Archive for the ‘research’ Category

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

https://www.mdpi.com/2079-6382/8/4/183

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

*Author to whom correspondence should be addressed.
Antibiotics 2019, 8(4), 183; https://doi.org/10.3390/antibiotics8040183
Received: 22 August 2019 / Revised: 6 October 2019 / Accepted: 9 October 2019 / Published: 11 October 2019
(This article belongs to the Special Issue Antibiotics Resistance of Borrelia)
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. View Full-Text
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**Comment**
When will there be enough evidence for mainstream medicine?

Study Shows Lyme Patients Treated With Immune Suppressants Have Frequent Comorbidities, Late Stage Symptoms, & Treatment Failure

https://danielcameronmd.com/is-suppressing-immune-system-harmful-to-lyme-patients/

IS SUPPRESSING IMMUNE SYSTEM HARMFUL TO LYME PATIENTS?

Lyme disease, treatment

There have only been a few published reports detailing the outcome of treatment on Lyme disease patients who are immunocompromised. Now, a study by Maraspin and colleagues¹ evaluates the impact of tumour necrosis factor-alpha (TNF-α) inhibitors, medications that suppress the immune system, on Lyme disease patients.

The authors compared 16 individuals receiving TNF-α inhibitors with 32 healthy controls. The individuals had confirmed Lyme disease with an erythema migrans rash manifestation. The patients received immune-suppressing medications, which included adalimumab, infliximab, etanercept, golimumab. These were often combined with other immunosuppressant drugs for rheumatic (13 patients) or inflammatory bowel (3 patients) disease.

Investigators found that, when compared to controls, patients receiving immunosuppressants had:

  1. frequent comorbidities other than immune-mediated diseases (62.5% vs. 25%)
  2. symptoms/signs of disseminated Lyme borreliosis (18.8% vs. 0%)
  3. treatment failure (25% vs. 0%.)

In fact, 4 out of 16 (25%) Lyme disease patients treated with immunosuppression therapy failed treatment. Three of these four patients required retreatment. One of them was quite ill.

“The immunocompromised patients were also more likely to fail treatment than patients who were not immunocompromised,” writes Maraspin.

The fourth patient, a 44-year-old man, remained well until his 6-month follow-up visit. But, “7 months after beginning antibiotic treatment he developed severe arthralgia, fatigue and back pain,” writes Maraspin in the Journal of Clinical Medicine.

A specialist was consulted but could not confirm whether the man had a relapse of rheumatoid arthritis. He remained ill for the next 5 months. And tests revealed his IgG antibody to VlsE borrelial antigens rose from 542.1 to 1462.0 AU/mL.

His symptoms improved following re-treatment with the antibiotic, ceftriaxone.
The authors recommended regular follow-up visits to carefully monitor immunocompromised Lyme patients.
References:
  1. Bransfield RC, Friedman KJ, Differentiating Psychosomatic, Somatopsychic, Multisystem Illnesses and Medical Uncertainty. Healthcare 2019, 7(4), 114.

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**Comment**

I would argue that ALL Lyme/MSIDS patients are immune suppressed even if they are not taking immune suppressing drugs, which means the outcome would be similar.  This issue desperately needs to be addressed as mainstream medicine and research continues to approach this as a singular pathogen illness when recent research shows 65% of TBD patients produce immune responses to various microbes:  https://madisonarealymesupportgroup.com/2018/10/30/study-shows-lyme-msids-patients-infected-with-many-pathogens-and-explains-why-we-are-so-sick/

Here’s a study shows patients with EM who were receiving rituximab (an immune suppressant) for underlying disease show more borrelia isolated in the blood and that their cases are more often disseminated than in immunocompetent patients : https://madisonarealymesupportgroup.com/2019/08/06/em-course-outcome-in-patients-treated-with-rituximab/

And here we see ticks have immunosuppressive proteins in their saliva:  https://madisonarealymesupportgroup.com/2019/08/14/what-tick-saliva-does-to-the-human-body/

