Dr Markov CBIS Theory of ME/CFS - General Discussion

[Garz]

i wore a mask to do gardening, then couldnt breath anymore. Now i’m fucked.

Wow, sorry to hear that Ben - its crazy how everyday things with these illnesses can absolutely floor us.

 

[Hip]

if the vaccines are not a valid option right now / for the foreseeable future- is it worth resurrecting some of the other ideas that address the same root cause eg

• the anti-biofilm protocols along with anti-microbials - to break up the biofilms and treat the bacteria that form them( other biofilm infections have been successfully treated like this )
• the auto-vaccine approach - eg mucosal - via killed culture of bacteria from the urine - perhaps with mmune activators as hip was looking into

In addition to biofilms, bacteria which switch to their L-form would appear to be involved in recurrent urinary tract infections, so a kidney L-form dysbiosis could be involved in ME/CFS too.

Bacteria can switch to L-form at any time. L-form bacteria lack a cell wall, and thus can hide inside human cells (where they are safe from most antibiotics).

Some years back when I was reading research by Dr Gerald J. Domingue on chronic/recurrent UTIs, he said that L-forms made these infections resistant to antibiotic treatment. He recommended antibiotics to target the L-forms, such as erythromycin.

This paper found that L-form bacteria were found in the urine of almost all elderly patients with recurrent UTIs. And they demonstrated that when when E. coli from patient urine samples were challenged with antibiotic that target the bacterial cell wall, the bacteria rapidly switch to their L-form morphology.


Prof Trevor Marshall of course has long posited that ME/CFS is due to L-form bacteria, and his Marshall Protocol (MP) is designed to kill these bacteria. But like the Markov Protocol, the Marshall Protocol takes a few years before benefits manifest.

The MP is based on switch on the vitamin D receptor (VDR) inside cells, which activates the cell's internal immune system, which in turn kills the L-form bacteria living in the cell.

 

[Atlas]

@bensmith I am starting this treatment soon... although the clinic is currently suggesting the photo method of identification because of logistics, I insisted that I wanted to attempt sending the dipslides anyway. I took photos first in case they didn't make it.

I was unable to find a courier provider but my national premium economy post service still is going to Ukraine, via Poland. Although it does not offer the same protection as courier, I was careful to follow all the Cat B packing instructions, and the package has still made it to Ukraine. If it hadn't gotten stuck in Kiev customs for a very long time it would have made it in about 9 days.

According to Dr. Oleg and Markov, the bacteria on dipslides can survive fine for 2-3 weeks at room temperature. There was a 2 week delay in customs for my package, so it has now been slightly over 3 weeks, but I am praying that the bacteria are still alive and well.

All this to say that if you can find any postal provider to send it, even by standard post, there is still a chance for it to make it — since I noticed you are reluctant to go the photos route.

.........

P.S. Actually I did find an operating courier, "World Courier", that is still operating to Ukraine. They specialize in sending medical samples and even do temperature control, but they only provide services to businesses and researcher groups, and I was unable to find anyone with a business account who could send on my behalf.

 

[bensmith]

@Atlas wow great thank you so much, i will def start the process! I need more
Meds so bad! Woo!

 

[Atlas]

@bensmith All the best!

i wore a mask to gadren though, havent been able to breath since august 4. So basically back down to beint very ill.

Btw, if that's the first time you've had breathing trouble... Are you sure you don't have pneumonia/Legionnaires' disease?

Just that I remember my uncle got Legionellosis once after gardening, it is sometimes caught from handling potting mix or breathing in soil dust, and definitely causes breathing trouble, although I think it also usually causes fever and other things.

 

[Garz]

This paper found that L-form bacteria were found in the urine of almost all elderly patients with recurrent UTIs. And they demonstrated that when when E. coli from patient urine samples were challenged with antibiotic that target the bacterial cell wall, the bacteria rapidly switch to their L-form morphology.

