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Critical Needs and Gaps in Understanding Prevention, Amelioration, and Resolution of Lyme and Other Tick-Borne Diseases: The Short-Term and Long-Term Outcomes - Workshop Report Overview Tick-borne diseases (TBDs) represent some of the world’s most rapidly expanding arthropod-borne infectious diseases, yet significant gaps remain in our understanding and knowledge about them. In the United States, many tick-borne diseases such as anaplasmosis and the borrelioses, ehrlichioses, and rickettsioses are on the rise. Reasons include shifts in the prevalence and distribution of animal reservoirs and tick vectors as well as the movement of humans into areas where the animal hosts and tick populations are abundant. From a public health standpoint, the burden of disease is of growing concern, as is the incomplete understanding of the complex interactions of ticks, hosts, pathogens, and habitats that underlie changing disease patterns and the potential for climate change to exacerbate these trends. The Committee on Lyme Disease and Other Tick-Borne Diseases: The State of the Science was formed at the request of the National Institute of Allergy and Infectious Diseases to hold a 2-day workshop on the state of the science of Lyme disease and other TBDs. The committee was requested to be inclusive in the breadth of scientific approaches and disciplines, but to exclude treatment guidelines from the workshop. Furthermore, the workshop was to provide a forum for broad scientific and public input and to produce a workshop report that would highlight the major themes of the workshop and commissioned papers. The committee was not constituted to develop conclusions or recommendations. The committee recognized that the limitation of a 2-day workshop meant that not all proposed topics or speakers could be accommodated; it did its best to cover a range of topics and speakers.
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Critical Needs and Gaps in Understanding Prevention, Amelioration, and Resolution of Lyme and Other Tick-Borne Diseases: The Short-Term and Long-Term Outcomes - Workshop Report The presentations summarized in this document represent the views of the individual speakers and should not be interpreted as a consensus or an endorsement by the Institute of Medicine, the committee, or its sponsors. Furthermore, the committee recognizes that the language and terminology used to describe various facets and manifestations of Lyme disease and coinfecting conditions are not uniform throughout the report—this reflects differences in scientific perspective among speakers and authors. As highlighted by many presenters, a standard lexicon that is consistently applied and understood would improve and advance research efforts related to Lyme disease and other tick-borne diseases. Furthermore, addressing the major knowledge gaps identified in this report is likely to lead to standardization of terminology as the unknown becomes the known. The following sections of the overview summarize the committee’s highlights of presentations and discussions from the scientific portion of the agenda. The committee appreciates the time and efforts of the presenters and commissioned paper authors and the many participants who shared their stories to provide a context for these discussions. The interactions with patients and advocates were useful and constructive and served as an effective reminder of why scientific observations and gaps in knowledge need to be filled. Science is lagging behind as the burden of these diseases increases. The reader is directed to Chapter 3 for the rich presentation of participant views. EMERGING INFECTIONS, TICK BIOLOGY, AND HOST–VECTOR INTERACTIONS The recognized number of serious diseases transmitted by ticks has increased over the past 30 years. The emergence and increased incidence of several major TBDs has been attributed to specific human activities and behaviors that disrupt ecosystems. Increases in human population and demographic shifts have brought dramatic changes in the distribution and composition of natural habitats, as people modify the land for living spaces, agriculture, or recreation. These changes mean that people and animals interact at many more interfaces, creating new opportunities for the transmission of zoonotic pathogens, including those responsible for TBDs. This session examined the natural history of ticks and their wildlife and domestic hosts; outlined the contributions of animal health experts to understanding human TBD; explored genetic diversity among pathogens, vectors, and hosts; and showed how scientists are investigating the microbial community found within the ticks themselves. During the session, the individual speakers highlighted a number of research gaps and opportunities for studying TBDs. Some of these gaps and opportunities cut across individual presentations and comments from the audience. A few of the themes discussed included
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Critical Needs and Gaps in Understanding Prevention, Amelioration, and Resolution of Lyme and Other Tick-Borne Diseases: The Short-Term and Long-Term Outcomes - Workshop Report Regional differences in the distribution of ticks and tick-borne pathogens and their contribution to human disease. Environmental systems and the “One Health” (i.e., the interface of human, animal, and environmental health that includes complexities of the ecosystems or the interface of biological communities and their physical or abiotic environment) approach to understanding tick-borne diseases. The biology and dynamic characteristics of disease vectors. The risk of TBDs as they relate to ecological fragmentation and reduced wildlife diversity. The tick microbiome and its role in transmission of pathogens to humans. SURVEILLANCE, SPECTRUM, AND BURDEN OF TICK-BORNE DISEASE, AND AT-RISK POPULATIONS An understanding of the science of Lyme disease and other TBDs begins with the surveillance, spectrum, and burden of disease. This session focused on the current state of knowledge of the prevalence, incidence, patterns, and severity of key TBDs in the United States