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Zatechka, Steve

ZatechkaSteve Zatechka, PhD, MBA
Chief Operating Officer
US BIOLOGIC, Memphis, TN

“A One-Health Path to Prevent Lyme and Other Tick-Borne Diseases”

Steve earned his PhD from the University of Nebraska Medical Center and his MBA from the University of Memphis. He completed his postdoctoral fellowship with the Howard Hughes Medical Institute at St. Jude Children’s Research Hospital.  Steve’s research and training focused on the development and utilization of gene targeting technologies for engineering animal models and the development of applied biotechnology-based protocols.

He now directs the research and development of the US BIOLOGIC production platform technology and is the company’s primary investigator for its SBIR-funded programs. He holds several patents in these areas and others across a spectrum of biotechnology foci. Steve publishes and speaks widely on zoonotic diseases and the positive impacts orally delivered vaccines can have on global health.


Conference Lecture Summary

“A One-Health Path to Prevent Zoonotic Disease” – With 75% of all emerging infectious diseases being zoonotic in nature, the need of safe, effective, and cost-efficient prevention methods becomes a necessary endeavor. Recognizing the complexities of addressing a range of species (human, animal, insect), diseases, and ecologies, a One Health approach is best suited to cause an effective change. This talk will focus on one example of a One Health program – effective oral delivery of vaccines and therapeutics to wildlife and food animals. Data will be presented from successful approaches, focusing on a successful orally delivered vaccine targeting the wildlife disease reservoir for Lyme disease, the white-footed mouse.




Tokarz, Rafal

TokarzRafal Tokarz, PhD
Associate Research Scientist
Center for Infection & Immunity
Columbia University Mailman School of Public Health, New York, NY

“Virome Analysis in Ticks”

Dr. Tokarz’s research focuses on microbial discovery and the epidemiology of human infectious diseases. His primary interests center on investigating respiratory and tick-borne pathogens and understanding their roles in human disease.

Dr. Tokarz’s work in the field of tick-borne disease has been driven by two main hypotheses: 1) co-infections in human-biting ticks are common and can result in human poly-microbial infections; and 2) viral infections represent a proportion of undiagnosed tick-transmitted diseases. He designed and implemented one of the first multiplex PCR assays that targeted tick-borne agents and was one of the first scientists to document high rates of pathogen co-infections in ticks within New York State. His recent work has focused on exploring the diversity of the tick virome. He performed the first investigation of the virome of the three main human-biting ticks in New York State and thus far has discovered over 20 novel tick-associated viruses. He is now examining the potential for transmissibility and pathogenesis of these viruses.

In an effort to understand the etiology of respiratory diseases, Dr. Tokarz has participated in pathogen surveillance studies on specimens originating from Asia, Africa, Europe, South and North America. As part of this work, he used cutting edge molecular platforms to identify and characterize novel viral agents. Dr. Tokarz identified and characterized the first defined cluster of one such virus, enterovirus D68, an emerging agent implicated in a severe outbreak of pediatric respiratory disease in the US in 2014. He performed the first comprehensive phylogenetic characterization of this virus, identified the three main clades circulating worldwide and developed a classification system now employed by investigators in this field. In his current work, Dr. Tokarz is examining the pathogenesis of this virus and how its genetic variation influences the severity of disease.


Conference Lecture Summary

Tick-borne diseases are the most common vector-borne illnesses in the United States. In a proportion of presumed tick bite-associated infections, the etiologic agent is never identified, and the full range of tick- borne pathogens has not yet been explored. In contrast to bacterial pathogens, there is a limited understanding of the diversity of tick-borne viruses and their role in human infection. We are performing a virome analysis of the three main human-biting ticks endemic to the New York metropolitan area, with the goal of uncovering novel viral agents and determining their geographic distribution and prevalence. For novel viruses with homology to known pathogens, we will design serological assays to examine sera from subjects with history of tick bites for evidence of spillover of these viruses into the human population.

