Changing Dynamics of Tick Ecology, Personal Protection, and Control Subcommittee Report to the Tick-Borne Disease Working Group

Co-Chairs: Robert J. Miller and Kirby C. Stafford III

Information and opinions in this report do not necessarily reflect the opinions of the Working Group, the U.S. Department of Health and Human Services, or any other component of the Federal Government. Readers should not consider the report or any part of it to be guidance or instruction regarding the diagnosis, care, or treatment of tick-borne diseases or to supersede in any way existing guidance. All subcommittee members actively participated in the development of this report. Members voted to approve submission of the report to the Working Group and on the wording of each of the potential actions contained in the report. The vote to submit the report indicates general agreement with the content of the document, but it does not necessarily indicate complete agreement with each and every statement in the full report.

Background

Tick-borne diseases constitute a clear and present danger to human health in the United States. Currently, the Centers for Disease Control and Prevention (CDC) recognizes 18 tick-borne pathogens or tick bite-associated medical conditions, such as tick paralysis, that cause human disease. This total does not include the many pathogens and diseases solely associated with livestock and companion animals. Researchers and clinicians continue to discover new and emerging diseases and other health conditions, such as Alpha-gal Syndrome (red meat allergy), associated with tick bites. Considering the current knowledge of tick biology, ecology, and population-control approaches, or lack thereof, and the increased number of tick-borne disease cases in the United States, this subcommittee sought to articulate the causes of tick and tick-borne disease (TBD) expansion, identify current and future strategies for managing exposure to TBDs, and examine barriers to the development and commercialization of tick bite prevention and tick control products. Importantly, the subcommittee did not wish to diminish focus on priorities and actions suggested previously. Instead, the subcommittee focused on areas not fully addressed in previous Tick-Borne Disease Working Group (TBDWG) subcommittees while building on the previous reports and recommendations.

Tick-borne diseases also pose a threat to the health of non-U.S. populations, as well as U.S. military personnel and civilians living and working abroad. While some of those diseases are not currently present in the United States, introductions of foreign ticks, as exemplified by the recent rapid geographical spread of the invasive Asian longhorned tick, illustrate the potential for exposure to new tick species and tick-borne pathogens. Examples of potential invasive tick-borne pathogens, some of significant biosecurity concern as expressed by the World Health Organization (WHO) and U.S. Department of Homeland Security (DHS), include Crimean-Congo Hemorrhagic Fever (CCHF) virus and tick-borne encephalitis (TBE) virus.

Critical need exists for novel concepts and approaches to prevent tick bites, control tick populations, and reduce tick-borne disease, as well as for evaluation of the effectiveness of existing strategies. While members of the public do take action to prevent tick bites, additional approaches and increased use of existing personal protection measures are needed. In addition, no national workplace requirements or standards related to ticks and tick-borne disease currently exist for employees in outdoor workplaces. Reducing the incidence of established and emerging tick-borne diseases requires an understanding of how ecological, environmental, and social factors contribute to the increased risk of tick bites and tick-borne diseases.

Ticks are small ectoparasites, often smaller than a poppy seed, that depend on the right environmental temperature and humidity, as well as on a variety of blood hosts, such as mice, racoons, and deer, to persist and thrive. Pathogens transmitted by ticks are all zoonotic, which means they are maintained in non-human hosts. Climate change, host makeup and abundance, and patterns of human use are factors that interact with each other and are currently driving an unprecedented increase in rates of tick-borne disease worldwide, but especially in the northeastern United States.

Some of these factors were explored by the 2020 Subcommittee on Tick Biology, Ecology, and Control, building on the work of their predecessors in the subcommittees of the 2018 Working Group. This subcommittee notes the unmet needs and the recommendations in the 2018 and 2020 reports, which still hold, and we briefly summarize these in the Summary of Needs and Priorities from Previous Subcommittees section. Our new priority issues are covered in more detail in the Results and Potential Actions section, which describes the priority issues identified and explains why they are important, identifies major challenges related to the priority issues, and introduces potential opportunities.

• Priority 1. Minimize roadblocks and streamline the process for getting new tick bite prevention and tick control products to market.
  • Action 1.1. Expand the purview of the Biomedical Advanced Research and Development Authority (BARDA) to include vector-borne diseases and provide BARDA with funding to bring new tick bite prevention and tick control products to market.
  • Action 1.2. Charge Federal entities (including the Environmental Protection Agency, Food and Drug Administration, U.S. Department of Agriculture, Centers for Disease Control and Prevention, Department of Defense, and National Institutes of Health) to work with industry to streamline regulatory pathways and target solutions for getting new tick bite prevention and tick control products to market.
  • Action 1.3. Enhance existing Federal proposal, review, and funding for research, development, and evaluation of new tick bite prevention and tick control products (for example, the Small Business Innovation Research Program and other Federal funding mechanisms which are open to academic institutions and all industry entities).
• Priority 2. Accelerate efforts to define and deploy tick bite prevention and tick control approaches and strategies.
  • Action 2.1. Fund research to validate the scale and degree of effectiveness of existing tick bite prevention and tick control strategies to reduce human tick bites and tick-associated disease.
  • Action 2.2. Support development of novel concepts to prevent human tick bites or by reducing tick populations and their associated pathogens in the environment (for example, acaricide products such as nootkatone capable of killing undetected human-feeding ticks, anti-tick vaccines for humans or wildlife, or transgenic ticks to suppress population growth).
  • Action 2.3. Define tick control strategies suitable for residential properties versus public properties and lands (for example, schools, parks, and high-use recreation areas) or entire communities.
  • Action 2.4. Support the establishment of local public health tick management programs to implement proven control strategies, and to advise their communities on tick bite prevention and tick control.
• Priority 3. Define the primary drivers of tick populations, tick pathogen prevalence, and geographic expansion of ticks and tick-associated diseases.
  • Action 3.1. Fund critical research on the effects of environmental variables on tick biology and ecology (for example, survival, reproduction, and ability of ticks to transmit pathogens that impact public health). 
  • Action 3.2. Fund capacity for rapid identification of tick species and discovery of the pathogens they may transmit to allow early detection and rapid response.
  • Action 3.3. Create browsable maps of current and forecasted distributions of tick species and tick-borne pathogens of public health significance so stakeholders can assess risk.
• Priority 4. Expand knowledge and increase adoption of tick bite prevention and tick control methods.
  • Action 4.1. Clarify the reasons behind the public’s limited use of tick bite prevention methods (such as repellents) and tick control methods (such as backyard treatments to kill ticks) and pursue solutions to overcome roadblocks. 
  • Action 4.2. Charge the U.S. Occupational Safety and Health Administration (OSHA) to work with employers to develop standards to mitigate occupational risk for ticks and tick-borne disease and educational requirements for occupational physicians.
  • Action 4.3. Develop information materials for tick bite prevention and tick control targeted to high-risk groups for tick bites (for example, children, animal health professionals, hunters, farmers, and park rangers and other outdoor workers) in multiple languages and styles to reach underserved communities.
  • Action 4.4. Incorporate tick-borne disease prevention strategies in livable environment design considering health equity issues and climate adaptation.

