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Occi, James L.

OcciJames L. Occi, MS, MA, PhD (in progress)
Center for Vector Biology, Department of Entomology
Rutgers University, New Brunswick, NJ
Research/Teaching Specialist
Rutgers New Jersey Medical School, Newark, NJ

Tick-Borne Disease Ecology: New Jersey, A Microcosm of the Northeastern US

James (Jim) Occi is a microbiologist who has been involved in searching for new antibiotic entities for almost 30 years. He has done research in big pharma for over 20 years and continues this endeavor as a research microbiologist at New Jersey Medical School in the Department of Emerging Pathogens (Newark).  Jim is pursuing his PhD at Rutgers University at the Center for Vector Biology (New Brunswick) and wants to be a medical entomologist when he grows up. For his thesis, Jim is studying tick-borne diseases in New Jersey tick populations under the direction of Dr. Dina Fonseca. He has a BS and MA in Biology from Montclair State University and an MS in Microbiology from Seton Hall University.

Note: Thanks to James L. Occi for replacing the scheduled speaker, Dr. Jerath, who was unable to attend.


Conference Lecture Summary

New Jersey is a microcosm of the entire northeastern US in terms of tick-borne disease ecology.  There are areas of high elevation, low elevation, deciduous forest, outer coastal plain and beaches. The three primary species of human-biting ticks in New Jersey are the blacklegged tick, the American dog tick and the lone star tick.  Things are not what they seem though. The de facto vector of Rocky Mountain Spotted Fever (RMSF) is the American dog tick.  However, Rickettsia rickettesii (the agent of RMSF), is rarely found in these ticks. Another observation in New Jersey is that there are a number of cases of human ehrlichiosis (caused by Ehrlichia spp) in northern New Jersey, but the vector of Ehrlichia spp (the lone star tick) has not been reported in the northern counties. My thesis is simple:  More tick-borne disease surveillance is needed to (1) explain these anomalies and (2) help protect the public from tick-borne diseases by identifying areas with potential risks.




Johnson, Lorraine

Lorraine Johnson, JD, MBAHS Johson
CEO, LymeDisease.org
Principle Investigator, MyLymeData
Member of Patient Centered Research Outcomes Institute, Expert Panel Open Access
Steering Committee, Consumers United for Evidence-Based Healthcare
Lymedisease.org

MyLymeData: The Value of Using Big Data and Subgroup Analysis in Lyme Disease

Lorraine Johnson, JD, MBA, is the Chief Executive Officer of LymeDisease.org, which launched the first national Lyme disease patient driven registry and research platform, MyLymeData in 2015. The registry has enrolled over 8,000 patients and is in the top 10% of patient registries in the nation.
She has published over 40 peer-reviewed articles on issues related to Lyme disease, including two large scale patient surveys and two commentaries on big data and patient-powered research networks. (Johnson, et al. 2011; Johnson, et al. 2014 ; Stricker and Johnson 2016; Fleurence RL, Beal AC, Sheridan SE, Johnson LB, Selby JV) She co-authored the treatment guidelines of the International Lyme and Associated Diseases Society.

She currently serves on the Open Science Expert Panel of the Patient Centered Outcomes Research Institute (PCORI). She has also served as a patient representative of the Patient Engagement Advisory Panel for PCORI, sat on the Executive and Steering committees of PCORI’s patient-centered big-data project, PCORnet, and chaired its Patient Council. She participated in the White House Citizen Science convening on precision medicine. She serves on the steering committee of Consumers United for Evidence-Based Healthcare, a nationwide coalition of consumer groups associated with the international Cochrane Collaboration.

She has spoken before government and scientific conferences nationally and internationally including as a plenary speaker at the Cochrane Colloquium, at the Stanford MedX conference, and at the National Institute of Health Collaboratory. She presented at the American Association for the Advancement of Science annual meeting on the topic of Big Data and Patient Powered Research.


 Conference Lecture Summary

In 2015, LymeDisease.org launched the first national Lyme disease patient centered registry and research platform, MyLymeData. The registry has enrolled over 8,000 patients and is in the top 10% of patient registries in the nation. The registry will be used to answer questions that are important to patients and to track real world treatment effectiveness and quality of care improvement. It will also be used as a framework for clinical trials. This presentation will focus on patient-generated data from Phase 1 of MyLymeData and the value of subgroup analysis using big data. This will be illustrated with examples drawing on chronic Lyme disease case definitions, average treatment effect verses subgroup analysis of treatment effect, and the use, effectiveness, and side effects associated with different alternative therapies.

