Ceftriaxone Pulse Dosing Fails to Eradicate Biofilm-Like Bb Persisters

Topics with information and discussion about published studies related to Lyme disease and other tick-borne diseases.
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Henry
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Re: Ceftriaxone Pulse Dosing Fails to Eradicate Biofilm-Like Bb Persisters

Post by Henry » Tue 6 Dec 2016 15:42

Duncan: I have tried my best to present an alternative explanation for the presence of background antibodies vs Borrelia in patients that have been correctly diagnosed and treated for Lyme disease, one that is not based on a persistent active infection. Unfortunately, you are unwilling to abandon the need for extended antibiotic therapy to eliminate "persisters" for which there is no clinical evidence, and continue hope that new methods will reveal their presence and prove that you are correct in your assumptions. But that's OK. This is a still a free country -- even after the election of Trump-- and one is entitled to their beliefs. However, there is good experimental data to support the fact that: (a) Borrelia posses at least 20 different kinds of integrins/adhesins on their surface that enable them to attach very tenaciously to mammalian tissues' and, that (b) such material is pharmacologicaly active and capable to stimulating the production of inflammatory cytokines in situ as well as stimulating the host's immune system to make antibodies.

In time, this "cell debris" or "stuff" will disappear or at least achieve levels where its effects are not significant. A study by Alan Steere indicates that in the case of antibiotic refractory Lyme-induced arthritis, there is a progressive -- almost linear-- decrease in arthritic episodes with time after initial treatment until there are no further episodes after 9 years -- in the absence of additional antibiotic treatment. So, the use of more or different antibiotics over longer periods of time is not going to makes this "stuff" disappear faster. What is now needed is to identify the key cytokines involved -- which investigators like Linda Bockenstedt and others are now doing, and then to enlist the assistance of good research pharmacologists to develop appropriate and safe ways to neutralize their effects. How long will it take for this "stuff" to disappear? I don't know, except to say that the antibiotic regimen recommended by the IDSA is effective in eliminating active infection; however, the longer one is infected before antibiotic therapy is commenced, the more "stuff" will accumulate in the tissues .... It is a well established fact that symptoms often persists for a long while after the infection has been cured by antibiotic therapy. So, although all is not lost if treatment is not commenced immediately after infection, knowing what we know about Lyme disease it is always best to begin treatment as soon as a valid diagnosis is made -- to avoid the accumulation of more of this "stuff".

duncan
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Re: Ceftriaxone Pulse Dosing Fails to Eradicate Biofilm-Like Bb Persisters

Post by duncan » Tue 6 Dec 2016 18:01

Too narrow. We are dealing with systemic issues in too many sufferers. Persistent infection fits better.

dlf
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Re: Ceftriaxone Pulse Dosing Fails to Eradicate Biofilm-Like Bb Persisters

Post by dlf » Tue 6 Dec 2016 18:42

@ duncan.......These two things are not mutually exclusive and in fact are most likely interconnected. Read to the bottom to see why I think that could be the case.

Henry wrote:
dlf: In other words, if other possible causes for the symptoms have been examined and ruled out, it must be Lyme disease. What else could it be? I know it when I see it.
Henry, I am not sure why you wrote this rather sarcastic and overly generalized statement. This diversion in the discussion thread was about duncan's case, his tick exposure history, his test results, his signs and symptoms and his medical history. As you suggested, this would require a physician to make a clinical judgement. However, given that in duncan's case all those things do point to Lyme, it should be hoped that any rational diagnostic decision would be based on the patient's individual personal case and not on a prior bias generated by dogma and reinforced by a quick read of the guidelines simply because the patient had some prior treatment.

Henry wrote:
Tell me, if it is so important to use ligands from strain 297 in diagnostic tests, why does IGenex not find new/extra bands in their WBs? Instead, they find the samebands that are revealed using B31 ligands. So what's the advantage? The main difference between their tests and those conducted by other labs is the liberal criteria they use. It requires the presence of fewer bands than those recommended by the CDC. Of course that will result is a higher percentage of positive tests ; however, such results are falsely positive. Except for a note published in a trade newsletter, they have no peer-reviewed comparative data to justify/validate their criteria, or the use of strain 297 ligands.


Henry, this could be a topic for another thread, which I think we may have already discussed at some length elsewhere on this forum. In this discussion it would only be another diversion. I only mentioned strain 297 in the context of this discussion and your assertion that neuroborreliosis is relatively infrequent in the U.S. where Borrelia burgdorferi is the predominant species. While it is true that Borrelia garinii is the most neurotropic species, if we are not identifying patients infected with Bb strain 297 which was isolated from human CSF (OspC type K) because two-tier serology using B31 strain is not particularly reliable for detecting it, then we are seriously underestimating the numbers of patients in North America who have neurological manifestations of Lyme.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2773679/

Henry wrote:
For your information, extensive and very sophisticated studies have been done to acquire evidence of a persistent infection in patients who believe that they have chronic Lyme disease.