The exact cocktail of a tick’s saliva proteins changes every few hours, Ribeiro says. The thousands of proteins in its saliva are highly redundant in function, and the tick cycles through them as a way of circumventing a host’s immune system. Immune systems take time to recognize and react to a foreign tick protein, and this strategy simply doesn’t give a host’s cells a chance to do that. Suppose, Ribeiro says, “Monday a tick starts feeding on you and injecting the saliva in you.” By Friday, when your body can mount a proper immune response against those first proteins, “the tick has already changed the repertoire.”

https://madisonarealymesupportgroup.com/2019/12/15/immunosuppressive-proteins-found-in-tick-saliva-in-every-life-stage/

Taken together, these results suggest that Ip-sL1 and Ip-sL2 confer immunosuppressive functions and appear to be involved in the transmission of pathogens by suppressing host immune responses, such as cytokine production and dendritic cell maturation.

In other words, there are immunosuppressants within tick saliva that makes it easier for transmission to occur.

It only follows that giving patients immunsuppressants (or those patients infected with numerous pathogens) will function similarly in the body – allowing for pathogen proliferation which will be demonstrated by more severe disease.

Emerging Tick-Borne Diseases

https://www.ncbi.nlm.nih.gov/pubmed/31896541/

2020 Jan 2;33(2). pii: e00083-18. doi: 10.1128/CMR.00083-18. Print 2020 Mar 18.

Emerging Tick-Borne Diseases.

Abstract

Increases in tick-borne disease prevalence and transmission are important public health issues. Efforts to control these emerging diseases are frustrated by the struggle to control tick populations and to detect and treat infections caused by the pathogens that they transmit. This review covers tick-borne infectious diseases of nonrickettsial bacterial, parasitic, and viral origins. While tick surveillance and tracking inform our understanding of the importance of the spread and ecology of ticks and help identify areas of risk for disease transmission, the vectors are not the focus of this document.

Here, we emphasize the most significant pathogens that infect humans as well as the epidemiology, clinical features, diagnosis, and treatment of diseases that they cause. Although detection via molecular or immunological methods has improved, tick-borne diseases continue to remain underdiagnosed, making the scope of the problem difficult to assess. Our current understanding of the incidence of tick-borne diseases is discussed in this review. An awareness of the diseases that can be transmitted by ticks in specific locations is key to detection and selection of appropriate treatment. As tick-transmitted pathogens are discovered and emerge in new geographic regions, our ability to detect, describe, and understand the growing public health threat must also grow to meet the challenge.

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**Of Note**

Migrating birds are transporting ticks everywhere:  https://madisonarealymesupportgroup.com/2018/11/07/ticks-on-the-move-due-to-migrating-birds-and-photoperiod-not-climate-change/

https://madisonarealymesupportgroup.com/2017/08/17/of-birds-and-ticks/

Detection of Novel Piroplasmid Species & Babesia Microti & Theileria Orientalis Genotypes Discovered in Chinese Hard Ticks

https://www.ncbi.nlm.nih.gov/pubmed/32060726/

2020 Feb 14. doi: 10.1007/s00436-020-06622-6. [Epub ahead of print]

Detection of novel piroplasmid species and Babesia microti and Theileria orientalis genotypes in hard ticks from Tengchong County, Southwest China.

Abstract

To reveal the genetic diversity of Babesia microti and Theileria orientalis in Southwest China, we conducted a molecular survey of piroplasms in hard ticks in a China-Myanmar border county. Host infesting and questing ticks were collected from Tengchong County in 2013 and 2014. Piroplasm infection in ticks was detected by PCR, and then, phylogenetic analysis was conducted to study the genetic diversity of the pathogens identified in ticks.

All in all, six piroplasm species comprising of the following have been identified after screening goat and cattle-attached ticks:

  • B. microti
  • B. orientalis
  • a novel Babesia species designated Babesia sp. Tengchong, China
  • T. orientalis
  • T. luwenshuni
  • an undescribed piroplasmid species referred to as Piroplasmid sp. Tengchong, China
  • B. bigemina has been identified by screening questing ticks

Phylogenetic analysis based on the 18S rRNA and partial β-tubulin gene revealed two novel potentially zoonotic genotypes designated B. microti Tengchong-Type A and B.