 




Smith, Patricia

SmithPatricia V. Smith, BA
President, Lyme Disease Association, Inc.
Advisory Board Member, Columbia University Lyme & Tick-Borne Diseses Research Center
Programmatic Panel Member, TBD Research Program, DoD Congressionally Directed Medical Research Program
Conference Organizer/Program Committee, Jackson, NJ

“Welcome/Overview of Lyme/Introductions”

Patricia V. Smith, a Monmouth University graduate, is in her 20th year as President of the all-volunteer run national non-profit Lyme Disease Association, Inc., LDA, and is a member of Columbia University’s Lyme & Tick-Borne Diseases Research Center Advisory Committee and has been appointed to the Fiscal Year 2016 (FY16) Programmatic Panel for the Tick-Borne Disease Research Program (TBDRP), a new program in the Department of Defense’s (DoD) Office of Congressionally Directed Medical Research Programs (CDMRP)─a typical 3-year term-of-service. She is a member of the Food & Drug Administration’s (FDA) PESP Partnership to promote avoidance of tick exposure, and member of the Tick IPM Working Group with federal and non-federal members, from the IPM Institute of North America, to eradicate tick-borne diseases.

Ms. Smith is also former Chair, (NJ) Governor’s Lyme Disease Advisory Council. She was EPA’s PESP 2011 Lyme prevention conference session co-chair with CDC. In 2011 she presented a Lyme session to the New Jersey Education Association’s Annual Meeting. She is a member & former officer of ILADS, International Lyme & Associated Diseases Society, a professional medical and research organization.

Ms. Smith is former President/12-year member of the Wall NJ Board of Education where she earned state board member-certified status. She is a former officer of Monmouth County School Boards Assn. and was a member of the Federal Relations Network for New Jersey School Boards Association/National School Boards Assn.

During her LDA presidency, Ms. Smith has led the effort to raise funds for researchers nationally, with more than 100 research grants awarded ─ research acknowledged in 39 scientific journals. She has organized 17 continuing medical education (CME) accredited Lyme scientific conferences for doctors and researchers with international faculty, held in different areas of the US, most jointly sponsored by Columbia University. She has spoken at many conferences on Lyme including those presented by the University of New Haven (CT), the American Association for the Advancement of Science (AAAS), and the California Lyme Disease Association (now LymeDisease.org), and the International Lyme & Associated Diseases Society. She has been a speaker at hundreds of public, school, business, & government events.

She led the LDA in its effort with a partner organization, to endow the Columbia Lyme & Tick-Borne Diseases Research Center in New York, which opened in 2007. She developed the ABCs of Lyme Disease pamphlet for parents and educators and also the LymeR Primer brochure now featuring 15 tick-borne diseases, the Tick Mark bookmark, and helped design Tick Awareness cards. More than 2.5 million of these items have been distributed.

Ms. Smith has testified for and secured passage of state and federal bills for Lyme research and physician’s right to treat. She has been invited to state capitals in CT, MA, MD, MN, NH, NJ, NY, PA, RI, to present oral testimony and education on Lyme and has provided written testimony in many others. Based on her written testimony, LDA was recently included in ground breaking Maine legislation as a website resource on Lyme disease on Maine’s DPH website. She was invited to testify on two occasions before the NY Assembly Health Care Committee and also before the Rhode Island (Governor’s) Lyme Disease Advisory Commission and has spoken before the California Lyme Disease Advisory Council. Over time, she has personally met with many State Health Commissioners and with Governors in NH, RI CT on Lyme issues and with then Governor Pataki’s office on many occasions along with several NY state legislators. She has also presented before the Pennsylvania House of Representatives Majority Policy Committee and was an invited speaker for Lyme forums hosted by a member of the Massachusetts House of Representatives and the Majority Caucus Administrator for the Pennsylvania House of Representatives and the Minnesota State Senate Health Committee.