By now I think we all know that trying to culture spirochetes after antibiotic treatment using the same old methods and BSK medium just won't be a useful exercise. Not being able to culture them this way proves nothing. Some species of spirochetes have never been successfully cultured. So, aside from attempts to culture spirochetes after they have had their transcriptomes altered by antibiotics, PCR (which you would be quick to tell us all proves nothing since that could be simply dead DNA remnants) and (of course) the xenodiagnosis study which has already been discussed at length, could you please provide reference citations for any other of these very sophisticated studies that you claim have been done looking for evidence of persistent infection in patients?

Henry wrote:
Since the symptoms of patients who believe they have chronic Lyme disease do not necessarily have the same cause or causes, the search for a single "cure" is likely to be as productive as trying to fit all of them with the same pair of shoes of the same size. The only ones who will benefit from such a process are the "quacks" who peddle their unproven remedies to those foolish enough to trust them. And THAT'S the real shame of it all.
Finally, you have written something we can sort of agree on. Although Lyme patients all start with a Borrelia burgdorferi sensu lato infection (by definition) not all borreliosis infections are the same, not all patients are the same and not all of them are diagnosed in a timely manner which can lead to poorer outcomes from currently recommended treatment.

Henry, patients say very similar things about the IDSA treatment protocol for Lyme as you have written about treatment for patients who believe they have"chronic Lyme". The one size fits all strategy has been amply demonstrated to not be effectively curative for all patients. I think that the real shame of it is, that after the IDSA recommended treatment has been provided and it has not been efficacious that the doctors abandon their patients and tell them that there is nothing more to be done except to learn to accept and live with the consequences along with maybe some CBT and/or GET or possibly DMARDS and synovectomy if one happens to have arthritis.

Do you really not understand that it is the IDSA policies and recommendations that destroy patients hopes for a decent quality of life and THAT is ultimately what drives them to seek out quack remedies?

Henry wrote:
Incidentally, my comments re: research experience were directed to dlf in response to her "snotty" remarks that clearly were in bad taste. Any one who does not know about the reciprocal expression of OspA and OspC in vivo doesn't know much about Lyme disease and shouldn't be writing about it -- or criticizing the good work of others.
Henry, I think I need to make it perfectly clear that I have the utmost respect for a great many researchers doing original scientific studies, including (but not limited to) the ones involved in this article that this forum thread is about. What I object to are researchers who undertake reviews and cherry pick the studies they include in order to push a particular bias as well as those that ignore significant data in studies and draw unsupported conclusions. My particular pet peeve is "research" and "opinion articles" that express a high level of dogma and those that appear to be designed to enforce the status quo and stifle any new or conflicting hypotheses.

As to your remark about me not knowing about "the reciprocal expression of OspA and OspC in vivo"........who the heck are you confusing me with???

You have no idea what my thoughts about this might be. I presume you are referring to something you think I wrote, but if you are referring to the thread about the Ceres nanotrap and that company's analysis and utilization of Osp A, I DID NOT WRITE OR POST ANY CONTRIBUTIONS TO THAT DISCUSSION. I was otherwise occupied at the time and barely even looked at it. If you do not believe me, I post as dlf. Here is the thread, check all 14 pages for yourself.

Anyone know the latest on the Ceres Nanotrap
http://www.lymeneteurope.org/forum/view ... f=6&t=5829

Back on page 5 of this discussion thread Henry wrote:
Although the IDSA guidelines are now being revised, as they frequently are to include the results of recent clinical and basic research, I seriously doubt whether substantial changes will be made in what has already been published. So, don't raise your hopes that there will be a major reversal in any of the recommendations made.
Henry, your most recent posts emphasizing the relatively newer research into the immunological aspects of Lyme, particularly the stimulation of cytokines both for diagnostics and to help explain ongoing symptoms (in some people) gives me hope that the statement you made above will prove to be wrong. This admission that there are immunological aspects to having a Lyme infection could be the paradigm shift the world needs to move forward, do additional research and acknowledge the problems that at least some patients face who do not get better with a few weeks of antibiotics. Past incarnations of the IDSA guidelines have avoided this topic and suggested that remaining symptoms and sequelae are simply the "aches and pains of everyday life". Having the IDSA finally accept that there are immunological repercussions that result from Lyme and finally examine and research the range of those effects would be a huge change.

