RECENT LITERATURE

2022: Jolien Plantinga: “Komt een dokter bij de dokter - overleven met Lyme” (“medical doctor visiting her general practitioner”)

Publisher Gopher, Harderwijk

This book, published last year, is the autobiographic story of a general practitioner (Dr Plantinga) who herself is infected with Lyme borreliosis and struggles with the disease and with getting her message across to the physicians who are treating her. This book was published last year in the Netherlands and is currently being translated into English for publication in the English-speaking market.

This website will report when the English version of this most informative and highly readable book has come out and will inform where it can be acquired.

December 2021: Senejani Ali G., Maghsoulou J., El-Zohiri D., Gaur G., Wawrzeniak K., Caravaglia C., Khatri Viswa A., MacDonald Alan, Sapi Eva

Article published as: "Borrelia burgdorferi Co-Localizing with Amyloid Markers in Alzheimer's Disease Brain Tissues"

Further information to be obtained on the follwing website: pubmed.ncbi.nlm.nih.gov/34897095/

Januari 2021, Dr. Alan B. MacDonald       

Article published under the title  "Borrelia Invasion of Brain Pyramidal Neurons and Biofilm Borrelia Plaques in Neuroborrelliosis Dementia with Alzheimer's Phenotype" (ISSN 2639-9458)

Further information to be obtained at:  https://scivisionpub.com/pdfs/borrelia-invasion-of-brain-pyramidal-neurons-and-biofilm-borrelia-plaques-in-neuroborreliosis-dementia-with-alzheimers-phenotype-1564.pdf

April 2021: Prof. Dr. Joppe Hovius et al under the auspices of Stichting Biowetenschappen en Maatschappij (the Netherlands Foundation for Biosciences and Society) (Publisher Lias)

In Lymeziekte, focussed on the Netherlands, the most recent knowledge about the disease is assembled. Not only the medical aspects of the disease are covered, but also the biological and ecological characteristics of the tick and its hosts. Frequently asked questions are discussed such as: what are the chances of being infected following a tickbite, what are the risks of not being treated, is it possible that you have been bitten by a tick without knowing it,  how frequently will an infection result in a chronic disease and what is the protocol in the treatment.

 

2019 Dr. Eva Sapi, Dr. Rumanah Kasliwala, Dr. Hebo Ismail et al

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

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.

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

2018  Austin Internal Medicine, Bielawski M.M. and Myers J.P.

Reversible Dementia due to Lyme Neuroborreliosis

In a case study published by the Austin Publishing Group in March 2019,  Dr. M.M. Bielawski of Department of Medicine, Division of Infectious Disease, Summa Health System, Ohio, USA and Dr J.P. Myers, Resident of Internal Medicine, Summa Health System/Northeast Ohio Medical University Program, Ohio, USA have found Dementia due to Lyme Neuroborreliosis to be Reversible.

Neuroborreliosis accounts for fewer than 10% of patients with Lyme disease. Drs Bielawski and Myers presented a patient with impaired memory and cognition, right leg weakness and left hip pain who was suspected of having Lyme disease because of atypical axillary erythema migrans.

This patient had Lyme neuroborreliosis presenting with signs of dementia. Neuroborreliosis is often difficult to diagnose because symptoms such as impaired short-term memory or confusion are non-specific and may be mistaken for other conditions such as Alzheimer-type dementia. Lyme disease is not a common cause for dementia. It is therefore essential to obtain a detailed history and to consider neuroborreliosis in the differential diagnosis of altered cognition/dementia, especially in conjunction with recent travel to Lyme endemic areas such as Western Pennsylvania. Early treatment usually avoids progression of neuroborreliosis and the development of the more devastating long-term complications.

PDF can be downloaded at: www.austinpublishinggroup.com

2018 Wien Klin. Wochenschrift:  Wolfgang Kristoferitsch, Fahmy Aboulenein-Djamshidian, Julia Jecel,Helmut Rauschka, Michael Rainer, Gerold Stanek and Peter Fischer

Secondary dementia due to Lyme neuroborreliosis

Abstract
 

Dementia-like syndromes are rare manifestations of Lyme neuroborreliosis. The clinical patterns are summarized using our own cases and case reports from the literature, which were diagnosed as definite Lyme neuroborreliosis according to the European guidelines. The cases disclose signs of subcortical dementia that occur more rapidly than in patients suffering from primary dementia. Gait disturbances early in the disease course is another frequently observed characteristic feature. The response to 2-4 weeks of antibiotic treatment with ceftriaxone was excellent. There were no indications for a prolonged antibiotic treatment. It is essential to be aware of this manifestation of Lyme neuroborreliosis, because early antibiotic treatment will prevent permanent sequelae that may occur throughout the further course of the untreated disease.

