Tick-Borne Disease Working Group Virtual Meeting 20 Summary - Day 2

March 1, 2022

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 be heard and valued based on merit and without the bias of titles, eminence, or prestige.

Welcome and Roll Call: Day 2

Linden Hu, MD, Professor Microbiology and Medicine and Vice Dean for Research, Tufts University School of Medicine; Tick-Borne Disease Working Group Co-Chair, welcomed attendees to Day Two of the Tick-Borne Disease Working Group’s virtual public meeting.

James (Jim) Berger, MS, MT(ASCP), SBB, Designated Federal Officer (DFO) for the Tick-Borne Disease Working Group, Senior Blood and Tissue Policy Advisor, Office of Infectious Disease and HIV/AIDS Policy (OIDP), Office of the Assistant Secretary for Health (OASH), U.S. Department of Health and Human Services (HHS), welcomed participants and called the meeting to order. Jim conducted roll call (see Appendix 1 and Appendix 2: Tick-Borne Disease Working Group Members and HHS Support Staff). All 14 members were present.

Recap of Day One

Holiday Goodreau, Executive Director, LivLyme Foundation; Co-creator, TickTracker; Tick-Borne Disease Working Group Co-Chair, greeted attendees and summarized the proceedings from the previous day’s meeting.

• Nine members of the public provided comments.
• Jim reviewed the mission, vision, and values of the Tick-Borne Disease Working Group.
• Co-chairs of the following subcommittees presented their findings:
  • Public Comments
  • Changing Dynamics of Tick Ecology, Personal Protection, and Control
  • Diagnostics
  • Disease Prevention and Treatment
• The Tick-Borne Disease Working Group engaged in open discussion.

Holiday explained that today’s meeting would feature presentations by the co-chairs of the Access to Care and Education and Clinical Presentation and Pathogenesis subcommittees; a Federal Inventory update; open discussions; and next steps for the Tick-Borne Disease Working Group.

Subcommittee Presentations

On Day Two, the two remaining subcommittees presented their reports to the Tick-Borne Disease Working Group. 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.

Access to Care and Education Subcommittee

Elizabeth (Betty) Maloney, MD, President of Partnership for Tick-Borne Diseases Education; co-chair of the Access to Care and Education Subcommittee, introduced herself and the other members of the subcommittee. She presented the background, methods (including votes taken), challenges, opportunities, and findings of her subcommittee’s report.

Background: Health Equity

Betty gave an overview on health equity, highlighting the following points:

The American Medical Association (AMA) defines health equity as “optimal health for all.” According to the Centers for Disease Control and Prevention (CDC), this goal is achieved when (a) “everyone has the opportunity to attain their full potential,” and (b) no one is “disadvantaged … by socially determined circumstances.” The burden of health disparities falls on marginalized or powerless groups and individuals, including those with stigmatized health care conditions, such as mental illness, HIV/AIDS, substance abuse, and persistent/chronic Lyme disease.

Health disparities cause differences in access to care, longevity, rates of disease, disease severity, disability, quality of life, and death. They are the result of both structural and social determinants of health. Structural determinants include institutions, policies, and practices that determine the distribution of power, funding, and availability of services. And social determinants include economic instability, access to quality education, community, neighborhood, environment, and access to quality health care.

As detailed in the 2020 Training, Education, Access to Care, and Reimbursement Subcommittee Report, health inequities of many tick-borne disease patients include decreased quality of life, increased disease severity, increased rate of disease, preventable death, and limited access to quality health care. These disparities are well-documented in patients with persistent/chronic Lyme disease, as well as those with Alpha-gal Syndrome (AGS), Rocky Mountain spotted fever, human monocytic ehrlichiosis, and Lyme carditis.

Subcommittee’s Goals

The subcommittee identified three goals to guide its activities:

• Highlight existing inequities experienced by patients with tick-borne diseases (with a special focus on persistent Lyme disease/chronic Lyme disease)
• Focus attention on the government policies and processes that are major root causes of these inequities
• Propose actionable solutions to improve health of this marginalized and often-neglected patient community

Results

Betty identified three interwoven contributors to health inequities in tick-borne diseases: patient-encountered barriers, clinician-encountered barriers, and medical education barriers. She described them as follows:

Patient-Encountered Barriers
Barriers that limit patient access to care include exclusion from research funding and medical education processes; limited access to care because of insurance denials, provider network restrictions, the lack of clinicians with knowledge of tick-borne diseases, and regulatory oversight targeting clinicians who treat persistent/chronic Lyme disease; and strict application of Lyme disease surveillance case criteria to clinical care.

Meaningful engagement of patients in tick-borne disease research and education requires selection of patients qualified to represent the community and early engagement in the process to influence outcomes.