As noted in the quote below from Immunobiology, 5th edition,The Immune System in Health and Disease, Charles A Janeway, Jr, Paul Travers, Mark Walport, and Mark J Shlomchik:
Humoral immunity refers to antibody production and the accessory processes that accompany it, including: Th2 activation and cytokine production, germinal center formation and isotype switching, affinity maturation and memory cell generation. It also refers to the effector functions of antibodies, which include pathogen and toxin neutralization, classical complement activation, and opsonin promotion of phagocytosis and pathogen elimination.
What we need to understand is whether aberrant immunological triggering of cytokines additionally over time causes an evolving broader dysfunctioning of the humoral immune system including class switching problems and eventually aspects of immunocompromise (at least for some patients). Since I developed hypogammaglobulinemia after I was infected but before I was diagnosed and treated and I know of several others who post on this forum who have varying degrees of immune dysfunction and compromise, the question I would like an answer for is; when a patient's immune system becomes dysregulated and/or immune-compromised does that not make pathogen killing and clearance a less sure thing (i.e. leading to pathogen persistence)?

Henry
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Re: Ceftriaxone Pulse Dosing Fails to Eradicate Biofilm-Like Bb Persisters

Post by Henry » Tue 6 Dec 2016 18:43

Suit yourself...........

Henry
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Re: Ceftriaxone Pulse Dosing Fails to Eradicate Biofilm-Like Bb Persisters

Post by Henry » Wed 7 Dec 2016 1:44

Duncan: One last word on this topic. If what I said is correct -- and I'd bet the bank that it is -- the controversy of chronic Lyme disease is "toast" and the solution is at hand. It's over.

Henry
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Re: Ceftriaxone Pulse Dosing Fails to Eradicate Biofilm-Like Bb Persisters

Post by Henry » Wed 7 Dec 2016 14:18

Duncan: And one last point, lest you think I am ignoring the plight of the many sufferers with chronic Lyme disease. What I propose would help more of them than you could possibly imagine. Think about that. Why once the relevant cytokines are identified, drug design technology would enable a skilled pharmacologist to develop a safe and drug to neutralize their effects.

duncan
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Re: Ceftriaxone Pulse Dosing Fails to Eradicate Biofilm-Like Bb Persisters

Post by duncan » Wed 7 Dec 2016 20:36

It is a good thought, Henry, and I am heartened and encouraged that you speak to the sufferers and their plight, and that you offer hope.

I suspect, as dlf alluded to, there is a component of immune dysfunction at play. I also suspect there is a subset of the Lyme population who will directly benefit from such developments as you've touched upon.

I am still keen on the role of persistent infection, but I wish to set that aside for a moment. What we are speaking to are downstream effects. I think it not reckless to extrapolate from Steer and Bockenstedt's work to suggest a system-wide immune malfunction - a corruption of the immune faculty, if you will, brought about or triggered by Borrelia. The interesting thing is that perhaps we can capture this with cytokine studies (Lipkin et al), or biometrecs (Naviaux et al). I think Aucott is leaning this way, no? It's fascinating stuff, and if we can corral what's going on, maybe we can devise diagnostics that demonstrate the malfunction, and even its scope. And then, as you propose, devise new treatment protocols with the help of pharma, perhaps some sort of immune modulators like Plaquenil or whatever.

There is merit to the broken immune system hypthesis. I just think persistent infection will prove to be the culprit. I would not mind being proven wrong if it helps us all.

A point of concern, though, is that IF we tinker with the immune system, and infection lingers, the ramifications could be bad. We need to get this right.

Henry
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Re: Ceftriaxone Pulse Dosing Fails to Eradicate Biofilm-Like Bb Persisters

Post by Henry » Wed 7 Dec 2016 21:48

There are many interesting studies in progress, Duncan. We will have to see what the future brings when all the results are in.

dlf
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Re: Ceftriaxone Pulse Dosing Fails to Eradicate Biofilm-Like Bb Persisters

Post by dlf » Thu 8 Dec 2016 6:28

Henry, I posted a response to some of your earlier comments to me, (along with a few questions), which I think you must have missed. It appears that we cross-posted contributions to this discussion - given that your post was exactly one second after mine. IF you did truly write "suit yourself....." in response to me, you deserve to be awarded the land speed record for reading and posting a reply.

This is what I wrote on Tue 6 Dec 2016 18:42:

http://www.lymeneteurope.org/forum/view ... =60#p44713

Henry
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Re: Ceftriaxone Pulse Dosing Fails to Eradicate Biofilm-Like Bb Persisters

Post by Henry » Thu 8 Dec 2016 15:04

dlf: No comment.

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