Summary of Needs and Priorities from Previous Subcommittees

A review of the scientific literature and expert presentations by the 2018 TBDWG Disease Vectors, Surveillance, and Prevention Subcommittee identified the following crucial needs related to control:  

• Reducing human exposure to infected ticks
• Identifying novel methods for controlling ticks and their associated pathogens, for example, methods aimed at blocking transmission of tick-borne pathogens to humans and animals  
• Adequately validating that tick control and pathogen-transmission blocking methods can effectively reduce the incidence of tick-borne illnesses using prospective studies that measure both acarological and human outcomes  

These broad objectives remain crucial, and many of the findings in the earlier report remain relevant and are reaffirmed in this report. The 2020 Tick Biology, Ecology, and Control Subcommittee identified two major priorities, and the 2020 Report to Congress made three recommendations, as follows.

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. 

Recommendation 3.1: Implement multi-agency, ecologically based One Health efforts on tick-borne diseases promoting research and enhanced vector surveillance to identify and validate integrated tick management in keystone wildlife hosts, particularly white-tailed deer, and the sustainable management of their populations. 

Recommendation 3.2: Minimize the public health threat of Lyme disease and other tick-borne diseases through special funding for integrated tick management, disruption of tick biological processes contributing to pathogen transmission, and the support of public-private partnerships to develop and promote area-wide tick control strategies. 

Recommendation 3.3: Provide funding to support CDC-directed expanded tick surveillance and promoting the development and implementation of best practices for integrated tick management capturing human tick bite events, and streamlining education, training, and coordination amongst relevant Federal, state, and local agencies. 

The major challenges associated with integrated tick management identified in the 2020 report include effectiveness, scale, cost, and implementation of interventions. However, effective control of ticks and their associated disease agents requires broader acceptance and use of current technologies, improved approaches, and additional resources to scale up many of these methods, as well as the development of an organizational structure for addressing the tick problem at a community level or broader scale. New methods and products, including those with a One Health approach, in addition to controlled field trials that measure human outcomes (tick encounters and bites and/or tick-borne disease incidence), were identified as urgent needs. Many of the barriers to the adoption or use of tick control and tick bite prevention efforts were also described. These barriers still exist despite overwhelming scientific data that support their safety or effectiveness (Eisen & Stafford, 2021).

Methods

Characteristics of the Subcommittee

At the public meeting held on August 26, 2021, TBDWG selected Robert J. Miller, a Federal representative, and Kirby C. Stafford III, a public representative, to serve as co-chairs of the Changing Dynamics of Tick Ecology, Personal Protection, and Control Subcommittee.

The subcommittee was composed of Federal (3), public health (1), academic (9), and patient (3) representatives (see Table 1: Members of the Changing Dynamics of Tick Ecology, Personal Protection, and Control Subcommittee). The subcommittee’s expertise in tick biology, ecology, control, and tick-borne diseases is supported by more than 250 years of basic and applied research experience.

Subcommittee Meetings

The subcommittee held 13 2-hour virtual meetings (see Table 2: Overview of Changing Dynamics of Tick Ecology, Personal Protection, and Control Subcommittee Meetings). Members spent this time:

• Considering relevant literature and public comments
• Discussing current Federal activities
• Identifying gaps in knowledge and areas where Federal funding is needed
• Hearing from five expert speakers (see Table 3: Presenters to the Changing Dynamics of Tick Ecology, Personal Protection, and Control Subcommittee)
• Formulating their report to the TBDWG  

Public Comment

The subcommittee reviewed relevant public comments and determined how best to include them in the report. There were 25 submissions in the Tick Ecology Comments document. There were two directly related to tick ecology, biology, bite prevention, or control. There was one submission simply noting a contribution of a paper on the role of wildlife hosts in the rise of ticks and tick-borne disease in North America (Tsao et al., 2021) and one submission on vector control with a focus on treating animals, wildlife, and pets to kill ticks.

Our subcommittee agrees that host-targeted strategies are a vital area for current and future research to control ticks. It was a major topic for this subcommittee. However, the impact of treating the few animals managed by researchers and wildlife personnel would be minimal. The challenge is treating a large percentage, potentially tens of thousands, of individuals of a wildlife population in order to reduce the tick population of a wide geographical area over time.  

Subcommittee Report Development

Potential topic areas identified at the TBDWG public meeting held on August 26, 2021, that related to tick biology, ecology, prevention, and control included covering all TBDs, climate or environmental change, tick control and integrated tick management (ITM), range expansion, new tick species and tick behavior, the state of the science for prevention tools, pathogen prevention, and reservoir-targeted vaccines. At the first meeting of the Changing Dynamics of Tick Ecology, Personal Protection, and Control Subcommittee (see Table 2), the members voted that the main objective of the subcommittee was to:

Minimize the Public Health Threat of Lyme Disease and Other Tick-Borne Diseases with Changing Climates Through Surveillance, Effective Ecologically Based Tick Management Strategies and Personal Protection Measures

Four areas were identified by the subcommittee at their first meeting, held on September 29, 2021, that incorporated potential topic areas or other areas that were not substantially covered in previous reports or that members felt required further exploration and update. These four areas are the focus of this report, with tick surveillance considered a vital activity to accomplish the covered topics and priorities.

• Tick Ecology, Environmental Change, and Range Expansion
• Tick Bite Prevention and Tick Control
• Host Behavior and Host-Targeted Control Methods
• New Innovations and Commercial Translation for Tick Control

Five individuals accepted roles as leaders or co-leaders of the subtopic writing groups created to develop the content for the four main topic areas. Other members volunteered to contribute to each section based on their expertise and knowledge. The groups exchanged ideas and drafts by email and communicated during conference calls to minimize overlap in the sections and to determine how the topic areas were interrelated. The Priorities and Potential Actions were generated by the subcommittee over the course of several meeting discussions.

Members of the four subtopic areas with lead or co-leads in bold:

• Tick Ecology, Environmental Change, and Range Expansion: Dina Fonseca, Holly Gaff, Lonnie Marcum, Daniel Salkeld, Kirby C. Stafford III, Pete D. Teel, Stephen K. Wikel
• Tick Bite Prevention and Tick Control: Jill Auerbach, Lars Eisen, Amanda Elam, Dina Fonseca, Rebecca Trout Fryxell, Holly Gaff
• Host Behavior and Host-Targeted Control Methods: Rebecca Trout Fryxell, Erika T. Machtinger, Kirby C. Stafford III, Stephen K. Wikel
• New Innovations and Commercial Translation for Tick Control: Jill Auerbach, Lars Eisen, Amanda Elam, Robert Miller

Brief for the Working Group

At Public Meeting 20 on February 28 and March 1, 2022, the subcommittee co-chairs will present their final report to TBDWG using a PowerPoint template provided to them by the leadership and support team. The co-chairs worked with the support writer to populate the slide deck using content from the subcommittee report. The presentation will be finalized after subcommittee members are given the opportunity to provide feedback via email.  