She has twice been invited to present to CDC Vector-Borne Diseases Division, Ft. Collins (2007, 2013); met with then CDC Director Dr. Julie Gerberding/5 Congressmen in DC; organized & led a team that met with HHS Asst. Sec. of Health with CDC/NIH officials teleconferenced in; met with military leaders in DC; and briefed the Senate HELP Committee Members and House Subcommittee on Health. She met several times with US Army CHPPM/Public Health Command at Aberdeen Proving Grounds. She met in DC with the NIH Program Director and research coordinator and presented educational PowerPoints on Lyme to employees at the Environmental Protection Agency (2008, 2014), to the Dept. of Energy, and to Homeland Security in 2014. In 2014, she helped develop language for a federal bill on Lyme and led the nationwide effort which successfully passed the bill through the House. Ms. Smith spoke at a 2014 press conference with Senator Charles Schumer (NY) on the doxycycline shortage for Lyme patients. In 2012, she testified before the House Foreign Affairs Committee, Africa, Global Health & Human Rights Subcommittee on issues affecting Lyme patients. In 2013, she testified before the House Energy & Commerce Health Subcommittee on HR 610 to establish a federal Lyme & Tick-Borne Diseases Advisory Committee. She co-authored an article which was read into the Congressional Record on Lyme disease research priorities from the patient perspective.

Chosen Jackson NJ’s Chamber of Commerce 2008 Woman of the Year, she has also received commendation from the NJ legislature, a Special Congressional Recognition certificate from RI Cong. Langevin, and had a flag flown over the US Capitol by request of NJ Cong. Chris Smith in honor of her Lyme work. Ms. Smith helped to organize and presented at educational forums held by 3 congressmen (Langevin, Pitts, C. Smith). She has received awards from Dr. Brian Fallon, Columbia, from various Lyme groups, and was given the Courage in Advocacy Award in 2015 from Connecticut based Lyme Connection.

Other activities include providing input into a NJ law requiring teacher education for staff who teach students with Lyme disease, performing school in-services for educators on Lyme disease, and working with parents of students who are classified due to Lyme disease. Working with author Amy Tan, she created LDA’s LymeAid 4 Kids, a fund for children with no health coverage for Lyme, a fund that has awarded $1/4 M for uninsured children to date. Click for Publications




Sellati, Timothy

SelattiTimothy J. Sellati, PhD
Distinguished Fellow & Chair Department of Infectious Diseases Drug Discovery Division, Southern Research
Southern Research Institute, Birmingham, AL

“Controlling the Inflammatory Response in Lyme Arthritis–What the Mouse Model teaches Us About Human Disease”

Timothy J. Sellati joined the Southern Research Institute as a Senior Research Fellow and Chair of the Department of Infectious Diseases in the Drug Discovery Division November 2015. He received a BA degree in Biology from Dowling College in 1985 and a PhD degree in Cellular and Developmental Biology from the State University of New York at Stony Brook in 1996. Dr. Sellati began postdoctoral training in 1996 at the University of Texas Southwestern Medical Center in Dallas and completed his training in 1999 at the University of Connecticut Health Science Center in Farmington. After joining the Center for Immunology and Microbial Disease at Albany Medical College as an Assistant Professor in December 2000 he was promoted to Associate Professor in 2005 and earned tenure in 2010. In July 2013 through October 2015 Dr. Sellati served as an Associate Member at the Trudeau Institute in Saranac Lake, NY.
During both his graduate and postdoctoral training he studied host responses to the spirochetal pathogens Borrelia burgdorferi and Treponema pallidum, the respective causative agents of Lyme disease and syphilis. Currently the major focus of the Sellati laboratory is to delineate the role of CD14 and TLR2 signaling in innate immunity to B. burgdorferi and Francisella tularensis, the causative agent of tularemia and a CDC Category A biological threat agent. Dr. Sellati was the Immunology Scientific Councilor for the International Endotoxin and Innate Immunity Society, the past President of the Eastern New York Branch of the American Society for Microbiologists, and has served as ad hoc member of a number of NIAID Study Section review panels and reviewer for several scientific journals in the areas of immunology and microbiology.