Clinician-Encountered BarriersIn a recent national survey, 155 U.S. clinicians who treat persistent/chronic Lyme disease patients identified the following barriers:

• Complexity of care
• Patients’ inability to pay out-of-pocket costs
• Lack of professional support from colleagues
• Opposition to the treatment of persistent/chronic Lyme disease from some physician organizations
• Cognitive impairment of patients
• Frequent patient calls between scheduled appointments
• Reimbursement for care
• Length of visits
• Communication issues with patients

Significant scientific gaps impede diagnosis and treatment of patients. These gaps include disease surveillance and ecology of tick-borne diseases, tick and tick-host interactions, Borrelia burgdorferi transmission, pathogen-host interactions, Lyme disease pathophysiology, diagnostic testing, treatment of all tick-borne diseases and coinfections, and AGS. Survey respondents emphasized that diagnostic and therapeutic uncertainty prevents clinicians from treating patients with tick-borne diseases.

In addition, clinician knowledge gaps impede patient access to care. There is insufficient understanding of clinical presentations of tick-borne diseases, treatment protocols, and AGS in general. Many clinicians underestimate the risk of Lyme disease for individual patients and mistakenly conclude that patients cannot have Lyme disease if they do not meet the surveillance case definition. The potential for false-negative and -positive test results compound these barriers.

Other barriers include professional stigma and sanctioning of clinicians who treat patients with tick-borne diseases, insurance-based models that do not adequately reimburse clinicians for time spent, and the need for research funding.

Betty explained that evidence-based medicine is the integration of best research evidence, clinical expertise, and patient values. She highlighted the importance of shared decision-making in this model, adding that when evidence is uncertain, care should be consistent with the patient’s values, goals, and preferences.

Betty emphasized that many clinicians, including those on regulatory bodies, have misconceptions regarding the strength of the evidence base, the nature of evidence-based medicine, shared decision-making, and the standard of care for different disease states (for example, early acute vs. chronic/persistent Lyme disease). She added that the standard of care for persistent/chronic Lyme disease should reflect the experiences of clinicians who treat chronically ill patients. She noted that regulatory action against clinicians stifles clinical innovation and discourages them from providing care to this patient population.

Medical Education Barriers
Citing Recommendation 7.2 from the 2020 Tick-Borne Disease Working Group Report to Congress, Betty underscored that the need to “increase the pool of qualified and practicing clinicians” remains. The current educational standards do not promote a deeper understanding of Lyme disease and other tick-associated illnesses. Clinicians must, therefore, acquire knowledge on their own. In addition, the absence of strong scientific understanding in the areas of diagnosis and treatment is a barrier to quality education.

Betty explained that the subcommittee reviewed CDC and National Institutes of Health (NIH) content on Lyme disease and found several issues that negatively impact patient care. She stated that CDC’s continuing medical education (CME) content (CDC TRAIN) does not clearly reflect the state of the science, and it inaccurately portrays the success and failure of antibiotic re-treatment of Lyme disease. She identified concerns about the content development process, specifically, the population-based perspective, the unclear selection of source material, and the exclusion of patients and advocates early in the process when their feedback is most meaningful.

Betty stated that the CDC webpages on Lyme disease have similar accuracy and development issues. She commented that detailed information about scientific evidence should be provided on the health care provider page; content about patient medical history and potential disease symptoms and signs is lacking; and clinicians are left ill-equipped to estimate patient-specific pre-test probabilities of disease. Betty expressed concern about bias in the health care providers page, including inaccurate and incomplete information as well as limited references.

Betty highlighted similar concerns about the NIH National Institute of Allergy and Infectious Disease (NIAID) webpages on Lyme disease. She noted that the portrayal of available evidence about persistent/chronic Lyme disease is inaccurate, and the conclusions about antibiotic retreatment regiments are erroneous and over-generalized. Betty explained that the content represents a missed opportunity to educate clinicians and the public about evidence gaps and ongoing debates. She expressed concern that portraying the issues as “settled science” may dissuade researchers and funding sources from pursing research in areas where it is needed.

Betty explained that CDC and NIH content is often taken at face value by clinicians and governing bodies. Inaccurate or incomplete information on these agency websites can result in regulatory action against clinicians who treat patients with persistent/chronic Lyme disease. It also causes patients to have limited access to knowledgeable clinicians.

Challenges

Betty outlined two major challenges related to persistent/chronic Lyme disease. First,
clinician engagement is limited due to scientific knowledge gaps, diagnostic and therapeutic uncertainty, the need for self-directed learning in a complex subject matter, and an insurance-based model that is poorly suited to the care of patients with persistent/chronic Lyme disease.

Second, patient access to care is restricted by policies and processes that exclude patients and advocates from meaningful participation in the development of clinician educational content and funding decisions. Research funding is not necessarily “patient-centered” (reflecting concerns of patients) and may divert funding from novel or innovative approaches and topics that patients value.