 

2018 MDPI/HEALTHCARE, Marianna J. Middelveen (Atkins Veterinary Services, Canada), Eva Sapi (University of New Haven, Conn., USA), Jennie M. Burke (Australikan Biologics) et al

Persistent Borrelia Infection in Patients with Ongoing Symptoms of Lyme Disease

Abstract

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.

PDF can be downloaded from: www.mdpi.com/2227-9032/6/2/33

2016 JOURNAL OF ALZHEIMERS DISEASE, Miklossy  J.

Bacterial Amyloid and DNA are Important Constituents of Senile Plaques: Further Evidence of the Spirochetal and Biofilm Nature of Senile Plaques

Abstract

It has long been known that spirochetes form clumps or micro colonies in vitro and in vivo. Cortical spirochetal colonies in syphilitic dementia were considered as reproductive centers for spirochetes. Historic and recent data demonstrate that senile plaques in Alzheimer's disease (AD) are made up by spirochetes. Spirochetes, are able to form biofilm in vitro. Senile plaques are also reported to contain elements of biofilm constituents. We expected that AβPP and Aβ (the main components of senile plaques) also occur in pure spirochetal biofilms, and bacterial DNA (an important component of biofilm) is also present in senile plaques. Histochemical, immunohistochemical, and in situ hybridization techniques and the TUNEL assay were used to answer these questions. The results obtained demonstrate that Aβ and DNA, including spirochete-specific DNA, are key components of both pure spirochetal biofilms and senile plaques in AD and confirm the biofilm nature of senile plaques. These results validate validate previous observations that AβPP and/or an AβPP-like amyloidogenic protein are an integral part of spirochetes, and indicate that bacterial and host derived Aβ are both constituents of senile plaques. DNA fragmentation in senile plaques further confirms their bacterial nature and provides biochemical evidence for spirochetal cell death. Spirochetes evade host defenses, locate intracellularly, form more resistant atypical forms and notably biofilms, which contribute to sustain chronic infection and inflammation and explain the slowly progressive course of dementia in AD. To consider co-infecting microorganisms is equally important, as multi-species biofilms result in a higher resistance to treatments and a more severe dementia.

2016 EUROPEAN JOURNAL OF MICROBIOLOGY AND IMMUNOLOGY,  Sapi E. et al

Evidence of In Vivo Existence of Borrelia Biofilm in Borrelial Lymphocytomas

Abstract

Lyme borreliosis, caused by the spirochete Borrelia burgdorferi sensu lato, has grown into a major public health problem. We recently identified a novel morphological form of B. burgdorferi, called biofilm, a structure that is well known to be highly resistant to antibiotics. However, there is no evidence of the existence of Borrelia biofilm in vivo; therefore, the main goal of this study was to determine the presence of Borrelia biofilm in infected human skin tissues. Archived skin biopsy tissues from borrelial lymphocytomas (BL) were reexamined for the presence of B. burgdorferi sensu lato using Borrelia-specific immunohistochemical staining (IHC), fluorescent in situ hybridization, combined fluorescent in situ hybridization (FISH)-IHC, polymerase chain reaction (PCR), and fluorescent and atomic force microscopy methods. Our morphological and histological analyses showed that significant amounts of Borrelia-positive spirochetes and aggregates exist in the BL tissues. Analyzing structures positive for Borrelia showed that aggregates, but not spirochetes, expressed biofilm markers such as protective layers of different mucopolysaccharides, especially alginate. Atomic force microscopy revealed additional hallmark biofilm features of the Borrelia/alginate-positive aggregates such as inside channels and surface protrusions. In summary, this is the first study that demonstrates the presence of Borrelia biofilm in hyman infected skin tissues.

Link: pubmed.ncbi.nlm.nih.gov/27141311/

2016 Dr. Herbert B. Allen

Alzheimer’s Disease: Assessing the Role of Spirochetes, Biofilms, the Immune System, and Amyloid-β with Regard to Potential Treatment and Prevention

Abstract:

Alzheimer’s disease (AD) is an infectious disease caused by spirochetes, and these spirochetes form biofilms, which attract the innate immune system. The innate immune system first responder, Toll-like receptor 2, generates both NF-κB and TNF-α which try to kill the spirochetes in the biofilm, but cannot penetrate the “slime”. NF-κB is also responsible for the generation of amyloid-β (Aβ) which itself is anti-microbial. Aβ cannot penetrate the biofilm either, and its accumulation leads to destruction of the cerebral neurocircuitry. Treatment with penicillin (as in tertiary syphilis, the comparator to AD) is outlined; a biofilm dispersing agent may need to be added to the protocol.

