The Long-Term Persistence of Borrelia burgdorferi Antigens and DNA in the Tissues of a Patient with Lyme Disease

[Dufresne]

The Long-Term Persistence of Borrelia burgdorferi Antigens and DNA in the Tissues of a Patient with Lyme Disease.

Sapi E1, Kasliwala RS2, Ismail H3, Torres JP4, Oldakowski M5, Markland S6, Gaur G7, Melillo A8, Eisendle K9, Liegner KB10,11,12, Libien J13, Goldman JE14.


Abstract
Whether Borrelia burgdorferi, the causative agent of Lyme disease, can persist for long periods in the human body has been a controversial question. The objective of this study was to see if we could find B. burgdorferi in a Lyme disease patient after a long clinical course and after long-term antibiotic treatment. Therefore, we investigated the potential presence of B. burgdorferi antigens and DNA in human autopsy tissues from a well-documented serum-, PCR-, and culture-positive Lyme disease patient, a 53-year-old female from northern Westchester County in the lower Hudson Valley Region of New York State, who had received extensive antibiotic treatments during extensive antibiotic treatments over the course of her 16-year-long illness. We also asked what form the organism might take, with special interest in the recently found antibiotic-resistant aggregate form, biofilm. We also examined the host tissues for the presence of inflammatory markers such as CD3+ T lymphocytes. Autopsy tissue sections of the brain, heart, kidney, and liver were analyzed by histological and immunohistochemical methods (IHC), confocal microscopy, fluorescent in situ hybridization (FISH), polymerase chain reaction (PCR), and whole-genome sequencing (WGS)/metagenomics. We found significant pathological changes, including borrelial spirochetal clusters, in all of the organs using IHC combined with confocal microscopy. The aggregates contained a well-established biofilm marker, alginate, on their surfaces, suggesting they are true biofilm. We found B. burgdorferi DNA by FISH, polymerase chain reaction (PCR), and an independent verification by WGS/metagenomics, which resulted in the detection of B. burgdorferi sensu stricto specific DNA sequences. IHC analyses showed significant numbers of infiltrating CD3+ T lymphocytes present next to B. burgdorferi biofilms. In summary, we provide several lines of evidence that suggest that B. burgdorferi can persist in the human body, not only in the spirochetal but also in the antibiotic-resistant biofilm form, even after long-term antibiotic treatment. The presence of infiltrating lymphocytes in the vicinity of B. burgdorferi biofilms suggests that the organism in biofilm form might trigger chronic inflammation.

KEYWORDS:
Borrelia burgdorferi; Lyme disease; antibiotic resistance; biofilms; persisters; spirochete
PMID: 31614557 DOI: 10.3390/antibiotics8040183

https://www.ncbi.nlm.nih.gov/pubmed/31614557

 

[Dufresne]

Come on, @barbc56, I've been waiting a long time for this... Explain to me how this is all pseudoscience.

 

[dyllanmurphy]

Come on, @barbc56, I've been waiting a long time for this... Explain to me how this is all pseudoscience.

Persistent Lyme as the cause of "chronic"/post-treatment Lyme symptoms is actually one side of an existing debate - most doctors in the know would acknowledge this, though if you asked them 5/10 years ago they wouldn't have admitted this. No pseudoscience here.

 

[Dufresne]

Persistent Lyme as the cause of "chronic"/post-treatment Lyme symptoms is actually one side of an existing debate - most doctors in the know would acknowledge this, though if you asked them 5/10 years ago they wouldn't have admitted this. No pseudoscience here.

"Doctors in the know" -I like the way that phrase reverberates in my mind as I read in the paper how the CDC was involved in this case. Apparently they had cultured Lyme from the patient's CSF back in 1991 after she'd received months of antibiotic therapy. Everything well documented. Hmmmmm... and they've been saying for subsequent decades that Lyme doesn't persist following antibiotic treatment?

Look at what this poor woman suffered. And what about all the others like her who couldn't get adequate treatment because doctors were being brought up on charges for prescribing antibiotics because "LYME CANT PERSIT FOLLOWING TREATMENT!" was what they kept saying. The studies showing it persists in all kinds of animals are legion. And there have been many instances of very good evidence for persistence in humans.

This whole "debate" has been bullshit for a long time. And speaking of time, why wasn't this paper submitted for publication 15 years ago?

 

[Pyrrhus]

New case report, also using multiple detection technologies:

Detecting Borrelia Spirochetes: A Case Study With Validation Among Autopsy Specimens (Gadila et al., 2021)
https://www.frontiersin.org/articles/10.3389/fneur.2021.628045/full

Excerpt:

The complex etiology of neurodegenerative disease has prompted studies on multiple mechanisms including genetic predisposition, brain biochemistry, immunological responses, and microbial insult. In particular, Lyme disease is often associated with neurocognitive impairment with variable manifestations between patients.

We sought to develop methods to reliably detect Borrelia burgdorferi, the spirochete bacteria responsible for Lyme disease, in autopsy specimens of patients with a history of neurocognitive disease.

In this report, we describe the use of multiple molecular detection techniques for this pathogen and its application to a case study of a Lyme disease patient. The patient had a history of Lyme disease, was treated with antibiotics, and years later developed chronic symptoms including dementia. The patient's pathology and clinical case description was consistent with Lewy body dementia.

B. burgdorferi was identified by PCR in several CNS tissues and by immunofluorescent staining in the spinal cord. These studies offer proof of the principle that persistent infection with the Lyme disease spirochete may have lingering consequences on the CNS.

