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Persistent Borrelia Infection in Patients with Ongoing Symptoms of Lyme Disease

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Posted 3/13/2018 11:54 AM (GMT 0)
Persistent Borrelia Infection in Patients with Ongoing Symptoms of Lyme Disease
Version 1 : Received: 7 March 2018 / Approved: 8 March 2018 / Online: 8 March 2018 (07:08:02 CET)


Introduction:

Lyme disease is a tickborne illness that generates controversy among medical providers and researchers. One of the key topics of debate is the existence of persistent infection with the Lyme spirochete, Borrelia burgdorferi, in patients who have been treated with recommended doses of antibiotics yet remain symptomatic. Persistent spirochetal infection despite antibiotic therapy has recently been demonstrated in non-human primates. We present evidence of persistent Borrelia infection despite antibiotic therapy in patients with ongoing Lyme disease symptoms.

Materials & Methods:

In this pilot study, culture of body fluids and tissues was performed in a randomly selected group of 12 patients with persistent Lyme disease symptoms who had been treated or who were being treated with antibiotics. Cultures were also performed on a group of 10 control subjects without Lyme disease. The cultures were subjected to corroborative microscopic, histopathological and molecular testing for Borrelia organisms in four independent laboratories in a blinded manner.

Results:

Motile spirochetes identified histopathologically as Borrelia were detected in culture specimens, and these spirochetes were genetically identified as Borrelia burgdorferi by three distinct polymerase chain reaction (PCR) methods. Spirochetes identified as Borrelia burgdorferi were cultured from the blood of seven subjects, from the genital secretions of ten subjects, and from a skin lesion of one subject. Cultures from control subjects without Lyme disease were negative for Borrelia using these methods.

Conclusions:

Using multiple corroborative detection methods, we showed that patients with persistent Lyme disease symptoms may have ongoing spirochetal infection despite antibiotic treatment, similar to findings in non-human primates. The optimal treatment for persistent Borrelia infection remains to be determined.

Middelveen, M.J.; Sapi, E.; Burke, J.; Filush, K.R.; Franco, A.; Fesler, M.C.; Stricker, R.B. Persistent Borrelia Infection in Patients with Ongoing Symptoms of Lyme Disease. Preprints 2018, 2018030062 (doi: 10.20944/preprints201803.0062.v1).

pre-print dx.doi.org/10.20944/preprints201803.0062.v1

Full article pre-print PDF format bit.ly/2FziZiI

Post Edited (mpost) : 3/13/2018 5:59:53 AM (GMT-6)

Posted 3/13/2018 1:02 PM (GMT 0)
Thanks for sharing.

How is your treatment going by the way? Last time I asked you seemed to have some progress
Posted 3/13/2018 1:11 PM (GMT 0)
What is preprints? Is this some kind of pre-publication that is in the process of review?
Posted 3/13/2018 1:31 PM (GMT 0)

Psilociraptor said...
What is preprints? Is this some kind of pre-publication that is in the process of review?

yes
Posted 3/13/2018 2:24 PM (GMT 0)

mpost said...

Psilociraptor said...
What is preprints? Is this some kind of pre-publication that is in the process of review?

yes

Cool, good to know. Can't wait for the final version of this to come out. How exciting. Looking forward to seeing McSweegans furious tweets.

One thing I don't like is the obfuscation of persister states. Listing "cyst" and "persister cell" seems redundant and confusing no? Aren't they one and the same for Borrelia? Or does borrelia actually have a type 1 dormant "cyst" and type 2 slow growing state? Also problematic is "cell wall deficient cysts (L-form)". Borrelia cysts (aka round bodies) have intact walls and are distinct from actively growing L-forms. Therefor their relevance to the pathogenesis and treatment outcomes is also distinct. As far as I can tell the only three consistent findings are spirochetes, dormant round bodies, and granular stages. Whether L-forms exist I think the responsible thing to do would be careful about keeping these distinct as much as possible since there are unique implications for all of them.
Posted 3/13/2018 2:44 PM (GMT 0)
eva sapi comes thru again

thanks for posting
Posted 3/13/2018 2:47 PM (GMT 0)

Psilociraptor said...

One thing I don't like is the obfuscation of persister states.

yes Psilociraptor i too think that listing of terminology is not useful. Especially that it was proven borrelia does not form structures that are traditionally identified as "cysts". This has been shown beyond any doubt by Leona Gilbert's team from Jyväskylä university, Finland, in 2015:

/www.ncbi.nlm.nih.gov/pmc/articles/PMC4339653/

...with some beautiful pictures done with the electron microscope, you can see the cysts are actually not cysts.