 




Jaradeh, Safwan

JaradehSafwan Jaradeh, MD
Professor of Neurology and Neurological Sciences
Autonomic and Neuromuscular Disorders
Stanford University School of Medicine
Stanford, CA
http://neurology.stanford.edu/faculty/overview.html
https://med.stanford.edu/profiles/safwan-jaradeh

Autonomic Dysfunction in Post-Infectious States

Clinical interests include autonomic disorders, small fiber neuropathies and the development of effective methods of testing and treating these disorders. Prior work has focused on small fiber painful and autonomic neuropathies; syndromes of orthostatic intolerance and syncope; gastrointestinal motility dysfunction; cyclic vomiting; protacted Gastroesophageal Reflux; non-allergic rhinitis syndromes; and the relationship between the autonomic nervous system and normal or abnormal sleep. Additional areas of interest include the neurology of phonation and swallowing disorders, and peripheral nerve injury and repair.


Conference Lecture Summary

A significant number of patients complain of persistent symptoms following the recovery from an acute infection. Many of the symptoms have a neurologic profile, but often neurologic traditional testing, such as imaging, EEG, evoked potentials, nerve conductions and EMG are either normal or non-contributory. However, quantitative autonomic testing in these patients often reveals abnormalities that shed light on the nature of their symptoms, and guide some of the pharmacologic and non-pharmacologic management. The purpose of the presentation is to review the current state of art of autonomic testing, and the most common findings in these patients who have persistent, post-infectious symptoms.

 




Fallon, Brian

FallonBrian A. Fallon, MD, MPH (Conference Director)
Professor of Psychiatry,
Director, Lyme and Tick-Borne Diseases Research Center,
Columbia University Medical Center;
Director, Center for the Study of Neuroinflammatory Disorders & Biobehavioral Medicine,
New York State Psychiatric Institute
New York, NY
baf1@columbia.edu
Lyme and Tick-Borne Diseases Research Center

Why do Symptoms Persist?

Brian A. Fallon, MD, MPH. Dr. Fallon is director of the Lyme & Tick-borne Diseases Research Center at Columbia University Medical Center where he leads a team focused on biomarkers, diagnostics and treatment of chronic Lyme symptoms. His team’s recent work has included the testing of novel diagnostic assays in a large community study, with the net result of the identification of a more sensitive Lyme Western blot. His team’s work on Lyme encephalopathy led to the discovery of hundreds of unique proteins present in the CSF of Lyme patients but not in the CSF of patients with chronic fatigue syndrome or healthy controls. His team’s current focus is on clarifying the immunologic profile and neural circuitry of patients with persistent symptoms. His team is also investigating the CNS metabolic effects of intravenous ceftriaxone using MR Spectroscopy to probe glutamatergic transmission. Dr. Dwork in his Center is examining the neuropathologic findings in post-mortem studies of patients with chronic Lyme symptoms. Dr. Moeller in his Center is examining the interaction between peripheral immunologic markers, central immune markers, and brain neurocircuitry among patients with chronic symptoms with the goal of identifying of biomarkers to help guide treatment recommendations.

Dr. Fallon serves on the editorial and review board of three journals, has lectured and published widely, and most recently has led an international team for the American Psychiatric Association’s revision of DSM-5 to clarify the prevalence of illness anxiety in the general population.


Conference Lecture Summary

Persistent symptoms after a course of antibiotic therapy can cause considerable distress, functional impairment, and controversy between patients and doctors and between doctors themselves. This talk will review the evidence in support of several potential causes of symptom persistence: persistent infection, tissue damage from prior infection, altered immune activation, altered brain neural networks, altered microbiome, unrecognized other diagnoses.




Embers, Monica

EmbersMonica E. Embers, PhD
Tenure-Track Assistant Professor
Division of Bacteriology and Parasitology
Tulane National Primate Research Center
Covington, LA
http://www.tnprc.tulane.edu/division_bacteriology.html

The Challenges of Diagnosing and Curing Late Stage Lyme Disease

Monica E. Embers obtained her Ph.D. in the Department of Microbiology and Immunology at the Pennsylvania State University College of Medicine in Hershey, P.A., where she studied immune responses to Papillomaviruses. She made the transition to the study of bacterial pathogenesis when performing her postdoctoral research on the Lyme disease spirochete at the Tulane National Primate Research Center (TNPRC). She subsequently joined the faculty at the TNPRC. Her research program regarding Borrelia burgdorferi and Lyme disease is designed around three major foci: (1) evaluating antibiotic efficacy against Lyme disease; (2) identifying treatments that can eradicate B. burgdorferi infection; and (3) immunodiagnosis for B. burgdorferi infection and cure. The first research goal is to examine, using xenodiagnosis, the efficacy of antibiotic treatment during disseminated B. burgdorferi infection in the nonhuman primate model of Lyme disease. The second goal is to use animal models of persistent infection to evaluate new therapeutic strategies. The third goal is to develop a quantitative multi-antigen test that expands detection limits and helps to distinguish persistent infection from clinical cure. By transmitting Lyme disease to nonhuman primates by tick, and studying the natural course of infection, her group hopes to facilitate a better understanding of the clinical quandaries of human Lyme disease, including effective diagnosis and treatment.