Table 1: Members of the Changing Dynamics of Tick Ecology, Personal Protection, and Control Subcommittee

Members	Type	Stakeholder Group	Expertise
Subcommittee Co-Chair Robert J. Miller, PhD United States Department of Agriculture, Agricultural Research Service, Beltsville, MD	Federal	Government Researcher	National Program Leader, NP104 Veterinary, Medical, and Urban Entomology, Agricultural Research Service, United States Department of Agriculture
Subcommittee Co-Chair Kirby C. Stafford III, PhD The Connecticut Agricultural Experiment Station, New Haven, CT	Public	Academic Researcher	Chief Entomologist, Department of Entomology, Center for Vector Biology and Zoonotic Diseases, NE Regional Center for Excellence in Vector Borne Diseases, The Connecticut Agricultural Experiment Station
Working Group Co-Chair Holiday Goodreau LivLyme Foundation, Denver, CO	Public	Advocate, Family Member	Executive Director, LivLyme Foundation; Co-Creator, TickTracker
Working Group Co-Chair Linden Hu, MD Tufts University School of Medicine, Boston, MA	Public	Medical Researcher	Professor of Microbiology and Medicine, Vice Dean for Research, Tufts University School of Medicine
Jill Auerbach Hudson Valley Lyme Disease Association, Poughkeepsie, NY	Public	Patient, Advocate, Family Member	Chairperson, Hudson Valley Lyme Disease Association; Coordinator, Tick Research to Eliminate Diseases: Scientist Coalition
Lars Eisen, PhD Centers for Disease Control and Prevention, Fort Collins, CO	Federal	Government Researcher	Research Entomologist, Division of Vector-Borne Diseases, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention
Amanda Elam, PhD Galaxy Diagnostics, Research Triangle Park, NC	Public	Diagnostics Provider	President/CEO, Galaxy Diagnostics
Dina Fonseca, PhD Rutgers University, New Brunswick, NY	Public	Academic Researcher	Professor and Director of the Center for Vector Biology, Department of Entomology, Rutgers University, The State University of New Jersey
Rebecca Trout Fryxell, PhD The University of Tennessee, Institute of Agriculture, Knoxville, TN	Public	Academic Researcher	Associate Professor, Medical and Veterinary Entomology, Department of Entomology and Plant Pathology, The University of Tennessee Institute of Agriculture
Holly Gaff, PhD Old Dominion University, Norfolk, VA	Public	Academic Researcher	Professor, Department of Biological Sciences, Old Dominion University
Erika T. Machtinger, PhD The Pennsylvania State University, State College, PA	Public	Academic Researcher	Assistant Professor of Entomology, College of Agricultural Sciences, The Pennsylvania State University
Lonnie Marcum, PT, BSHCA LymeDisease.org, San Ramon, CA	Public	Healthcare Provider, Patient Advocate, Family Member	Physical Therapist; Health and Science Writer for LymeDisease.org
Daniel Salkeld, PhD Colorado State University, Fort Collins, CO	Public	Academic Researcher	Research Scientist, Department of Biology, Colorado State University
Pete D. Teel, PhD Texas A&M University, College Station, TX	Public	Academic Researcher	Regents Professor, Department of Entomology, Texas A&M University
Stephen K. Wikel, PhD Quinnipiac University, Hamden, CT	Public	Academic Researcher	Professor and Chair Emeritus of Medical Sciences, St. Vincent’s Medical Center, Quinnipiac University

Table 2: Overview of Changing Dynamics of Tick Ecology, Personal Protection, and Control Subcommittee Meetings