The author(s) write:

"Previously, the round bodies (RBs) of B. burgdorferi have been ambiguously named in various ways. These terms include CWD and L-forms, spheroplasts, protoplasts, propagules and even cysts (Domingue & Woody, 1997; Stricker & Johnson, 2011). Nonetheless, all of these labels describe the same spherical structures. This terminology is confusing and makes presumptions about the biochemical and morphological characteristics of B. burgdorferi RBs, such as a lack of cell wall (CWD, spheroplasts and protoplasts), or that these forms are encysted with a capsulated outer membrane (cysts). However, the cell envelope components and morphology of B. burgdorferi RBs have not been clearly studied before.
.....

Here we confirmed for the first time that RBs actually have an intact cell envelope with a peptidoglycan layer (Figs 5 and ​and7),7), indicating that they do not fulfil clearly the definitions of spheroplasts, CWD or encysted forms although there are some modifications in the cell envelope and cell wall architecture. Furthermore, the intact cell envelope of RBs (Fig. 5), similar to the spirochaete, provides evidence for the previous suggestion (Alban et al., 2000) that RBs are not degrading cells. To avoid confusing terminology, we suggest that B. burgdorferi spherical shapes are termed ‘round bodies’ to describe these forms better.
"

So yes you are right, Borrelia DOES NOT MAKE CYSTS. Let's call these round and dormant things "persisters" or round bodies. Sorry for the caps smile
Posted 3/13/2018 3:48 PM (GMT 0)

RedLabel said...
Thanks for sharing.

How is your treatment going by the way? Last time I asked you seemed to have some progress

treatment going well, getting close to 100%. i still take 3 antibiotics and my llmd extended treatment for 2 more months. lymespot test still shows active infection, although very low titres.
Posted 3/13/2018 5:19 PM (GMT 0)
Yeah, that was the study I was mostly basing my questions off of. Seems like it's pretty well established at this point that cyst and L-form are bad terminology. L-forms especially are known to multiply and divide which round bodies don't do. On the other hand this study shows L-form colony growth. Haven't gotten to the bottom of that one yet. If you know anything about it and how it connects to the typical round bodies I'd be interested to know. Haven't had as much time to read this stuff lately. https://www.ncbi.nlm.nih.gov/pubmed/8811359
Posted 3/13/2018 6:01 PM (GMT 0)

mpost said...

RedLabel said...
Thanks for sharing.

How is your treatment going by the way? Last time I asked you seemed to have some progress

treatment going well, getting close to 100%. i still take 3 antibiotics and my llmd extended treatment for 2 more months. lymespot test still shows active infection, although very low titres.

Lymespot meaning armin labs elispot?

Glad to hear you are doing well.
Posted 3/13/2018 6:16 PM (GMT 0)

k07 said...

Lymespot meaning armin labs elispot?
Glad to hear you are doing well.

yes, BCA lymespot. it's probably the same as armin's.
Posted 3/13/2018 6:26 PM (GMT 0)

mpost said...

RedLabel said...
Thanks for sharing.

How is your treatment going by the way? Last time I asked you seemed to have some progress

treatment going well, getting close to 100%. i still take 3 antibiotics and my llmd extended treatment for 2 more months. lymespot test still shows active infection, although very low titres.

Good to hear it! I'm taking 4 abx now and maybe had a little progress. What kind of doses are you on? I think I'll have to ask them to evaluate that
Posted 3/13/2018 7:33 PM (GMT 0)
What about hands falling asleep. Mine are constantly falling asleep. Mostly when I'm laying down
Posted 3/13/2018 10:23 PM (GMT 0)
I used to have major issues with whole limbs falling asleep. Since starting treatment the only thing that still falls asleep is half of my right hand. I never logged it as a Lyme symptom, but maybe it was.
Posted 3/14/2018 12:11 AM (GMT 0)

mpost said...

Psilociraptor said...

One thing I don't like is the obfuscation of persister states.

yes Psilociraptor i too think that listing of terminology is not useful. Especially that it was proven borrelia does not form structures that are traditionally identified as "cysts". This has been shown beyond any doubt by Leona Gilbert's team from Jyväskylä university, Finland, in 2015:

/www.ncbi.nlm.nih.gov/pmc/articles/PMC4339653/

...with some beautiful pictures done with the electron microscope, you can see the cysts are actually not cysts.

The author(s) write:

"Previously, the round bodies (RBs) of B. burgdorferi have been ambiguously named in various ways. These terms include CWD and L-forms, spheroplasts, protoplasts, propagules and even cysts (Domingue & Woody, 1997; Stricker & Johnson, 2011). Nonetheless, all of these labels describe the same spherical structures. This terminology is confusing and makes presumptions about the biochemical and morphological characteristics of B. burgdorferi RBs, such as a lack of cell wall (CWD, spheroplasts and protoplasts), or that these forms are encysted with a capsulated outer membrane (cysts). However, the cell envelope components and morphology of B. burgdorferi RBs have not been clearly studied before.
.....

