TBDWG January 28, 2020 - Meeting Summary

Welcome from ADM Giroir and Working Group
Mission Statement, Vision Statement, and Values
Objectives, Update, and Goals
NIH, CDC and FDA Updates
Public Comment / Public Comment Subcommittee
Tick Biology, Ecology, and Control Subcommittee
Pathogenesis and Physiology of Lyme Disease Subcommittee
Clinical Aspects of Lyme Disease Subcommittee
Training, Education, Access to Care, and Reimbursement Subcommittee
Alpha-gal Syndrome Subcommittee
Appendix 1: TBDWG Members and HHS Support Staff
Appendix 2: TBDWG Subcommittees

Note: For context and clarity, speaker credentials will be included upon first mention in each meeting’s summary. Subsequently, individuals will be referenced by their first names to equalize expertise across the many diverse disciplines represented in this document. All perspectives and expertise, including patient-lived experience, is valued equally. Speaking on a first-name basis helps the Tick-Borne Disease Working Group ensure that all voices are heard and valued based on merit and without the bias of titles, eminence, or prestige.

Welcome and Roll Call

James (Jim) Berger, MS, MT (ASCP), SBB, Senior Blood and Tissue Policy Advisor, Office of Infectious Disease and HIV/AIDS Policy, Office of the Assistant Secretary for Health, U.S. Department of Health and Human Services (HHS); Designated Federal Officer (DFO) for the Tick-Borne Disease Working Group, called the meeting to order and conducted roll call (see Appendix 1: Tick-Borne Disease Working Group Members and HHS Support Staff). Working Group members announced their names, the organizations they represent, and the subcommittees they co-chair. The meeting started with a quorum.

Jim then introduced ADM Brett Giroir, Assistant Secretary for Health, HHS.

Welcome Remarks from ADM Giroir

ADM Giroir welcomed all meeting participants and expressed his appreciation for the Working Group members’ effort, dedication, and commitment. He assured the Working Group that he will personally review the Working Group’s assessments on the issues and recommendations, and he encouraged the Working Group to make their recommendations “as specific and as actionable as the evidence and science allows.”

ADM Giroir provided a brief background about tick-borne diseases, and highlighted the increasing cases reported to the Centers for Disease Control and Prevention (CDC), the emerging pathogens, and the economic impact of the diseases. Addressing tick-borne diseases, and in particular Lyme disease, he stated, is now a priority of HHS, and he will be personally involved in leading the initiative.

ADM Giroir noted that the Kay Hagan Tick Act, signed into law in December 2019, is a monumental step forward in beginning to address the research and funding gaps that the Tick-Borne Disease Working Group identified in the 2018 Report to Congress. He explained that the Act calls for the development of a national strategy to combat vector-borne diseases, and that his office has been tasked with leading the development of this national strategy.

ADM Giroir acknowledged the many challenges associated with addressing tick-borne diseases. He noted that now is the time for the Working Group to impact policy and science, and he expressed his eagerness to hear the Working Group’s recommendations.

Welcome from the Working Group

David Hughes Walker, MD, Professor, Department of Pathology, the Carmage and Martha Walls Distinguished University Chair in Tropical Diseases; Executive Director, UTMB Center for Biodefense and Emerging Infectious Diseases; Working Group Co-Chair, thanked ADM Giroir and urged the Working Group members to work effectively and diligently to tackle the issues.

Leigh Ann Soltysiak, MS, Owner, Principal, Silverleaf Consulting, LLC; Adjunct Professor, Stevens Institute of Technology, Entrepreneurship Thinking; Working Group Co-Chair, echoed David’s comment and reviewed the agenda for the two-day meeting.

Overview of the Working Group’s Mission Statement, Vision Statement, and Values

Jim reviewed the Working Group’s Mission Statement, as follows:

The Tick-Borne Disease Working Group’s mission, as mandated through the 21^st Century Cures Act, is to provide expertise and to review all efforts within the Department of Health and Human Services related to all tick-borne diseases, to help ensure inter-agency coordination and minimize overlap, and to examine research priorities. As part of this mandate, and in order to provide expertise, we will ensure that the membership of the Working Group represents a diversity of scientific disciplines and views and is comprised of both Federal and non-Federal representatives, including patients, and family members or caregivers, advocates of non-profit organizations in the interest of the patient with tick-borne illness, scientists and researchers. A major responsibility of our mission will be to develop and regularly update the action of HHS from the past, present, and the future.

Jim then reviewed the Working Group’s Vision Statement, as follows:

SHARED VISION: A nation free of tick-borne diseases where new infections are prevented and patients have access to affordable care that restores health.

Finally, Jim gave an overview of the Working Group’s Core Values, the complete versions of which are provided below.

RESPECT: Everyone is valued

We respect all people, treating them and their diverse experiences and perspectives with dignity, courtesy, and openness, and ask only that those we encounter in this mission return the same favor to us. Differing viewpoints are encouraged, always, with the underlying assumption that inclusivity and diversity of minority views will only strengthen and improve the quality of our collective efforts in the long term.

INNOVATION: Shifting the paradigm, finding a better way

We strive to have an open mind and think out of the box. We keep what works and change what doesn’t. We will transform outdated paradigms when necessary, in order to improve the health and quality of life of every American.

HONESTY and INTEGRITY: Find the truth, tell the truth

We are honest, civil, and ethical in our conduct, speech, and interactions with our colleagues and collaborators. We expect our people to be humble, but not reticent, and to question the status quo whenever the data and the evidence support such questions, to not manipulate facts and data to a particular end or agenda, and to acknowledge and speak the truth where we find it.

EXCELLENCE: Quality, real-world evidence underlies decision-making

We seek out rigorous, evidence-based, data-driven, and human-centered insights and innovations—including physician and patient experiences—that we believe are essential for scientific and medical breakthroughs. We foster an environment of excellence that strives to achieve the highest ethical and professional standards, and which values the development of everyone’s skills, knowledge, and experience.

COMPASSION: Finding solutions to relieve suffering

We listen carefully with compassion and an open heart in order to find solutions which relieve the suffering of others. We promise to work tirelessly to serve the greater good until that goal is achieved.

COLLABORATION: Work with citizens and patients as partners

The best results and outcomes won’t be created behind closed doors, but will be co-created in the open with input of the American public working together with these core values as our guide. We actively listen to the patient experiences shared with us, respect the lived experiences of patients and their advocates, and learn from their experiences in our pursuit of objective truth. Across diverse audiences, we communicate effectively and collaborate extensively to identify shared goals and leverage resources for maximum public health impact.

ACCOUNTABILITY: The buck stops here

We, as diligent stewards of the public trust and the funds provided by our fellow citizens, pledge to be transparent in all of our proceedings and to honor our commitments to ourselves and others, while taking full responsibility for our actions in service to American people.

Objectives, Update, and Goals of Meeting 11

Objectives

Leigh Ann briefly reviewed the Working Group’s objectives, which are to provide expertise and review all efforts within HHS related to all tick-borne diseases, to help ensure interagency coordination and minimize overlap, and to examine research priorities. She outlined the Working Group’s duties, as follows:

No later than two years after the date of enactment of the authorizing legislation, develop or update a summary of
1. Ongoing tick-borne disease research, including research related to causes, prevention, treatment, surveillance, diagnosis, diagnostics, duration of illness, and intervention for individuals with tick-borne diseases;
2. Advances made pursuant to such research;
3. Federal activities related to tick-borne diseases, including
  1. Epidemiological activities related to tick-borne diseases; and
  2. Basic, clinical, and translational tick-borne disease research related to the pathogenesis, prevention, diagnosis, and treatment of tick-borne disease.
4. Gaps in tick-borne disease research described 3b;
5. The Working Group’s meeting; and
6. The comments received by the Working Group.
Make recommendations to the Secretary regarding any appropriate changes or improvements to such activities and research; and
Solicit input from States, localities, and non-governmental entities, including organizations representing patients, health care providers, researchers, and industry regarding scientific advances, research questions, surveillance activities, and emerging strains and species of pathogenic organisms.

Update on Subcommittee Activities

Leigh Ann highlighted progress made by the Working Group since the last public meeting (Meeting #10), including establishing subcommittees at the Working Group’s in-person meeting in June 2019 and hearing subcommittees’ updates on their efforts in developing subcommittee reports during the Working Group’s virtual meeting in September 2019. She noted that all of the subcommittees completed and submitted to the Working Group their subcommittee reports in early January 2020.

What to Accomplish Today

David noted that today the Working Group will

Hear presentations on subcommittee reports;
Hear public comments and learn about patients’ concerns;
Hear update on Federal inventory;
Plan next Working Group public meeting; and
Summarize decisions.

Timeline

Leigh Ann reviewed the timeline for the Working Group’s 2020 Report to Congress. She reiterated that the current Working Group formed its subcommittees at its inaugural meeting in June 2019, heard updates from the subcommittees on their activities during the Working Group’s 10^th public meeting in September 2019, and is to hear subcommittee report presentations today. The Working Group, she added, will prioritize the output of the reports at the March 2020 meeting, complete the Working Group Report to Congress in September 2020, and submit the final report in November 2020.

David then transitioned the meeting to updates on Federal agencies’ strategic plans.

National Institutes of Health Strategic Plan on Tick-Borne Disease Research

Sam Perdue, PhD, Section Chief, Basic Sciences and Program Officer, Rickettsial and Related Diseases, Bacteriology and Mycology Branch, Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), HHS, provided a brief update on the NIH Strategic Plan for Tick-borne Disease Research (https://www.niaid.nih.gov/sites/default/files/NIH-Strategic-Plan-Tickborne-Disease-Research-2019.pdf).

Sam noted that the NIH Strategic Plan for Tick-borne Disease Research was developed in October 2019 based on recommendations from a panel. The plan incorporated input from the public and other NIH institutes, and it outlines an approach to addressing the diseases. He explained that NIH is still early in the process, and that the agency will continue to address gaps and research opportunities.

Sam shared that the agency, before the development of the plan, called for research on tick-borne disease prevention and received many applications. He noted that other NIH agencies and centers also have interest in tick-borne diseases and the new NIH strategic plan will help expand collaborations across institutes and centers.

CDC-led Domestic Framework

Ben Beard, Deputy Director, Division of Vector-Borne Diseases, CDC; Associate Editor, Emerging Infectious Diseases, first expressed gratitude for the passage of the Kay Hagan Tick Act, adding that CDC is prepared to implement its provisions when funds are appropriated. He then explained that the CDC Framework is a foundational document that outlines a high-level strategy on which a national action plan can be laid out. He noted that the Framework is currently under review at HHS.

