerd

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I only knew of Trypanosome as an educational example for how western medicine disregarded a serious disease for years because there was no profit to make. It's just another parasite speculated to be involved. But all of the speculated ones seem to be blood-based at least in a certain stage. Ivermectin is a typical antiparasitic. This seems to include trypanosomes (10.1016/j.pt.2014.07.005). 300mcg/kg would be the suggested dose. But I doubt it's the most effective medication.

I think the best way to identify if it's any kind of known pathogen is the sequencing of Aperiomics. But if it's an unknown one, I guess you'd have to give the data to a scientist and hope that they can come up with something.

I'd also like to reexplore the idea of treatment via bacterial infection at some time. Interestingly, my keto diet caused some kind of chronic rash. Keto rashes seem to be bacterial most of the time, though topic antibiotics haven't worked in my case. But I have developed monocytosis. This means my body is fighting something. Maybe this is the reason for the improvement? But is it a directed improvement or is it an indirect effect from it, like TLR-mediated, cytokine-mediated...
 
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Aperiomics is a bit of a joke. They give you a list of dozens of pathogens they found and can't tell you whether they have any clinical significance. They also can't seem to reliability differentiate between human and non-human DNA in blood. I know of about 10 people who tested through them and no trepanosomes showed up. Which in my opinion doesn't mean anything because the test is so bad.

Ivermectin also doesn't work (I've tried).

Suramin might work. I believe Naviaux is using it in a CFS trial, but possibly for other effects of the drug.
 

godlovesatrier

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Is the Aperiomics test reliable? After the Armin Labs incident I am very cautious these days. Also how would it differentiate between multiple infections (active)?
 

nerd

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Which in my opinion doesn't mean anything because the test is so bad.
The test is oversensitive. This means that there is one-directional reliability. When they don't find trypanosomes in the blood, there aren't any. However, it doesn't mean there aren't in the CSF. You'd have to send them CSF liquid for that. It doesn't exclude brain tissue parasites either.

They give you a list of dozens of pathogens they found and can't tell you whether they have any clinical significance.
The test is oversensitive. The purpose of it isn't the confirmation of a suspected pathogen but to figure out what you're even supposed to look for. It's the same problem as with nasal PCRs. You can breathe in pathogens and the PCR would pick them up, even if you don't have an infection in the lungs or blood.

Ivermectin also doesn't work (I've tried).
If the pathogen sits in brain tissue or the CSF, Ivermectin and many other medications that can't cross the blood-brain barrier (BBB) won't help, unfortunately. It's the same as with antivirals and HHV. Even if the antiviral shows efficacy in vitro, and you take a sufficient dosage, there won't be any efficacy in the brain unless the antiviral crosses the BBB easily. If there is only low BBB permeability, it even increases the chance of resistance. This counts for antivirals, antibiotics, and antiparasitics.

If it is a virus and not a parasite, antivirals would have to be taken for a long time to show any benefit, unless combined with other treatments. It's similar with Azithromycin and Lyme.

Also how would it differentiate between multiple infections (active)?
It's difficult to differentiate because some pathogens just have higher loads than others but with the same degree of pathology. It just serves as an indication of where to look further. But I think their service is overpriced. It can be done cheaper. They know that they can ask for any price. It's just their database and matching algorithm that grants them their leading position. The testing itself can be done by many laboratories. When we consider how expensive their overseas services and shipping are, it's surprising that they don't offer a separate analytics service or partner with local laboratories.
 
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African sleeping sickness ? can it be transmitted through the air ? seems unlikely I would have it in europe. What other vectors of transmission ? food ? and yes doctors just look at you do one test and say you don't have an infection but I am realizing there are all these loopholes like with the lyme disease Borrelia burgdorferi.
 

nerd

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African sleeping sickness ? can it be transmitted through the air ? seems unlikely I would have it in europe. What other vectors of transmission ? food ? and yes doctors just look at you do one test and say you don't have an infection but I am realizing there are all these loopholes like with the lyme disease Borrelia burgdorferi.
I think insects are the suspects, like ticks or mosquitos. Due to globalization, more and more of these are imported to previously safe countries and spread all over the world. Like Dengue in Brazil. In Germany, I know that many new dangerous mosquito types have been detected and spread rapidly. In the US, they test genetically modified mosquitos now to disrupt the spread.
 