Conference Lecture Summary

Genotype profoundly influences disease severity in the murine model of Lyme borreliosis, caused by the spirochetal bacterium Borrelia burgdorferi. Infected C57BL/6 (B6) and C3H/HeN (C3H) mice develop very mild and severe Lyme arthritis, respectively. Expression of the immunosuppressive cytokine interleukin-10 (IL-10) by B6, but not C3H mice has long been associated with these strain differences in disease presentation. However, the underlying mechanism(s) of genotype-specific IL-10 regulation remained elusive. Herein, we reveal a cyclic AMP (cAMP)-mediated mechanism of IL-10 regulation in B6 mice that is absent in C3H mice, which provides insight into the clinical spectrum of human Lyme disease, particularly those suffering from treatment-refractory arthritis. We show that bone marrow-derived monocytes (BMDMs) from B6 mice mount a more tempered, protective immune response to borrelial infection by virtue of the action of cAMP and CD14-p38-MAPK signaling; which, in combination, is responsible for increased production of the anti-inflammatory cytokine IL-10 and decreased production of potent pro-inflammatory and arthritogenic cytokines, including TNF. cAMP relaxes chromatin structure through modification of histones while CD14-dependent p38 MAPK activity increases binding of STAT3 and SP1 to their cognate sites on the now accessible IL-10 promoter, facilitating increased IL-10 production. Thus, cAMP and CD14 regulate IL-10 production and dampen the release of pro-inflammatory mediators elicited by B. burgdorferi by changing the epigenetic ‘landscape’. In stark contrast, arthritis-susceptible C3H mice lack basal levels of cAMP comparable to those of their disease-resistant B6 counterparts and thus are ill equipped to mitigate the damaging consequences of B. burgdorferi-induced TNF through production of IL-10. Intriguingly, reciprocal regulation of IL-10 and TNF by cAMP- and CD14-dependent mechanisms are operative in primary human peripheral blood monocytes and cAMP-enhancing drugs show therapeutic efficacy in our mouse model of Lyme arthritis.




Pritt, Bobbi

PrittBobbi S. Pritt, MD, MSc, DTM&H
Director, Clinical Parasitology and Vector-Borne Diseases,
Associate Professor, Pathology of Laboratory Medicine Division of Clinical Microbiology
Mayo Clinic, MN

“Borrelia Mayonii: A New Cause of Lyme Disease in the Upper Midwestern US”

Bobbi Pritt, MD, FCAP is an Associate Professor of Pathology and Director of the Clinical Parasitology and Vector-borne Diseases Laboratories in the Division of Clinical Microbiology at Mayo Clinic in Rochester, MN. She is board certified in Anatomic and Clinical Pathology as well as Medical Microbiologist, and holds a Master’s degree in Medical Parasitology from the London School of Hygiene and Tropical Medicine and Diploma in Tropical Medicine from the Royal College of Physicians in London.

Dr. Pritt has presented and published on many topics, including detection and characterization of two new tick-borne organisms, an Ehrlichia and Borrelia species, that infected humans in the midwestern United States.


Conference Lecture Summary

Dr. Bobbi Pritt will describe the discovery of a novel pathogen causing Lyme disease in the upper Midwestern United States. This new bacterium, preliminarily called Borrelia mayonii, causes higher levels of spirochetemia than what is seen with Borrelia burgdorferi, and has been associated with potential neurologic involvement and severe disease. Dr. Pritt will discuss the tests that lead to the detection of B. mayonii, the clinical features observed so far, and the preferred diagnostic methods.




Nigrovic, Lise

Lise Nigrovic, MD, MPH nigrovic
Associate Professor of Pediatrics & Emergency Medicine;
Director of Education, Clinical Research Center Senior Associate Physician in Medicine
Boston Children’s Hospital, MA

Lise Nigrovic, MD, MPH nigrovic
Associate Professor of Pediatrics & Emergency Medicine;
Director of Education, Clinical Research Center; Senior Associate Physician in Medicine
Boston Children’s Hospital, MA

“Initial Management of a Child with Potential Lyme Disease”

I am a pediatric emergency medicine physician at Boston Children’s Hospital with a research focus on the evaluation of children with infectious emergencies. My recent research focus is the diagnostic evaluation of children with possible Lyme disease. I founded a five-center pediatric Lyme disease network (Pedi Lyme Net) with prospective patient enrollment with biosample collection. Our network goal is to evaluate novel approaches to the diagnose of Lyme disease in children presenting to the emergency department.


