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