Meeting No.	Date	Present	Topics Addressed
1	September 9, 2021	Robert Miller (Subcommittee [SC] co-chair), Kirby C. Stafford, III (SC co-chair), Holiday Goodreau (WG co-chair), Jill Auerbach, Lars Eisen, Amanda Elam, Dina Fonseca, Rebecca Trout Fryxell, Holly Gaff, Erika T. Machtinger, Lonnie Marcum, Daniel Salkeld, Stephen K. Wikel Debbie Seem (DFO representative), Sue Visser (CDC/Meeting support)	SC member introductions; SC objectives and focus areas; Planning for invited speakers
2	October 13, 2021	Robert Miller (SC co-chair), Kirby C. Stafford, III (SC co-chair), Holiday Goodreau (WG co-chair), Linden Hu (WG co-chair), Jill Auerbach, Lars Eisen, Amanda Elam, Dina Fonseca, Rebecca Trout Fryxell, Holly Gaff, Erika T. Machtinger, Lonnie Marcum, Daniel Salkeld, Pete D. Teel, Stephen K. Wikel James Berger (Designated Federal Officer [DFO]), Debbie Seem (DFO representative), Sue Visser (CDC/Meeting support)	Schedule of upcoming meetings; Subtopic area assignments; Guest speaker brainstorming
3	October 27, 2021	Kirby C. Stafford, III (SC co-chair), Holiday Goodreau (WG co-chair), Linden Hu (WG co-chair), Jill Auerbach, Lars Eisen, Amanda Elam, Dina Fonseca, Rebecca Trout Fryxell, Holly Gaff, Erika T. Machtinger, Lonnie Marcum, Daniel Salkeld, Pete D. Teel, Stephen K. Wikel Lauren Overman (DFO Representative), Mike Kavounis (Contractor support), Cat Thomson (Contractor support), Meghan Walsh (Contractor support)	Discussion of subtopic areas and assignment of subgroup leads; Review of currently funded projects and identification of possible gaps; Review of subgroup next steps
4	November 10, 2021	Kirby C. Stafford, III (SC co-chair), Jill Auerbach, Lars Eisen, Amanda Elam, Dina Fonseca, Rebecca Trout Fryxell, Holly Gaff, Erika T. Machtinger, Lonnie Marcum, Daniel Salkeld, Stephen K. Wikel Jean Amick (Guest speaker), Lauren Overman (DFO Representative), Mike Kavounis (Contractor support), Cat Thomson (Contractor support)	Presentation on NootkaShield; Subgroup updates; Discussion of priorities and potential recommendations
5	November 17, 2021	Robert Miller (SC co-chair), Kirby C. Stafford, III (SC co-chair), Jill Auerbach, Lars Eisen, Dina Fonseca, Rebecca Trout Fryxell, Holly Gaff, Erika T. Machtinger, Lonnie Marcum, Daniel Salkeld, Pete D. Teel, Stephen K. Wikel Tammi L. Johnson (Guest speaker) Cedric Pulliam (DFO representative), Derek Smith (Contractor support), Cat Thomson (Contractor support)	Procedural updates: Meeting schedule; Report outline; Presentation on Texas A&M’s white-tailed deer anti-tick vaccine project; Presentation on Texas A&M’s study on the susceptibility of the southern cattle tick to Nootkatone; Subgroup updates
6	December 1, 2021	Kirby C. Stafford, III (SC co-chair), Linden Hu (WG co-chair), Jill Auerbach, Lars Eisen, Dina Fonseca, Rebecca Trout Fryxell, Holly Gaff, Erika T. Machtinger, Lonnie Marcum, Daniel Salkeld, Pete D. Teel, Stephen K. Wikel Cedric Pulliam (DFO representative), Derek Smith (Contractor support), Cat Thomson (Contractor support)	Suggestions for the SC report; Discussion of recommendations for each subtopic; Potential speakers; Meeting schedule/report finalization and voting; Next steps
7	December 8, 2021	Robert Miller (SC co-chair), Kirby C. Stafford, III (SC co-chair), Linden Hu (WG co-chair), Jill Auerbach, Lars Eisen, Amanda Elam, Dina Fonseca, Rebecca Trout Fryxell, Holly Gaff, Erika T. Machtinger, Daniel Salkeld, Pete D. Teel, Stephen K. Wikel Monika Gulia-Nuss (Guest speaker), Lauren Overman (DFO representative), Mike Kavounis (Contractor support), Cat Thomson (Contractor support)	Presentation on transgenic tick research; Discussion of report recommendations
8	December 15, 2021	Kirby C. Stafford, III (SC co-chair), Linden Hu (WG co-chair), Jill Auerbach, Lars Eisen, Dina Fonseca, Holly Gaff, Erika T. Machtinger, Lonnie Marcum, Daniel Salkeld, Pete D. Teel, Stephen K. Wikel Christopher Houchens (Guest speaker), Lauren Overman (DFO representative), Damon Kane (Contractor support), Cat Thomson (Contractor support)	Presentation on the Biomedical Advanced Research and Development Authority (BARDA); Discussion of draft report recommendations, Background section, and report preparation; Next steps
9	January 5, 2022	Kirby C. Stafford, III (SC co-chair), Robert Miller (SC co-chair), Linden Hu (WG co-chair), Jill Auerbach, Lars Eisen, Dina Fonseca, Rebecca Trout Fryxell, Erika T. Machtinger, Lonnie Marcum, Daniel Salkeld, Pete D. Teel,  Stephen K. Wikel Laruen Overman (DFO representative), Gina Castelvecchi (Contractor support), Damon Kane (Contractor support)	Upcoming speakers, Report preparation; Discussion of draft priorities and potential actions; Revisions; Next steps
10	January 19, 2022	Kirby C. Stafford, III (SC co-chair), Linden Hu (WG co-chair), Jill Auerbach, Lars Eisen, Dina Fonseca, Rebecca Trout Fryxell, Holly Gaff, Erika T. Machtinger, Lonnie Marcum, Daniel Salkeld, Pete D. Teel, Stephen K. Wikel Anderson Hedgecock (Guest speaker), Agenor Mafra-Neto (Guest speaker), Mike Sullivan (Guest speaker), Lauren Overman (DFO representative), Damon Kane (Contractor support)	Presentation on the flea and tick control product commercialization process for animal products; Presentation on commercial translation of tick control products; Next steps
11	February 2, 2022	Robert Miller (SC co-chair), Kirby C. Stafford, III (SC co-chair), Linden Hu (WG co-chair), Jill Auerbach, Lars Eisen, Amanda Elam, Dina Fonseca, Rebecca Trout Fryxell, Holly Gaff, Erika T. Machtinger, Lonnie Marcum, Pete D. Teel, Stephen K. Wikel Lauren Overman (DFO representative), Mike Kavounis (Contractor support), Cat Thomson (Contractor support)	Status update and deadlines for the Tick Ecology Report; Review and refinement of wording of Priorities and Potential Actions and vote to accept them
12	February 7, 2022	Robert Miller (SC co-chair), Kirby C. Stafford, III (SC co-chair), Jill Auerbach, Lars Eisen, Dina Fonseca, Rebecca Trout Fryxell, Lonnie Marcum, Pete D. Teel, Stephen K. Wikel Lauren Overman (DFO representative), Mike Kavounis (Contractor support), Meghan Walsh (Contractor support)	Review of Background section and wording of narratives for Priorities; Vote on word substitutions in two Potential Actions
13	February 9, 2022	Robert Miller (SC co-chair), Kirby C. Stafford, III (SC co-chair), Linden Hu (WG co-chair), Jill Auerbach, Lars Eisen, Dina Fonseca, Rebecca Trout Fryxell, Holly Gaff, Erika T. Machtinger, Lonnie Marcum, Daniel Salkeld, Pete D. Teel, Stephen K. Wikel Laruen Overman (DFO representative), Damon Kane (Contractor support), Mike Kavounis (Contractor support), Cat Thomson (Contractor support), Meghan Walsh (Contractor support)	Vote on word substitution in one Potential Action; Review and vote on Background section; Review and vote on entire report

Table 3: Presenters to the Changing Dynamics of Tick Ecology, Personal Protection, and Control Subcommittee

Meeting No.	Presenter(s)	Topics Addressed	Ok to Share?
4	Jean Amick, PhD, Evolva	NootkaShield	Yes
5	Tammi L. Johnson, PhD, Texas A&M AgriLife Research	Optimizing Protocols for Research at the White-tailed Deer-Tick Interface: Quantifying Baseline Feeding Parameters and Measuring the Immune Response of White-tailed Deer to Repeated Tick Infestation Susceptibility of Rhipicephalus (Boophilus) microplus to Nootkatone	NA
7	Monika Gulia-Nuss, PhD, University of Nevada, Reno	Developing Genetic Tools for Ticks and Tick-Borne Disease Management	NA
8	Christopher Houchens, PhD, Biomedical Advanced Research and Development Authority (BARDA)	How BARDA Supports the Accelerated Research, Development, and Delivery of Medical Countermeasures Against Public Health Threats	Yes
10	Mike Sullivan, U.S. Diagnostics at Zoetis	Flea and Tick Product Considerations in Animal Health	NA
10	Agenor Mafra-Neto PhD, ISCA, Inc.	Application of Semiochemicals with Comments on Commercial Translation to Tick Control	Yes

Table 4: Votes Taken by the Changing Dynamics of Tick Ecology, Personal Protection, and Control Subcommittee

Meeting Number	Motion	Result In Favor	Result Opposed	Result Abstained	Result Absent	Minority Response
1	Adopt an overall objective for the subcommittee	13	0	0	0	None
11	Approve Priority 1	11	0	0	2	None
11	Approve Priority 2	11	0	0	2	None
11	Approve Priority 3	11	0	0	2	None
11	Approve Priority 4	11	0	0	2	None
11	Approve Potential Action 1.1	11	0	0	2	None
11	Approve Potential Action 1.2	11	0	0	2	None
11	Approve Potential Action 1.3	11	0	0	2	None
11	Approve Potential Action 2.1	11	0	0	2	None
11	Approve Potential Action 2.2	12	0	0	1	None
11	Approve Potential Action 2.3	11	0	0	2	None
11	Approve Potential Action 2.4	11	0	0	2	None
11	Approve Potential Action 3.1	12	0	0	1	None
11	Approve Potential Action 3.2	12	0	0	1	None
11	Approve Potential Action 3.3	12	0	0	1	None
11	Approve Potential Action 4.1	12	0	0	1	None
11	Approve Potential Action 4.2	12	0	0	1	None
11	Approve Potential Action 4.3	12	0	0	1	None
11	Approve Potential Action 4.4	12	0	0	1	None
12	Approve word change Action 1.1	9	0	0	4	None
12	Approve wording change Action 2.2	9	0	0	4	None
13	Approve wording change Action 2.4	12	0	0	1	None
13	Approve Background section	12	0	0	1	None
13	Approve final report, including additional references work and copyediting	12	0	0	1	None

Results and Potential Actions

For consideration by TBDWG, the Changing Dynamics of Tick Ecology, Personal Protection, and Control Subcommittee has identified four major priorities and 14 potential actions to achieve them.