Opportunities

Betty identified several opportunities to reduce health disparities and promote equity for tick-borne disease patients:

• Reassess all existing Federal health care tick-borne disease content and messaging to determine whether it reflects the current state of the science and appropriately delineates areas of scientific uncertainty
• Produce high-quality continuing medical education (CME) modules on tick-borne diseases by CDC’s Division of Vector-Borne Diseases by using the process described in the “Standards Required for the Development of CDC Evidence-Based Guidelines” (Morbidity and Mortality Weekly Report, January 14, 2022)
• Provide clinically useful educational materials
• Reduce stigma and professional risks faced by clinicians who treat persistent/chronic Lyme disease and other complex tick-borne disease cases
• Promote telementoring opportunities
• Develop solutions to the failed economic care delivery model for persistent/chronic Lyme disease
• Produce clinician educational materials on lifelong educational skills regarding:
  • Addressing and managing uncertainty;
  • Developing differential diagnoses;
  • Interpreting evidence; and
  • Understanding the role of clinical practice guidelines, particularly when there is disagreement between guidelines on the same topic
• Decrease the number of patients who develop persistent/chronic Lyme disease through clinician education and primary and secondary prevention strategies
• Reduce the disease burden in Black and Hispanic populations through outreach and education
• Promote patient-centered research through the inclusion of patients in research funding processes
• Develop innovative research methods that reflect the underlying heterogenous nature of persistent/chronic Lyme disease and includes the development and grow of community research capacity
• Promote ongoing research to investigate potential mechanisms of B. burgdorferi persistence
• Develop novel therapeutics for persistent/chronic Lyme disease and other tick-borne diseases

Findings

Betty provided the findings of the Access to Care and Education Subcommittee for consideration by the Tick-Borne Disease Working Group.

Finding 1.1: Fund and support a directive for the CDC to conduct a review of CDC webpages and the current CDC TRAIN educational modules pertaining to the prevention, diagnosis, and treatment of Lyme disease.

Betty explained that the rationale for this finding is to determine whether the webpages best reflect the current state of the science and appropriately delineate areas of scientific uncertainty. She clarified that the review should be conducted by a newly formed committee under HHS. The committee, which could be established under the Federal Advisory Committee Act, will include meaningful stakeholder engagement of subject matter experts, including patients, caregivers, advocates, clinicians who treat persistent/chronic Lyme disease, and researchers whose experience represents diverse scientific perspectives on the full spectrum of Lyme disease. The committee will conduct a “red team exercise” involving rigorous analysis to determine the strengths and weaknesses in the program.

Finding 1.2: Fund and support modification of the Federal government websites, starting with CDC and NIH websites, as well as educational materials and seminars for clinicians, the public, and public health departments to incorporate the following language: “The state of the science relating to persistent symptoms associated with Lyme disease, is limited, emerging, and unsettled; and increase public awareness that there are divergent views on diagnosis and treatment. [Clinicians should] consider that shared medical decision-making may be appropriate in some circumstances.”

Betty noted that Finding 1.2 is similar to Recommendation 7.1 in the 2020 Tick-Borne Disease Working Group Report to Congress.

Finding 1.3: Provide the HHS Secretary with discretionary authority to maintain telehealth flexibilities independent of Public Health Emergency declaration.

Betty explained that the COVID-19 pandemic enabled the Public Health Emergency declaration, and retaining this capability would help patients access care.

Finding 1.4: Fund, support, and encourage community-based participatory research for persistent/chronic Lyme disease and complex presentations of late Lyme disease.

• Develop and grow community research capacity to accelerate the fundamental knowledge base using “big data” registries, data-sharing platforms, specimen and tissue sample repositories, and genomic and precision medicine approaches that reflect the underlying heterogeneous nature of persistent/chronic Lyme disease
• Leverage existing NIH resources and expand collaborations across NIH to promote a multidisciplinary approach to tick-borne disease research with, for example, the NIH Community-Based Participatory Research Program (CBPR)

Finding 1.5: Utilize tick-borne diseases as a use case in the catalyzation of innovative change across Federal agencies.
Betty commented that implementing this finding would accelerate the pace of innovation to transform medicine and health.

Finding 1.6: HHS should explore opportunities to leverage telementoring to equip more primary care practitioners to deliver high-quality care to the persistent/chronic Lyme disease community.

Betty cited the Project ECHO (Extension for Community Healthcare Outcomes) telementoring platform as an example that has demonstrated significant impact on improving access to care for underserved and stigmatized populations. She explained that the video conferencing technologies enable patients to access both primary and specialty care.

Finding 1.7: NIH will identify and fund research investigating the influence of sex, race, ethnicity, pregnancy status, and socioeconomic status on:

• The clinical manifestations of Lyme disease and other tick-borne diseases
• The accuracy of diagnostic testing
• Therapeutic responses

Conclusions

Betty highlighted the continuing mismatch between patient needs and the care clinicians can provide. She stated that CDC and NIH educational policies, processes, and practices limit patient access to care and contribute to professional barriers encountered by clinicians. Undertaking the following actions would help ensure health equity for marginalized tick-borne disease patients:

• Training and engaging more clinicians who can treat complex cases
• Enhancing basic science and clinical research to improve diagnostic certainty and therapeutic outcomes
• Examining and rebuilding NIH and CDC websites, including the CDC TRAIN CME modules

Betty explained that agency websites with Lyme disease content should include primary literature representing divergent scientific perspectives on persistent/chronic Lyme disease with a clear delineation of scientific gaps as well as strengths and weaknesses. The content development process should involve a wide spectrum of stakeholders with meaningful participation. Such changes would enable clinical judgment and shared decision-making, increase knowledge of front-line clinicians, reduce regulatory pressure on clinicians who treat persistent/chronic patients, and provide an environment that is more attractive to new clinicians.