Yes, bacterial "L-forms" are a thing - as are "Persister cells" - i would say both of these bacterial behaviours are associated with and best understood as just a part of the wider pleomorphic diversification that occurs when many bacterial species transition from the more familiar planktonic fast replicating mode, to established slow growing biofilm communities - driven by the epigenetic changes in response to signals in their environment.

chronic UTI's have recently (in the last 2 years i think) been demonstrated to be caused by biofilm forming infections.

i think the picture that is emerging is that, in many common species of bacteria. this is part of a diverse spectrum of possible forms and corresponding gene expression - which reaches maximum diversity within biofilms where individuals cells roles are quite varied, some are specialised towards adhesion, some are structural, some are involved in circulation, some more in signalling, and all existing within an extra cellular matrix or goo which makes it very difficult indeed to determine where one cell starts and another stops.

this paper may be of interest to you - in terms of helping understanding of how biofilm communities in the body, like the one proposed by Markov in the kidney, suppress various arms of the immune response - allowing them to persist in chronic form - and perhaps inform strategies for improving immune response.

https://molmed.biomedcentral.com/articles/10.1186/s10020-022-00435-2#Tab1

its intriguing how the vaccines discussed here may be doing this - as in general white blood cells have little impact on bacterial biofilms - and are kind of locked in a stalemate with the bacterial biofilm community - neither making much progress - the WBC's trying to erode only the outer layers of the biofilm with their enzymes (as they cannot access the insides), and meanwhile the biofilm deactivating WBC on contact, triggering them to apoptosis and even using their constituents to build more biofilm, its an arms race that has been running for millennia. so its not clear exactly how the vaccines are helping - even though empirically it looks like they are.

 

[Hip]

so its not clear exactly how the vaccines are helping - even though empirically it looks like they are.

It may be the vaccines help kill off the biofilm dysbiosis during a vulnerable spot in the biofilm lifecycle (that cycle detailed in this post), where part of the biofilm breaks off, and the bacteria inside revert to
free-floating bacteria (planktonic bacteria).

 

[Garz]

It may be the vaccines help kill off the biofilm dysbiosis during a vulnerable spot in the biofilm lifecycle (that cycle detailed in this post), where part of the biofilm breaks off, and the bacteria inside revert to
free-floating bacteria (planktonic bacteria).

its possible that the bits that break off are indeed more vulnerable - more surface area exposed to the immune system and if they can be surrounded by white blood cells then i could see that allowing the bit that breaks off to be fully broken down by the WBC - but the parent colony would then still be intact - and much larger - and still adhering to a surface and still doing its thing.......

the mechanisms by which vaccines act on biofilm forming infections are very mysterious to me

at a high level it seems straightforward - eg the very general statement "vaccines increase immune response" - but when you get into the nitty gritty at the cellular or molecular levels - and look at the actual tools we know about in the immune system's tool box - then its not at all clear which tools are being enhanced or how.

perhaps they are somehow switching back on exactly the immune responses the biofilms are switching off....?
( ie the ones the paper i posted above talks about )

 

[Garz]

i don't know if its the most comprehensive review available- but this paper has a visual representation of what neutrophils are doing at the biofilms surface



"Fig. 1. A depiction of some important interaction mechanisms between neutrophils and biofilms in the oral cavity. Microbial adhesion to tooth surfaces and to epithelial cells, the invasion of fibroblasts and recognition by innate immune cells lead to the release of different chemotactic factors, e.g. IL-8, whereas biofilms produce chemotactically active molecules [exemplified with N-acyl homoserine lactone (AHL) and N-formyl-MetLeuPhe (fMLF)] as well. Recognition of PAMPs and antigens by neutrophils is mediated by various receptors that bind to opsonized or unopsonized biofilm components (PRRpattern recognition receptor, FcgRimmunoglobulin G receptor, C3bRcomplement component 3b receptor). Biofilms, however, are able to shield themselves from being recognized by expressing certain exopolysaccharides (EPSs) or lipooligosaccharides (LOSs). Upon stimulation, neutrophils respond by NETosis (a), phagocytosis (b) or degranulation (c,d), although biofilms are often protected against phagocytosis and some microbes can render themselves unsusceptible to cationic AMPs by adding positive charge to their surfaces. Instead, several bacteria are able to invade neutrophils and survive intracellularly (d) or may influence gene expression (b). Adversely, NETs are thought to stabilize biofilm structures on the one hand, but are cleaved by bacterial nucleases on the other hand. Autoantibodies against NETs presumably promote inflammation, whereas NET clearance by other phagocytes could be facilitated at the same time. Neutrophil antimicrobial granule contents and ROS (blue and purple dots) frequently also lead to collagen degradation and subsequent host tissue injury, enhanced by microbial detergent molecules that rapidly lyse neutrophil membranes (a)."