Conference Lecture Summary

Children commonly get Lyme disease. Initial diagnostic decisions must be made before Lyme disease test results are available. I will present three common clinical case scenarios of children with potential Lyme disease. I will then will review the best available evidence to guide clinical decision-making.

 




Ericson, Marna

EricsonMarna Ericson, PHD
Director, Cutaneous Imaging Center
Department of Dermatology
University of Minnesota, Minneapolis, MN

“Mechanisms of Persistence of Bartonella ssp”

Our goal is to understand mechanism(s) of persistence of vector-borne infectious diseases and in particular the stealth pathogen Bartonella. This pathogen is indeed under-diagnosed due to its fastidious and unique growth characteristics; factors that lead to difficulties in detection. Of particular interest to our lab is the role of biofilms in persistent Bartonellosis and the resulting pathologies. Though the ability of Bartonella species to cause biofilm-mediated endocarditis is reported, the role of Bartonella species biofilm formation elsewhere in the mammalian body is unknown. We are using new imaging technologies and cross-disciplinary approaches to understand these disease mechanisms. Advanced imaging techniques we employ include single- and multi-photon microscopy, correlative microscopy, electron microscopy, microPET imaging, super-resolution confocal microscopy and second harmonic generation. We analyze human tissues and blood for Bartonellae as well as in vitro biofilm and culture methods and we are developing several different mouse models to aid in our research efforts.

Collaboration and innovation are hallmarks of my research endeavors; working with local, national and international colleagues in e.g. Brazil, Germany, England, North Carolina, Massachusetts, California, Maryland, District of Columbia, and the Hormel Institute in Austin, MN. Past successful collaborations include endeavors in infectious disease, skin cancer, myeloma, breast cancer and tumor pain, and hair disease.

Our mission is to use best science practice to address the complicated and under-appreciated complications of chronic Bartonellosis.


Conference Lecture Summary

Bartonella spp, are vector-borne stealth pathogens. Our goal is to understand the role of biofilms in manifestation of prolonged bacteremia and resulting pathologies caused by persistent Bartonella spp. infection. Bartonella species are known to cause life-threatening biofilm-mediated endocarditis. We use advanced imaging techniques to characterize Bartonella spp. biofilms, both in vitro and in vivo. We use single- and multi-photon microscopy and correlative microscopy with electron microscopy, microPET imaging, super-resolution confocal microscopy and second harmonic generation imaging to accomplish these ends. We are using these advanced tools and new mouse models to understand disease persistence and stealth mechanisms.




Bloch, Evan

BlochEvan M. Bloch, MD, MS
Assistant Professor
Associate Director, Transfusion Medicine
Johns Hopkins University, Baltimore, MD

“Babesia & the Blood Supply: Lessons Learned”

Evan M. Bloch, MBChB (M.D.), M.S. is an Assistant Professor in the Department of Pathology where he is an Associate Director in the Division of Transfusion Medicine. Dr. Evan Bloch is an Assistant Professor at Johns Hopkins University in the Department of Pathology and an Associate director in the Transfusion Medicine division at Johns Hopkins Hospital.

His major interests include both transfusion transmitted babesiosis and other neglected infectious diseases, particularly in the context of international blood safety. His interest in babesiosis was spurred by a case of transfusion-transmitted babesiosis during his transfusion medicine fellowship. He has since participated in studies of assay development and cost effectiveness related to transfusion screening in the United States.

Dr. Bloch is originally from South Africa where he completed his medical school (University of Cape Town) and clinical training, which first spurred an interest in infectious disease. Following completion of a combined residency in Anatomic and Clinical Pathology (Tufts Medical Center), post-graduate fellowship in Transfusion Medicine (University of California San Francisco [UCSF]) and Masters in Global Health (UCSF) he continued research at Blood Systems Research Institute, while continuing to teach at UCSF in Laboratory Medicine and Global Health Sciences. He joined the faculty of at Johns Hopkins University in the Department of Pathology in 2015.