Here we confirmed for the first time that RBs actually have an intact cell envelope with a peptidoglycan layer (Figs 5 and ​and7),7), indicating that they do not fulfil clearly the definitions of spheroplasts, CWD or encysted forms although there are some modifications in the cell envelope and cell wall architecture. Furthermore, the intact cell envelope of RBs (Fig. 5), similar to the spirochaete, provides evidence for the previous suggestion (Alban et al., 2000) that RBs are not degrading cells. To avoid confusing terminology, we suggest that B. burgdorferi spherical shapes are termed ‘round bodies’ to describe these forms better.
"

So yes you are right, Borrelia DOES NOT MAKE CYSTS. Let's call these round and dormant things "persisters" or round bodies. Sorry for the caps smile

Okay - I have wondered if persisters and “cysts” were one and the same.

So please clarify for me - there are spirochetes and persisters. What about biofilms? Are these clusters of spirochetes surrounded by a biofilm? What about the round bodies - are they included in the biofilm colonies?
Posted 3/14/2018 9:12 AM (GMT 0)

Girlie said...

So please clarify for me - there are spirochetes and persisters. What about biofilms? Are these clusters of spirochetes surrounded by a biofilm? What about the round bodies - are they included in the biofilm colonies?

"
Case 2. Blood culture was performed and fluid from the culture demonstrated spherical bodies
under darkfield microscopy. Dieterle staining and anti-Bb immunostains demonstrated
spherical bodies. Anti-Bb immunostaining was positive. Vaginal culture was performed and fluid
from the culture demonstrated spirochetes and biofilm under darkfield microscopy. Dieterle
staining and anti-Bb immunostaining demonstrated spirochetes and biofilm. Skin specimens
were not submitted for staining or culture. Repeat blood and vaginal cultures were positive for
Borrelia by immunostaining and PCR (see Tables 2-4). "


so yes, biofilm.

see page 37 of the pre-print pdf (last link in my first post) there is a nice table there and they put for each case what they found.

anyway, i know about this for a long time. after 3 months of antibiotics i re-tested my blood with dark field microscopy and i had live spirochetes and bartonella clearly visible and alive, this is while under antibiotics. i realized there is a big problem with this disease early on. But what can you do ...

So a few things that this article proves false
- chronic patients treated with abx only have few remaining spirochetes in their deep tissues but not in their blood - FALSE, they are in blood, too (at least for 7 out of 12 subjects) !
- chronic patients treated with abx only have debris of dead spirochetes but not live one - FALSE all cases have live culture-able spirochetes
- chronic patients treated with abx have some autoimmune process ongoing but the borrelia organism is long dead - FALSE, live spirochetes are present in all subjects treated with abx
- seminal fluids have few or no spirochetes - FALSE
- antibiotics may not kill spirochetes in vitro but in vivo things are different because the body also fights the infection and may get rid of it - FALSE, it's obvious the norm is the body CANNOT remove the bacteria, with or without antibiotics present months of antibiotics, combinations or not....

So all your worst nightmares are proven correct. I hope this article gets published and would like to know if we can do something to spread the word about it. It's an in vivo test on humans, this should matter somehow in the grand picture of things with this disease.

Post Edited (mpost) : 3/14/2018 3:15:53 AM (GMT-6)

Posted 3/14/2018 1:32 PM (GMT 0)
I haven't had time to read this carefully, but one thing I'm struggling with. What did they claim to do differently that allowed them to culture borrelia? This is widely known to be an insensitive method and if it were that simple this debate would have been over decades ago. Other authors who found borrelia post treatment could only get it to grow on MKP and at very low frequency and often wouldn't subculture. What did this team do different?
Posted 3/14/2018 2:27 PM (GMT 0)

Psilociraptor said...
I haven't had time to read this carefully, but one thing I'm struggling with. What did they claim to do differently that allowed them to culture borrelia? This is widely known to be an insensitive method and if it were that simple this debate would have been over decades ago. Other authors who found borrelia post treatment could only get it to grow on MKP and at very low frequency and often wouldn't subculture. What did this team do different?