note: the paper is discussing oral biofilms - but the processes are largely the same in other locations

https://www.tandfonline.com/doi/full/10.3402/jom.v6.26102?scroll=top&needAccess=true

 

[bensmith]

@Atlas no just cfs issues. “Normal” life with this bastard.

damn i thought world courier did normal people deliveries. Rip.

What country are you in, did you just send it via your countries post office.

 

[Atlas]

What country are you in, did you just send it via your countries post office.

New Zealand, yup just sent via local post office. They could not offer courier but could offer tracked premium economy. So like I said we were very careful to pack it securely and according to Cat B instructions, because economy post does not offer the same protection as courier. My post shop said: it might get stopped at any border.

Because Ukrposhta is one of the only providers still operating inside Ukraine, I think that other postal providers are handing over to them in neighboring countries before the border.

 

[Hip]

Because Ukrposhta is one of the only providers still operating inside Ukraine, I think that other postal providers are handing over to them in neighboring countries before the border.

I believe this is the usual process anyway, with the EMS international post system.

Local postal operators cooperate to send mail internationally, handing over the mail from one operator to another.

The EMS operator in NZ is New Zealand Post Limited, according to this list. In the US, the EMS operator is the United States Postal Service. In the UK it is Parcelforce. In the Ukraine, it is Ukrposhta.

 

[Atlas]

Ah yes, that must be it, useful to know... I did see that NZ Post was a provider of EMS but wasn't aware what EMS was because it is not marketed as that here.

 

[Garz]

possible crazy idea - but perhaps worth airing

logically;
since vaccines typically contain very tiny amounts of actual antigens
and
since there are enough microbes to grow colonies on dipsticks pretty reliably

is it a totally crazy idea to make a "vaccine" by simply deactivating any microbes in urine with heat - ie boiling (a method previously used in vaccine manufacture)

then perhaps taking as a oral mucosal vaccine - with some immune adjuncts as mentioned by Hip to enhance the immune response - to avoid potential risks from injection.

it might not have the ideal quantity of antigens - but it will have some - and they will be "tailored" to the patient they came from

the lower quantity could lead to a slower response - but my understanding is that patients have to go slow anyway to avoid adverse reactions

just thinking out load - as an idea for those that cannot access Dr Markov

 

[BrightCandle]

Making our own auto vaccines has been discussed, I posted a link to a paper many pages ago on it but it was from the early 1900s! There hasn't been much on making auto vaccines in western medicine in a long time. As a process we were discussing using the urine dipstick to capture, separating them out into agars to grow and then killing with heat in something like an oven at a relatively low temperature for an hour or so, washing off the contents into viles, testing the mixture to ensure nothing grows (very important) and then maybe injectioning it or under the tongue to be adsorbed.

Its kind of dangerous is the reason none of us has done it. Its also a bunch of work over a few days and highly likely to cause crashes but its the danger factor we need to ideally grow and kill each bacteria based on knowledge of the species but we can't identify them with out equipment and the chance of contamination on your kitchen table is relatively high. I don't think its worth it, the best option is to pay a professional to get this done and that is Dr Markov.

 

[Garz]

Making our own auto vaccines has been discussed, I posted a link to a paper many pages ago on it but it was from the early 1900s! There hasn't been much on making auto vaccines in western medicine in a long time. As a process we were discussing using the urine dipstick to capture, separating them out into agars to grow and then killing with heat in something like an oven at a relatively low temperature for an hour or so, washing off the contents into viles, testing the mixture to ensure nothing grows (very important) and then maybe injectioning it or under the tongue to be adsorbed.