Food and Drug Administration Update on Tick-Borne and Vector-Borne Diseases

CDR Todd Myers, PhD, HCLD (ABB), MB (ASCP), Office of Counterterrorism and Emerging Threats, Office of the Chief Scientist, Office of the Commissioner, U.S. Food and Drug Administration (FDA), HHS, reported that FDA has been working with NIH and CDC on various issues. He noted that FDA appreciates being included in their initiatives and wants to ensure that FDA reviewers have the tools needed to review related applications for approvals. He explained that FDA is looking for knowledge gaps and is working with other agencies so that newly developed tests, assays, or treatment options can be reviewed expeditiously.

Public Comments

Leigh Ann welcomed public commenters and encouraged the public also to submit written comments to [email protected].

Marlene Jones: Marlene described her four-year experience with three different tick-borne diseases, including ehrlichiosis, contracted in her home state of North Carolina. She explained that, despite multiple treatments with doxycycline, she remains ill with neurological symptoms. She emphasized the need for enhanced clinician awareness, especially of Rocky Mountain spotted fever, so clinicians will know which illnesses to consider in their differential diagnoses and which tests to order. She also stressed the need for treatment options beyond antibiotics, specifically immune therapy. Marlene noted that she is a board member of Tick-Borne Conditions United.

Grant Roseman: Grant stated that he was speaking on behalf of Tick-Borne Conditions United. He explained that he is 16 years old and at age 8 he was diagnosed with Alpha-gal Syndrome (AGS). He outlined the many challenges he has experienced trying to understand food labels and find food that would not cause an allergic reaction, especially in social situations like Boy Scout outings and dinner at a friend’s house. He added that, as a result of these struggles, he experiences significant anxiety.

Grant described his science fair project on AGS and host-seeking behavior of lone star ticks. He reported that there were over 1,800 attendees at the fair; he won first place at the regional level; and he intends to further his research on alpha-gal in the future.

Gregg Skall: Gregg stated that he is the legal counsel for the National Capital Lyme and Tick-Borne Disease Association (NatCapLyme). He highlighted that Lyme disease and HIV/AIDS emerged at around the same time, yet only HIV/AIDS is considered treatable. He noted the recent passage of the Kay Hagan Tick Act. He expressed concern that the authorization language was changed from “tick-borne diseases” to “vector-borne diseases” and questioned whether or not the funding would be diverted away from tick-borne diseases and toward rare but highly publicized mosquito-borne viruses such as Zika and West Nile viruses.

Gregg called for unbiased Federally-funded research—conducted by researchers with innovative ideas and methods—devoted to finding effective diagnostic and treatment protocols for the persistent forms of tick-borne diseases. He also called for more clinical trials involving chronically ill patients.

Sue Faber: Sue stated that she is a registered nurse from Canada and a co-founder and the president of LymeHope. She stressed that maternal-fetal transmission of Lyme disease is an urgent issue with far-reaching health implications. She highlighted the need for public acknowledgment of the risk of transmission and dedicated research to address the issue. She cited multiple case studies and reports dating back to the 80s in which researchers documented transplacental transmission of Borrelia burgdorferi.

Sue acknowledged that there are many other case reports of newborns with infected mothers who are deemed healthy at birth. She stated that these studies are often used to support the idea that transmission is rare or does not occur. However, she added, this conclusion does not take into account the limitations of the studies (for example, small sample sizes and limited follow-up with respect to long-term sequelae) and the need for larger scale research. She shared that she was asymptomatic and untreated during pregnancy; however, her children struggled with health issues from birth, were later confirmed as having been exposed to Lyme disease, but were unable to access comprehensive care. She called for research funding on the issue.

Charlotte Meyer: Charlotte noted that she has AGS and is a supporter of Tick-Borne Conditions United. She shared that the organization is conducting a large-scale survey, which had received 500 patient responses within the first two weeks of its launch. The significant response to the survey, she noted, is an indicator of how eager patients are for information and to have their challenges heard, understood, and addressed.

Charlotte read multiple quotes from patients, who identified a range of issues associated with AGS, including lack of recognition by healthcare providers; lack of treatment options; stress associated with eating in restaurants and cafeterias; avoidance of, and isolation from, social situations that involve meals; anxiety in children whose parents have AGS; difficulty living with and accepting the effects of the condition; and fear of losing employment and housing.

Charlotte urged the Tick-Borne Disease Working Group to address the information gap about AGS in the medical community and provide support for people affected by the condition.

Dorothy Leland: Dorothy provided comment over the phone. She explained that she is a vice-president of LymeDisease.org, lives in California, and her daughter received an 8-month delayed diagnosis of Lyme disease and coinfections 15 years ago. She expressed her view that the CDC incidence maps are misleading, contributing to missed and delayed diagnoses of patients who live in states that are identified as “low incidence” because clinicians believe Lyme disease does not occur in their states. She gave several examples of CDC reported cases by state compared to FAIR Health insurance claims for Lyme disease, and she noted the discrepancies between the numbers in states considered low incidence. She also referenced a Quest Laboratory study to demonstrate an increase in positive test results in low-incidence states.

Dorothy commented that the system for tracking Lyme disease cases is flawed and urged the Tick-Borne Disease Working Group to raise awareness that Lyme disease is a risk in every state.

Bruce Fries: Bruce began his comment by recognizing the Lyme disease patients who have died or who remain chronically ill. He thanked the Tick-Borne Disease Working Group members for their efforts, and he acknowledged the NIH Strategic Plan for Tick-borne Disease Research and the Kay Hagan Tick Act. He stressed the importance of translating recommendations into action.

Bruce highlighted several challenges facing the Lyme disease community, including complexity of illness, lack of funding for research, and the omission of the International Lyme and Associated Diseases Society (ILADS) guidelines from CDC’s website. He then called for the following actions:

Effective policies, increased funding, and stringent oversight to monitor performance and protect taxpayer dollars;
CDC acknowledgment of persistent infection seronegativity; and
NIH-funded research, especially in the areas of congenital and pediatric Lyme disease.

Bruce referenced a forthcoming report to Congress that outlines funding discrepancies for Lyme disease compared to that of other vector-borne diseases. He also referenced an antitrust lawsuit brought against the Infectious Disease Society of America (IDSA) researchers and insurance companies.

Allison Caruana: Allison stated that she is the president of the May Day Project. She expressed concern about the following issues:

Patient representation on the Tick-Borne Disease Working Group patient;
Lack of acknowledgment of a viral component to Lyme disease; and
Lack of transparency involving the work of Wilhelm Burgdorfer.

Allison expressed her frustrations over seeing Lyme disease patients struggle and suffer, and she urged the Tick-Borne Disease Working Group to make significant changes.

Enid Haller: Enid noted that she is a Lyme disease advocate with the Lyme Center of Martha’s Vineyard. She explained that she has chronic Lyme disease and served on one of the subcommittees of the 2018 Tick-Borne Disease Working Group. She explained that her focus is on the history of Lyme disease, government transparency, and conflicts of interest in Lyme disease-related activities. She expressed displeasure with her experience on the subcommittee and called for the creation of a new subcommittee, entitled Conflicts of Interest in Lyme Disease, with the purpose of tracking government funding, publishing information on patent ownership, and identifying conflicts of interest.

Leigh Ann and David thanked the public for providing comments and welcomed the Public Comments Subcommittee to provide related updates.

Public Comment Subcommittee Update

Comments Received and Reviewed

Subcommittee Co-Chair Angel M. Davey, PhD, Program Manager, Tick-Borne Disease Research Program, Congressionally Directed Medical Research Programs, U.S. Department of Defense (DoD), thanked the public for providing comments, and explained that the Public Comments Subcommittee was established to review and share public comments submitted to the Working Group.

Angel noted that the subcommittee systematically reviewed all of the public comments provided at Tick-Borne Disease Working Group public meetings or through [email protected] from January 2019 to December 2019. The subcommittee also held monthly conference calls between June 2019 and December 2019 to further support the review process. The subcommittee communicated with the other eight subcommittees between November 2019 and January 2020 and recommended the subcommittees review and consider addressing the key themes of the public comments in respective subcommittee reports. She clarified that some subcommittees had already completed their reports by that time and that the comments will be considered as the Working Group proceeds.

Angel explained that when communicating with other subcommittees, the Public Comments Subcommittee shared not only the synthesized key themes but also detailed comments. She noted that written comments presented at the Working Group’s public meetings can be reviewed on the HHS website (https://www.hhs.gov/ash/advisory-committees/tickbornedisease/index.html).

Overall Themes

Leigh Ann reiterated the background of the subcommittee and reported the perspectives of the three co-chairs (see Appendix 2 for subcommittee membership). She noted that the co-chairs synthesized the comments received through the year and highlighted the key themes for other subcommittees to consider.

Leigh Ann explained how the Public Comments Subcommittee shared the information with other subcommittees and showed the key themes month by month. For example, one of the key themes of the public comments received in January 2019 was treatment of persistent Lyme disease with negative testing results, which, Leigh Ann noted, was relevant to, and shared with, the Clinical Aspects of Lyme Disease Subcommittee and the Pathogenesis and Physiology of Lyme Disease Subcommittee.

Leigh Ann noted that the Working Group plans to post the information (key themes of public comments and relevant subcommittees) on the Tick-Borne Disease Working Group website.

Subcommittee Presentations

Following the update from the Public Comments Subcommittee, the other eight subcommittees, one by one, presented their reports. The co-chairs of each subcommittee outlined subcommittee membership (see Appendix 2 for complete subcommittee membership), provided background information, reported the subcommittees’ evidence and findings, and presented potential actions for the Working Group to consider.

Methods

All eight subcommittees used a similar approach to conduct their work. Specific methods and strategies used include the following.

Membership of the subcommittees represents diverse scientific disciplines and views, and subcommittee members include researchers, public health professionals, clinicians, patients, and patient advocates.
All subcommittees conducted weekly or bi-weekly conference calls, during which they invited patients, patient advocates, and subject matter experts, including experts both within and outside the subcommittees, to provide information and share perspectives on issues pertinent to each subcommittee’s work.
All subcommittees reviewed and addressed public comments relevant to their respective subcommittees—public comments received after the subcommittee reports have been written are under review and will be addressed as the Working Group proceeds.
Members of the subcommittees collaborated in developing their presentations and reports to the Working Group.
Members of each subcommittee proposed, discussed, and voted on the potential actions for the Working Group to consider.
Members of each subcommittee discussed, revised, and approved the submission of the final version of their subcommittee report to the Working Group.