Conference Lecture Summary

According to recent estimates, the number of new Lyme disease cases in the United States may exceed 300,000 per year. Given the breadth of clinical manifestations that can result from infection with the spirochete Borrelia burgdorferi, reliable laboratory diagnostic testing is essential. Currently, the two-tier test which involves an initial enzyme immunoassay followed by a confirmatory western blot is the standard. However, this serological testing falls short in sensitivity, especially in the early/acute phase. Another significant issue is the proportion of patients who continue to experience signs and/or symptoms of disease following antibiotic therapy. This phenomenon, known as post-treatment Lyme disease syndrome (PTLDS) may be defined by fatigue, musculoskeletal pain, and cognitive problems that persist for 6 months or more after completion of antibiotic therapy. It is clear that two-tier serologic testing is neither sensitive nor specific enough for diagnosis of PTLDS because of variability in serologic responses after treatment of early Lyme disease. A multiplex assay that utilizes Luminex® technology has been developed and includes five antigens (OspA, OspC, DbpA, OppA-2 and the C6 peptide). We are using this test to identify differences in serum responses during early disease and in PTLDS. Initial studies indicate a significant improvement over two-tier for detecting exposure in PTLDS patients.

The efficacy and accepted regimen of antibiotic treatment for Lyme disease has been a point of significant contention among physicians and patients. While experimental studies in animals have offered evidence of post-treatment persistence of B. burgdorferi, variations in methodology, detection methods and limitations of the models have led to some uncertainty with respect to translation to human infection. We sought to mimic human infection and treatment in the closest animal model, namely, the nonhuman primates. Rhesus macaques were inoculated with B. burgdorferi by tick bite and a portion were treated with recommended doses of doxycycline for 28 days at four months post-infection. Signs of infection, clinical pathology, and antibody responses were monitored throughout the ~1.2 year study. Our results demonstrate host-dependent signs of infection and variation in antibody responses. In addition, we observed evidence of persistent, intact, metabolically-active B. burgdorferi and associated foci of inflammation in central and peripheral nervous tissue, joints and heart after antibiotic treatment of the disseminated infection.

 




Ehrlich, Garth

Garth D. Ehrlich, PhD, FAAASEhrlich
Professor of Microbiology & Immunology
Executive Director, Center for Biofilms and Chronic Infections
Drexel University College of Medicine
Philadelphia, PA
http://drexel.edu/medicine/Faculty/Profiles/Garth-Ehrlich/

Development of Pan-Domain Diagnostics to Provide Accurate and Comprehensive Analyses of Lyme Disease and Tick-Borne Co-Infections