Boba

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First, i want to thank you for your great work to help us all! So good to see researchers speak with the ppl they are researching. Its refreshing not to feel like only a rat in laboratory haha.

My name is Christopher Rudolph, im from germany ( english is not my native language so please overlook possible grammar mistakes haha ) and a doctor myself. I got CFS after an infection with the legionnaires disease in 2014. After i saw the OMF speak from you Dr. Phair i was very interested in the whole idea about a trap keeping us down, but something bothers me since then. Maybe the trap isnt just keeping itself up with the bistability rather the immune system does it. I found a bunch of studies saying that ß2 adrenergic autoantibodies , which a lot of ppl with CFS/ME seem to have, put fuel to the problem. They elevate the brain tryptophan. So autoantibodies elevate the tryptophan, which on the other side elevate the autoantibodies.

https://www.researchgate.net/public...renergic_receptors_increases_brain_tryptophan

Besides Carmen Scheibenbogen another researcher in Germany named Gerd Wallukat is working with g-coupled autoantibodies and identifies these AABs with a very sensitive Bioessay. First he found this AAB in Chagas especially Beta 1 adrenergic, m2 muscarinergic and in a group also Beta2.
(The wallukat study in Chagas and the evidence of aabs https://www.ncbi.nlm.nih.gov/m/pubmed/20117461/ )

Chagas is a Trypanosome triggered disease. Whats interresting about this is that Ron just said in his IIMEC speech that CFS looks like a trypanosome infection.
Now the clue: Wallukat researched a group of dysautonomia patients ( a lot of them have cfs Symptoms ) with ß2 and M2. Wallukat found this pattern in over 80% , Scheibenbogen in 40% with the unsensitive elisa test.


Wallukat develops with the Enterprise Berlin CURES an aptamer (called BC007). In cardiomyopathy, where beta 1 adrenergic autoantibodies are dominant, he tested the aptamer with great success. Now Berlin CURES planning to test the aptamer also in CFS.

Here the link to the aptamer BC007 (in english) -> https://berlincures.de/pipeline/

Full of greatness and thanks for your hard work- keep going !

Cheers

Christopher
:
 

nerd

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I also have high levels of legionella in the water. Is this a thing for CFS/ME or just a coincidence?

It's a pity we barely have any data on the CSF. This is where we would have to look for viral residues and parasites.

Why has nothing happened to the trypanosomes theory since then? Or has it? Even a single confirmation in the CSF of any kind of trypanosome would be progress. Is it possibly another parasite and the sequencing results are just confounded by the CFS/ME pathology, which is similar to the sleeping sickness pathology?

None of the effective treatment options for sleeping sickness seem to be a possibility in the western world. Fexinidazole is available in the Democratic Republic of the Congo. Although it was approved by the EMA, it's only applicable to countries outside the EU. What a hybris... this reminds me of Ivermectin. It's ok when poor countries take it for decades, but as soon as Europeans are supposed to take it, we'll discredit its safety profile. Next, Suramin seems to be effective in the blood, but not in the CSF, and it's also toxic. It would be helpful to understand Suramin's mechanism of action.

One theory is that it's just the G6PD inhibition that helps (10.1111/j.1432-1033.1996.0592h.x). In this case, fava beans could have therapeutic effects. But it's unclear if it can cross the BBB and it's very harmful for people with G6PD deficiency.

The disruption of glycolysis is also a speculated mechanism of action because trypanosomes depend on high amounts of glucose. Consistently, hypoglycemia has shown a mild therapeutic effect (10.3390/tropicalmed5010014). The insulin analog synthalin showed promising efficacy. The keto diet could help reduce the elevated glycolytic activity in CFS/ME patients and the energy supply of the parasite all along, but not eliminate the problem. The brain still relies on certain amounts of glucose for its function. But after a long period of keto diet, when the brain adapted to BHB as a fuel source, hypoglycemia might not be as harmful anymore.

Suramin also inhibits thymidine kinase, which is a target for many herpes virostatics (diva2:1071945). Adenosine kinase would be the other target identified by the same researcher. Within this model, he found
Smyrnium olusatrum (aka Alexanders) and its active compound isofuranodiene to show efficacy. But it's unclear to me how much of the fruits or plants you would have to eat to reach the IC50. I don't think it can cross the BBB anyway. A microfluidic encapsulation could circumvent this.