Tick Biology, Ecology, and Control Subcommittee

Subcommittee Co-Chair Kevin R. Macaluso, PhD, MS, Locke Distinguished Chair, Chair of Microbiology and Immunology, College of Medicine, University of South Alabama, first provided a brief background and explained methods used to develop the subcommittee report.

Kevin and Co-Chair Adalberto (Beto) Pérez de León, MS, PhD, Director, Knipling-Bushland U.S. Livestock Insects Research Laboratory, U.S. Department of Agriculture—Agricultural Research Services, together reported the subcommittee’s priorities, evidence and findings, and proposed potential actions.

Goal, Evidence, and Findings

The subcommittee’s main goal was to identify the causes for, and strategies to manage, the increased number of tick-borne disease cases in the U.S. Through expert presentations, literature reviews, a topic development brief developed for the Working Group, and a gap analysis, the subcommittee identified the following major drivers.

Climate variability
Environmental changes
Host and vector population increases
Range expansion
Human use of tick habitats
Introduction of foreign ticks

The gap analysis also helped the subcommittee identify knowledge gaps, research needs, and barriers to accelerate research. Based on the evidence and findings, and in consideration of public comments and input from other subcommittees, the Tick Biology, Ecology, and Control Subcommittee identified and addressed two priorities and proposed a total of eight potential actions for the Working Group to consider.

Priorities and Potential Actions

Priority 1: Minimize the Public Health Threat of Lyme Disease and Other Tick-Borne Diseases

Potential Action 1.1: Assess and enhance the effectiveness of Integrated Tick Management strategies.

Support continued assessment of existing and new area-wide Integrated Tick Management (ITM) strategies with the ultimate goal of reducing tick-borne disease. Create best practices for using evidence-based ITM strategies that: 1) are tick species-specific; 2) can be implemented by vector biologists, ecologists, entomologists, pest management specialists, and other practitioners of area-wide ITM; 3) consider cost-effectiveness; 4) minimize non-target effects and pesticide resistance in vector ticks; 5) maximize the likelihood of public acceptance and adoption; and 6) can demonstrate reduction of human tick bites or tick-borne disease.

Beto explained that tick species are different and there is no silver bullet in addressing them. When assessing and implementing tick management strategies, factors such as cost-benefit and risk-benefit ratios need to be considered. Successful implementation, he noted, may also require working with social scientists.

Potential Action 1.2: Support research on ways to disrupt tick feeding, reproduction, and pathogen transmission.

Fund research addressing the knowledge gap on target pathways that disrupt tick feeding, reproduction, and transmission of pathogens causing Lyme disease and other tick-borne diseases. Using our expanding knowledge of the genes and molecules controlling tick feeding, tick reproduction, and transmission of tick-borne pathogens, it should be possible to precisely target and block these processes. For example, develop vaccines that block tick feeding before transmission of microbes can occur, especially for use in areas where tick-borne diseases are common. Further research is needed to develop and implement the use of these methods.

Potential Action 1.3: Promote the development of integrated tick management methods and adoption by commercial applicators.

Encourage incorporation of ITM methods into the current pest control model and commercial development of new effective tick control products. These actions would: 1) expedite the implementation of existing and development of promising new intervention technologies; 2) need broad funding that incorporates basic, translational, and applied research, as well as a seed support initiatives—such as Small Business Innovation Research; and 3) facilitate the commercialization or marketing of existing and new intervention products for tick and tick-borne disease control to reach the widest possible segments of the populations at risk of Lyme disease and other tick-borne diseases.

Potential Action 1.4: Encourage public-private partnerships.

Support these critical partnerships will expedite the progress of intervention strategies, including to commercialize and market the most promising new and/or existing technologies so as to reach the widest possible segments of the populations at risk of Lyme disease and other tick-borne diseases in the United States.

Kevin presented priority 2 and the four actions it includes. He explained that the goal is to implement best practices.

Priority 2: Establish and Sustain a National Network to Support Tick Surveillance and Control by Fiscal Year 2021

Potential Action 2.1: Develop and implement best practices for tick vector surveillance.

Develop and implement evidence-based best practices for national surveillance of tick vector species, their distributions, their abundance, and their associated pathogens. This surveillance will help identify and monitor existing, emerging, and new tick vector species, their environmental drivers, as well as their associated pathogens, important to medical and veterinary public health. Specific activities will: 1) document and monitor tick species ranges, range expansions and contractions, and geographic overlaps; 2) identify and monitor non-native tick species to minimize the risk of invasive ticks entering the U.S. and, if possible, rapidly abate or manage establishing invasive species; and 3) assess favorable host ranges, vegetation habitats, and the impacts of changing landscapes and other environmental factors on tick populations.

Potential Action 2.2: Foster coordination among Federal, state, and local agencies.

Increase coordination and support of tick vector surveillance activities and data management across Federal, state, and local agencies, as well as experiment stations, universities, and public entities and networks.

Potential Action 2.3: Provide resources for local tick management programs.

Create local tick management programs that are: 1) professionally-staffed; 2) adequately resourced to operate using Integrated Pest Management principles and follow standardized guidelines; 3) responsible for surveillance of tick vectors and their associated pathogens; 4) responsible for public outreach; and 5) applicable to control of tick vectors on publicly and/or privately-owned lands, possibly in part through homeowner incentives.

Potential Action 2.4: Provide education and training to all stakeholders.

Develop and promote a broad range of improved, science-based educational materials, training programs, and outreach initiatives that provide adequate background knowledge about tick vectors and tick-borne disease prevention, for stakeholders at the local, regional, and national levels. This includes vector control professionals, health care providers, students in K-12, university students, postdoctoral fellows, those at occupational risk, and members of the general public.

At the end of presentation, Beto noted that the subcommittee believes the proposed potential actions are achievable, and that they encourage all stakeholders to work together to minimize the public health threat of Lyme disease and other tick-borne diseases.

Discussion

After the presentation, Beto and Kevin responded to questions and comments from Working Group members. The main discussion points are summarized below.

The group discussed what is currently being done to control ticks, in particular the blacklegged tick (Ixodes scapularis), and what opportunities there might be for the future. Beto and Kevin explained that many states are currently implementing both research and legislation that can be learned from, expanded upon, and translated into impactful practices to disrupt the transmission of pathogens at the local level. This, Beto stated, could be achieved using the established mechanism of the CDC Centers of Excellence. Beto emphasized the importance of using comparable parameters when drawing conclusions from research to avoid comparing “apples to oranges,” and he pointed out the need for more coordination. In addition, Beto stated that global initiatives, such as the plan to eradicate malaria by 2040, can be used as a model for tick-borne diseases.

Pat asked how the subcommittee’s proposed actions take into account ticks such as the winter tick (Dermacentor albipictus) and the brown dog tick (Rhipicephalus sanguineous). Kevin responded that the plan is to provide education at all levels about the different tick species and their biology. Using what the Centers of Excellence have already accomplished, he added, the goal is to put in place a process through which methods can be prescribed that are tailored to each unique tick species and locality.

Ben concurred with the priorities and potential actions identified in the Tick Biology, Ecology, and Control Subcommittee Report and agreed that the model for managing mosquitos could be tailored to target ticks. He added that mosquito control is often funded by local taxes and mill rates. He also stated that a community-coordinated approach for integrated pest control is needed and provided several suggestions for what could be done to minimize exposure to ticks.

Pathogenesis and Physiology of Lyme Disease Subcommittee

Subcommittee Co-Chair Sam T. Donta, MD, Professor of Medicine (retired); Consultant, Infectious Diseases, presented the subcommittee report.

Sam first introduced the subcommittee membership, provided background information, and explained the methods used to develop their subcommittee report. He then reviewed the subcommittee’s goals, reported findings, and presented potential actions.

Goals

Sam explained that the subcommittee’s goals were based on addressing the following questions.

What are the initial events and mechanisms involved in the entry of B. burgdorferi into host tissues?
What are the events and pathophysiology involved after the entry of B. burgdorferi into host tissues?
What are the pathogenetic and pathophysiologic mechanisms involved in the development of symptoms and signs?
What underlies the persistence of Borrelia in host tissues?
Does immune evasion or suppression or autoimmunity contribute to the process of persistent symptoms?
Is there a role for antibiotic tolerance in “resistance” to successful antibiotic treatment?

Priorities, Evidence and Findings, and Potential Actions

Sam stated that the subcommittee identified four priority areas and focused on priorities 1 and 2. Because of time constraints, he added, the subcommittee did not have time to address Lyme-related carditis.

Priority 1: **Determine the Mechanisms Underlying the Persistence of Borrelia burgdorferi in the Host**

Evidence and Findings

Sam explained that studies have reported that B. burgdorferi begins to multiply once it senses feeding is to take place, and it begins to disseminate after entering into the host through a tick bite. He noted, however, that knowledge gaps exist and additional studies are needed to better understand the following issues.

What happens inside the tick. For example, what signals “tell” B. burgdorferi that a vector tick is feeding?
Processes of, and factors assisting, the initial entry into the host. For example, what kinds of tissues does the bacteria adhere to?
The process of the dissemination inside the host. For example, does it enter the lymphatic system? Which genes are required for dissemination of Borrelia and its colonization of tissues during later stages of infection?

Sam noted that studies suggest B. burgdorferi can suppress the immune system and prevent CD4 T cells from mounting an effective immune response to infection. However, it remains unknown how Borrelia induces immune suppression, what signals are involved, and what role CD47 plays. Studies, Sam added, also suggest that B. burgdorferi utilizes multiple immune evasion mechanisms to establish persistent infection in its hosts. The precise mechanism that leads to persistence, however, remains unknown.

In addition, Sam noted, animal studies have shown that persisting B. burgdorferi can be metabolically active, expressing certain bacterial genes and inducing gene expression changes in the infected host, even though it can’t be cultured after antibiotic treatment.

Based on the findings, the subcommittee proposed the following potential actions.

Potential Actions

Potential Action 1.1: Support targeted funding of research that aims to better understand the initial events and mechanisms involved in the entry of B. burgdorferi into the host.

Potential Action 1.2: Support targeted funding of research that aims to better understand the mechanisms involved in the establishment of infection and its persistence in host tissues.

Potential Action 1.3: Support targeted funding of research that aims to better understand the interactions between B. burgdorferi and host immune systems and development of more efficient tools to characterize host-pathogen interaction and facilitate approaches to genetically manipulate B. burgdorferi.

