Lyme & Other Tick-Borne Diseases: New Strategies to Tackle an Expanding Epidemic
Saturday & Sunday, October 15-16, 2016 Doubletree by Hilton St. Paul, Minnesota
AMA Credit Designation Statement: The College of Physicians and Surgeons designates this live activity for a maximum 14 AMA PRA Category 1 Credits TM.
Target Audience: The target population is physicians from all specialties, nurses, psychologists, scientists, public health workers. It is also open to the public, and Lyme disease educators generally attend. The geographic area being reached is nationwide. No special background is required for effective participation, although those whose practices contain a high proportion of Lyme disease patients and those whose research concentrates on Borrelia burgdorferi will receive the most benefit.
Robert D. Moir, PhD Keynote
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.
Judith Miklossy, MD, PhD
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.
Brian A. Fallon, MD, MPH
Dr. Fallon will review the acute and chronic neuropsychiatric manifestations of Lyme disease. Mechanisms of disease, neuroimaging and neurocognitive findings, and treatment approaches will be discussed. New findings from a sample of 200 patients with prior Bb infection will be presented.
Kevin Esvelt, PhD
The island communities of Nantucket and Martha’s Vineyard are guiding a project to prevent Lyme and other tick-borne diseases by heritably immunizing local populations of wild white-footed mice. Past studies have shown that immunizing mice can substantially reduce the number of infected ticks, which are the source of human infections. We are now sequencing vaccinated mice to identify the antibodies they have evolved to acquire resistance. We will test these mouse antibodies to find the ones that are most protective, then encode them in the genome to create mice that are immune from birth. Releasing these mice on the islands in reasonable numbers over multiple generations would stably introduce the trait to a large fraction of the native mouse population. Island citizens, which were invited to direct the project before any experiments were performed, will make all key decisions and ultimately determine whether the project moves forwards at each stage. If successful, mainland communities could choose to gain the same benefits by using daisy drive systems to spread the antibodies through their own local mouse populations. Precisely blocking disease transmission at its source may be the smallest possible intervention capable of permanently preventing tick- borne disease.
Steve Zatechka, PhD, MBA
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.
Rafal Tokarz, PhD
Tick-borne diseases are the most common vector-borne illnesses in the United States. In a proportion of presumed tickbite-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.
Kerry Clark, PhD, MPH
Lyme disease continues to be a controversial subject in the southern United States. Based solely on 2-tiered serological laboratory confirmation test results, the disease continues to appear to be relatively rare in this region compared to highly endemic areas of the Northeast and Upper Midwest. However, some more recently obtained evidence challenges this belief. Borrelia burgdorferi sensu lato (Bbsl) DNA has been detected in scores of human patients and dogs from southern states, many of which have no travel history to other regions. Bbsl has also been isolated in culture from several human patients from Florida and Georgia, most of which have not been described in the scientific literature. DNA evidence of Bbsl continues to be detected in lone star ticks (Amblyomma americanum), which may serve as a bridge vector of transmission to humans under certain circumstances. This report summarizes some of the published and unpublished evidence of Lyme Borrelia infection in humans, dogs, and ticks from several southern states, attempts to help explain the disparity between surveillance case numbers and observed Lyme-like illness in the southern U.S., and provides insights into better understanding the ecology and epidemiology of Lyme disease in the South.
Bobbi S. Pritt, MD
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.
Timothy Lepore, MD, FACS
Tularemia is a tick-borne pathogen traditionally associated with rabbit hunting. Tularemia in Massachusetts has a very definite history, only appearing after 1935 with the introduction of Midwestern rabbits. The islands of Nantucket and Marthas Vineyard have a very different history with Tularemia involving a pneumonic presentation. The discussion will be about the ecology of this atypical presentation.
Evan M. Bloch, MBChB, MD, MS
Babesia and the Blood Supply: Lessons Learned
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.
Alessandra Luchini, PhD
Nanotrap Urinary Lyme Antigen Test
Progress on conquering Lyme disease is severely hindered by the poor quality of existing diagnostic tests for Lyme. Patients with a missed diagnosis harbor Lyme that persists to invade brain, heart, joints, and other tissues. We also need a test to monitor if the disease is successfully treated. Our Laboratory is dedicated to the development of a highly specific and sensitive urine antigen test for Lyme disease that can be used for diagnosis or monitoring therapy. We created a special nanotechnology, called the Nanotrap, that enables us to increase the sensitivity of our test one thousand times higher than previous testing methods. We are testing for regions of the Lyme surface proteins that are absolutely specific for the Lyme bacteria and detect all species and strains. We are also developing a tick panel test for other tick-borne bacteria and viruses that infect patients. We have published our first clinical study and are we are now using ourtest in a nationwide clinical study.