Priority 1. Minimize roadblocks and streamline the process for getting new tick bite prevention and tick control products to market.

Background

Roadblocks for getting new tick bite prevention and tick control products to market were discussed by Eisen and Stafford (2021). The authors noted that industry has three broad roles in the field of tick control and tick bite prevention: (1) production of already marketed products to kill or repel ticks; (2) development and commercialization of new acaricide or repellent active ingredients and formulations and other novel products such as anti-tick vaccines; and (3) the services provided by pest management professionals (that is, local pest control companies or franchises). It was also noted that development, registration, and commercialization of tick control products targeting companion animals is a more effective process compared to that of tick bite prevention and tick control products intended to reduce human tick bites and human disease (Blagburn & Dryden, 2009; Pfister & Armstrong, 2016; Stafford, 2017). This may be in part because industry has a clearer understanding of the market for pet products than for repellents for human use. However, the market for environmental tick control products is more difficult to understand in the absence of public health tick management programs as a sustainable consumer base and a national organization for tick control (similar to the American Mosquito Control Association) providing an interface between industry and consumer communities. This problem is compounded by the issue that implementation of novel technologies requires long-term research followed by commercial product development with associated costs, patent or licensing issues, registration approvals, marketing, and actual acceptance and use by the public or pest management professionals (Graf et al., 2004).

Summary of Evidence and Findings

Part of the solution to this problem could be to expand the purview of BARDA to include vector-borne diseases, and to provide BARDA with funding to work with industry to bring a new focus on getting tick bite prevention and tick control products to market (Action 1.1). BARDA has the infrastructure and regulatory expertise in place to rapidly improve the process for getting new tick bite prevention and tick control products to market. BARDA has extensive experience working with diverse scientific and industrial partners. The organization is already expressing interest in the biothreat posed by some potentially invasive tick species and their pathogens, which emphasizes the importance of surveying tick populations and deep sequencing a representative sample to determine their microbiomes and viromes (see Priority 3). Subject matter experts from other Federal agencies (including the Environmental Protection Agency [EPA], Food and Drug Administration, U.S. Department of Agriculture [USDA], CDC, DoD and National Institutes of Health [NIH]) can be engaged to support BARDA in this process. All relevant Federal agencies should also be charged to work more closely with industry to define roadblocks and target solutions for getting new tick bite prevention and tick control products to market (Action 1.2).

Another effective way to ensure that Federal funds are invested in research, development, and evaluation of new tick bite prevention and tick control products is to target Federal funding opportunities specifically to these topics (Action 1.2). Targeted opportunities could be realized within the context of existing funding mechanisms such as the Small Business Innovation Research Program (CDC or NIH), a Research Project Cooperative Agreement (CDC or NIH), the CDC Broad Agency Announcement Program, and the NIH Research Project Grant Program (R01), Small Grant Program (R03), or Exploratory/Developmental Research Grant Program (R21). Recent examples of such targeted funding initiatives include:  

• The 2019 CDC Broad Agency Announcement Program, which included two topics entitled “Novel approaches to suppress tick vectors, disrupt natural transmission of tick-borne pathogens and prevent human tick bites” and “Improved understanding of (i) tick- or human behavior-related factors leading to increased risk of human contact with tick vectors and (ii) specific roadblocks leading to limited use of existing personal protective measures and environmentally based tick/pathogen control methods”
• The DoD Tick-Borne Disease Research Program, which has been active since 2016 and in which the Treatment and Prevention focus area includes tick bite prevention and tick control

Additional targeted funding initiatives posted by CDC in late 2021 include:

• The 2021 Broad Agency Announcement Program, including a topic titled “Address critical gaps in human tick bite prevention”
• Research Project Cooperative Agreements for “Vector-Borne Disease Regional Centers of Excellence” with an applied research focus on approaches to prevent vector bites or suppress regionally important vectors and their associated human disease agents in the environment
• A Research Project Cooperative Agreement entitled “Optimization and standardization of methods to suppress Ixodes scapularis and disrupt enzootic pathogen transmission in settings posing an elevated risk to humans”

Challenges

The path from proof of concept in the laboratory to commercial product now stands at roughly 15 years. Shortening the time for development of novel tick bite prevention and tick/pathogen control products is a critical need for effective future intervention programs. Another barrier to industry engagement, the synergism of existing technologies, and the emergence of new products is the development of new products combining currently available technology such as oral systemic acaricides, reservoir-targeted vaccines, and different delivery systems under patent by different companies.

In addition, regulatory obstacles may exist for product concepts that must pass through different Federal regulatory agencies, depending on the product and required registrations and approvals. For example, launching an on-skin repellent product with a multi-million-dollar investment can take approximately 4 years (presentation to subcommittee, Jean Amick, Evolva). Another tick product facing development challenges is a combination semiochemical and pesticide product (Splat TK, ISCA, Inc.). Semiochemical-based strategies utilize an attract-and-kill approach to suppress populations of disease-carrying arthropods (Mafra-Neto et al., 2018).

Opportunities

The promising product concept outlined below illustrates the critical need for a more effective pathway to develop, register, and commercialize tick bite prevention and tick control products. Nootkatone, from Alaskan yellow cedar and grapefruit essential oil, was shown to be both repellent and toxic to four tick species, Amblyomma americanum (lone star tick), Dermacentor variabilis (American dog tick), I. scapularis (blacklegged tick, or deer tick), and Rhipicephalus sanguineus (brown dog tick), in a series of federally funded laboratory and field studies published from 1997 to 2012 (Bharadwaj et al., 2012; Dietrich et al., 2006; Dolan et al., 2009; Flor-Weiler et al., 2011; Jordan et al., 2012; Panella et al., 2005). Nootkatone is commonly used in foods and fragrances, and, very importantly, now can be mass-produced using a yeast fermentation process to reduce production cost to the point where nootkatone-based products to repel and kill ticks should be commercially viable at a cost accepted by the public. Nootkatone-based products targeting mosquitoes and ticks are being developed under the name NootkaShield by Evolva under license from CDC, and nootkatone was registered by EPA as a biopesticide in 2020 (Evolva, 2021). With a more effective process in place for getting new tick bite prevention and tick control products to market, promising new products could emerge on timelines far shorter than we have experienced over the last decades.