Its kind of dangerous is the reason none of us has done it. Its also a bunch of work over a few days and highly likely to cause crashes but its the danger factor we need to ideally grow and kill each bacteria based on knowledge of the species but we can't identify them with out equipment and the chance of contamination on your kitchen table is relatively high. I don't think its worth it, the best option is to pay a professional to get this done and that is Dr Markov.

agreed - actually making an injectable vaccine is a lot of work - and injecting anything has risks associated

whereas collecting ones own urine - heating it briefly - allowing it to cool and drinking or swilling mouth with it would not be much effort - could be easily done by even a sick person every day

minimal effort - minimal cost -minimal risk - as people drink even untreated urine all the time - Gandhi famously did it every day

seems to be little to lose ....

(I'm think for the people who cannot access Markov - or cannot afford it - and the wider community could then learn if this Markov theory and vaccine approach does in fact have any legs in it - as that's currently very hard to do from the 2 or 3 people here currently doing it via his clinic)

 

[bensmith]

Not getting any bacteria growth on this round of dipslides. The slides are expired but a bit concerning. Maybe his last round wiped out bac.

also had no bacteria on 3 urine tests by doctor in town. But this could be because its not the same testing prodical.

thinking about getting some new dipslides.

pretty weird though.
Oh also havent been double and triple dipping.

 

[Cipher]

its intriguing how the vaccines discussed here may be doing this - as in general white blood cells have little impact on bacterial biofilms - and are kind of locked in a stalemate with the bacterial biofilm community - neither making much progress - the WBC's trying to erode only the outer layers of the biofilm with their enzymes (as they cannot access the insides), and meanwhile the biofilm deactivating WBC on contact, triggering them to apoptosis and even using their constituents to build more biofilm, its an arms race that has been running for millennia. so its not clear exactly how the vaccines are helping - even though empirically it looks like they are.

I think the vaccines' effectiveness is mostly mediated via antibody production:

Spoiler

How the innate and adaptive immune systems react to biofilms and what type of immune response is protective is still not well understood. Biofilm infections trigger an inflammatory response, as reflected by the infiltration and activation of phagocytes at the site of infection, and the release pro-inflammatory cytokines, promoting a Th1/Th17 response and the production of antibodies, predominantly of the human IgG1 subclass [34–36]. While neutrophils are capable of infiltrating the biofilm and efficiently phagocytose enclosed cells, this defense mechanism is less effective in mature biofilms [37]. This exemplifies the inefficiency of the induced host response in clearing a persistent biofilm infection [37,38].

Similarly, the protective potential of antibodies in biofilm infections is not well defined. S. aureus infection stimulates the production of specific antibodies against a broad range of surface and secreted staphylococcal proteins, but these generally do not prevent a re-infection with this notorious pathogen [39]. However, antibody profiling in sepsis patients at the time of diagnosis showed that high antibody titers might confer protection from an adverse outcome [40]. This implies that the immunological “starting position” is important for disease outcome, a fact that is encouraging for efforts in vaccine development. For biofilm infections, clinical data are scarce, but suggest that biofilms also trigger or boost an antibody response against a broad range of S. aureus antigens: adhesins and cell wall-modifying enzymes, biofilm matrix components, toxins and immune evasion factors (discussed in detail in Chapter 5) [41–43].

In line with these patient data, animal experiments indicate that boosting the antibody response by active or passive vaccination prevents or at least reduces the severity of biofilm-associated S. aureus infections [18,35,44]. For example, in a murine model of mesh-associated biofilm infection, a vaccination approach using biofilm matrix exoproteins significantly reduced the number of bacterial cells inside a biofilm and on the surrounding tissue [18]. Another multivalent S. aureus vaccine comprising four cell wall-associated proteins prevented the formation of biofilm-mediated osteomyelitis in the majority of the treated animals when combined with an antimicrobial therapy [44]. Hence, animal data suggest that antibodies can contribute to biofilm prevention and clearance.