That's a great question, although at this point I think there is enough evidence out there to support the idea that borrelia can persist despite antibiotic challenge. I'm not sure IDSA would even contend that now. The debate now is whether or not persistent infection=persistent symptoms. We are all infected with viruses/bacteria that are not part of our natural microbiome so how can we prove that symptoms are from borrelia? This will have to be the next step in research.
Posted 3/14/2018 2:58 PM (GMT 0)
The IDSAs position is absolutely moronic and in contradiction with the revised kochs postulates which state disease should correlate with with the presence of organismal DNA. Further more if one believes in the amber hypothesis in which spirochetal fragments contribute to PLDS then one must accept that viable metabolically active spirochetes = continued production and expression of spirochetal fragments = continued disease. That they tried to turn this around by claiming they are "attenuated" is absolutely ludicrous since lyme disease has always been an inflammatory disease and not an exotoxin producing organism and the IDSA incorporates this basic knowledge into their own vision of PLDS. for all their self declared "rigor" and "expertise" they really have a knack for pseudoscience and logical fallacy.

And I feel you might be optimistic. Look at Edward mcsweegans Twitter and wormser publications. There is no shortage of creative approaches they express to denigrating the work that shows persistent infection and they are quite apt to make off the cuff claims about non persistence supported with literally no evidence for "proof of cure". Fortunately many other scientists are climbing back on the fence and awaiting more research and these goons will be regarded as irrelevant once people realize what a circus act this has been
Posted 3/14/2018 9:33 PM (GMT 0)

Psilociraptor said...
I haven't had time to read this carefully, but one thing I'm struggling with. What did they claim to do differently that allowed them to culture borrelia? This is widely known to be an insensitive method and if it were that simple this debate would have been over decades ago. Other authors who found borrelia post treatment could only get it to grow on MKP and at very low frequency and often wouldn't subculture. What did this team do different?

see tables starting page 36. there are many tests, all confirming:
-DFM, dieterie, immunostain
- PCR of culture


the PCRs are done in 3 distinct labs all acredited.

so how cam all these tests be positive at same time and still we deny these people have live spirochetes in them? are we completely mad?
Posted 3/15/2018 1:39 PM (GMT 0)
I'm not denying I'm just trying to understand why they were able to culture it when others haven't been. Post treatment especially have been regarded as viable but non cultivable
Posted 3/15/2018 2:48 PM (GMT 0)

Psilociraptor said...
Post treatment especially have been regarded as viable but non cultivable

it's true, the general norm was if u were treated with abx, you could not culture anything. But PCR would always be positive because you know ... "debris" .... :P

i've no idea, we need to wait for final article to get published and see what else have they done. i will have some time today to read the matherials and methods section and see what was done differently, maybe they explain what.

Post Edited (mpost) : 3/15/2018 9:13:29 AM (GMT-6)

Posted 3/15/2018 3:36 PM (GMT 0)

mpost said...

Psilociraptor said...
Post treatment especially have been regarded as viable but non cultivable

it's true, the general norm was if u were treated with abx, you could not culture anything. But PCR would always be positive because you know ... "debris" .... :P

i've no idea, we need to wait for final article to get published and see what else have they done. i will have some time today to read the matherials and methods section and see what was done differently, maybe they explain what.

Yeah, hopefully i can squeeze in the time at some point. I'd like to make a couple comments on the points we discussed but I want to make sure I didn't just overlook them. This paper is very interesting for sure, but my feelings are that this first draft is a tad sloppy. I don't see any point in making easy targets for chronic Lyme deniers. Wormser has already attacked another paper for culture positive results that defied general findings and that paper clearly expressed the use of MKP medium over BSK as the defining factor of their success. Any contradictory results are going to have to go through great lengths to justify their approach and why it is better than past attempts.

I need to get a research job so I can keep up with this stuff on the clock lol.
Posted 4/17/2018 5:41 PM (GMT 0)
The draft study this thread was about has just been published !

www.mdpi.com/2227-9032/6/2/33/htm
Posted 4/29/2018 1:55 AM (GMT 0)
I wish they would give more information on the control subjects, and I wonder what consistencies in lifestyle one might see (besides the probable discrepancy in hiking/outdoors activities). There was a microscopist who saw round body forms in the blood of most people they tested (healthy and symptomatic), albeit more l forms and damaged cells in people with known LD.

If Borrelia is (theoretically) easily transmitted sexually, is present in temperate climates worldwide, and is often present in sufficient concentrations in the body to enter a fetus transplacentally, I wonder what proportion of people actually carry this bacteria. That said, I wonder if the number of different species/strains of Borrelia or other bacteria/nematodes/etc that outdoor inclined people are likely to pick up is sufficient to push sparse low grade chronic infections into full blown illness, and what the tipping point is.

I think that there needs to be very similar study on people who were treated very early with antibiotics, that would really change the way that people think about this bacteria.
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