Dr Ehrlich is Professor of Microbiology and Immunology, and Otolaryngology-Head and Neck Surgery at Drexel University College of Medicine (DUCOM) in Philadelphia, PA, USA. He also directs both the Center for Genomic Sciences (CGS) and the Center for Advanced Microbial Processing (CAMP) within the Institute for Molecular Medicine and Infectious Disease, and the Core Genomics Facility within the Clinical and Translational Research Institute. CGS scientists utilize a broad array of comparative genomic techniques and bioinformatic tools, many developed in-house, to identify and characterize both virulence genes within pathogens, and susceptibility genes to pathogens within their hosts. Dr Ehrlich is also one of the founders of the field of Clinical Molecular Diagnostics (MDx), having been involved in the original application of PCR for the detection of human retroviruses in 19851. He founded the MDx Division at UPMC and used these experiences to author the first text book/lab manual for infectious disease (ID) MDx2. Together with a team of like-minded pioneers he was one of the founders of the Association for Molecular Pathology and served as the first co-chair of the ID section. Dr Ehrlich counts among his major contributions to science the mapping and cloning of several major human disease genes3,4, and the re-writing of much of our understanding of chronic bacterial pathogenesis5,6. This began with his promulgation of the biofilm paradigm to explain many facets of chronic mucosal microbial infections7-9. Working with Chris Post, he started his explorations into chronic middle-ear disease in children in the early 90’s which he has since repeatedly generalized such that it is now widely accepted that the vast majority of all chronic microbial infections are biofilm-associated10,11. He also advanced the Distributed Genome Hypothesis (DGH12,13) to explain the enormous clinical variability among strains of a bacterial species, which together with the biofilm paradigm form the bases for his rubric of Bacterial Plurality3,4. His work in human genetics combined with the laboratory resources necessary to test the DGH have resulted in his having played a role in the development of several waves of genomic technology over the last quarter century including microsatellite mapping, microarrays, and next-generation sequencing. More recently he has developed the concept of bacterial population-level virulence factors and has used statistical genetics for the first time within the field of bacterial genomics to identify distributed genes that are associated with virulence. This computational methodology provides a non-biased, top-down approach to prioritize the annotation of hypothetical genes14. Coincident with the recent relocation of his research enterprise to DUCOM he founded CAMP which functions as a collaborative multi-discipline facility for exploitation of a suite of technological advances, many developed within the CGS, which permit the identification, cloning, heterologous expression, and biochemical verification of commercially important biosynthetic and biodegradative pathways from what he refers to as the “Genomic Dark Matter”. This approach came out his successful collaborative studies with Dr. David Sherman at the University of Michigan wherein they used multiple omics technologies (and developed the term meta-omics) to isolate and characterize all of the genes for a novel biosynthetic pathway for an important anti-cancer drug from an unculturable endosymbiotic bacterium of a tunicate. Dr. Ehrlich’s lifelong interest in emergent MDx2 and “omic” technologies led to his recent appointment as Director of the Meta-Omics Core Facility at the Sidney Kimmel Cancer Center, a consortium NCI-designated Cancer Center involving Thomas Jefferson University and Drexel University. Dr Ehrlich’s latest paradigm-changing hypothesis is that Alzheimer’s disease results from a combination of chronic bacterial infections of the brain (primarily originating from the periodontium) and the brain’s anti-microbial and inflammatory responses to these infections. Dr. Ehrlich was elected as fellow of the American Association for the Advancement of Science in 2014.

  1. Kwok, S., Mack. D.H., Mullis, K.B., Poiesz, B., Ehrlich, G., Blair, D., Friedman-Kien, A., and Sninsky J.J.: Identification of human immunodeficiency virus sequences by using in vitroenzymatic amplification and oligomer cleavage detection. J. Virology, 61:1690-1694, May 1987.</>
  2. Ehrlich, G.D., and Greenberg, S.J.: PCR-Based Diagnostics In Infectious Disease. Boston: Blackwell Scientific Publications, 1994, 697 pages.
  3. Preston, R.A., Post, J.C., Keats, B.J.B., Aston, C.E., Ferrell, R.E., Priest, J., Nouri, N., Losken, H.W., Morris, C.A., Hurtt, M.R., Mulvihill, J.J., and Ehrlich, G.D. A gene for Crouzon craniofacial dysostosis maps to the long arm of chromosome 10. Nature Genetics 7:149-153, 1994
  4. Whitcomb, D.C., Gorry, M.C., Preston, R.A., Furey, W.F., Sossenheimer, J.J., Ulrich, C.D., Martin, S.P., Gates, L.K. Jr., Amann, S.T., Toskes, P.P., Liddle, R., McGrath, K. Uomo, G., Post, J.C., and Ehrlich, G.D.^ Hereditary pancreatitis is caused by a mutation in the cationic trypsinogen gene. Nature Genetics 14:145, 1996.</>
  5. Ehrlich, G.D.^, Ahmed, A., Earl, J., Hiller, N..L, Costerton, J.W., Stoodley, P., Post, J.C., DeMeo, P., and Hu, .FZ. The Distributed Genome Hypothesis as a Rubric for Understanding Evolution in situ During Chronic Infectious Processes. FEMS Immunology and Medical Microbiology. 2010 Aug;59(3):269-79.
  6. Ehrlich, G.D., Hu, F.Z., Shen, K., Stoodley, P., Post, J.C., Bacterial Plurality as a General Mechanism Driving Persistence in Chronic Infections. Clinical Orthopaedics and Related Research 437:20-24, 2005.
  7. Rayner, M.G., Zhang, Y., Gorry, M.C., Chen, Y., Post, J.C., and Ehrlich, G.D. Evidence of bacterial metabolic activity in culture-negative otitis media with effusion. JAMA 279:296-299, 1998.
  8. Ehrlich, G.D., Veeh, R., Wang, X., Costerton, J.W., Hayes, J.D., Hu, F.Z., Daigle, B.J., Ehrlich, M.D., Post, J.C. Mucosal Biofilm Formation on Middle-ear Mucosa in the Chinchilla Model of Otitis Media. JAMA 287:1710-1715, 2002.
  9. Hall-Stoodley, L., Hu, F.Z., Stoodley, P., Nistico, L., Link, T.R., Burrows, A., Post, J.C. Ehrlich, G.D., and Kerschner, K.E. Direct Detection of Bacterial Biofilms on the Middle-Ear Mucosa of Children With Chronic Otitis Media. JAMA 296:202-211, 2006.
  10. Costerton, J.W., Veeh, R., Shirtliff, M., Pasmore, M., Post, J.C. and Ehrlich, G.D. The application of biofilm science to the study and control of chronic bacterial infections. Journal of Clinical Investigation 112(10):1466-77 2003
  11. Wolcott, R.D., and Ehrlich, G.D. Biofilms and Chronic Infections. 2008 JAMA Jun *11;299(22):2682-4
  12. Hogg, J.S., Hu, F.Z., Janto, B., Boissy, R., Gladitz, J., Swierczek, N., Hayes, J., Keefe, R., Yu, S., Post, J.C., and Ehrlich, G.D. Characterization and Modelling of the Haemophilus influenzae Core and Supra-Genome based on the Complete Genomic Sequences of Rd and 12 clinical Nontypeable16 Strains. Genome Biology. 8(6)R103, 2007
  13. Hiller, N.L., Ahmed, A., Powell, E., Eutsey, R.E., Earl, J., Martin, D., Janto, B., Hogg, J.S., Boissy, R., Barbadora, K., Post, J.C., Hu, F.Z., and Ehrlich, G.D. Generation of Genic Diversity among Streptococcus pneumoniae Strains via Horizontal Gene Transfer during a Chronic Polyclonal Pediatric Infection. PLoS Pathogens 6(9): e1001108, 2010
  14. Kress-Bennett, J., Hiller, N.L., Eutsey, R., Powell, E., Longwell, M.J., Hillman, T., Blackwell, T., Byers, B., Post, J.C., Hu, F.Z., Ehrlich, G.D., and Janto, B. Identification and Characterization of msf, a Novel Virulence Factor in Haemophilus influenzae PLoS ONE 11(3):e0149891, 2016
  15. Rath, C.M., Janto, B., Earl, J., Ahmed, A., Hu, F.Z., Hiller, N.L., Dahlgren, M., Kreft, M., Yu, F., Wolff, J.J., Kweon, H.K., Christiansen, M.A., Håkansson, K., Williams, R.M., Ehrlich, G.D., Sherman, D.H. Meta-omic characterization of the marine invertebrate microbial consortium that produces the chemotherapeutic natural product ET-743. ACS Chemical Biology 6(11):1244-56, 2011.