Discussion

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

Members discussed obstacles that patients encounter when attempting to access care as well as initiatives that may help address some of them. Jennifer Platt, DrPH, Co-founder, Tick-Borne Conditions United, commented that a major obstacle for many patients, particularly those in rural communities, is the inability to obtain even the most basic health care. The impact of the Affordable Care Act is yet to be determined. Betty responded that even patients who have health care coverage struggle because many clinicians do not accept insurance, and out-of-pocket expenses can be prohibitive. Telemedicine and telementoring would be especially helpful to rural patients.

The Working Group also talked about coverage in the subcommittee report related to health equity and the development of CDC’s website and clinician education content. Charles Benjamin (Ben) Beard, PhD, Deputy Director, Division of Vector-Borne Diseases, CDC, agreed that health equity is a critical issue that CDC prioritizes. He expressed concern that health equity and social determinants of health are not clearly differentiated in the report. He also commented that CDC’s actions and updates in recent years were not represented; CDC has revised Lyme disease content with input from a wide spectrum of stakeholders and will continue to do so. He also stated that including the perspectives of some of the prominent medical societies (for example, American College of Rheumatology) would enhance the report. Betty explained that the primary aim of the report is to educate clinicians about the existing scientific uncertainty regarding chronic/persistent Lyme disease and the need for clinical judgment and shared decision-making. She agreed that the development process for Lyme disease content on agency websites (outlined in Finding 1.1) should include diverse clinical perspectives. One of her concerns, she noted, is that the current content is too general and broad to be useful to clinicians who treat complex cases. She encouraged collaboration among stakeholders to address content issues.

Clinical Presentation and Pathogenesis Subcommittee

Leith States, MD, MPH (FMF), Deputy Chief Medical Officer, OASH; co-chair of the Clinical Presentation and Pathogenesis Subcommittee, introduced himself and the other members of the subcommittee (see Appendix 2 for subcommittee membership). He presented the goals, methods (including votes taken), and the results and findings outlined in his subcommittee’s report.

Subcommittee’s Goals

The subcommittee was charged with addressing the following topics and identifying challenges, opportunities, and actions for the Tick-Borne Disease Working Group to consider.

• Challenges facing tick-borne disease sufferers with chronic symptoms with emphasis on mechanisms of pathogenesis, autoimmunity, latency, persistence, reemergence, and complications related to coinfections and underlying conditions
• Mental health issues and neurologic and neuropsychiatric manifestations associated with tick-borne diseases
• Concerns associated with Lyme disease and pregnancy
• Tick-borne disease long haulers and what can be learned from post-COVID-19 sequelae
• Health equity concerns

Results and Findings

Leith presented Priorities 1 and 2 as follows.

Priority 1: Mechanisms of pathogenesis including autoimmunity, latency, persistence, and reemergence
Leith explained that the pathogenic mechanisms of persistent, chronic symptoms associated with tick-borne illnesses, autoimmunity, and other sequalae from prior infections are poorly understood. Defining these mechanisms is critical for safe and effective treatment of the disease or condition.

Finding 1.1: Provide funding to support local, regional, and national investigation and reporting for tick-borne diseases and conditions, including detailed information to include complications and presentations of illness, by the state public health departments and the CDC.

Finding 1.2: Support additional research on the mechanisms of pathogenesis of tick-borne disease, with a particular focus on central nervous system infection (including neuropsychiatric illness and neuropathic injury), persistent symptoms, allergy (Alpha-gal Syndrome), immunity, autoimmunity, pregnancy, and adverse fetal outcomes.

Leith underscored the lack of existing research in each of the areas identified in Finding 1.2.

Finding 1.3: Build on U.S. “National Strategy” framework to clearly delineate the roles of various federal agencies in describing the clinical presentation of emerging infectious diseases. Specifically, define how the NIH and CDC cooperate to answer research questions at the interface of clinical and translational research and epidemiology of emerging tick-borne diseases.

Leith highlighted the opportunity for enhanced inter-agency collaboration due to recent improvements in governmental data infrastructures, propelled by the COVID-19 pandemic. These advancements enable data collection and sharing between agencies at a more rapid pace.

Finding 1.4: Establish controlled, prospective studies of tick-borne disease cases during pregnancy and prioritize research studies at the maternal-fetal interface, including the mechanisms of placental injury and transplacental passage by tick-borne pathogens.
Leith emphasized that systematic longitudinal study of pregnancy and vertical transmission related to tick-borne diseases is currently lacking.

Finding 1.5: Providing funding to support a multi-site, longitudinal study of adults and children to define mechanisms of pathogenesis of post-treatment Lyme disease, using lessons learned from research into PCC (post-COVID conditions).
Leith described Finding 1.5 as an opportunity to discover and leverage synergies between research on post–COVID-19 conditions and post-treatment Lyme disease to gain insight into the mechanisms of both illnesses.