Priority 1 Potential Actions

Potential Action 1.1. Expand the purview of the Biomedical Advanced Research and Development Authority (BARDA) to include vector-borne diseases and provide BARDA with funding to work with industry to bring new tick bite prevention and tick control products to market.

These actions would: (1) expedite the development of promising new intervention technologies and (2) facilitate the commercialization of new intervention products for tick and tick-borne disease control to reach the widest possible segments of the populations at risk for Lyme disease and other tick-borne diseases.

Table 5: Vote on Potential Action 1.1

Number in Favor	Number Opposed	Number Abstained	Number Absent
11	0	0	2

Table 6: Vote on one word substitution in Potential Action 1.1

Number in Favor	Number Opposed	Number Abstained	Number Absent
9	0	0	4

Potential Action 1.2. Charge Federal entities (including the Environmental Protection Agency, Food and Drug Administration, United States Department of Agriculture, Centers for Disease Control and Prevention, Department of Defense, and National Institutes of Health) to work with industry to streamline regulatory pathways and target solutions for getting new tick bite prevention and tick control products to market.

As noted in the 2020 Tick Biology, Ecology, and Control Subcommittee Report, we reaffirm that supporting these critical partnerships will expedite the progress of intervention strategies, including to commercialize and market the most promising new and/or existing technologies to reach the widest possible segments of the U.S. population at risk for Lyme disease and other tick-borne diseases.

Table 6: Vote on Potential Action 1.2

Number in Favor	Number Opposed	Number Abstained	Number Absent
11	0	0	2

Potential Action 1.3. Enhance existing Federal proposal, review, and funding for research, development, and evaluation of new tick bite prevention and tick control products (for example, the Small Business Innovation Research Program and other Federal funding mechanisms which are open to academic institutions and all industry entities).

These actions would help fulfill the need for broad funding that incorporates basic, translational, and applied research, as well as seed support for initiatives such as Small Business Innovation Research grants.

Table 7: Vote on Potential Action 1.3

Number in Favor	Number Opposed	Number Abstained	Number Absent
11	0	0	2

Minority Responses

There were no minority responses.

Priority 2. Accelerate efforts to define and deploy tick bite prevention and tick control approaches and strategies.

Critical need exists for novel concepts and approaches, including host-targeted methodologies, as well as for evaluation of the effectiveness of existing approaches to prevent tick bites and reduce tick-borne disease (Actions 2.1 and 2.2). Ticks are increasingly the foci of genomics and functional genomics studies with significant potential to provide new insights for development of novel control approaches with greater target specificity. While research on genetically modified ticks (that is, transgenic ticks) is in its infancy, the potential benefits of utilizing recent advances in vector genomics and genetic manipulations are significant, and sustained research funding support for this research area is needed.

Background

Currently available personal protection measures to prevent tick bites that incur no or minimal cost include avoiding tick habitat; wearing clothing that forces ticks to travel a long distance before contacting skin; and conducting regular cursory tick checks while outside in tick habitat as well as a thorough tick check when coming back indoors (aided by removing outdoor clothing articles and running them in a dryer on high heat and taking a shower/bath). Additional chemical measures that incur low to moderate cost include applying a tick repellent to skin and clothing (low cost), treating clothing with a permethrin spray (low cost), or wearing commercially available long-lasting permethrin-treated clothing (moderate cost).

Currently available methods to suppress ticks in the environment include hardscaping/xeriscaping, vegetation management, broadcasting conventional synthetic acaricides, natural product-based acaricides or biological control agents (such as entomopathogenic fungus), and applying acaricides to tick hosts including rodents and deer. Numerous studies have evaluated the impact of these methods on host-seeking ticks (Eisen & Dolan, 2016). The evidence base for tick suppression is strongest for broadcast of conventional synthetic acaricides, moderately strong for broadcast of natural product-based acaricides/biological control agents or acaricide treatment of rodents and deer, and weakest for hardscaping/xeriscaping and vegetation management. However, to date, evidence is lacking to show that these environmental tick suppression methods reduce either human tick bites or tick-borne disease (Eisen, 2021; Eisen & Mead, 2021; Eisen & Stafford, 2021; Hinckley et al., 2016, 2021). Additional research is needed to determine how environmental tick suppression methods are to be optimally used, singly or in combination, to most effectively reduce human tick bites or tick-borne disease based on variable application schemes (Action 2.1).

Tick control can be implemented in multiple settings, including privately owned residential properties, public properties and lands (such as schools, parks, and high-use recreation areas), and entire communities. Improved guidance for implementation of suitable tick control methods based on the type and spatial extent of the targeted environment and the tick species present would be of value for stakeholders ranging from homeowners to pest control firms and public health programs engaging in tick control (Action 2.3).

A major driver of tick and tick-borne pathogen emergence is the geographic and demographic expansion of ticks and their associated pathogens through movement of their wild and domestic host populations (covered in more detail under Priority 3). Tick-borne infectious diseases of humans are zoonoses (Eisen et al., 2017). Pathogen transmission cycles are dependent, in part, on an array of animal hosts, depending on the tick species. While some animals are recognized as key tick reproductive hosts or pathogen reservoirs, the ticks of major medical and veterinary concern generally feed on diverse animal species (for example, birds, raccoons, squirrels, and shrews, as well as humans, livestock, and companion animals), which may account for local and geographical variation in the results of studies with host-targeted interventions. Ticks can be transported via humans, domestic and wild animals, and animal and plant products (Burridge, 2011). However, long-distance movement is likely associated with humans, companion animals, migrating birds, or, to a more limited extent, large mammalian hosts.

Given that the dispersion and distribution of ticks is linked to that of the host animals, a major avenue for control is host-targeted tick control. Identified key hosts have been the focus of host-target strategies for blacklegged ticks, but more attention is needed on the ecology of other tick species and how to address control in alternative hosts. Some species like the lone star tick and Asian longhorned tick infest a range of medium and large mammals and wild birds but not small mammals like rodents. Host-targeted methods include the topical application of acaricides to rodents and deer, host reduction, perimeter fencing/host exclusion, and rodent-targeted and perhaps deer-targeted vaccines; these are primarily linked to managing blacklegged ticksand have not been evaluated in southern locations where more tick species occur.

We highlight in Summary of Evidence and Findings host-targeted methods currently available and potential approaches under investigation to improve or expand this strategy to reduce tick abundance, infection prevalence in ticks, or both. This includes developing technologies for reservoir host-targeted strategies, use of semiochemicals, anti-tick vaccines, and genetic manipulation of ticks to reduce the risk of tick-borne disease.