The T. orientalis genotypes identified in the present study represent the seven known genotypes 1-5, 7, and N3 as revealed by phylogenetic analysis of 18S rRNA and MPSP genes. Importantly, an additional genotype designated N4 has also been identified in this study, which brings the number of recognized T. orientalis genotypes to a total of twelve.

Thus, besides the two novel species, Babesia sp. Tengchong, China, closely related to Babesia species isolated from yak and Piroplasmid sp. Tengchong, China, our study demonstrates that additional novel B. microti and T. orientalis genotypes exist in Southwest China.

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**Comment**

Babesia Microti is pathogenic in humans.

Babesia orientalis is pathogenic in water buffalo.

Theileria orientalis is pathogenic in cattle.

Theileria luwenshuni is pathogenic in sheep and goats.

Babesia bigemina is pathogenic in cattle.

They also discovered a NEW Theileria orientalis genotype  (N4).

The study identified TWO NEW Babesia microti genotypes (B. micro Tengchong- Type A & B) which may be pathogenic to humans.

 

 

Fatal Case of Neuroborreliosis

https://danielcameronmd.com/fatal-case-of-neuroborreliosis/

FATAL CASE OF NEUROBORRELIOSIS

In their article, Neuroborreliosis with Unusual Presentation: A Case Report, Khan and colleagues describe “a case of neuroborreliosis with very high cerebrospinal fluid (CSF) protein content and devastating neurological injury.” The patient, a 41-year-old woman, had been ill for two months with “headaches, nausea, vomiting, 30-lb weight loss, and newly developed bilateral vision loss and dysphonia.” ¹

Neuroborreliosis manifestations typically include headaches and symptoms of meningitis, encephalopathy and stroke-like symptoms. The diagnosis is based on clinical symptoms and lumbar puncture findings.

The woman had other serious health problems, which included lupus, a left-posterior parietal ventriculoperitoneal (VP) shunt due to congenital hydrocephalus, and migraine headaches, explains Khan.

Diagnostic tests revealed renal failure and over shunting by brain CT. On day 2 of her hospitalization, she suffered cardiac arrest, requiring defibrillation. “Dopamine and vasopressin infusion was started for bradycardia and hypotension,” writes Khan.

The brain MRI revealed an acute ischemic insult. And the woman was subsequently transferred to another hospital intubated, sedated and requiring infusions of norepinephrine and dopamine.

The MRI of the brain had multiple abnormalities. The chest CT revealed bilateral pulmonary emboli and stress-induced cardiomyopathy. A rheumatologic workup suggested the woman suffered from discoid lupus rather than systemic lupus.

A spinal tap revealed a pleocytosis of 318 cell/deciliter, high protein of 1,208 mg/dl and evidence of Lyme disease.

“Lumbar puncture results revealed elevated Borrelia burgdorferi antibodies in the cerebrospinal fluid (CSF) at 1.37 (normal <0.99),” writes Khan. Blood tests for Lyme disease, however, were negative.

The woman remained vent-dependent and showed minimal improvement in her overall condition despite intravenous (IV) ceftriaxone.

“A goals-of-care discussion was held, and the family decided to withdraw care after a two-week hospital stay,” writes Khan. “She passed away soon after relieving her from the ventilator with her family at her bedside.”

Editor’s note: I appreciate that the authors shared this devastating case of Lyme disease. The cause of death typically is related to multiple factors.  For example, she had lupus and a left-posterior parietal ventriculoperitoneal (VP) shunt due to congenital hydrocephalus.  Her lupus and congenital problems may have made it difficult to recognize her Neuroborreliosis.

References:
  1. Khan S, Bhattal GK, Shah NH, Lascano J, Karki A. Neuroborreliosis with Unusual Presentation: A Case Report. Cureus. 2019 Sep 25;11(9):e5758.

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**Comment**

Others have died from Lyme disease as well:  https://madisonarealymesupportgroup.com/2019/07/12/when-lyme-kills/

Since 2013 Lyme advocate Lisa Hilton has been keeping track of Lyme deaths in this memorial:  http://whatislyme.com/rip-lyme-friends-memorial/