Conference Lecture Summary

Lyme disease, strictly speaking, is defined as infection by the tick-borne spirochete, Borrelia burgdorferi. B. burgdorferi itself reveals extensive genomic plasticity which manifests itself clinically as highly variable disease symptoms in infected individuals. These include great variations in the severity of the disease, the chronicity of the disease, and the tissue tropism. However, this complexity is combinatorically amplified as there are both several other tick-transmitted Borrelial species that cause similar symptoms; and in a high proportion of cases the transmitting tick bite will also result in infection with one or more other pathogens which can be viral, bacterial (including Rickettsia and other obligate intracellular bacterial pathogens), or even eukaryotic parasites. Thus, both the epidemiological characterization of region-specific endemic tick populations and the diagnosis of tick-borne infections requires multiple pan-domain technologies to determine the spectrum of co-infections, as well as strain specific diagnostics once the species are determined. Only then will it be possible to provide adequate therapeutic and prognostic information for the management of affected persons. Toward these ends we have been developing pan-domain, species-specific rRNA gene-based diagnostics for both bacterial and eukaryotic pathogens using the third generation, long-read DNA sequencing system produced by Pacific Biosciences (PacBio). This platform provides for circular consensus sequencing of entire genes (16S for bacteria and 18S + ITS for eukaryotes). Therefore, it is possible for the first time to perform error correction on single molecule sequencing which provides highly accurate species-specific analysis. Co-incident with the development of the laboratory methods we also developed and validated a multi-step data processing algorithm which eliminates the over-calling of the number of taxa present, and constructed new databases to support the long-read technology. Data will be presented showing the fidelity of these systems using blinded complex microbiota challenge sets. This will be followed by investigations of patient specimens and tick microbiomes.