Summary of Evidence and Findings

Field studies have shown application of repellents or permethrin to coveralls, uniforms, or work clothing can effectively reduce tick bites (Mitchell et al., 2020; Vaughn et al., 2014). Yet similar studies are scarce for summer-weight clothing articles worn by the public during their normal daily activities (Miller et al., 2011). Multiple studies have evaluated associations between tick-borne disease incidence and use of different personal protection measures by the public, including use of non-treated protective clothing, wearing repellents, conducting tick checks, and bathing/showering soon after coming inside (Connally et al., 2009; Finch et al., 2014; Kianersi et al., 2020; Vázquez et al., 2008). Results are mixed for each of these personal protection measures, with some studies indicating that regular use of the measure is associated with a reduction in tick-borne disease while other studies found no similar protective effect. One possible interpretation is that these measures can protect against tick-borne infection, but the information gathered in studies to date has not been sufficiently detailed to clarify the circumstances under which protection is achieved (frequency of use, parts of the body being protected, and use of combinations of two or more potentially protective measures). Additional research is needed to clarify the effectiveness of existing personal protection measures to reduce human tick bites and tick-borne disease (Action 2.1).

The human itch response (cutaneous hypersensitivity) following repeated blacklegged tick bites has been associated with a significantly lower risk of developing infection with a tick-transmitted pathogen (Burke et al., 2005). The importance of cutaneous inflammatory response-induced grooming to remove ticks was established decades ago by studies involving experimental infestations of cattle (Snowball, 1956). These itchy immune responses might alert people to the presence of a tick and prompt removal, possibly before transmission of a pathogen occurs.

Researchers have sought to identify tick saliva molecules that could be used in vaccination to induce a resistance or itching response. Similar to naturally acquired resistance, this response blocks tick feeding and is accompanied by the small amount of skin inflammation needed for resistance or a notable itch. Results to date of anti-tick vaccination efforts with single and, in some cases, multiple tick-derived antigens have been highly variable and largely incompatible with blocking tick feeding and pathogen transmission at a level that would be commercially viable (van Oosterwijk & Wikel, 2021). A question yet to be answered is what amount of cutaneous inflammation and itch at the bite site would be acceptable in an anti-tick vaccine licensed for human use. A corollary consideration is that with repeated exposures to tick bites, the intensity of inflammation and itch continues to increase. The same considerations are important for any anti-tick vaccine intended for the companion animal market.

The recent report by Sajid et al. (2021) incorporated an mRNA vaccination platform with multiple blacklegged tick antigens to induce resistance in the guinea pig to both infestation and pathogen transmission similar to classically acquired tick resistance. Sajid et al. (2021) incorporated 19 blacklegged tick salivary proteins into a nucleoside modified mRNA lipid particle, nano-encapsulated vaccine formulation, well beyond the number of epitopes used in prior studies, to successfully mimic the acquired tick resistance response. However, interpretation of the findings reported by Sajid et al. (2021) regarding blocking tick transmission of the Lyme disease agent, Borrelia burgdorferi, are more nuanced than they initially appear due to experimental design considerations in the timing of removing ticks, and longer attachment resulted in effective pathogen transmission.

Current host-targeted methods include 4-poster devices (C. R. Daniels, Inc., Ellicott City, MD) for topical application of acaricide to deer (Schulze et al., 2008; Williams et al., 2021), deer reduction (Kilpatrick et al., 2014; Telford, 2017; Williams et al., 2018a), perimeter fencing/host exclusion (Ginsberg & Stafford 2005; Stafford, 1993), rodent-targeted vaccines against Lyme disease spirochetes (Gomes-Solecki, 2014; Stafford et al., 2020), and topical acaricide products to target juvenile tick stages on rodents. The latter include Thermacell (Thermacell Repellents, Inc., Bedford, MA) or Damminix (EcoHealth, Inc., Brookline, MA) tick control tubes containing permethrin-treated cotton for use as rodent nesting material (Eisen & Dolan, 2016; Eisen & Stafford, 2021; Jordan & Schulze, 2019b), and rodent-targeted bait boxes in which fipronil is applied topically as the rodent is moving towards the food bait (Select TCS, Connecticut Tick Control, LLC, Norwalk, CT; Jordan & Schulze, 2019; Williams et al., 2018a). 

White-tailed deer are a major host for the blacklegged tick, lone star tick, and Asian longhorned tick. White-tailed deer serve mainly as the host for the adult stage of these ticks, although immature stages also feed on deer. The resurgence of the deer population over the last 50 years in the eastern United States is linked to the emergence of multiple tick-borne pathogens associated with these and other tick species (Childs & Paddock, 2003; Paddock & Yabsley, 2007). These disease agents include B. burgdorferi (Lyme disease), Babesia microti (human babesiosis), Anaplasma phagocytophilum (anaplasmosis), Ehrlichia chaffeensis and E. ewingii (ehrlichiosis), Powassan virus, and likely Heartland and Bourbon viruses.

Currently, one host-targeted product is on the market for the topical treatment of deer: 4-poster devices. These devices use bait to lure deer to self-apply an acaricide to their heads and necks and have had variable success based on arrangement, deployment density, availability of bait, and social and hierarchical behavior (Williams et al., 2021). The 4-poster passive deer treatment bait stations topically apply an acaricide to the head, ears, and neck of white-tailed deer as they contact treated rollers while feeding on whole kernel corn. This can provide effective control of blacklegged and lone star ticks on the host animal and of the free-living stages of the ticks (Stafford & Williams, 2017; Williams et al., 2021), and a reduction in human Lyme disease cases has been documented (Garnett et al., 2011). Efficacy of the 4-poster in studies has been variable dependent upon rate of deployment and deer density with recent work with A. americanum suggesting one device per 8-12 animals, regardless of land area (Williams et al., 2021). However, a low-density deployment of 4-poster stations in a deer-dense setting may not lead to lone star tick control (Harmon et al., 2011).

The advantage of 4-poster devices is that they target deer with large home ranges and do not require placement or action by each homeowner. However, 4-posters as currently designed present several issues. They can be expensive to implement and maintain for delivery to free-ranging wildlife. Human exposure is possible (deployment is restricted to more than 100 yards from residential communities, playgrounds, and areas where children may be present unless a protective fence is used). Other drawbacks include potential public opposition; non-target species use; environmental concerns; acaricide resistance; and concern about spread of communicable diseases among deer (many states will not allow use due to chronic wasting disease).

Currently, two host-targeted products are on the market for rodents, mainly white-footed mice, with licensing anticipated shortly for a third, a reservoir-targeted Lyme disease oral vaccine delivered via a foodbait. Rodent use of permethrin-treated material found within Thermacell and/or Damminix tick tubes is somewhat limited by the availability of other natural, preferred bedding materials and may not be used by eastern chipmunks (Jordan & Schulze, 2019). Tick tubes contain 7.4% permethrin-treated cotton, which is used for nesting material by mice. They are economical (approximately $3 a tube), available to the public, and relatively easy to apply. Targeting ticks with topical application of fipronil on the primary reservoir host, the white-footed mouse, is typically met with minimal resistance from the public and this strategy has reduced abundances of both tick and tick-associated pathogens in numerous studies, although efficacy in reducing host-seeking I. scapularis nymphs on treated properties has been highly variable, with results ranging from 0% to 20.3% to 27.6% (Dolan et al., 2004; Hinckley et al., 2021; Little et al., 2020; Schulze et al., 2017; Williams et al., 2018a; Williams et al., 2018b). Application is limited to the small home ranges of the mouse host, requiring placement approximately every 30 feet at the perimeter of a treated property, and the bait boxes must be deployed by pest control professionals. 