and their impact on patients. The presenters discussed efforts to track the movement of pathogens in the environment, how infection moves from animals to people, and the burden of human infection and disease, especially among vulnerable populations. Some themes discussed included The relative contributions of changes in surveillance, clinical recognition, and testing patterns to the rising incidence of all of the major tick-borne diseases. The impact of coinfection in severity of human TBDs. Biological understanding of persistent symptoms. PATHOGENESIS Understanding pathogenesis of an infectious disease at the cellular and molecular levels is critical for discovering, developing, and implementing methods to prevent infection, and to improve patient outcomes after treatment. Scientists rely on several approaches to study the pathogenesis of tick-borne diseases. These include in vitro laboratory studies, in vivo studies of experimental and natural infections in animals, and patient studies based on clinical trials and specimens from biopsies and autopsies. While no one approach can represent the full spectrum and complexity of human disease,
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Critical Needs and Gaps in Understanding Prevention, Amelioration, and Resolution of Lyme and Other Tick-Borne Diseases: The Short-Term and Long-Term Outcomes - Workshop Report the ability to “reduce” or “control” the number of variables by using in vitro and in vivo models allows more rapid and less equivocal determination of key variables in disease progression—knowledge required to improve prevention, diagnosis, and treatment of tick-borne disease in patients. This session focused on the state of the science regarding the pathogenesis of tick-borne infections—specifically those caused by pathogens in the genera Anaplasma, Borrelia, Ehrlichia, and Rickettsia. Themes discussed included the following: Research based on animal models for the testing of hypotheses related to the clinical manifestations and severity of symptoms or disease. The role of the immune response to tick-borne infection and its effect on bacterial load and disease manifestations. New technologies in animal models that explore mechanisms of pathogen persistence following antibiotic treatment. Translating research findings from the animal model to clinical application. DIAGNOSTICS AND DIAGNOSIS Diagnostics and diagnosis, which are essential to improve outcomes of tick-borne diseases, have different connotations. Diagnostics provide a cluster of objective measures directed toward identifying the cause of a disease. After scientists discover the causative agent of an emerging infectious disease, such as Borrelia burgdorferi or Ehrlichia chaffeensis, they develop, evaluate, and refine diagnostic tests over time. Diagnosis, in contrast, rests on a patient’s history and symptoms and observed physical and laboratory findings in a particular epidemiologic context. Ultimately, accurate diagnosis requires knowledge of the epidemiology and clinical manifestations, as well as specific and sensitive diagnostic tests. In this session, the presenters explored the limitations of existing tests for Lyme borreliosis and other tick-borne diseases, and they discussed promising new approaches to diagnostics that may improve the diagnosis of these diseases, and the challenges and needs for improving initial diagnosis. Some themes discussed in this session included The current status of diagnostic tests and biomarkers for TBDs. The role of central system sensitivity and fatigue and other sequelae as possible biomarkers of TBDs. Measurement of qualitative symptoms reported by patients. Biorepositories for tick-borne diseases. Syndromic-based diagnostics for TBDs.
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Critical Needs and Gaps in Understanding Prevention, Amelioration, and Resolution of Lyme and Other Tick-Borne Diseases: The Short-Term and Long-Term Outcomes - Workshop Report PREVENTION Research efforts have been focused on ameliorating the symptoms and consequences of tick-borne diseases through treatment. However, the development, deployment, and evaluation of strategies to prevent the occurrence of tick-borne diseases were also discussed as a high priority. Prevention of infection is much more preferable to treating the short- and long-term consequences of disease. In this session, the presentations addressed current and future opportunities for vaccine development, the role and effectiveness of behavior change, and vector-control strategies. A few of the themes discussed in this session included Research and development of safe, effective, multipathogen human and animal vaccines for tick-transmitted diseases. Land-use practices and public education as current tools to improve mitigation and prevention of TBDs. Social and behavioral considerations for TBD prevention interventions. Educational programs for the public. Assessing the impact of educational programs for patients and clinicians. SUMMATION The committee invited a panel of stakeholders to listen to the presentations and discussions during the course of the 2-day workshop and to share their observations regarding the research gaps and priorities in the science of tick-borne diseases. The panel members were not asked to come to a consensus but rather to express their individual viewpoints. The panelists included a representative from a patient advocacy group, a clinician specializing in Lyme disease, a clinician-scientist specializing in Ehrlichia and Anaplasma, a clinician-scientist studying pathogenesis, and a European clinician-scientist who provided a global perspective. Following the discussion, the committee invited participants to share their thoughts. A few of the views presented during this session included perspectives on the following: Research funding gaps for other TBDs. Contribution of a national integrated research plan for advancing the science on TBDs. The merits of a long-term study of Lyme disease and other TBD patients. The role of public-private partnerships and other collaborative efforts to enhance the research on TBDs.
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