Anti- S. aureus antibodies can penetrate the biofilm matrix [45,46], and interfere with all three stages of biofilm formation. Initial attachment can be prevented by targeting surface-bound or soluble adhesins (Figure 2). Biofilm maturation is disturbed by blocking surface proteins involved in cell-to-cell adhesion, and biofilm dispersal is enhanced by targeting matrix-stabilizing proteins. Moreover, high affinity IgA and IgG antibodies can neutralize secreted bacterial factors (e.g. toxins, enzymes, immune evasion molecules). Finally, surface-bound antibodies can enhance biofilm elimination by neutrophils and macrophages, either via antibody-binding Fc receptors or by inducing complement activation and C3b deposition on the bacterial surface (Figure 2) [18,47,48]. In conclusion, antibodies can potentially interfere with biofilm formation and/or promote dispersal of established biofilms by several mechanisms. However, since the natural antibody response in many cases seems to be insufficient to eliminate established biofilms, boosting the antibody response by active or passive vaccination seems a promising approach to reduce the severity of biofilm-associated S. aureus infections.

source

whereas collecting ones own urine - heating it briefly - allowing it to cool and drinking or swilling mouth with it would not be much effort - could be easily done by even a sick person every day

The concentration of urinary bacteria in a typical CBIS patients is low and would therefore be ineffective at producing a strong immune response. Low dose antigen exposure could theoretically even result in immunotolerance, which is the opposite of immunostimulation. The bacteria needs to be enriched and concentrated in order to function as a vaccine.

One possible alternative to Dr. Markov's autovaccines is commercially available bacterial vaccines. There's also a list of other custom autovaccine producers at the bottom of the spreadsheet.

 

[Garz]

@ cipher - thanks for the article - that looks interesting - i will certainly read that

The concentration of urinary bacteria in a typical CBIS patients is low and would therefore be ineffective at producing a strong immune response. Low dose antigen exposure could theoretically even result in immunotolerance, which is the opposite of immunostimulation. The bacteria needs to be enriched and concentrated in order to function as a vaccine.

I'm not sure the published material on autovaccines supports those statements.

for example live blood taken from a vein is simply re-injected under the skin in sheep autovaccination and was proven effective in the studies discussed earlier in this thread. That would also have had v low counts of bacteria in it - or the animal would have been dead already from acute bacteraemia.

also, since the patients with CFS/ME are already exposed to antigens at some level from the biofilm colonies inside them ( if Markov is correct ) - adding more antigens - no matter if its a small amount more - is unlikely to cause immunotolerance as it will be moving in the other direction.

 

[Garz]

I think the vaccines' effectiveness is mostly mediated via antibody production:

Spoiler

source

OK - i read that paper -thanks for the link. - it was very much on target.

indeed most of the paper describes the so far unsuccessful attempt to produce monoclonal antibodies that work in real world trials - especially against established biofilm colonies - which are the ones we are interested in n the context of Markov's theory of CFS.

the paper explains some of the factors driving these difficulties
eg
considerable redundancy in many of the chemicals the bacterial use to stick to surfaces and form biofilm - so that making an antibody to one of these chemicals is not enough to stop formation of biofilm - as the organism has many more chemicals it can use for the same purpose instead.

most of these approaches were in any case more appropriate for passive vaccination - where you give the vaccine before the biofilm gets established - hoping to prevent it getting established should the person get an infection later

there were a couple of examples that gave a little more cause for optimism and shed some light on mechanisms that might be useful in vaccination against existing biofilm infections.

1- antibodies against pore forming toxins - these are chemicals made by the bacteria ( sometimes in higher concentrations when they are in biofilm state vs planktonic) - that destroy immune cells by punching holes in them - and thereby protect the biofilm from breakdown by the immune system. antibodies to these toxins effectively mop up the toxins before they can kill the immune cells - leading to better breakdown of the biofilm by phagocytosis ( being "eaten" by white blood cells)

2 - antibodies against structural proteins in the biofilm matrix - here it seemed to suggest that even in established biofilms these antibodies were small enough to penetrate into the biofilm colony - surround these proteins and somehow prevent them from doing their structural jobs - thereby actually helping to disperse the biofilm ( though not kill the bacteria )

this was both useful and interesting to me - that these two approaches at least, have the potential to help break down even existing biofilms - one by helping keep white blood cells alive in contact with the biofilm so they can gradually break it down - and the other by mechanically weakening its structure so it can be dispersed.

the authors do conclude by saying they think combinations of these approaches in multivalent vaccines and antibiotics may be needed to treat these infections.

perhaps Markov's autovaccines generate such a broad array of antibodies that they can achieve the above without antibiotics

thanks again for the link!