Finding 1.6: Allocate dedicated funding and prioritize research efforts to defining 1) the burden of symptoms and extent of persistent symptoms and 2) disease mechanisms with the goal of disrupting mechanisms of pathogenesis to offer new treatment approaches for patients suffering from sequelae of tick-borne disease.

Finding 1.7: Ensure that tick-borne disease research and educational efforts include a representative cross-section of patients from a variety of geographic, racial, ethnic, and socioeconomic backgrounds.

Leith underscored the issue of burnout in the health care workforce, adding that many people have left the field since the start of the COVID-19 pandemic. More and better health equity training is needed, but perhaps most importantly, the workforce must be expanded in a sustainable way.

Finding 1.8: Invest in research to develop and maintain repositories of biospecimens from patients with well-characterized tick-borne diseases to improve the performance of serological assays and to promote development and validation of newer diagnostic technologies.

Leith noted that Findings 1.6, 1.7, and 1.8 overlap with the findings brought forth by other subcommittees (for example, Diagnostics Subcommittee).

Priority 2: Neuropsychiatric Lyme disease and mental health issues
Leith stated that current Lyme disease definitions miss many of the more complicated clinical presentations that are difficult to recognize, including neuropsychiatric and other mental health manifestations. The goal of this priority is to identify mechanisms that cause neuropsychiatric symptoms, which will (a) lead to more targeted treatment, (b) help guide clinical care, (c) ensure better education of health care providers, and (d) improve mental health outcomes.

Finding 2.1: Provide funding to support research on mechanisms leading to, and perpetuating, neuropsychiatric disease among individuals with Lyme disease and/or other emerging vector-borne diseases reported among individuals with tick-borne illness.

Finding 2.2: Provide funding to support research on treatment of neuropsychiatric diseases related to Lyme disease and/or other emerging vector-borne diseases reported among individuals with tick-borne illness.

Leith emphasized that many potential tick-borne pathogens could contribute to neuropsychiatric disease.

Finding 2.3: Provide funding to support collaborative research studies among investigators of different infection-related syndromes, focusing on shared mechanisms of disease between Lyme disease and other “long hauler” syndromes (e.g., autoimmunity, inflammation, autonomic dysregulation, damage, microbial persistence).

Finding 2.4: Provide funding to support research on individuals with acute or persistent symptoms attributed to tick-borne illness (but who may not have received a definitive diagnosis) to better characterize, understand, and treat this large group of patients.

Leith explained that Finding 2.4 focuses on individualized care for patients with complex presentations who have not yet received a definitive diagnosis.

Finding 2.5: Provide funding to develop educational modules and update state and federal websites for healthcare professionals and trainees on the knowns and unknowns (including mental health aspects) regarding Lyme disease and other emerging vector-borne diseases that are reported among individuals with tick-borne illness.

Leith highlighted the importance of regularly updating government websites and educational models over time. There is a current need to incorporate mental health information in medical education and public outreach to ensure improved care.

Finding 2.6: Provide funding to support research investigating the prevalence of undetected tick-borne illness among subgroups of the population that may have a high burden of multi-systemic chronic conditions (e.g., mental illness, musculoskeletal diseases, etc.) that has been adequately medically evaluated (e.g., individuals in psychiatric facilities, prisons, homeless shelters, other populations experiencing health disparities).

Priority 3: Pathogenesis and clinical presentation of allergy to Galactose-alpha-1,3-galactose
Jennifer Platt, co-chair of the Clinical Presentation and Pathogenesis Subcommittee, presented the Priority 3 findings. She explained that the subcommittee’s intention was for this priority to build on the findings presented in the 2020 Alpha-gal Syndrome Subcommittee Report and provide updates on new research.

AGS is characterized by an allergy to Galactose-alpha-1,3-galactose, which is associated with bites from the Lone star tick (Amblyomma americanum). There is some evidence to indicate that it may also be associated with the blacklegged tick (Ixodes scapularis). People with the allergy may develop mild to severe symptoms, including anaphylaxis, upon exposure to red meat, mammal products, and certain medications. Symptoms can affect all body systems; patients can experience skin, gastrointestinal, cardiovascular, and/or respiratory manifestations, and emerging research shows there may be behavioral and emotional health symptoms as well. Some patients experience periods of latency while others fail to improve despite extensive treatment. Coinfections with other pathogens are possible and may complicate clinical presentation.

Finding 3.1: Provide continuing education to healthcare professionals (primary care providers, emergency providers, specialists, and subspecialists) and the general community on risk and recognition and testing for Alpha-gal Syndrome and tick-borne coinfections.

Citing the Public Comment Subcommittee report-out from Day 1, Jennifer commented that the primary concerns of patients with AGS are misdiagnosis, disregard, and clinical education. This feedback from the public prompted the formation of Finding 3.1.

Finding 3.2: Educate patients about symptoms and avoidance measures, including avoiding tick bites, and an action plan on how to treat an allergic reaction.