Potential Action 1.4: Support targeted funding to develop and assess animal models of neuroborreliosis and human studies to better understand the molecular mechanisms involved in the pathogenesis of neuroborreliosis.

Potential Action 1.5: Support targeted funding of research that aims to determine the potential roles of antibiotic tolerance and immunomodulation in the persistence of B. burgdorferi despite antibiotic treatment.

Potential Action 1.6: Support targeted opportunities for graduate students and postdoctoral researchers (for example, through NIH F and K awards) and junior and senior investigators (for example, through NIH R03 and R21 awards) to become involved in research that addresses the gaps in our understanding of the pathogenesis and pathophysiology of Lyme disease, including studies of Borrelia persistence. Support targeted clinical studies and the analysis of veterinary clinical data on Lyme disease in dogs, horses, and other species.

**Priority 2: Determine the Role of Persistence of B. burgdorferi or Its Components in the Pathogenesis of Lyme Arthritis and Persistent Lyme Disease**

Evidence and Findings

Sam noted that studies have suggested multiple genetic and environmental factors may contribute to persistent Lyme arthritis, such as infections by certain arthritogenic strains of B. burgdorferi and remaining spirochetal antigens (for example, peptidoglycans, the primary component of the bacterial cell wall). It has been suggested that B. burgdorferi-induced infection may trigger autoimmunity over time; however, the role of infection as an autoimmune trigger as well as the potential roles of B. burgdorferi products (for example, peptidoglycan) in Lyme disease remains poorly understood.

Based on the scientific findings and the remaining unknowns, the subcommittee proposed the following potential actions.

Potential Actions

Potential Action 2.1: Support targeted funding opportunities for research to better understand the role of bacterial antigens, including peptidoglycan, and the host immune response in the persistence of ongoing symptoms of Lyme disease, including Lyme arthritis.

Potential Action 2.2: Support targeted funding opportunities for research that determines whether different antibiotic regimens from those previously reported would be effective in resolving Lyme disease.

Potential Action 2.2: Support targeted funding opportunities for research to determine whether the use of targeted immunomodulatory medications are effective in resolving Lyme arthritis and/or other residual Lyme disease symptoms that are not responsive to standardly recommended therapeutics.

Priority 3: Determine the Pathogenesis, Pathophysiology, and Effective Treatment of Lyme Carditis.

Sam noted that due to time constraints, the subcommittee did not address Lyme carditis. The subcommittee nonetheless considers it a priority focus for further study because it can lead to patient death.

Potential Actions

Potential Action 3.1: Support targeted funding opportunities for research to develop an animal model of Lyme carditis.

Potential Action 3.2: Establish a clinical network to study patients with Lyme carditis and its treatment.

Priority 4: Develop Targeted Treatments for Lyme Disease

Evidence and Findings

Sam acknowledged that prompt antibiotic treatment during the early stages of Lyme disease can prevent the persistence of B. burgdorferi and persistent Lyme disease. However, he pointed out that similar antibiotic treatments for persistent B. burgdorferi in animal models and in patients with persistent Lyme disease appear to be ineffective. The reasons for this difference are unclear.

There are indications, Sam explained, that certain treatment regimens (for example, tetracycline instead of doxycycline, the combination of a macrolide antibiotic and an alkalinizing agent) are effective in treating the persistent state if given over longer durations of time rather than the usual 2–4-week periods. There is also indication that the intestinal microbiota may play an important role in the persistence of, or ability to eradicate, persisting organisms.

Potential Actions

Potential Action 4.1: Support targeted funding toward a better understanding of the persistent state of B. burgdorferi, especially if antibiotic tolerance and/or immunomodulation plays a role in persistence.

Potential Action 4.2: Support targeted funding exploring the use of novel compounds or combinations of antibiotics in both preventing and resolving the persisting state.

At the end of the presentation, Sam noted that additional research on the pathogenetic and pathophysiologic mechanisms will improve our understanding of the processes involved and can help develop better strategies for prevention and treatment of persistent Lyme disease.

Discussion

After the presentation, Sam and Working Group members discussed various topics ranging from antibiotic treatment options to the need to understand the mechanisms. The key discussion points are summarized as follows.

Dennis and Sam discussed the potential of treating persistent infection with acidification of the intracellular environment. They both agreed, however, that conducting clinical trials may be difficult given the limitations of currently available patients.

Beto asked if the subcommittee had considered manipulation of the white-footed mouse genome. Sam responded that the issue had not been addressed in the report, but he agreed that it would be helpful to better understand resistance in certain mouse genera.

David stated that it would be most effective to first understand the persistence of B. burgdorferi before studying the mechanisms that mediate it and the role of antibiotic tolerance and immunomodulation. He described the method for tissue collection in an NIH-funded study of neurological AIDS and suggested that a similar approach could be used for studying persistence of B. burgdorferi. David added that the development of animal models can only be done once the human pathology of neuroborreliosis and Lyme carditis is known. He also commented on the role of DNA and RNA as indicators of persistent infection. Sam agreed that these factors are all important to consider.

Clinical Aspects of Lyme Disease Subcommittee

Sam T. Donta, MD, Professor of Medicine (retired); Infectious Disease Consultant, Falmouth Hospital; Co-Chair of the Clinical Aspects of Lyme Disease Subcommittee reported the subcommittee’s work.

Sam first reviewed the subcommittee membership and methods. He then presented the subcommittee’s priorities and potential actions. Sam explained that the subcommittee focused on addressing persistent Lyme disease.

Goals

Sam noted that the subcommittee’s primary goals were to identify gaps in: 1) our understanding of the clinical picture of persistent Lyme disease and its symptoms and signs; 2) the use of current laboratory tests and other diagnostic modalities; and 3) the treatment of patients with persistent Lyme disease.

Priorities, Evidence and Findings, and Potential Actions

Sam reported the following priorities and corresponding potential actions. He clarified that the subcommittee spent most of the time on Priority 1.

Priority 1: Conduct Additional Targeted Controlled Clinical Treatment Trials in Patients with Early and Persistent Lyme Disease, Using Different Antibiotic Regimens and Longer Durations of Treatment than Those Used in Previously Conducted Trials

Issues, Evidence, and Findings

Sam highlighted the following issues and findings.

Clinical assessment of persistent Lyme disease is challenging.
Laboratory tests have limited sensitivity, and test results are frequently negative for patients with persistent Lyme disease.
CDC’s criteria for surveillance purposes are often used to support clinical diagnosis.
There are no existing direct detection tests to assess the presence or absence of active B. burgdorferi infection in patients with persistent Lyme disease.
Proteins unique to patients with persistent Lyme disease have been found in cerebrospinal fluid; further studies of these proteins may help identify potential biomarkers that could aid the clinical diagnosis of persistent Lyme.
Other potential host biomarkers (for example, CCL19 and interleukin 23) have also been reported.
Radiotracer imaging of the brain has been suggested as an adjunctive diagnostic and monitoring tool.

Sam explained that the subcommittee also reviewed the results of previously published controlled studies of antibiotic treatment, and discussed the shortcomings of those studies, including the types of antibiotics used, the numbers of patients included, the duration of treatment, and the interpretation of the outcomes. Gaps, he noted, exist between published controlled treatment studies and clinical observations (published and unpublished) regarding antibiotic regimens for the treatment of patients with persistent Lyme disease.

Potential Actions

Potential Action 1.1: Establish a clinical treatment trials network to evaluate the potential of various antibiotic and non-antibiotic treatment regimens in patients with persistent Lyme disease.

A planning committee including involved stakeholders (clinicians and researchers representing a range of scientific and medical perspectives, patient advocates, and government funding agencies) should be established to discuss the essential components of future clinical trials, with a focus on studies that include antibiotic regimens differing from those used in previously conducted studies and of longer durations.
Experts in clinical trial design and biostatistics should be included to ensure the integrity of patient inclusion criteria, study design, selection of outcome measures, and methods used to analyze the results of the trials.
Patient inclusion criteria could include: a) patients previously treated (for example, patients with Post-Treatment Lyme Disease Syndrome); b) patients not previously treated with persisting symptoms; and c) patients with less stringent serologic evidence of exposure to B. burgdorferi. A particularly more homogeneous group of patients to be studied would be those with early Lyme disease, using longer courses of treatment, a combination of antibiotics, or both, to determine whether the results of these studies would lead to a lower incidence of subsequent persistent Lyme disease.

Potential Action 1.2: Target research funding for the development of specific detection tests or biomarkers to determine whether persistent Lyme disease is due to continuing infection by B. burgdorferi and to monitor the results of treatment.

Priority 2: Educate Clinicians as to the Limitations of Currently Available Tests in the Diagnosis and in the Monitoring of Treatment of Patients with Persistent Lyme Disease

Sam highlighted the disparities between professional associations, government agencies, and clinicians regarding recommendations on the use of existing tests for the diagnosis of persistent Lyme disease and treatment.

To resolve these issues, Sam noted, there is a need to consider if additional controlled treatment trials are feasible, given the absence of specific corroborative tests, the challenge of identifying sufficiently homogeneous clinical populations, and the lack of consensus about the best antibiotic regimens to be tested. Until research results are sufficiently conclusive to support the recommendation of a specific regimen for general use, healthcare providers, he noted, should consider the use of currently available, apparently successful treatment regimens.

Potential Actions

Potential Action 2.1: CDC should develop educational modules on limitations of available testing in the diagnosis and in the monitoring of treatment of persistent Lyme disease and of the limitations in the interpretations of the results of previously conducted controlled antibiotic treatment trials.

Potential Action 2.2: Provide Federal and state support for the use of regional and local clinician forums to educate clinicians as to the limitations of available testing in the diagnosis and in the monitoring of treatment of persistent Lyme disease and of the limitations in the interpretations of the results of previously conducted controlled antibiotic treatment trials.

Priority 3: Provide Funding for Research to Support or Refute the Purported Human-to-Human Sexual Transmission of Lyme Disease

Sam noted that the subcommittee addressed Priority 3 to certain degree. The subcommittee concluded that there was limited evidence supporting sexual transmission of Lyme disease. However, because of the implications of sexual transmission, some subcommittee members suggested that further studies be conducted to validate or refute this possible mode of transmission.

Potential Actions

Potential Action 3.1: Provide funding for research to support or refute the purported human-to-human sexual transmission of Lyme disease.