Ying Zhang, MD, PhD
In this presentation, I will discuss the problem of post-treatment Lyme disease syndrome (PTLDS) and its possible causes, the phenomenon of Borrelia persistence despite antibiotic treatment in animal models, the demonstration of Borrelia persister bacteria that are tolerant to current Lyme antibiotics in vitro. I will then discuss our recent work on identification of FDA-approved drugs that are more active than the current Lyme antibiotics against Borrelia burgdorferi persisters. In addition, I will discuss various drug combinations and their effectiveness to eradicate more resistant Borrelia persisters including round bodies and biofilm-like microcolonies in in vitro systems. The implications of these findings for more effective treatment of persistent Lyme disease will be discussed.
Daniel Cameron, MD, MPH
Lyme disease trials continue to frustrate doctors. Short-term successes following treatment for early Lyme disease were followed by reports of chronic manifestations including chronic neurologic Lyme disease, Lyme encephalopathy, Post Treatment Lyme disease and neuropsychiatric Lyme disease. Retreatment trial outcomes have been mixed following early reports of successful treatment for Chronic Neurologic Lyme, Lyme Encephalopathy and Post Lyme Disease. Watchful waiting outcomes trials are similarly mixed. 14.47 % of 76 subjects in one watchful waiting study suffered from Post Treatment Lyme Disease Syndrome (PTLDS) at either six or twelve months despite a one time 3-week course of doxycycline. Eleven percent of individuals in another watchful waiting study suffered from PTLDS for more than 11 years despite timely treatment. Future trial designs will need to adapt to our growing understanding of the complexity of tick borne illnesses.
Lise Nigrovic, MD, MPH
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.
Elizabeth L. Maloney, MD
This presentation begins with a case presentation before moving to a broader discussion of Lyme carditis. It traces the evolution of the patient’s clinical picture from multiple erythema migrans lesions to third degree heart block. In addition to reviewing the literature on Lyme carditis, the presentation highlights some unique features of the case-patient’s course that may inform the care of other patients.
Tim Sellati, PhD
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.
Patricia K. Coyle MD, FAAN, FANA
Lyme disease is our major human spirochetal infection. The nervous system is a favored target organ. This talk will discuss the diagnosis of neurologic Lyme disease in practical terms. It will cover when to suspect the infection, characteristic as well as unusual syndromes, the main differential diagnoses, and appropriate workup including how to interpret the variety of test results. The goal is not to miss the diagnosis of neurologic Lyme disease, so that appropriate and timely treatment may be provided.
John Aucott, MD
The host immune response plays a critical role in determining the outcome of infectious diseases. In addition, ongoing host immune and inflammatory responses can perpetuate symptoms that persist and drive illness. Studies of the human immune response in Lyme disease are showing the complexity of the interaction between Borrelia burgdorferi and the innate and adaptive immune responses. Data will be presented to show the unique immune responses among patients with early Lyme disease before and after treatment.
C. Ben Beard, MS, PhD
Ixodes scapularis or Ixodes pacificus are now found in over 49% of counties in 43 states across the United States. This marks an increase of 44.7% in the number of positive counties since 1996. The number of counties where I. scapularis is now established has more than doubled over the last 20 years. Over a similar period of time, the number of high incidence counties for Lyme disease in the northeastern U.S. increased by greater than 320% and in the north-central U.S. by over 250%. The numbers of Lyme disease cases in the U.S. continue to increase, and the geographic distribution of both Lyme disease and its tick vectors is greater than ever before. These findings highlight the critical importance of safe and effective prevention and control tools and methods.
Marna E. Ericson, PhD
Mechanisms of persistence of Bartonella spp.
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 mechanism
Kenneth B. Liegner, MD
Internist Private Practice, Pawling, NY, Sunday Morning Facilitator
Dr. Kenneth Liegner is a Board Certified Internist with additional training in Pathology and Critical Care Medicine, practicing in Pawling, New York. He has been actively involved in diagnosis and treatment of Lyme disease and related disorders since 1988. He has published articles on Lyme disease in peer-reviewed scientific journals and has presented poster abstracts and talks at national and international conferences on Lyme disease and other tick-borne diseases. He is the author of In the Crucible of Chronic Lyme Disease, a documentational history of the struggle to characterize the nature of Lyme disease in the late 20th and early 21st centuries. He has cared for many persons seriously ill with chronic and neurologic Lyme disease. His work has focused on the serious morbidity and (occasional) mortality that can eventuate from this aspect of the illness. He has emphasized the urgent need for widespread clinical availability of improved methods of diagnostic testing and for development of improved methods of treatment for Lyme disease in all its stages. He holds the first United States patent issued proposing application of acaricide to deer for area-wide control of deer-tick populations as a means of reducing the incidence of Lyme disease.