Suramin also interacts with P2X7, a driver of autism and Alzheimer's disease. Kudzu and its active compound puarine also downregulate P2X7 and its pain induction (10.1016/j.burns.2012.08.013). But I don't think that P2X7 is part of trypanosome pathology. It's probably just a coincidence because Suramin interacts with many enzymes. It's still worth a shot though.

What about natural sources of Suramin? Suramin is a colorless version of Trypan Blue. This is synthesized from Toluidine. This is found in pine oil, where it has been originally found. However, it's unlikely that pine oil contains sufficient amounts of it. Trypan Blue probably is as toxic or even more toxic than Suramin. This is why Suramin normally is given as a slow infusion. Either way, it can not cross the BBB.

I already mentioned Ivermectin (pmid: 23135008), but it won't work against the chronic type in the CNS due to its limited BBB permeability.

Another option might be Quercetin (10.1128/AAC.48.3.924-929.2004; 10.1016/j.exppara.2010.10.011; 10.1021/acsomega.0c01818). It has a good safety profile and could be taken long-term. It can cross the BBB (10.1155/2016/2986796), though liposomal delivery could even improve this further.

Another idea is the support of the immune innate system that the trypanosomes evade. But I leave this for another time.
 
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dylemmaz

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Why has nothing happened to the trypanosomes theory since then? Or has it? Even a single confirmation in the CSF of any kind of trypanosome would be progress. Is it possibly another parasite and the sequencing results are just confounded by the CFS/ME pathology, which is similar to the sleeping sickness pathology?
in the video mentioned ron said he was working on dna probes for all known trypanosomes and parasites. he’s also been working with quest and labcorp to get some testing for cfs patients, so it’s very possible the testing he has been working on developing relates to the parasite/trypanosome route of illness. i can’t imagine it’s a theory he would drop, given the genetic similarities between cfs and trypanosome induced illness that he mentioned. plus suramin being successful with the salt stress device and returning sick cfs cells to “health.”
 

nerd

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But when I did some calculations to determine quercetin's in vivo antiviral effects on various viruses (those calculations based on data from in vitro antiviral studies on quercetin), the calculations indicated that quercetin has zero antiviral effects in vivo for those viruses (namely the viruses CMV, VZV, CVA16).
@Hip Do you have any opinion on Quercetin as antiparasitics? Microfluidic delivery could increase the cellular uptake and reduce plasma interactions. But it might still be insufficient, just like many natural supplements. What in vivo concentration did you calculate to be achievable by the recommended oral dose?
 
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I also have high levels of legionella in the water. Is this a thing for CFS/ME or just a coincidence?

It's a pity we barely have any data on the CSF. This is where we would have to look for viral residues and parasites.

Why has nothing happened to the trypanosomes theory since then? Or has it? Even a single confirmation in the CSF of any kind of trypanosome would be progress. Is it possibly another parasite and the sequencing results are just confounded by the CFS/ME pathology, which is similar to the sleeping sickness pathology?

None of the effective treatment options for sleeping sickness seem to be a possibility in the western world. Fexinidazole is available in the Democratic Republic of the Congo. Although it was approved by the EMA, it's only applicable to countries outside the EU. What a hybris... this reminds me of Ivermectin. It's ok when poor countries take it for decades, but as soon as Europeans are supposed to take it, we'll discredit its safety profile. Next, Suramin seems to be effective in the blood, but not in the CSF, and it's also toxic. It would be helpful to understand Suramin's mechanism of action.

One theory is that it's just the G6PD inhibition that helps (10.1111/j.1432-1033.1996.0592h.x). In this case, fava beans could have therapeutic effects. But it's unclear if it can cross the BBB and it's very harmful for people with G6PD deficiency.

The disruption of glycolysis is also a speculated mechanism of action because trypanosomes depend on high amounts of glucose. Consistently, hypoglycemia has shown a mild therapeutic effect (10.3390/tropicalmed5010014). The insulin analog synthalin showed promising efficacy. The keto diet could help reduce the elevated glycolytic activity in CFS/ME patients and the energy supply of the parasite all along, but not eliminate the problem. The brain still relies on certain amounts of glucose for its function. But after a long period of keto diet, when the brain adapted to BHB as a fuel source, hypoglycemia might not be as harmful anymore.