Priority 4: Further Evaluate Potential Maternal-fetal Transmission of Lyme Disease and of Congenital Lyme Disease

Evidence and Findings

Sam explained that the subcommittee spent some time discussing this topic and found limited evidence linking gestational Lyme disease to adverse pregnancy outcomes. While it appears that the prognosis for the fetus is favorable when gestational Lyme disease is promptly diagnosed and treated with appropriate antibiotics, untreated gestational disease is associated with a higher rate of adverse pregnancy outcomes. Although a broad spectrum of adverse fetal outcomes has been noted, a congenital syndrome has not been identified.

Potential Action 4.1: Provide funding for a registry and more studies to determine the extent of maternal-fetal transmission of Lyme disease and of any congenital Lyme disease.

Summary

In summary, Sam noted, it is likely that a continuing active infection is responsible for the continuing symptoms and signs in patients with persistent Lyme disease. While the mechanisms underlying the pathophysiology of persistent Lyme disease remain to be defined, targeted controlled clinical trials on antibiotic, and perhaps non-antibiotic, treatment in patients with persistent Lyme disease may help identify better treatment regimens.

Discussion

After the presentation, the Working Group members discussed treatment options, antibiotic resistance, ongoing studies, clinical trials, and how to move forward. The main discussion points are summarized below.

The Working Group members generally agreed that better approaches are needed to tackle the problems identified by the subcommittee. Dennis M. Dixon, PhD, Chief, Bacteriology and Mycology Branch, NIAID, NIH, noted that conducting clinical trials should be the ultimate goal; however, trial design around antibiotic resistance/persistent infection can be challenging and several activities need to take place first. Specifically, investigators will need to 1) determine the relevance and potential frequency of persistence; 2) demonstrate persistence; and 3) understand how common it is. Dennis highlighted another major challenge associated with this type of clinical study; that is, there is no marker to identify patients with the disease (or persistent pathogen) that the investigators intend to treat with a particular antibiotic treatment regimen.

In response, Sam emphasized the importance of addressing the issue around the effectiveness of antibiotic treatment. He noted that clinicians currently rely heavily on observational studies and clinical experiences. He then suggested changing the name in Potential Action 1.1 from “clinical trials network” to “persistent Lyme disease study group.” He explained that a network can bring people together, but it is just a first step. Pat Smith, President, Lyme Disease Association, stated that she is in favor of establishing a network or think tank in order to give healthcare providers a means to exchange information about their clinical experience and observations.

Leigh Ann asked about antibiotic resistance and the effectiveness of doxycycline in patients who have been previously treated with antibiotics. Sam explained that it is possible to effectively treat patients with antibiotics even if they have taken them in the past. However, he added, biomarkers that can be used to determine antibiotic resistance are lacking.

Beto asked if the subcommittee had considered the potential clinical outcome when a tick is coinfected with multiple pathogens. Sam replied that the members did not directly discuss the issue.

David and Sam discussed the use of animal models in evaluating treatment regimens for persistent infection. Sam noted that published studies have shown that some treatments—usually combinations of two or three antimicrobials—were effective in clearing infection in animals that were not previously treated with the combinations.

Regarding the recommended clinical trial network (Potential Action 1.1), Todd pointed out the need to communicate proactively with FDA, which is not a funding agency, and suggested including regulatory authorities in the network. Sam agreed and stated that this was the intention.

Sam and Dennis further discussed the feasibility of conducting additional clinical trials on antibiotic treatment. They also discussed avenues by which clinicians can compile and analyze anecdotal information gathered from clinical observations. Dennis enumerated several possibilities, including the following.

Patient registries
Basic translational research
Investigator-initiated pilot trials
Predictive animal models, especially a persistence animal model reflecting human pathology

Dennis stated that many of these activities can be overlapping; however, the important factor is to use a homogenous population to ensure credible analysis. Better markers, he added, are needed to select patients and to get the answer everyone is seeking.

Pat pointed out that there are fewer clinical studies for Lyme disease than for leprosy, which has about 200 cases annually.

Training, Education, Access to Care, and Reimbursement Subcommittee

Pat Smith, President of Lyme Disease Association, Co-Chair of the Training, Education, Access to Care, and Reimbursement Subcommittee, and Elizabeth (Betty) Maloney, MD, Family Physician, President of the Partnership for Tick-Borne Diseases Education, member of the subcommittee co-presented the subcommittee report.

Pat first introduced subcommittee membership and provided background information. She highlighted the major challenges in diagnosing and treating Lyme disease, stressed the consequences of delayed diagnosis and misdiagnosis, pointed out the disproportionate allocation of research funding, and identified conflicting treatment guidelines as a major barrier to accessing healthcare insurance, coverage, and reimbursement.

After Pat explained the methods used to develop the subcommittee report, Betty and Pat together reported the priority issues the subcommittee addressed in their report and the corresponding potential actions for the Working Group to consider.

Priorities, Evidence and Findings, and Potential Actions

Priority 1: Access to Care

Evidence and Findings

Betty explained that surveys and publications have reported that many patients with persistent Lyme disease face substantial barriers to access health care including institutional and structural barriers and hidden barriers such as stigma and discrimination. While structural barriers caused by power imbalances (for example, between IDSA and ILADS guidelines) make it difficult for patients with persistent Lyme disease to obtain health care through usual channels, stigma and discrimination can lead to delayed care and denied treatment.

The subcommittee evaluated persistent Lyme disease patients’ access to care using the Penchansky and Thomas Model of Access to Care Registry, and they found that the majority of patients with persistent Lyme disease are not able to obtain adequate care locally, have difficulty finding a treating clinician, have difficulty obtaining medical care in usual healthcare settings, can’t afford the care they do receive because of low insurance coverage and high out-of-pocket costs.

Potential Actions

To reduce the barriers and address patient needs, the subcommittee proposed the following potential actions.

Potential Action 1: Increase public awareness that there are two divergent approaches reflected in guidelines to the diagnosis and treatment of Lyme disease. Encourage the disclosure that there are two diagnostic and treatment approaches on all state and Federal government web pages that discuss Lyme disease or tick-borne illness, including CDC, NIH, and the Agency for Healthcare Research and Quality (AHRQ); and encourage inclusion of the two diagnostic and treatment approaches in any government educational seminars, clinical materials, and other educational materials for both health care providers and the public.

Potential Action 2: Encourage all state and Federal government committees and panels, including the CDC, NIH, DoD, AHRQ, and medical specialty societies to use authentic and meaningful representation of patients with persistent Lyme disease in health care policy matters, the determination of research grants, and in the development of diagnostic and treatment guidelines.

To serve as a meaningful representative, patients or advocates representing the persistent Lyme disease community should: a) have or have had persistent Lyme disease or be someone who serves or has served as a caregiver to a persistent Lyme disease patient; and b) should be an officer or director of a recognized and trusted patient advocacy representing patients with persistent Lyme disease, or someone vetted and approved by such a group.
To ensure process integrity in the selection of patient representatives through open and transparent selection processes, including public calls for nominations and soliciting nominations through recognized and trusted patient advocacy group representing patients with persistent Lyme disease.

Priority 2. Reducing Diagnostic Errors and Delays in Lyme Disease

Evidence and Findings

While the majority of patients with Lyme disease are able to restore their health with early diagnosis and prompt treatment, publications and survey data suggest that errors and delays in diagnosis of Lyme disease are common. Delayed and misdiagnosis can lead to treatment delays, incorrect treatment, and poor treatment outcomes. Potential sources of the errors include inaccurate geographic exclusions, failure to recognize the full spectrum of Lyme disease-related symptoms, inability to identify erythema migrans (EM) rashes and/or other Lyme disease-related findings on physical exam, and over-reliance on inaccurate diagnostic tests.

Potential Actions

To address these issues, the subcommittee proposed the following actions.

Potential Action 3: Renew and expand the recommendation for CDC to develop a multi-leveled curriculum on Lyme disease for clinicians. This should include instructional programs for medical students, residents, physician assistants, mental health professionals, and nurse practitioners. Ongoing education via continuing medical education programs should also be included.

In addition to providing background information on all aspects of these infections, the content should highlight the most frequent sources of diagnostic errors identified in this report, including:

Inappropriately excluding Lyme disease from the initial differential diagnosis because of geographic exclusions that inaccurately reflect the geographic scope of the disease;
Failing to recognize the full spectrum of Lyme disease-related symptoms;
Failing to identify EM rashes and/or other Lyme disease-related findings on physical exam; and
Cautioning clinicians against over-reliance on inaccurate diagnostic tests.

The training should also emphasize the inclusion of Lyme disease in the differential diagnosis of complex illnesses.

The curriculum development team should include representatives of all stakeholder groups, including meaningful patient representation (as defined in Potential Action 2). Clinicians and research scientists with expertise in this field should be selected such that the team represents the spectrum of scientific and clinical perspectives on tick-borne diseases.

Potential Action 4: Recommend that CDC provide input to the Council of State and Territorial Epidemiologists, CSTE, that the Lyme disease surveillance case definition be revised such that it abandons the use of geographic parameters for Lyme disease.

Potential Action 5: Recommend funding CDC to periodically conduct studies using available laboratory data from a number of the major diagnostic labs utilizing big-data technology methods. Findings from these studies would not replace the current surveillance system but would provide an additional information source that would increase our understanding of the geographic exposure and growth in the incidence of Lyme disease.

Potential Action 6: Recommend that CDC, NIH, and other government agency websites, brochures, and educational materials abandon the use of geographic parameters for the diagnosis of Lyme disease and that clinicians and the public be made aware that Lyme disease has been reported in all states.

Potential Action 7: Recommend that CDC, NIH, and other government agency websites, brochures, and educational materials acknowledge the diagnostic limitations of clinically available laboratory tests for all stages of Lyme disease.

Priority 3. Reducing Psychiatric Misdiagnoses in Lyme Disease

Evidence and Findings

Studies have found that tick-borne diseases can lead to brain dysfunction. Neuropsychological and neurocognitive symptoms caused by Lyme disease may include depression, anxiety and panic disorders, sleep disturbances, and auditory as well as visual processing impairments. Neuropsychiatric manifestations (for example, anxiety and cognitive impairment) in children can lead to misdiagnosis with learning disorders, inadequate academic accommodations, and inappropriate legal actions. A lack of consensus among experts and medical associations may has contributed to confusion over appropriate diagnosis and treatment.

To address this issue, the subcommittee proposed the following potential actions.