Finding 3.3: Develop a food management operations protocol around food allergies to include standardized staff training and education, ingredient/allergen identification, critical control points for cross contact, consumer information and first aid. Allergen management plans should be documented and reviewed as part of routine oversight through local health inspection agencies. This will likely be an interagency collaboration including USDA and FDA and other HHS operating divisions.

Jennifer noted that Finding 3.3 is intended to target any organization that serves food, including restaurants, schools, in-patient care facilities, and correctional facilities.

Finding 3.4: Labeling requirements, for the protection of consumers, must include at the minimum this statement, “this product contains mammal by-product,” for any food, alcohol, beverage, medical, hygiene, beauty, or textile product that has been processed with or contains any mammalian derivative. This will necessitate action by the FDA and the Bureau of Alcohol, Tobacco, Firearms, and Explosives. Create an easy-to-identify symbol that indicates a product contains mammal by-product. Create a comprehensive list of all mammal ingredient names that is public and easily accessed.

Finding 3.5: Funding to agencies such as HRSA [Health Resources and Services Administration] and CDC to educate clinicians and pharmacists across the training continuum about mammal ingredients in medications.

Jennifer described how burdensome it is for patients to determine whether a medication has mammal ingredients, which often includes having to call the manufacturers directly. The impetus for Finding 3.5 is to alleviate this hardship, so that patients can take prescribed medicine without fear of an allergic response.

Finding 3.6: Continue support for research into the pathogenesis of Alpha-gal allergy.

Priority 4: Pregnancy and Lyme disease
Jennifer emphasized that Lyme disease and pregnancy is an area of special concern that merits further research. Past studies have shown evidence that B. burgdorferi can cross the placenta to infect a developing fetus. However, research gaps remain regarding incidence, clinical spectrum, pathogenesis, and impacts on pregnancy outcome and child development.

Finding 4.1: Convene a multidisciplinary expert forum to review evidence, identify research gaps, with a goal of establishing interim guidelines for evaluations, testing, and management of infants born to mothers who have a Lyme borreliosis and/or other tick-borne diseases diagnosed during their pregnancy.

Finding 4.2: Provide funding for prospective cohort studies of women infected with Lyme disease during pregnancy and their offspring to understand the effects of this infection on maternal health, as well as child health and development.

Finding 4.3: Provide funding for RFA studies focused on Lyme disease and pregnancy including maternal/fetal/placental pathophysiology and clinical outcomes, immune responses of disease, possible biomarkers of congenital infection and efficacy of therapeutics.

Finding 4.4: Provide funding to support development and maintenance of repositories of specimens from pregnant and lactating persons including placenta, breast milk, cord blood, and autopsy specimens for Lyme disease and tick-borne diseases research.
Jennifer noted that Finding 4.4. builds on a similar finding by the Diagnostics Subcommittee.

Priority 5: Clinical comparisons of long-hauler syndromes related to COVID-19 and Lyme disease to elucidate mechanisms of disease
Jennifer emphasized that many parallels exist among chronic, persistent symptoms of Lyme disease, sequelae from several other tick-borne illnesses, and long-haul COVID-19. Priority 5 is focused on determining clinical similarities and common etiologies between these illnesses to improve clinical management.

Finding 5.1: Provide funding for prospective studies that evaluate clinical similarities; mechanisms of pathogenesis; and common etiologies for PCC [post-COVID conditions], other post-infectious fatiguing illness, post-treatment Lyme disease, and chronic symptoms attributed to Lyme disease and other tick-borne diseases.

Priority 6: Health equity and its impacts on clinical presentation and pathogenesis
Jennifer commented that health equity is essential for ensuring adequate and appropriate patient care. The Executive Order on Advancing Racial Equity and Support for Underserved Communities Through the Federal Government (# 13985), adopted on January 20, 2021, expands the definition of underserved groups as defined in the 2018 Tick-Borne Disease Working Group’s Report to Congress. According to the Executive Order, the following groups are considered to be underserved: Black, Latino, and Indigenous and Native American persons, Asian Americans and Pacific Islanders and other persons of color; members of religious minorities; lesbian, gay, bisexual, transgender, and queer (LGBTQ+) persons; persons with disabilities; persons who live in rural areas; and persons otherwise adversely affected by persistent poverty or inequality. Scant literature is available about the clinical presentations of these populations, including individuals who are homeless or incarcerated.

Finding 6.1: Provide funding to expand communication materials to include underserved populations and update healthcare clinical training and educational materials to address race/characteristic-based tick-borne disease presentations.

Finding 6.2: Provide funding to update tick-borne and other commonly associated vector-borne diseases education, prevention materials, and outreach programs for high-risk populations such as pregnant and immunocompromised people; Indigenous, immigrant, and migrant farming communities; urban and rural poor; and persons experiencing homelessness. Materials should be available in a variety of languages and culturally appropriate for the intended audience.

Finding 6.3: Funding to expand bartonellosis education among clinicians and high-risk patients, for example, persons experiencing homelessness and individuals who are immunosuppressed and/or immunocompromised.