Cadavid, Diego

CadavidDiego Cadavid, MD
Adjunct Associate Professor, Neurology and Neuroscience
New Jersey Medical School, Rutgers, Newark, NJ
Vice President of Clinical Development
Fulcrum Therapeutics, Cambridge, MA
http://njms.rutgers.edu

Treatment of Neurological Lyme Disease

Dr. Diego Cadavid graduated in Medicine and Surgery from the Pontificia Universidad Javeriana in Bogotá, Colombia, in 1991 followed by 3 years of Post-doctoral training in Microbiology and Immunology at The University of Texas Health Science Center in San Antonio, Texas (UTHSCSA), 1 year Internship in Internal Medicine also at UTHSCSA, 3 years of Clinical Neurology Residency training at Georgetown University and 1 year Fellowship training in Neuropathology at the Armed Forces Institute of Pathology, both in Washington, DC. He was for nearly 10 years a Faculty Member in the Department of Neurology and Neuroscience at Rutgers-New Jersey Medical School in Newark, NJ. Between 2008 and 2016 he was a member of the Neurology Clinical Development Group at Biogen in Cambridge, MA and lead of the CNS remyelination Development Group. Between 2008 and 2015 he was Consultant at the Center for Immunology and Inflammatory Diseases at Massachusetts General Hospital in Boston. Over his 25 years career since graduation from Medical School Dr. Cadavid has worked in clinical practice, basic research, clinical research, education, and administration in academia and the biopharmaceutical industry. He has published over 100 peer-reviewed publications, review papers, and book chapters on the fields of borrelial infections (relapsing fever and Lyme disease), multiple sclerosis, cerebral infarction, and progressive multifocal leukoencephalopathy. He is currently Vice President of Clinical Development at Fulcrum Therapeutics, a start-up biotechnology company seeking to develop small molecule treatments for genetic diseases of gene regulation, including Fragile X syndrome and FSHD. He has a non-active medical license in Massachusetts and is currently adjunct Associate Professor of Neurology at Rutgers-New Jersey Medical School, and Fellow of both the American Academy of Neurology and the American Neurological Association. He is married with 3 children.


Conference Lecture Summary

In humans, Borrelia burgdorferi causes Lyme disease. People become infected when bitten by ticks carrying the bacterium. The person may experience symptoms in the joints, skin, muscles, and nervous system (peripheral nerves (nerves outside the brain and spinal cord), the brain, and the spinal cord). Without antibiotic treatment, neurological Lyme disease either may resolve or cause long-term problems. Neurological Lyme disease differs between Europe and the United States, probably because of differences in B. burgdorferi. Limited information exists about which antibiotics are better for the treatment of neurological Lyme disease. A recently completed Cochrane review of the existing evidence found seven trials studying antibiotic treatments for neurological Lyme disease. All but one trial compared different antibiotics. The other trial compared the treatment effects of oral amoxicillin to placebo following initial ceftriaxone treatment. The trials included 450 Europeans. The antibiotics tested were penicillin G, doxycycline, ceftriaxone, and cefotaxime. One of the trials involved children only, while the others included mostly adults. We only selected studies in which treatment allocation was determined by chance (randomly), as such studies provide the best information for comparing the effects of different treatments. Most studies were not blinded (meaning that those taking part and the study staff knew the treatment being given). We could not find any studies of antibiotic treatments for neurological Lyme disease from the United States. No studies assessed the effects of delaying the start of treatment. The seven studies were too different for their results to be combined, so they were analyzed individually. The results showed that none of the studies provided clear evidence that one antibiotic was better than another. One study failed to find evidence that a second and longer treatment with an oral antibiotic (amoxicillin) offered any extra benefit following initial intravenous treatment with ceftriaxone. As none of the other studies used a dummy treatment (placebo), the extra benefit offered by antibiotic treatment over recovery that occurs naturally is unknown. In general, the treatment was tolerated well, although the quality of adverse event reporting in most studies appeared to be low. This systematic review of the existing literature indicate that treatment with penicillin G, doxycycline, ceftriaxone, and cefotaxime produced similarly good outcomes for treatment of neurological Lyme disease in Europe. A second treatment with amoxicillin does not appear to provide added benefit to ceftriaxone. We found no trials of antibiotics for treatment of neurological Lyme disease in the United States that met our inclusion criteria.




Ahmet Z. Burakgazi, MD

BurakgaziAhmet Z. Burakgazi, MD
Associate Professor
Neuroscience Section/Department of Neurology
Virginia Tech Carilion School of Medicine
Roanoke, VA
azburakgazi@carilionclinic.org

Case Report: Optic Neuritis and Probable Lyme Disease

Ahmet Burakgazi, MD is currently an Associate Professor in the Department of Medicine. He is board certified in neurology by ABPN and clinical neurophysiologist by AANEM EMG board. After successfully completion of neurology residency and fellowship training in clinical neurophysiology-EMG track at George Washington University, he joined to Virginia Tech Carilion School of Medicine in 2011. He has successfully established my own outpatient clinic diagnosing and treating wide spectrum neurological diseases, particularly neuromuscular diseases. He is the founder and director of MDA/ALS multidisciplinary clinic. He has conducted several research projects, published several peer-review articles, and presented posters/abstracts at international, national, and local conferences during my time at VTCSOM. His researches have been mainly focused on nature and treatment of peripheral neuropathies.