Potential Action 8: Provide information and training to health care professionals regarding the full spectrum of potential Lyme disease symptoms, including the potential impact on brain function. Lyme disease should be included in the differential diagnosis of patients with neuropsychiatric symptoms in order to promote appropriate diagnostic evaluations and subsequent treatment. Clinicians should be cautioned not to default to a psychiatric diagnosis when the cause of symptoms has not yet been determined.

Potential Action 9: Provide education and training to neuropsychologists, clinical and school psychologists, social workers, and other pertinent school personnel regarding the extent and complexity of the emotional, physical, cognitive, sensory, and other aspects of brain dysfunction that may be experienced by students with Lyme disease.

Potential Action 10: Encourage the development of multidisciplinary treatment teams that recognize medical, neuropsychiatric, and neuropsychological symptoms that may be experienced by some patients with Lyme disease. Recommend funding for NIH to develop an in-patient unit for multidisciplinary treatment of Lyme disease patients who present with neuropsychiatric symptoms.

Priority 4. Shared Decision-Making

Evidence and Findings

Shared decision making has been promoted by many organizations including AHRQ and CMS. It has been recognized as the best approach to generate an individualized treatment plan, when there is uncertainty (for example, uncertain evidence, or more than one “right” treatment option).

For Lyme disease, scientific evidence for safe and effective treatment options is limited and unsettled, indicating the need for shared decision-making. However, major challenges exist, including time constraints of treating clinicians, concerns about overwhelming patients with information, beneficent paternalism, and vested interests of professional medical organizations.

To improve shared decision-making in Lyme disease, the subcommittee proposed the following potential actions.

Potential Action 11: Increase public awareness that there are two divergent diagnostic and treatment approaches reflected in guidelines for Lyme disease, encourage the disclosure on all state and Federal government websites that discuss Lyme disease or tick-borne diseases, including CDC, NIH, AHRQ, that there are two diagnostic and treatment approaches; and Encourage inclusion of the two diagnostic and treatment approaches in any government educational seminars, clinical materials, and other educational materials for both health care providers and the public.

Potential Action 12: Encourage the disclosure on all state and Federal government websites that discuss Lyme disease or tick-borne diseases, including CDC, NIH, AHRQ, that the state of the science in Lyme disease, particularly for persistent Lyme disease, is limited, emerging, and unsettled; and encourage the inclusion of the two diagnostic and treatment approaches in any government educational seminars, clinical materials, and other educational materials for both health care providers and the public.

Action 13: Encourage the use of shared decision-making in Lyme disease on all state and Federal government websites that discuss Lyme disease or tick-borne diseases, including CDC, NIH, AHRQ; and encourage inclusion of the two diagnostic and treatment approaches for Lyme disease in any government educational seminars, clinical materials, and other educational materials for both health care providers and the public.

Priority 5. Patient and Public Health Education on Lyme Disease and Other Tick-Borne Diseases

Evidence and Findings

Given that many patients use the internet to find information on tick-borne diseases, the subcommittee reviewed the websites of 10 state health departments, representing high- and low-incidence states (as designated by CDC). The subcommittee found that recommendations for prevention of tick bites are consistent on these sites. However, certain important information is either inaccurate (for example, disease transmission and tick-attachment time), inadequate (for example, guidance on occupation-related risk of tick-borne diseases, diagnosis, and treatment), or non-existent (for example, the possibility of tick-borne disease transmission [babesiosis] through blood transfusion). In addition, all of the sites recommend the CDC two-tiered testing for Lyme disease.

While information on tick-borne diseases abound on the internet, members of the subcommittee found that finding accurate information can be challenging, and not all information is up to date.

To improve the situation, the subcommittee proposed the following potential actions.

Potential Action 14: Recommend that CDC, NIH, and other government agency websites, brochures, and educational materials on Lyme disease and other tick-borne diseases be developed by a curriculum development team and, given the differences in scientific perspectives regarding tick-borne diseases, that this team should include clinical and research experts that represent a broad range of scientific and clinical perspectives.

Potential Action 15: Improve public information about occupational risks of tick-borne diseases and the risks associated with blood transfusions and organ transplants.

Priority 6. Clinician Training on Tick-Borne Diseases

Evidence and Findings

Pat pointed out that clinicians’ knowledge about tick-borne diseases is critical for the treatment of patients with tick-borne disease. However, education on tick-borne disease for medical professionals (medical school students, residents, and practicing physicians) and corresponding coverage in licensing exams are limited.

To improve education and training for medical professionals, the subcommittee proposed the following potential actions.

Potential Action 16: Recommend that CDC develop a multi-leveled curriculum on U.S. tick-borne diseases for clinicians. There should be instructional programs for medical students, residents, physician assistants, and nurse practitioners. While the emphasis should be on training the clinical specialists most likely to encounter patients during their initial presentation of tick-borne diseases (for example, family practitioners, pediatricians, general internists, and emergency medicine physicians), specialty and subspecialty-specific training should be developed for other clinician groups.

Potential Action 17: Recommend to DoD:

Develop stand-alone educational modules for Uniformed Services University students that cover the spectrum of tick-borne diseases. Training should specifically highlight the risks of military occupational hazards from tick-borne diseases as a result of training environments (both domestic and overseas), deployments, and reassignments. The transient nature of military assignments, which increases the risk of misdiagnoses and diagnostic delays for both service members and military dependents, should also be emphasized.
Institutionalize tick-borne diseases training and education via the Defense Health Agency (DHA). Standardize training, education, and military force health protection guidelines across the Military Services. Implement continuing medical education programs via existing forums such as the DHA Primary Care Clinical Community Speaker Series, and disseminate information on relevant tick-borne diseases programs (for example, the Army Public Health Center’s Human Tick Test Program).

Discussion

After the presentation, Pat and Betty responded to questions and comments from the Working Group members. The main discussion points are summarized below.

Sam suggested including educational modules in various meetings held by different medical specialty societies and other organizations, such as the American College of Physicians. Betty agreed and added that the first step is to develop the content, which can then be deployed in those types of venues.

Kevin expressed appreciation for the subcommittee’s differentiation between regions in the United States and the tick-borne diseases that occur there. This coverage, he added, complements the content in the Tick Biology, Ecology, and Control Subcommittee Report.

Alpha-gal Syndrome Subcommittee

Subcommittee Co-Chair Leigh Ann started the presentation by reviewing the description of Alpha-gal Syndrome, as follows.

Alpha-gal is a carbohydrate found in all mammals but not in humans or Great Apes. Mammals are warm-blooded animals that give live birth, have hair (or fur), and nurse their young. Examples of commonly consumed mammalian meats that contain alpha-gal include beef, pork, lamb, venison, rabbit, goat, squirrel, and buffalo. Alpha-gal is present in the milk from these animal sources as well as their organ meats. Chicken, turkey (that is, poultry), fish and shellfish (that is, seafood) do not have alpha-gal and are safe for patients with Alpha-gal Syndrome (AGS) allergy to consume. For the purposes of the Alpha-gal Syndrome Subcommittee Report, the term “mammalian meat” and “mammalian-derived” will be used to refer to non-primate mammalian meat (beef, pork, lamb, etc.) and its animal sources, as these are alpha-gal containing foods or products. Equally, report references may state “mammalian meat” or “red meat” yet these also refer to non-primate mammalian meat, which is the primary source of alpha-gal.

Leigh Ann then provided brief background information about AGS and explained the subcommittee’s methods, which is similar to those of the other subcommittees.

Subcommittee Co-Chair Angel M. Davey, PhD, Program Manager, Tick-Borne Disease Research Program, Congressionally Directed Medical Research Programs, DoD, introduced the subcommittee membership and highlighted their expertise related to AGS and tick-borne diseases in general. She then presented the subcommittee’s first priority area, evidence and findings, and potential actions.

Priorities, Evidence and Findings, and Potential Actions

Priority 1. Surveillance, Epidemiology, and Role of Tick Bites in AGS

Issues, Evidence, and Findings

Angel explained that AGS is an emergent allergy and is increasingly widespread in tick-endemic areas in the U.S. Currently no known pathogen has been linked to AGS, and careful consideration must be taken to properly surveil its risk to human health.

While it is known that tick bites can cause AGS, it is also clear that not all tick bites result in AGS. Certain tick species (for example, the lone star tick in North America) have been implicated; however, the range of species associated with the risk of AGS remains unknown, and the nature and extent of AGS tick-borne etiology remains obscured. In addition, the pathogenesis of AGS and the mechanism of tick bite triggered allergic reactions are unknown.

The subcommittee proposed the following potential actions to surveil human-biting ticks associated with AGS and to use that surveillance information to clarify the epidemiological circumstances of this disease, including the risk factors associated with tick bites.

Potential Action 1.1: Fund “Novel Surveillance” of human-biting ticks (that is, ticks captured actively feeding on human hosts) to identify specific exposure factors such as the characteristics of the tick bite pertaining to its species, duration of feeding, and/or potential pathogens. This “Novel Surveillance” is critical, as we already know that people are acquiring AGS through tick bites. Interestingly, however, not all tick bites result in disease (acute or chronic). Determining the factors that affect clinical outcomes is crucial to preventing and treating AGS. This “Novel Surveillance” will be accomplished by systematically characterizing human-biting ticks and conducting longitudinal follow-up of tick-bite victims for signs and symptoms of AGS. The effort will further determine the specific factors of exposure risk and how to advise the public to best mitigate those risks.

Potential Action 1.2: Fund investigation of the cellular mechanisms that lead to AGS, including influence of the host, potential role of tick salivary factors, and tick-related diagnostic testing for AGS.

Potential Action 1.3: Establish guidelines for case reporting of human AGS and funding research on the incidence and prevalence of AGS.

Priority 2. Diagnosis and Management of AGS

Subcommittee Co-Chair Scott Palmer Commins, BS, MD, PhD, Associate Professor of Medicine and Pediatrics, University of North Carolina; Member, UNC Food Allergy Initiative, Thurston Research Center, presented the priority topic on diagnosis and management of AGS.

Issues, Evidence, and Findings

Scott noted that currently an accurate AGS diagnosis is based on a combination of clinical history of delayed allergic reaction that typically occurs 3-8 hours after eating non-primate mammalian meat, and a supporting positive blood test (>0.1 IU/mL) for IgE to the alpha-gal oligosaccharide. Currently there is no FDA-approved AGS treatment, and the primary management strategy for patients with AGS is avoiding a wide range of products, including mammalian meat, dairy in some cases, and products (daily household products as well medical products) containing mammalian-derived ingredients for some patients.