Finding 6.4: To require new studies on tick-borne diseases in humans to address health equity concerns, including the following, as appropriate:

• Conduct/include a retrospective assessment to understand disparities and their root causes
• Account for intersectional issues
• Evaluate methods for blind spots and consider mixed methods research to remove and/or reduce them
• Strive to have research teams mirror/represent the populations/research questions of focus

Finding 6.5: Funding to develop equity-oriented educational materials on prevention for schools and communities.

Referencing Finding 1.1., Jennifer underscored that investigation and reporting of incidence and prevalence of illness is needed at all levels of the government and in all areas of the country, inclusive of all populations.

Challenges

Ben Beard, PhD, co-chair of the Clinical Presentations and Pathogenesis Subcommittee, outlined several gaps in knowledge that directly impact patient outcomes. Specifically, the full spectrum of signs and symptoms for various tick-borne diseases, particularly the less common ones, are not fully understood. Lyme encephalitis can have diverse manifestations, including neuropsychiatric ones, that may be misdiagnosed as a primary psychiatric disorder. Increased recognition that Lyme disease can impact mental health and potentially contribute to suicide is critical to effective and timely patient care.

The fear and frustration associated with Alpha-gal allergy cannot be alleviated by avoiding red meat. Many people worry constantly about medications, products, and cross-contamination, which is detrimental to their daily lives.

Significant data gaps remain regarding how Lyme disease impacts pregnancy in cases of acute versus late-stage or subclinical illness. The most sensitive diagnostic and effective treatment approaches for both mother and baby have yet to be determined. Moreover, little information exists on the potential for long-term health impacts of babies born to mothers with gestational Lyme disease.

Prompt action is required to glean lessons learned from diagnosis and clinical management of post-COVID conditions that may be relevant to other post-infectious illnesses, such as chronic Lyme disease and persistent symptoms associated with it. Ben emphasized that the opportunity may be lost if steps are not taken now to obtain this information.

Finally, research is needed to determine tick-borne disease incidence, clinical presentation, and pathogenesis for underserved groups.

Opportunities

Ben described several opportunities that, if leveraged fully, could improve health outcomes for all patients, including those belonging to underserved groups. These include:

• Increased awareness and attention to the concerns of people suffering from tick-borne diseases due in part to legislation, efforts of patients and advocates, recent publications that document disease burden, and previous HHS and Tick-Borne Disease Working Group reports
• Positive dialogue about validating patient concerns and better defining specific needs related to research and clinical care
• Lessons learned from the COVID-19 pandemic and the realization that parallels exist between post-COVID conditions and long-term symptoms associated with tick-borne illnesses
• Prospects for additional funding to support research on pathogenesis and new therapeutics

Discussion

Betty raised the issue of wording related to Lyme disease in its later stages, specifically when referring to it as a post-infectious state. She highlighted the possibility that at least some patients may have persistent infection, adding that more research is needed in this area. Ben responded by describing the wide spectrum of poorly understood illness states associated with long-haul COVID-19. Some patients appear to be viremic for extended periods of time, which has prompted debate about whether they are infectious. Other patients suffer from tissue and organ system damage caused by the infection. Still others experience autoimmune and immune processes that amplify illness. Ben concluded that there are likely many similarities between these manifestations and those experienced by patients who remain after treatment of Lyme disease.

Monica E. Embers, PhD, Associate Professor and Director, Vector-borne Disease Research, Tulane National Primate Research Center, thanked the subcommittee for including congenital Lyme disease and neuropsychiatric and neurological symptoms in the report.

Monica asked the co-chairs to expand on Finding 6.3 related to bartonellosis, noting the increasing evidence of neuropsychiatric symptoms from Bartonella infections. Ben highlighted the ubiquitous nature of bartonellosis, adding that it is caused by many species, most commonly Bartonella henselae. The Clinical Presentation and Pathogenesis Subcommittee agreed, he noted, that it is commonly associated with people who have tick-borne illnesses, and it often compounds the challenges of diagnosis. Ben stated evidence is insufficient to conclude that bartonellosis is transmitted by ticks in the United States; however, the debate on that issue should not impede acknowledging its importance as a coinfection with other tick-borne diseases and conditions. Jennifer added that many public commenters asked for the inclusion of Bartonella in the report, and the subcommittee wanted to be responsive to those requests.

Federal Inventory Update

Chinedu Okeke, MD, MPH-TM, MPA, Acting Chief Medical Officer, OIDP, OASH, HHS, explained that his office (OIDP), on behalf of the Working Group, will conduct an inventory of Federal activities related to tick-borne diseases, as it has done for the two previous Reports to Congress. The difference with the 2022 inventory survey is that it will include the top nine states with the highest tick-borne disease cases each year according to CDC data. He added that the Working Group will be continually updated on the process, and results will be provided to members as they prepare their report content.

Ben added that about 10 states account for approximately 95% of all reported Lyme disease cases each year.

Open Discussion

The Working Group identified several needs that were raised by multiple subcommittees, as follows.