(spacing added for readability)

Related article:
https://news.tulane.edu/pr/study-fi...n-brain-despite-aggressive-antibiotic-therapy

 

[dyllanmurphy]

New case report, also using multiple detection technologies:

Detecting Borrelia Spirochetes: A Case Study With Validation Among Autopsy Specimens (Gadila et al., 2021)
https://www.frontiersin.org/articles/10.3389/fneur.2021.628045/full

Excerpt:

(spacing added for readability)

Related article:
https://news.tulane.edu/pr/study-fi...n-brain-despite-aggressive-antibiotic-therapy

The whole enterprise of diagnosing let alone treating Lyme is a mess.

Lyme is difficult to culture. Ideally you can culture an infection, so that you have a "gold standard" for diagnosis that is highly accurate. A "gold standard" diagnosis like a culture might take too long for commercial use, but it's helpful for research purposes to assess the sensitivity and specificity of other tests, like antibody and PCR tests. Since you can't culture Lyme easily, you have no gold standard.

What about the bullseye rash? While the bullseye rash might mean someone has Lyme 100%, not everyone gets a bullseye rash. So in studies, if you use the bullseye as the gold standard against which you measure the sensitivity/specificity of other tests like the Western Blot, you are basically saying that the tests you measure are X% sensitive and Y% specific for people who get the bullseye rash.

In generalizing these results to the entire population, you'd be taking a big risk. You'd be assuming that people who got the bullseye are biologically similar to the whole population, with respect to their immune responses. From living in the era of COVID, we know peoples' immune responses vary significantly.

So the end result is that these antibody tests might be really insensitive for people who don't produce a bullseye with Lyme. Yet doctors assume the tests are 95-99% sensitive and specific in later Lyme disease.

Thanks for linking/ summarizing the article.

 

[5vforest]

Lyme is difficult to culture. Ideally you can culture an infection, so that you have a "gold standard" for diagnosis that is highly accurate. A "gold standard" diagnosis like a culture might take too long for commercial use, but it's helpful for research purposes to assess the sensitivity and specificity of other tests, like antibody and PCR tests. Since you can't culture Lyme easily, you have no gold standard.

They were supposedly coming up with a culture test, it has since faded into oblivion. It was being developed by "Advanced laboratory services" with the endorsement of Joe Burrascano, amongst others. (Some of this is documented on the now-mostly-defunct LymeNetEurope.)

Actually, this is mentioned in Kinderlehrer's recently published Lyme book. He writes that iGenex acquired the rights for this test and is working to validate it.

There are some other outfits that are supposedly able to do this. I think there is a European organization working on an enhanced culture. Maybe some of you have seen this; I think it was linked on the r/lyme subreddit at some point. I couldn't find it just now.

I've personally given up hope of ever getting to the bottom of this.

I am pretty sure that personally, I am infected. However, I have tried so many different types of treatment but I am still sick. I have no way of knowing if I still harbor a pathogenic infection, or if it simply started an ME/CFS-like process in my body. I am certain that many people have borrelial infections and are asymptomatic. Who knows what differentiates them from those who are symptomatic.

The science is just so poor. Then it is compounded with the legacy interests, and aspects of conspiracy. There are some specks of hope here and there ($16m for Columbia Lyme) but I think the outside forces are just too strong.

 

[Dufresne]

They were supposedly coming up with a culture test, it has since faded into oblivion. It was being developed by "Advanced laboratory services" with the endorsement of Joe Burrascano, amongst others. (Some of this is documented on the now-mostly-defunct LymeNetEurope.)

Actually, this is mentioned in Kinderlehrer's recently published Lyme book. He writes that iGenex acquired the rights for this test and is working to validate it.

There are some other outfits that are supposedly able to do this. I think there is a European organization working on an enhanced culture. Maybe some of you have seen this; I think it was linked on the r/lyme subreddit at some point. I couldn't find it just now.

I've personally given up hope of ever getting to the bottom of this.

I am pretty sure that personally, I am infected. However, I have tried so many different types of treatment but I am still sick. I have no way of knowing if I still harbor a pathogenic infection, or if it simply started an ME/CFS-like process in my body. I am certain that many people have borrelial infections and are asymptomatic. Who knows what differentiates them from those who are symptomatic.

The science is just so poor. Then it is compounded with the legacy interests, and aspects of conspiracy. There are some specks of hope here and there ($16m for Columbia Lyme) but I think the outside forces are just too strong.

I'm interested in the Lyme phage test as possibly being the sensitive, incontrovertible answer to getting people diagnosed. But it's going to have to be tested and confirmed by other labs before it's taken seriously. If it does turn out to be solid it might make one wonder about the "next generation sequencing" Dr Lipkin used to look at ME/CFS blood, that which I'd say steered a lot of focus and energy away from pathogens in this disease.

https://redlabs.be/phelix-phage-borrelia/

 

[Martin aka paused||M.E.]

I'm interested in the Lyme phage test as possibly being the sensitive, incontrovertible answer to getting people diagnosed. But it's going to have to be tested and confirmed by other labs before it's taken seriously. If it does turn out to be solid it might make one wonder about the "next generation sequencing" Dr Lipkin used to look at ME/CFS blood, that which I'd say steered a lot of focus and energy away from pathogens in this disease.

https://redlabs.be/phelix-phage-borrelia/

It's not a reliable test. It diagnosed me with reluctant fever (that's a rare Lyme disease), though I've never had it

 

[Pyrrhus]

Related discussion:

Persistent Borrelia Infection in Patients with Ongoing Symptoms of Lyme Disease (Middelveen et al., 2018)
https://forums.phoenixrising.me/thr...-with-ongoing-symptoms-of-lyme-disease.78520/

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.

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 ten 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)-based approaches. 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.