To address the unmet needs in the diagnosis and management of AGS, the subcommittee proposed the following potential actions.

Potential Action 2.1. Fund/support an AGS "Health Alert" to all relevant professional medical societies/associations for timely distribution nationwide to generate awareness and provide the groundwork for provider education/training, especially within endemic areas.

Potential Action 2.2. Support development of consensus guidelines or expert opinion on AGS diagnosis, management, natural history, and risk assessment.

Potential Action 2.3. Fund studies that evaluate health risks from exposure to alpha-gal that include threshold testing, airborne (fume) risk, and effect of continued dairy exposure.

Priority 3. Education, Awareness, and Support from Patients’ Perspectives

Scott noted that the subcommittee discussed the following issues and needs, and proposed corresponding potential actions to raise awareness and better support patients with AGS.

Wide-scale education for patients, their families, and healthcare providers
Awareness of AGS as a tick-borne condition
Ongoing support for people with AGS
Data on disease prevalence and patient perspectives

Potential Actions

Potential Action 3.1: Require labeling of foods, products, beverages (including alcohol), cosmetics, and pharmaceuticals that contain non-primate mammalian ingredients (active or inactive).

Potential Action 3.2: Update the FDA’s Food Safety Modernization Act to incorporate AGS awareness training into their “Retail Food Industry/Regulatory Assistance and Training” Program.

Potential Action 3.3: Support a "Call-to-Action" for Standard-of-Care/Evidence-based Guidelines – professional societies/associations will collaborate to form an "AGS Task Force" to set clinical research in motion to generate evidence in support of best treatment practices for AGS.

Priority 4. Tick Bite Prevention and Tick Control

Issues, Evidence, and Findings

Leigh Ann noted that effective tick bite prevention tools are available, but protective behaviors are often not adopted. In terms of AGS, the effectiveness of available strategies for managing I. scapularis and Lyme disease in northeastern U.S. are not well-evaluated for ticks of public health importance in southern U.S. (Amblyomma americanum, Dermacentor variabilis). In addition, geographical areas with high prevalence of lone star ticks are home to numerous major U.S. Army installations, and AGS in military service personnel has been reported.

To improve prevention strategies of bites of ticks associated with AGS, the subcommittee proposed the following potential actions.

Potential Action 4.1: Fund research on chemical repellents for personal protection against lone star tick and other ticks associated with AGS.

Potential Action 4.2: Fund research to understand how public knowledge, attitudes, and practices related to ticks may/may not inhibit adoption of tick bite prevention behaviors and to understand how prevention practices for lone star tick may impact (increase/decrease) AGS risk.

Potential Action 4.3: Fund research to develop economical and practical methods for homeowners to eliminate ticks in peridomestic landscapes and for municipalities to use in towns, commercial properties, and common spaces.

Summary

In summary, Leigh Ann noted that the implications of AGS are profound; however, awareness and understanding of the condition are alarmingly limited. AGS is managed differently from other tick-borne conditions and requires effective labeling, education, and training. The emergence of AGS as a non-infectious tick-borne disease that can be induced by a lone star tick bite calls for efforts to better understand the mechanisms behind the allergic reaction to alpha-gal, as well as tick and human factors involved in AGS.

Discussion

After the presentation, the three co-chairs responded to questions and comments from the Working Group members. The main discussion points are summarized below.

Pat asked for clarification about what types of ticks can retrigger an alpha-gal immune response. Scott replied that there have been instances in which the allergy has been renewed in humans after tick bites from the lone star and other ticks. However, he added, no studies have been conducted to provide concrete evidence.

Beto asked about the possibility of cross-reactivity in people bitten by a tick in the U.S. and then by a different tick in another country where alpha-gal allergy occurs (for example, Australia or New Zealand). Scott offered a related anecdote but stated that there are not yet concrete data to demonstrate this phenomenon.

Ben commented that, while AGS is not yet reportable, there appears to be a strong correlation between the distributions of AGS, ehrlichiosis, and the lone star tick in the U.S.

Kevin first asked why AGS is not yet nationally notifiable, to which Ben responded that the topic is under discussion. Kevin then asked if AGS results from one-time exposure or repeated exposure over time, to which Scott responded that a case-controlled study is ongoing, and many patients have reported that their allergic reactions seem to be linked to one tick bite that is different from all other bites.

In response to a question from Sam, Scott stated that pets can get AGS as well, and that pet dander can elicit an immune response in patients with AGS.

Beto asked if the genetic background of an individual plays a role in the susceptibility to allergy. Scott responded that his group is interested in the topic, and that a whole host of other potential causes need to be ruled out first.

David and Scott discussed experimental designs to determine novel exposure factors, cellular factors leading to AGS, and the mechanism of the allergic reaction. They agreed that determining the percentage of lone star ticks that are linked to AGS is a gap that needs to be addressed. In addition, Scott confirmed that there is currently a mouse model for AGS.

Several members discussed whether or not AGS is an emerging disease. They acknowledged anecdotal evidence that it may have been present in the U.S. for at least several decades, and they discussed the possible contributors to the increased number of cases in recent years. They agreed that there is still much to be learned about the illness and the ticks that cause it, and there is a need for education. David suggested focusing on basic research in order to better understand the mechanisms of the syndrome.

Adjournment

The meeting was adjourned at 3:52 pm.

Appendix 1: Tick-Borne Disease Working Group Members and HHS Support Staff

Tick-Borne Disease Working Group Members (in alphabetical order)

Co-Chair
Leigh Ann Soltysiak, MS, Owner, Principal, Silverleaf Consulting, LLC; Adjunct Professor, Stevens Institute of Technology, Entrepreneurship Thinking

Co-Chair
David Hughes Walker, MD, Professor, Department of Pathology, the Carmage and Martha Walls Distinguished University Chair in Tropical Diseases; Executive Director, UTMB Center for Biodefense and Emerging Infectious Diseases

Charles Benjamin (Ben) Beard, PhD, Deputy Director, Division of Vector-Borne Diseases, Centers for Disease Control and Prevention, U.S. Department of Health and Human Services; Associate Editor, Emerging Infectious Diseases

CDR Rebecca Bunnell, MPAS, PA-C, Senior Advisor, Learning and Diffusion Group, Innovation Center, Centers for Medicare and Medicaid Services, U.S. Department of Health and Human Services (Absent) – CAP Scott J. Cooper, MMSc, PA-C, Senior Technical Advisor and Lead Officer for Medicare Hospital Health and Safety Regulations Centers for Medicare and Medicaid Services (CMS), U.S. Department of Health and Human Services (Alternate present)

Scott Palmer Commins, BS, MD, PhD, Associate Professor of Medicine & Pediatrics
University of North Carolina; Member, UNC Food Allergy Initiative, Thurston Research Center

Angel M. Davey, PhD, Program Manager, Tick-Borne Disease Research Program, Congressionally Directed Medical Research Programs, U.S. Department of Defense

Dennis M. Dixon, PhD, Chief, Bacteriology and Mycology Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, U.S. Department of Health and Human Services - Samuel (Sam) S. Perdue, PhD, Section Chief, Basic Sciences and Program Officer, Rickettsial and Related Diseases, Bacteriology and Mycology Branch, Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, U.S. Department of Health and Human Services (Alternate present)

Sam T. Donta, MD, Professor of Medicine (retired); Consultant, Infectious Diseases

CAPT Estella Jones, DVM, Deputy Director, Office of Counterterrorism and Emerging Threats, Food and Drug Administration, U.S. Department of Health and Human Services (Absent) – CDR Todd Myers, PhD, HCLD (ABB), MB (ASCP), Office of Counterterrorism and Emerging Threats, Office of the Chief Scientist, Office of the Commissioner, U.S. Food and Drug Administration, U.S. Department of Health and Human Services (Alternate present)

Kevin R. Macaluso, PhD, MS, Locke Distinguished Chair, Chair of Microbiology and Immunology, College of Medicine, University of South Alabama

Adalberto (Beto) Pérez de León, MS, PhD, Director, Knipling-Bushland U.S. Livestock Insects Research Laboratory, United States Department of Agriculture—Agricultural Research Service

Eugene David Shapiro, MD, Professor of Pediatrics, Epidemiology, and Investigative Medicine, Yale University School of Medicine; Vice Chair for Research, Department of Pediatrics; Co-Director of Education, Yale Center for Clinical Investigation; Deputy Director, Yale PhD Program in Investigative Medicine (Absent)

Patricia V. Smith, President, Lyme Disease Association, Inc.

Leith Jason States, MD, MPH (FMF), Deputy Chief Medical Officer, Office of the Assistant Secretary for Health, U.S. Department of Health and Human Services (Present for the morning session)

HHS Support Staff

James (Jim) Berger, MS, MT (ASCP), SBB, Designated Federal Officer, Tick-Borne Disease Working Group Senior Blood and Tissue Policy Advisor, Office of Infectious Disease and HIV/AIDS Policy, Office of the Assistant Secretary for Health, U.S. Department of Health and Human Services

Kaye Hayes, MPA, Alternate Designated Federal Officer, Tick-Borne Disease Working Group, Executive Director, Presidential Advisory Council on HIV/AIDS, Principal Deputy Director, Office of Infectious Disease and HIV/AIDS Policy, Office of the Assistant Secretary for Health, U.S. Department of Health and Human Services

Chinedu Okeke, MD, MPH-TM, MPA, Senior Policy Advisor, Office of Infectious Disease and HIV/AIDS Policy, Office of the Assistant Secretary for Health, U.S. Department of Health and Human Services

Allison Petkoff, ORISE Policy Fellow, Office of Infectious Disease and HIV/AIDS Policy, Office of the Assistant Secretary for Health, U.S. Department of Health and Human Services

Debbie Seem, RN, MPH, Health Policy Advisor, Office of Infectious Disease and HIV/AIDS Policy, Office of the Assistant Secretary for Health, U.S. Department of Health and Human Services

Appendix 2: TBDWG Subcommittees

Alpha-Gal Subcommittee

Co-Chair
Scott Palmer Commins, BS, MD, PhD, Associate Professor of Medicine & Pediatrics University of North Carolina; Member, UNC Food Allergy Initiative, Thurston Research Center

Co-Chair
Angel M. Davey, PhD, Program Manager, Tick-Borne Disease Research Program, Congressionally Directed Medical Research Programs, U.S. Department of Defense

Co-Chair
Leigh Ann Soltysiak, MS, Owner, Principal, Silverleaf Consulting, LLC; Adjunct Professor, Stevens Institute of Technology, Entrepreneurship Thinking