2015 JOURNAL OF ALZHEIMER'S DISEASE, Maheswari P. en Eslick G.

Bacterial infection and Alzheimer's disease: a meta-analysis

Abstract

The possibility of an infectious etiology for Alzheimer's disease (AD) has been repeatedly postulated over the past three decades. We provide the first meta-analysis to address the relationship between bacterial infection and AD. Studies examining the association between AD and spirochetal bacteria or Chlamydophila pneumoniae (Cpn) were identified through a systematic search of the databases MEDLINE, EMBASE, PubMed, and Google Scholar. Data combined from 25 relevant, primarily case-control studies demonstrated a statistically significant association between AD and detectable evidence of infection of either bacterial group. We found over a ten-fold increased occurrence of AD when there is detectable evidence of spirochetal infection (OR: 10.61; 95% CI: 3.38-33.29) and over a four-fold increased occurrence of AD in a conservative risk estimate (OR: 4.45; 95% CI: 2.33-8.52). We found over a five-fold increased occurrence of AD with Cpn infection (OR: 5.66; 95% CI: 1.83-17.51). This study shows a strongly positive association between bacterial infection and AD. Further detailed investigation of the role of bacterial infection is warranted.

Link: www.ncbi.nlm.nih.gov/pubmed/25182736

2014 JOURNAL OF ALZHEIMERS DISEASE, F. Blanc et al

Lyme neuroborreliosis and dementia

Abstract

Introduction: Descriptions of Lyme disease and dementia are rare.

Objective: To describe patients with dementia and a positive "intrathecal anti-Borrelia antibody index" (AI), specific for neuroborreliosis.

Methods: Among 1,594 patients seen for dementia, we prospectively identified and studied 20 patients (1.25%) with dementia and a positive AI. Patients underwent a battery of neuropsychological tests brain, MRI, FDG-PET, and cerebrospinal fluid (CSF) analysis. An etiological diagnosis of the dementia was made at the end of the follow-up of 5.0 ± 2.9 years.

Results: We found two groups of patients with dementia, the first (n = 7, 0.44%) with certain neuroborreliosis and stability or mild improvement of dementia after treatment by antibiotics and the second (n = 13, 0.81%) with progressive worsening of dementia, despite the antibiotics. In the second group, the final diagnoses were Alzheimer's disease (AD) (n = 4), AD and Lewy body disease (LBD) (n = 3), LBD (n = 1), FTLD (n = 3), hippocampal sclerosis (n = 1), and vascular dementia (n = 1). We did not observe any differences in cognitive test between the two patient groups at baseline. Brain MRI showed more focal atrophy and FDG-PET showed more frontal hypometabolism in the second group. Tau, p-tau, and Aβ42 concentrations in the CSF were normal in the neuroborreliosis group, and coherent with diagnosis in the second.

Conclusion: Pure Lyme dementia exists and has a good outcome after antibiotics. It is advisable to do Lyme serology in demented patients, and if serology is positive, to do CSF analysis with AI. Neurodegenerative dementia associated with positive AI also exists, which may have been revealed by the involvement of Borrelia in the CNS.

Link: www.ncbi.nlm.nih.gov/pubmed/24762944

December 2016, University of New Haven, New Haven Connecticut,  Lyme Research Group

Dr Ali Senejani PhD, Associate Professor Genetics, University of New Haven, sent us this report:

My lab is involved in multiple projects to examine cell survival and the level of DNA damage in neuron and fibroblast cells exposed to various environmental conditions. One area we particularly focus on recently is the link between inflammation, oxidative stress and level of DNA damage. Chronic infections that cause chronic inflammation along with enhanced oxidative stress has long been suspected to be a key player in several human diseases such as neurodegenerative conditions. We study the molecular mechanism of DNA damage resulting from increased level of inflammation and/or reactive oxygen species (ROS) and will be examining whether chronic inflammation and increased level of ROS is one of the primary causes, or simply a downstream consequence of some diseases such as the neurodegenerative process. Since last year I have had the opportunity and the pleasure of starting collaboration with a senior member of our department, Dr. Eva Sapi, who has a very active and successful Lyme research group. We are very excited examining both the nature and the consequences of DNA damage, occurring in cells and tissues of people exposed to pathogenic bacteria such as Lyme disease causing bacteria Borrelia burgdorferi. Preliminary findings from our study indicate Borrelia bacterial infection induces DNA damage in neuron-like cells. This study is likely to uncover a link between Borrelia bacterial infection and induced level of ROS and free radical attack on neural cells; and how this can lead to neurodegeneration in many neural disorders.

 



 

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