Dr. Bloch has long been interested in babesiosis and other transfusion transmitted infections. Babesiosis is a tick-borne parasitic infection that is endemic to parts of the United States. Although infection is characterized by mild illness (e.g. flu-like symptoms) in immune competent adults, it poses significant risk to those patients at extremes of age, the immunocompromised and the asplenic. These high-risk groups are notably overrepresented among the transfused population accounting for complicated disease and even death in transfusion-transmitted babesiosis (TTB). Despite an increase in both naturally acquired- and TTB, there are currently no effective strategies to prevent TTB, nor any FDA licensed tests for blood product screening. Dr. Bloch has participated in studies to develop both antibody and molecular testis for detection of Babesia in blood donors. The studies have also been used to understand the biology of Babesia infection.

Dr. Bloch is also interested in blood safety in resource-constrained settings. He is an investigator on the Recipient Epidemiology and Donor Evaluation Study (REDS-III) in South Africa where he has helped lead a series of studies on transfusion practice and HIV in the obstetric population. Blood transfusion is a severity outcome measure for a variety of disease states; as such it can be used to highlight deficiencies in care, thereby informing rational intervention. Dr. Bloch also participated in an evaluation of transfusion infectious screening in twelve African countries; the findings highlighted the challenges surrounding extant testing methods and emphasized the need for proficiency testing for donor screening in Africa. He has been actively involved in education and operational outreach related to blood safety in Africa.

Dr. Bloch’s research has been funded through the National Heart, Lung and Blood Institute of the National Institutes of Health (NIH) through SBIR and R21 grant mechanisms.

The author of 27 peer-reviewed publications, Dr. Bloch is a member of the International Society of Blood Transfusion infectious disease working party (co-chair parasite sub-group) and has consulted on policy and development of clinical transfusion guidelines. He continues to be interested in rare and neglected infections and hopes to use blood transfusion as a platform for infectious surveillance so as to guide programmatic support, particularly in low-resource settings.


Conference Lecture Summary

Babesiosis is the clinical illness named for infection by Babesia, a genus of tick borne, intraerythrocytic protozoan parasites that are endemic to parts of the United States (US). Babesia is readily transfusion transmissible: following an increase in naturally acquired- (i.e. tick borne) and transfusion transmitted babesiosis (TTB) in the US, TTB, the overwhelming majority of which is caused by Babesia microti, has been recognized as the foremost infectious risk to the US blood supply for which licensed donor screening is still not available. Change is underway whereby new tools have been developed, including novel assays and pathogen reduction technology. The purpose of this talk is to discuss Babesia as a model for understanding the response to an emerging infectious disease in the context of blood safety. The talk will include lessons that were learned during the evolution from recognition of risk, to selection of a mitigation strategy, research and development through to implementation and policy. While nuanced challenges may be specific to babesia, the same principles apply to other pathogens, both known as well as emerging.

 




Miklossy, Judith

MiklossybJudith Miklossy MD, PhD, DSc
Director, International Alzheimer Research Center
President then Director, Prevent Alzheimer International
Switzerland
www.miklossy.ch
www.prevetionalzheimer.org

“Historic and Recent Evidence that Spirochetes Are Able to Reproduce the Clinical, Pathological and Biological Hallmarks of Alzheimer’s Disease.”

Dr. Miklossy, founder, Prevention Alzheimer International Foundation and director, International Alzheimer Research Center in Switzerland (CH) also practices memory and Lyme disease consultation in Vigimed Medical Center, CH. She is board certified in neurology, psychiatry and psychotherapy (Faculty of Medicine, University of Debrecen, Hungary) and in neuropathology (Swiss Society of Neuropathology and Swiss Medical Federation). She has received the degrees of Private docent (Dr habil or DSc) and Maître d’Enseignement et de Recherche (MER) in the University Hospital Center of Lausanne (CHUV), University of Lausanne. She was head of the Neurodegeneration research group for more than ten years in the University Institute of Pathology, Lausanne, CH.