Suramin also inhibits thymidine kinase, which is a target for many herpes virostatics (diva2:1071945). Adenosine kinase would be the other target identified by the same researcher. Within this model, he found
Smyrnium olusatrum (aka Alexanders) and its active compound isofuranodiene to show efficacy. But it's unclear to me how much of the fruits or plants you would have to eat to reach the IC50. I don't think it can cross the BBB anyway. A microfluidic encapsulation could circumvent this.

Suramin also interacts with P2X7, a driver of autism and Alzheimer's disease. Kudzu and its active compound puarine also downregulate P2X7 and its pain induction (10.1016/j.burns.2012.08.013). But I don't think that P2X7 is part of trypanosome pathology. It's probably just a coincidence because Suramin interacts with many enzymes. It's still worth a shot though.

What about natural sources of Suramin? Suramin is a colorless version of Trypan Blue. This is synthesized from Toluidine. This is found in pine oil, where it has been originally found. However, it's unlikely that pine oil contains sufficient amounts of it. Trypan Blue probably is as toxic or even more toxic than Suramin. This is why Suramin normally is given as a slow infusion. Either way, it can not cross the BBB.

I already mentioned Ivermectin (pmid: 23135008), but it won't work against the chronic type in the CNS due to its limited BBB permeability.

Another option might be Quercetin (10.1128/AAC.48.3.924-929.2004; 10.1016/j.exppara.2010.10.011; 10.1021/acsomega.0c01818). It has a good safety profile and could be taken long-term. It can cross the BBB (10.1155/2016/2986796), though liposomal delivery could even improve this further.

Another idea is the support of the immune innate system that the trypanosomes evade. But I leave this for another time.
Setting aside the practical challenges of obtaining the drugs for a moment, how strong would the rationale be - in your view - for trialling the most effective known treatment options for sleeping sickness - i.e. Fexinidazole or Suramin - on ME/CF patients (obviously in a safe, controlled setting under appropriate supervision)? Basically, I'm interested to understand the theory of action better under the trypanosomes hypothesis that Ron Davis mentions. Also, to your knowledge, has any ME/CFS patient anywhere yet tried these treatments? Thanks in advance for any thoughts on this.
 

nerd

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Setting aside the practical challenges of obtaining the drugs for a moment, how strong would the rationale be - in your view - for trialling the most effective known treatment options for sleeping sickness - i.e. Fexinidazole or Suramin - on ME/CF patients (obviously in a safe, controlled setting under appropriate supervision)?
I think that a Fexinidazole trial could be justified because it's not as risky as Suramin and also an oral medication for poor countries, so no money-grabbing is involved that reserves the medication to a few in the end. From my perspective, every trial is justified when the risk-benefit ratio of the treatment outweighs the damage of a disease for which there is no recommended treatment at all.

Basically, I'm interested to understand the theory of action better under the trypanosomes hypothesis that Ron Davis mentions.
What do you mean by theory of action?

Also, to your knowledge, has any ME/CFS patient anywhere yet tried these treatments?
Not to my knowledge, but I'm not the best-informed when it comes to small trials and case studies. There are so many. Every naturopath thinks that their vitamin injection can cure CFS/ME. Oftentimes, they are not controlled studies, so might just be placebo effects.
 
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It seems like as good a thing to try as any.

Have there really not been any studies looking for pathogens in the CSF?

If not, what would it cost? We should raise money to fund one.
 

nerd

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Have there really not been any studies looking for pathogens in the CSF?
Not all negative study results are published, unfortunately. It's a bad scientific practice, but they sometimes still don't publish because it takes time to get it written, peer-reviewed, and published. It's possible that some researchers checked it but never published their results.

Lyme borreliosis is a disease that originally was only recognized in the blood, but over time, they developed very sensitive and specific tests for the CSF.

If not, what would it cost? We should raise money to fund one.
1000-2000 USD. But I think this should be done as part of a proper study. There are many open questions when it comes to the CSF of CFS/ME patients. They should check for many things, e.g. for BH4/BH2 levels, neurotransmitters, viral proteins, cytokines, lymphocyte profile, inflammation.