Conference Lecture Summary

Optic neuritis (ON) is one of the most common manifestations of central nervous system involvement caused by various etiologies. Lyme ON is an exceedingly rare ocular manifestation of Lyme disease (LD) and only a few cases have been published in the literature. Lyme ON is very rare but should be included in the differential diagnosis in unexplained cases, particularly in Lyme endemic areas. Careful and detailed examination and investigation are warranted to make the diagnosis. I will talk on this case to increase awareness of clinicians to include Lyme disease in differential diagnosis of ON for unexplained cases of ON. I will present a unique case with a unilateral ON caused by LD along with pre- and posttreatment findings and literature review.




Breitschwerdt, Ed

BreitschwerdtEdward B. Breitschwerdt BS, DVM
Professor of Medicine and Infectious Diseases,
N. Carolina State Univ. College of Veterinary Medicine;
Adjunct Professor of Medicine, Duke;
Dir., Intracellular Pathogens Research Laboratory, Center for Comparative Medicine &Translational Research;
Co-Director, V-B Diseases Diagnostic Lab;
Chief Scientific Officer, Galaxy Diagnostics, Inc.
Raleigh, NC

https://cvm.ncsu.edu/directory/breitschwerdt-ed/

http://www.galaxydx.com/web/our-team/

Bartonellosis: Update on an Emerging Infectious Disease

Dr. Edward B. Breitschwerdt is a professor of medicine and infectious diseases at North Carolina State University College of Veterinary Medicine. He is also an adjunct professor of medicine at Duke University Medical Center, and a Diplomate, American College of Veterinary Internal Medicine (ACVIM). Dr. Breitschwerdt directs the Intracellular Pathogens Research Laboratory in the Comparative Medicine Institute at North Carolina State University. He also co-directs the Vector Borne Diseases Diagnostic Laboratory and is the director of the NCSU-CVM Biosafety Level 3 Laboratory.

A graduate of the University of Georgia, Breitschwerdt completed an internship and residency in Internal Medicine at the University of Missouri between 1974 and 1977. He has served as president of the Specialty of Internal Medicine and as chairperson of the ACVIM Board of Regents. He is a former associate editor for the Journal of Veterinary Internal Medicine and was a founding member of the ACVIM Foundation.

Breitschwerdt’s clinical interests include infectious diseases, immunology, and nephrology. For over 30 years, his research has emphasized vector-transmitted, intracellular pathogens. Most recently, his research group has contributed to cutting-edge research in the areas of animal and human bartonellosis. In addition to authoring numerous book chapters and proceedings, Dr. Breitschwerdt’s research group has published more than 350 manuscripts in peer-reviewed scientific journals. In 2012, he received the North Carolina State University Alumni Association Outstanding Research Award and in 2013, he received the Holladay Medal, the highest award bestowed on a faculty member at North Carolina State University. In 2017, Dr. Breitschwerdt received the American Association of Veterinary Medical Colleges Outstanding Research Award.


Conference Lecture Summary

Bartonella species are fastidious Gram-negative bacteria that are highly adapted to a mammalian reservoir host and within which the bacteria usually cause a long-lasting intra-erythrocytic and endotheliotropic bloodstream infection. These facts are of particular importance to veterinarians, physicians, diagnosticians and public health officials, as an increasing number of animals have been identified as reservoir hosts for zoonotic Bartonella species. Among numerous examples, Bartonella henselae, Bartonella koehlerae and Bartonella clarridgeae have co-evolved with cats, Bartonella vinsonii subsp. berkhoffii and Bartonella rochalimae have co-evolved with wild canines, and Bartonella bovis has co-evolved with cattle. Importantly, the list of reservoir-adapted Bartonella species, including a large number of recently identified bat and rodent species, continues to expand exponentially, as new Bartonella spp. and additional reservoir hosts are discovered throughout the world.