She has done molecular biology research and participated in the introduction of Alzheimer’s research in the Center of Neurovirology, Department of Neuroscience, Temple University, Philadelphia.. She headed the neuropathology of the Kinsmen Laboratory of Neurological Research, in The University of British Columbia, Vancouver, Canada. She is on the board of directors or scientific advisory board of several international organizations or foundations.

For more than 25 years she is actively involved in research on Alzheimer’s disease and Lyme disease in the framework of international collaborations. Her presentations on international meetings and her publications were repeatedly considered for CME and press releases.

Our research interests include the pathogenesis of Alzheimer’s disease (AD) and other neurodegenerative and chronic inflammatory disorders. From 1993 my research focused on the role of bacteria, particularly of spirochetes, in persistent chronic infection, inflammation and amyloidogenesis in AD.

A century ago, Fischer (1907) has been suggested and Alois Alzheimer and his colleagues cited his view on the possibility that microorganisms might play a role in senile plaque formation. Additionally, there is an example in the history of medicine that chronic bacterial infection, namely chronic spirochetal infection (Treponema pallidum can cause slowly progressive dementia & reproduce the pathological and biological hallmarks of AD.

Increasing amount of recent data indicate, as we have suggested in 1993, that several types of spirochetes, including Borrelia burgdorferi and periodontal pathogen spirochetes are involved in the pathogenesis of AD. Recently, reviewing all data available in the literature a statistically strongly significant association, with a high risk factor was found between spirochetes and AD, fulfilling Hill’s criteria in favor of a causal relationship.

Exposure of human and mammalian primary CNS cells and organotypic cultures to spirochetes, showed that similarly to Treponema pallidum, Borrelia burgdorferi reproduces the pathological and biological hallmarks of AD (increased AβPP, Aβ and (p)tau levels).

Now from three decades we are involved in Lyme disease research. We have published the first pathological confirmation of the meningovascular form of chronic or late Lyme neuroborreliosis leading to cerebral vascular infarcts. Together with other authors we contributed to the pathological confirmation of the other major form of chronic Lyme neuroborreliosis, which is identical to the atrophic form of general paresis associated with slowly progressive dementia caused by Treponema pallidum in syphilis. We presented evidences on the direct involvement of Borrelia burgdorferi in the major tertiary forms of chronic Lyme neuroborreliosis. On invitation we contributed with a chapter on the pathology and biology of dementia in syphilis and Lyme disease in the prestigious Handbook of Clinical Neurology.

We have published observations on the presence of various pleomorphic forms, including the more resistant cystic, granular and L forms of Borrelia burgdorferi, in pure Borrelia cultures in infected cell cultures and in brains of demented patients with clinically, serologically and pathologically confirmed Lyme neuroborreliosis. We have also shown that Borrelia burgdorferi spirochetes cultivated from thebrains of these patients are virulent and invade neuronal and glial cells and cause apoptosis. Recently, reviewing descriptions and illustrations available on the pathology of Lyme neuroborreliosis from the past 30 years, we reported that the major late or chronic forms of neurosyphilis were pathologically confirmed in Lyme disease as well and Borrelia burgdorferi was cultivated from tertiary lesions by various authors. These observations definitely indicate that chronic Lyme disease exists and Borrelia burgdorferi, similarly to Treponema pallidum plays a direct role in the pathogenesis of the tertiary manifestations of chronic/late Lyme disease.


Conference Lecture Summary

That pathogens suppress, subvert or evade host defences and establish chronic or latent infection had received little attention in the past. Various spirochetes, including Treponema pallidum (T. pallidum), Borrelia burgdorferi (B. burgdorferi) and several periodontal pathogen spirochetes have the ability to escape host defences and establish chronic infection. Various spirochetes, in an analogous way to Treponema pallidum, are involved in the pathogenesis of several chronic disorders including cerebrovascular disorders and in slowly progressive cognitive decline with dementia.

T. pallidum, B. burgdorferi, and periodontal pathogen Treponemes (T. denticola, T. pectinovorum, T. amylovorum, T. maltophilum, T. medium, T. socranskii) persisting in the brain cause dementia and beta amyloid deposition. The two major tertiary forms of chronic neuroborreliosis, namely the meningovascular form with cerebral infarcts and cognitive decline resulting in dementia have been clinically and pathologically confirmed more that 20 years ago, indicating that Borrelia burgdorferi can cause chronic Lyme disease and chronic neuroborreliosis.