• Enhanced surveillance and reporting of both ticks and disease
• Increased research in areas of uncertainty, including pregnancy and maternal-fetal transmission
• A national biorepository with well-characterized samples of all disease states
• Additional education for providers and at-risk populations, including broad stakeholder engagement in the different types of education
• Solutions that streamline and facilitate the process for bringing new products to market
• Support of the vector-borne disease division of the Biomedical Advanced Research and Development Authority
• Taking a foundational approach to health equity, ensuring that it permeates all aspects relate to tick-borne diseases and conditions, including bartonellosis
• Implementation of occupational standards for employees at high risk
• Increased awareness and consideration of mental issues related to tick-associated illnesses
• Actions taken to address the needs of patients with AGS
• Advisory panels to ensure follow-through on recommendations by the Tick-Borne Disease Working Group

Ben reminded Working Group members that issues from previous reports may not have been addressed. He suggested that the group develop a strategy to integrate those issues with the newer concerns that have been identified for inclusion in the 2022 Report to Congress.

Members discussed existing mechanisms within the Federal government to ensure follow-through on the Working Group’s recommendations. Ben explained that any group or organization that makes consensus recommendations to the government would be subject to Federal Advisory Committee Act regulations. He added that there are other ways to work with agencies without forming an advisory committee. DFO Jim Berger commented that, unless instructed otherwise by Congress, the Tick-Borne Disease Working Group will end its tenure in December 2022, and the three reports it has generated provide Congress with many recommendations to consider and act upon.

The Working Group also talked about health equity. CAPT Rebecca Bunnell, MPAS, PA-C, Senior Advisor, Division of Model Learning Systems, Learning and Diffusion Group, Center for Medicare and Medicaid Innovation, Centers for Medicare & Medicaid Services, suggested that members work together to frame the content in their report in terms of health equity because it likely affects the majority of patients with long-haul tick-associated illnesses. She added that, while many of these people may have access to care at the start of their illness, some may lose access as their health declines and their burden intensifies. Many individuals, she noted, cannot work and even experience homelessness. She clarified that the Federal government, particularly CDC, provides the foundation for access to care, and she hoped Working Group members could frame the recommendations in a way that will resonate with the agencies and encourage restructuring of that foundation. Dennis Dixon, PhD, Chief, Bacteriology and Mycology Branch, National Institute of Allergy and Infectious Diseases, NIH, commented that NIH incorporates diversity, equity, and inclusion (DEI) into its processes, including clinical trial review panels and enrollment. He added that DEI can be very challenging to execute; however, NIH is committed to it.

Linden asked whether Betty and Rebecca (co-chairs of the Access to Care and Education Subcommittee) could provide more detail about what they learned and discussed related to health equity during their meetings. Rebecca offered to present that information at the next public meeting after she and Betty have had the opportunity to review and consider the presentations of the other subcommittees.

Jennifer raised the issue of treatment for patients who need immediate help. She commented that necessary research will take years to conduct, yet patients need effective treatment today. She underscored that epidemiology and guidelines should not interfere with a clinician’s ability to use antibiotics to treat a critically ill patient with suspected tick-borne illness (for example, Rocky Mountain spotted fever). She stated that overuse of antibiotics takes place primarily in the agricultural realm with livestock.

Members also discussed actions for the Working Group to consider over the coming months. Holiday suggested that for the next meeting, Working Group members identify what actions Congress can implement immediately to help patients who are very sick now. Jennifer recommended that, in the process of writing the report, members also generate a fact sheet or checklist of actionable recommendations that can be used as an advocacy tool. She also asked that members compile a list of major gaps that the Working Group was not able to cover because of time constraints, including under-recognized tick-borne conditions. Kirby reminded members of the importance of entomology in tick-borne disease prevention.

Discussion of Next Steps and What is Expected for the April Meeting

In anticipation of the report preparation process, Linden, Holiday, and Jim provided the Working Group with the following information:
The next Tick-Borne Disease Working Group public meeting will take place on April 27-28, 2022, during which time the Working Group will discuss the report outline, template, and recommendations.

Working Group members should focus on the following tasks prior to the April meeting:

• Read the subcommittee reports
• Identify your subcommittee’s top three to five findings for the Working Group to consider
• Look for synchronizations between your subcommittee’s findings and those of other subcommittees
• Identify issues from the 2018 and 2020 Reports to Congress that should be highlighted in the Working Group’s 2022 report

The Working Group is expected to finalize the 2022 Report to Congress by the end of August or early September. At this time, OIDP will submit the report to the relevant Federal agencies (those identified or potentially affected by the recommendations) for clearance. This is a courtesy for informational purposes, so the agencies know what to expect from the report. Also prior to submission, the Assistant Secretary for Health will brief the Secretary of Health and Human Services on the contents of the report. The Working Group’s report will then be submitted to Congress by early December 2022.

Working Group members will not vote on the subcommittee report contents or findings. At the April meeting, they will work together to generate the recommendations for their 2022 Report to Congress based on discussions with the subcommittee co-chairs regarding their top three to five findings. Working Group members will then vote on the final report content and recommendations. Discussions of content to be included in the report will take place at public meetings.

Adjournment

The meeting was adjourned at 1:48 pm Eastern Standard Time.