Charles Apperson, PhD, Professor Emeritus, Arthropod Vector Biology and Management, Department of Entomology, NC State

Beth Carrison, AGS Patient/Advocate and Co-founder of Tick-Borne Conditions United

Shahid Karim, PhD, Professor, Arthropod Vector Biology, Tick-Borne Diseases, Functional Genomics, Biological Science, University of Southern Mississippi

Stephen M. Rich, PhD, Professor of Microbiology, Director of the Laboratory of Medical Zoology UMASS

Sarah Stuart, Alpha-gal Advocate/Patient

Clinical Aspects of Lyme Disease Subcommittee

Co-Chair
CDR Rebecca Bunnell, MPAS, PA-C, Senior Advisor, Learning and Diffusion Group, Innovation Center, Centers for Medicare and Medicaid Services

Co-Chair
Sam T. Donta, MD, Professor of Medicine (retired); Infectious Disease Consultant, Falmouth Hospital

John Aucott, MD, Director, Johns Hopkins Lyme Disease Clinical Research Center

Rex G. Carr, MD, FAAPMR, Specialist in Physical Medicine and Rehabilitation

Brian A. Fallon, MD, MPH, Professor, Clinical Psychiatry Director, Lyme & Tick-Borne Diseases Research Center, Columbia University Irving Medical Center

Elizabeth Maloney, MD, Family Physician; President, Partnership for Tick-Borne Diseases Education

Katherine Murray Leisure, MD, Infectious Disease Specialist

James K. Mingle, President & CEO, MyCareTeam

Pathogenesis and Physiology of Lyme Disease Subcommittee

Co-Chair
Sam T. Donta, MD, Professor of Medicine (retired); Consultant, Infectious Diseases

Co-Chair
Leith Jason States, MD, MPH, Acting Chief, Medical Officer, Office of the Assistant Secretary for Health, U.S. Department of Health and Human Services

Wendy Adams, Research Grant Director, Bay Area Lyme Foundation

Troy Bankhead, PhD, Associate Professor, School of Veterinary Microbiology and Pathology, Washington State University

J. Nicole Baumgarth, DVM, PhD, Professor, Center for Comparative Medicine and Department of Pathology, Microbiology and Immunology, University of California, Davis

Monica E. Embers, PhD, Director of Vector-Borne Disease Research, Division of Immunology, Tulane National Primate Research Center

Robert Lochhead, PhD, Assistant Professor of Microbiology and Immunology, Medical College of Wisconsin

Brian Steveson, PhD, Professor, Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky College of Medicine

Tick Biology, Ecology, and Control Subcommittee

Co-Chairs
Adalberto (Beto) Pérez de León, MS, PhD, Director, Knipling-Bushland U.S. Livestock Insects Research Laboratory, United States Department of Agriculture—Agricultural Research Service

Co-Chair
Kevin R. Macaluso, PhD, MS, Locke Distinguished Chair, Chair of Microbiology and Immunology, College of Medicine, University of South Alabama (Joined the Working Group and became subcommittee co-chair in August 2019)

Trey Cahill, MUrP, Public Health Analyst, Location Intelligence (GIS); Health Regulation and Licensing Administration, DC Department of Health

Neeta Pardanani Connally, PhD, MSPH, Associate Professor and Director, Tick-borne Disease Prevention Laboratory, Department of Biological and Environmental Sciences, Western Connecticut State University

Maria Diuk-Wasser, PhD, Associate Professor, Department of Ecology, Evolution and Environmental Biology, Columbia University

Lars Eisen, PhD, Research Entomologist, Division of Vector-Borne Diseases, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention

Lonnie Marcum, PT, BSHCA, Physical Therapist, Health and Science Writer for LymeDisease.org

Howard Ginsberg, PhD, Research Ecologist and Field Station Leader of the USGS Rhode Island Field Station; Professor in Residence, University of Rhode Island

R. Michael Roe, PhD, William Neal Reynolds Distinguished Professor, Department of Entomology and Plant Pathology, North Carolina State University

Bob Sabatino, Founder and Executive Director, Lyme Society Inc. (After his Working Group membership expired in August 2019, Bob switched his role as a subcommittee co-chair to a subcommittee member representing patients)

Daniel Sonenshine, PhD, Guest Researcher, LMVR, NIAID, NIH Eminent Professor of Biological Science, Old Dominion University

Kirby C. Stafford III, PhD, Chief Entomologist/State Entomologist, Department of Entomology; Center for Vector Biology and Zoonotic Diseases, Connecticut Agricultural Experiment Station; NE Regional Center for Excellence in Vector Borne Diseases

Pete D. Teel, PhD, Regents Professor and Interim Department Head, Department of Entomology, Texas A&M University

Stephen Wikel, PhD, Professor and Chair Emeritus of Medical Sciences, St. Vincent’s Medical Center, Quinnipiac University

Training, Education, Access to Care, and Reimbursement Subcommittee

Co-Chair
Patricia V. Smith, President, Lyme Disease Association, Inc.

Co-Chair
CDR Rebecca Bunnell, MPAS, PA-C, Senior Advisor, Learning and Diffusion Group, Innovation Center, Centers for Medicare and Medicaid Services

Co-Chair
Elizabeth Maloney, MD, President, Partnership for Tick-Borne Diseases Education

Megan Dulaney, MS, Patient Representative, Senior Interagency Liaison & Policy Advisor, Henry M. Jackson Foundation for the Advancement of Military Medicine in support of DoD Health Affairs and Center for Global Health Engagement, Uniformed Services University

Doug Fearn, President, Lyme Disease Association of Southeastern Pennsylvania, Inc

Lorraine Johnson, JD, MBA, Health Care Policy Expert; CEO, LymeDisease.org

Sheila M. Statlender, PhD, Clinical Psychologist, Private Practice; Chair, Massachusetts Lyme Legislative Task Force

Public Comment Subcommittee

Scott Palmer Commins, BS, MD, PhD, Associate Professor of Medicine & Pediatrics, University of North Carolina; Member, UNC Food Allergy Initiative, Thurston Research Center

Angel M. Davey, PhD, Program Manager, Tick-Borne Disease Research Program, Congressionally Directed Medical Research Programs, U.S. Department of Defense

Leigh Ann Soltysiak, MS, Owner, Principal, Silverleaf Consulting, LLC; Adjunct Professor, Stevens Institute of Technology, Entrepreneurship Thinking

TBDWG January 28, 2020 - Meeting Summary

Welcome and Roll Call

Welcome Remarks from ADM Giroir

Welcome from the Working Group

Overview of the Working Group’s Mission Statement, Vision Statement, and Values

Objectives, Update, and Goals of Meeting 11

Objectives

Update on Subcommittee Activities

What to Accomplish Today

Timeline

National Institutes of Health Strategic Plan on Tick-Borne Disease Research

CDC-led Domestic Framework

Food and Drug Administration Update on Tick-Borne and Vector-Borne Diseases

Public Comments

Public Comment Subcommittee Update

Comments Received and Reviewed

Overall Themes

Subcommittee Presentations

Methods

Tick Biology, Ecology, and Control Subcommittee

Goal, Evidence, and Findings

Priorities and Potential Actions

Priority 1: Minimize the Public Health Threat of Lyme Disease and Other Tick-Borne Diseases

Priority 2: Establish and Sustain a National Network to Support Tick Surveillance and Control by Fiscal Year 2021

Discussion

Pathogenesis and Physiology of Lyme Disease Subcommittee

Goals

Priorities, Evidence and Findings, and Potential Actions

Priority 1: Determine the Mechanisms Underlying the Persistence of Borrelia burgdorferi in the Host

Priority 2: Determine the Role of Persistence of B. burgdorferi or Its Components in the Pathogenesis of Lyme Arthritis and Persistent Lyme Disease

Potential Actions

Priority 3: Determine the Pathogenesis, Pathophysiology, and Effective Treatment of Lyme Carditis.

Potential Actions

Potential Actions

Discussion

Clinical Aspects of Lyme Disease Subcommittee

Goals

Priorities, Evidence and Findings, and Potential Actions

Priority 1: Conduct Additional Targeted Controlled Clinical Treatment Trials in Patients with Early and Persistent Lyme Disease, Using Different Antibiotic Regimens and Longer Durations of Treatment than Those Used in Previously Conducted Trials

Potential Actions

Priority 2: Educate Clinicians as to the Limitations of Currently Available Tests in the Diagnosis and in the Monitoring of Treatment of Patients with Persistent Lyme Disease

Potential Actions

Priority 3: Provide Funding for Research to Support or Refute the Purported Human-to-Human Sexual Transmission of Lyme Disease

Potential Actions

Priority 4: Further Evaluate Potential Maternal-fetal Transmission of Lyme Disease and of Congenital Lyme Disease

Discussion

Training, Education, Access to Care, and Reimbursement Subcommittee

Priorities, Evidence and Findings, and Potential Actions

Priority 1: Access to Care

Priority 2. Reducing Diagnostic Errors and Delays in Lyme Disease

Priority 3. Reducing Psychiatric Misdiagnoses in Lyme Disease

Priority 4. Shared Decision-Making

Priority 5. Patient and Public Health Education on Lyme Disease and Other Tick-Borne Diseases

Priority 6. Clinician Training on Tick-Borne Diseases

Discussion

Alpha-gal Syndrome Subcommittee

Priorities, Evidence and Findings, and Potential Actions

Priority 1. Surveillance, Epidemiology, and Role of Tick Bites in AGS

Priority 2. Diagnosis and Management of AGS

Priority 3. Education, Awareness, and Support from Patients’ Perspectives

Priority 4. Tick Bite Prevention and Tick Control

Discussion

Adjournment

Appendix 1: Tick-Borne Disease Working Group Members and HHS Support Staff

Tick-Borne Disease Working Group Members (in alphabetical order)

HHS Support Staff

Appendix 2: TBDWG Subcommittees

Alpha-Gal Subcommittee

Clinical Aspects of Lyme Disease Subcommittee

Pathogenesis and Physiology of Lyme Disease Subcommittee

Tick Biology, Ecology, and Control Subcommittee

Training, Education, Access to Care, and Reimbursement Subcommittee

Public Comment Subcommittee

Priority 1: **Determine the Mechanisms Underlying the Persistence of Borrelia burgdorferi in the Host**

**Priority 2: Determine the Role of Persistence of B. burgdorferi or Its Components in the Pathogenesis of Lyme Arthritis and Persistent Lyme Disease**