Spirochetes, including Borrelia burgdorferi are able to reproduce in vitro and in vivo the pathological and biological hallmarks defining AD dementia. A strong statistically significant association between spirochetes and AD fulfills Hill’s criteria and confirms a causal relationship between spirochetes and dementia. Validation of these observations by historic and recent reports further confirm that senile plaques are made up by spirochetes and correspond to biofilms. That host pathogen interactions in chronic spirochetal infection are identical to those occurring in AD indicates that escaping host immune reactions, spirochetes, including Borrelia burgdorferi, sustain chronic infection and cause, in addition to cerebral infarcts, slowly progressive dementia associated with amyloid deposition in the brain. Association of co-infecting pathogens and formation of multi-bacterial biofilms further aggravate the degenerative process and the outcome of dementia. Importantly, these observations indicate that Alzheimer’s dementia can be prevented.




Moir, Robert

MoirRobert Moir, PhD
Assistant Professor in Neurology, Genetics and Aging Research Unit
Massachusetts General Hospital and Harvard Medical School, Charlestown, MA

“Aβ, Alzheimer’s, and Lyme Disease”

Dr Moir complete his Ph.D at the University of Melbourne in Australia under the mentorship of Prof Colin Masters, one of the founders of the modern field of Alzheimer’s disease (AD) research. Dr Moir immigrated to the US in 1994 and joined the Genetics and Aging Research Unit (GARU) shortly after the group’s formation. Dr Moir now heads his own research lab within GARU and has been a faculty member of Harvard Medical School and Massachusetts General Hospital since 1998. Dr Moir’s research focus is the interaction of biomolecules involved in AD pathology.

Dr Moir’s research focuses on the biochemical and cellular mechanisms of neurodegeneration in Alzheimer’s disease (AD) and aging. His work has uncovered new therapeutic targets aimed at preventing the accumulation of beta-amyloid (Aβ), the primary neurotoxic agent in AD. Moir was the first to identify the low-density lipoprotein receptor protein (LRP) as the mediator of an important early step in Aβ production in the brain. Today, LRP-mediated Aβ clearance pathways are increasingly recognized as major targets for therapeutic intervention. His work revealed the importance of metals in the pathological aggregation of Aβ, leading directly to the investigation of the copper and zinc chelator clioquinol in clinical trials for AD. Dr Moir has also helped establish Aβ’s role in the formation of eye lens cataracts in AD patients, which could lead to better diagnosis of the disease.

His studies on the immune response to amyloid have revealed potential abnormalities in protective Aβ-reactive autoantibodies in AD patients. Therapeutic strategies for AD that are based on this find have lead to the development of artificial antibodies currently in third phase clinical trials. Dr Moir’s most recent studies have identified the normal biological function of Aβ. Aβ is a member of the antimicrobial peptide family of innate immune proteins. Antimicrobial peptides are natural antibiotic that acts as part of the innate immune system to trap and kill pathogens invading the brain. This novel discovery suggests AD may be an inappropriate response to a real or falsely perceived infection in the brain. This finding may also shed light on the pathological mechanisms associated with other major amyloid-associated diseases, including diabetes and arteriosclerosis.


Conference Lecture Summary

Recent confirmation of a protective antimicrobial role for the amyloid-β (Aβ) protein of Alzheimer’s disease (AD) has fueled debate on the role of infection in AD etiology. Aβ appears to belong to the antimicrobial peptide (AMP) family of immune proteins. AMPs are natural antibiotics and immunomodulators that act as the foot soldiers of innate immunity. Infection in transgenic animal models of AD leads to protective entrapment of microbes within β-amyloid plaques. Deposition of β-amyloid is a histological hallmark of AD. Here we discuss pathways leading to β-amyloid mediated microbial entrapment and the implications of Aβ’s emerging innate immune role for an AD/Lyme disease link.