Bartonellosis is a zoonotic infectious disease of worldwide distribution, caused by the expanding number of recently discovered Bartonella spp. Of comparative medical importance, Bartonella spp. are transmitted by several arthropod vectors, including fleas, keds, lice, sand flies, ticks and potentially mites and spiders. Prior to 1990, there was only one named Bartonella species (B. bacilliformis), whereas there are now over 36 species, of which 17 have been associated with an expanding spectrum of animal and human diseases. Recent advances in diagnostic techniques have facilitated documentation of chronic bloodstream infections with Bartonella spp. in healthy and sick animals, and in immunocompetent and immunocompromised human patients with vascular, neurological and rheumatologic symptoms.

A Comparative Medicine and One Health approach to this emerging infectious disease is clearly needed to define disease manifestations, to establish the comparative infectious disease pathogenesis of this stealth pathogen, to validate effective treatment regimens and to prevent zoonotic disease transmission from animals to humans.

 




Bransfield, Robert

BransfieldRobert C. Bransfield, MD, DLFAPA
Clinical Associate Professor
Rutgers Robert Wood Johnson Medical School
Private Practice in Psychiatry
Red Bank, NJ
www.MentalHealthandIllness.com

 

The Psychoimmunology of Lyme and Associated Diseases

Dr. Bransfield’s primary activity is an office based private practice of psychiatry. In addition, Dr Bransfield is the Past President of the International Lyme and Associated Diseases Educational Foundation, Past President of the International Lyme and Associated Diseases Society, Past President of the New Jersey Psychiatric Association and has held a number of administrative positions with organizations involved with health, mental health and community related activities.

He is a Clinical Associate Professor of Psychiatry at Rutgers—Robert Wood Johnson Medical School and has previously held teaching appointments at Hahnemann Medical College, Drexel University School of Medicine and Eastern Virginia Medical School. He has taught in many settings to physicians, mental health professionals and the public. He has performed research, and has a particular interest in a unified theory of mental health and illness, the link between microbes and mental illness, the causes of autism, Lyme and other tick-borne disease, the link between microbes and violence, psychopharmacology, pharmaceutical benefit management, mental health parity, healthcare delivery issues and preserving the integrity of the physician patient relationship. Dr Bransfield he is the founder and administrator of the Microbes and Mental Illness Listserv. He has authored a number of articles on topics related to tick-borne disease, psychiatry and healthcare policy issues. He has held a number of administrative positions for various organizations involved with a number of health, mental health and community related activities.


Conference Lecture Summary

Attention to psychoimmunology helps us understand the pathophysiological sequence that begins as a tick-borne or other infection and results in psychiatric symptoms. The nervous system and immune system communicate with each other and have many similarities—both have innate and adaptive capabilities, both involve complex communication between cells, both have similar pathophysiological processes. Many genes associated with mental illness involve immune functioning. Although there are multiple other contributors that provoke and weaken the immune system, acute and persistent infections are a major cause of pathological immune reactions resulting in disease progression. Adaptive functioning involves recognition of danger and early inflammation followed by adaptive immunity. Borrelia burgdorferi has the capacity to evade and suppress the immune system. In pathophysiological processes, this can result in persistent infection, persistent inflammation with cytokine effects without adaptive immunity, sometimes accompanied with autoimmune reactions. Persistent infection in the body can result in persistent immune effects that cross the blood brain barrier and result in neuropsychiatric symptoms. Sickness syndrome associated with interferon treatment and autoimmune limbic encephalopathies are models to understand inflammatory and molecular mimicry effects upon neuropsychiatric symptoms. Progressive inflammatory reactions have been proposed as a model to explain disease progression in depression, psychosis, dementia, epilepsy, autism, suicide, violence and other mental illnesses. Pathophysiological changes have been associated with oxidative stress, excitotoxicity, changes in homocysteine metabolism and altered tryptophan catabolism. Lyme disease has been associated with the proinflammatory cytokines IL-6, IL-8, IL-12, IL-17, IL-18, IL-10 and interferon-gamma, the chemokines CXCL12 and CXCL13, CRP, CNS gliosis, Bb impacting neuronal and Schwann and glial cells, proinflammatory lipoproteins, increases in quinolinic acid, Bb surface glycolipids and flagella antibodies eliciting anti-neuronal antibodies and anti-neuronal antibodies and dissemination of immune reactions from the periphery to inflame the brain. Immune mediated effects of Lyme and other tick-borne diseases contribute to cognitive impairments, dementia, depression, anxiety, autism, violence and other psychiatric illnesses. Autism spectrum disorders associated with Lyme/tick-borne diseases may be mediated by a combination of inflammatory and molecular mimicry mechanisms. Reactivity to OspA and/or OspB appears significant in Lyme associated autism.

Greater interaction is needed between infectious disease specialists, immunologists and psychiatrists to benefit from this awareness and to further understand these mechanisms.