More than 80 years ago, the potential for developing an anti-tick vaccine was established when guinea pigs immunized by intracutaneous administration of an extract of American dog tick (D. variabilis) larvae rejected up to 100% of a larval challenge. From that point onward, tick tissue extracts and eventually specific molecules used in anti-tick vaccine studies increased in number, diversity, and complexity, in large part due to advances achieved in characterizing multiple aspects of tick physiology and tick-host interactions at the cellular, molecular, and genomic levels. Although advances continue to be made, a significant impediment to anti-tick vaccine development and understanding the tick-host-pathogen interface is the inability to link specific tick saliva molecules with specific biological activities. With a few notable exceptions, the majority of anti-tick vaccination experiments achieved partial protection that would be insufficient to provide sufficient protection against infestation and tick-borne pathogen transmission in the field. These topics and the issues surrounding anti-tick vaccines have been the topics of recent comprehensive reviews (Almazan et al., 2018; de la Fuente et al., 2016; Neelakanta & Sultana, 2015; Rego et al., 2019; Bhowmick and Han, 2020; van Oosterwijk, 2021; van Oosterwijk & Wikel, 2021; Willadsen, 2004).

Incremental advances in understanding the complex, dynamic interface of tick-host-pathogen interactions can be attributed to salivary gland transcriptomics and proteomics, high throughput next-generation sequencing, gene silencing by RNA interference, and the sequencing of the first tick genome (Boulanger and Wikel, 2021; Chmelař et al., 2016; Gulia-Nuss et al., 2016; Karim et al., 2008; Kazimírová and Štibrániová, 2013; Kitsou et al., 2021; Ribeiro et al., 2006; Šimo et al., 2017; Wikel, 2018a; Wikel, 2018b). Major rapid advances in characterizing tick saliva began with construction of tick salivary gland cDNA libraries and with incremental advances in transcript sequencing, next-generation sequencing, quantitative proteomics, and bioinformatics resources that revealed in increasing detail the complexity, redundancy, diversity, differential expression, and interspecies and intraspecies variations of saliva molecules (Boulanger & Wikel, 2021; Chmelař et al., 2016; Kotál et al., 2015; Martins et al., 2021; Nuttall, 2019). Salivary gland transcriptome expression patterns are known to vary among individual ticks within a species (Mans, 2020) and in response to differences in blood feeding from different host species (Narasimhan et al., 2019). Similar analysis tools are being applied to other tick tissues, including midgut (Heekin et al., 2013; Feng and Cheng, 2020), ovary (Zhao et al., 2021), and hemocytes (Kotsyfakis et al., 2015). These studies are identifying genes, many of which are novel to ticks, that regulate metabolic pathways, modulate host defense, and contribute to successful tick tissue colonization and transmission of pathogenic microbes. The opportunity is to utilize these findings as an important element to help underpin emerging novel control strategies.

Challenges

The two broad challenges identified in the 2020 Tick Biology, Ecology, and Control Subcommittee Report remain valid. These were essentially:

• Capacity for organized tick control is either lacking or poorly developed across the United States.
• Evidence for ITM or individual strategies to result in reduced human tick bites or human tick-borne illness is lacking.

Establishment of local public health tick management programs (potentially via extension of the scope of responsibilities of existing mosquito management programs) could have multiple benefits. Such programs could provide the following services: 

• Tick identification for local community members experiencing tick bites
• Active tick surveillance to define local high-risk environments for tick exposure
• Testing of ticks for human pathogens
• Posting of warning signs on public lands
• Tick control for public properties or high-use portions of public lands (including assessments of the impact of the control interventions on host-seeking ticks)
• Assistance for homeowners regarding options for locally appropriate tick control on their properties and working with homeowners and pest control firms on operational quality control projects to assess the impact of tick control implemented by residents or pest control operators on residential properties on host-seeking ticks
• Outreach to the local community on where and when during the year they are at risk for bites by different tick species and their associated pathogens/tick-borne diseases
• Outreach to the local community with advice on personal protection measures to prevent tick bites

A similar model currently exists in which areawide mosquito control and outreach is performed by publicly funded authorities. Consequently, several thousands of people are dedicated to mosquito control, whereas far fewer are dedicated to public-health-related tick control (Eisen, 2021; Piesman & Eisen, 2008). A recent national survey conducted by the National Association of County and City Health Officials found that only 3% of 491 surveyed local operational vector control programs or health departments engaged in any tick control activity (Roy et al., 2021). In suburban residential settings, the burden of tick control thus falls on residential property owners, who have the choice of doing it themselves or hiring pest control firms to control ticks. Operational tick control on residential properties is likely to remain primarily a homeowner responsibility, but the emergence of local tick management programs staffed with public health professionals could provide increased support and objective advice for homeowners to select a suitable combination of tick control actions based on the characteristics of their property. Operational tick control on public lands or at a community-wide scale requires a local tick management program, minimally with oversight responsibility if the work is contracted out to pest control firms. 

White-tailed deer provide an important target for tick control measures as the main reproductive host for several tick species as well as a reservoir host for ehrlichiosis.  However, some difficulties attend current deer-targeted interventions. Installation and maintenance of deer fencing is expensive. Population reduction (culling) can be expensive and raises ethical concerns as well as frequent community pushback. Issues with topical and oral delivery of acaricides to deer (for example, using a 4-poster device) include maintenance, potential development of acaricide resistance, environmental concerns, required withdrawal period before human consumption, human safety, congregation of deer, and potential for disease spread. lvermectin, a broad-spectrum systemic parasiticide derived from the soil bacterium Streptomyces avennitilis, was shown to successfully control cattle ticks, lone star ticks, and blacklegged ticks on deer (Miller et al., 1989, 1999; Pound et al., 1996; Rand et al., 2000). However, the current withdrawal period required for ivermectins in food animals (Baynes et al. 2000), including hunted deer, prior to human consumption prevents the widespread use of virtually all systemic agents in the United States for the control of ticks on deer.

One project at a proof-of-concept stage is examining the oral delivery to white-tailed deer of a formulation of the cattle parasiticide moxidectin that has a zero-withdrawal period for the management of lone star ticks and blacklegged ticks. Another project is evaluating a mineral lick presented to white-tailed deer to systemically control blacklegged ticks and reduce Lyme disease. Deer-targeted anti-tick vaccines are a promising tool with the potential to control ticks on these hosts. They are more environmentally and socially acceptable and have fewer non-target consequences. However, white-tailed deer are challenging to work with. There has been a lot of research to identify antigenic targets in laboratory animal systems, but proteins expressed by ticks on lab animals are not necessarily the same as those expressed in ticks feeding on deer and may not be the same between tick species; thus, there is a need for the identification of new tick antigens.

With genomic approaches for tick control, the products of many newly discovered genes may be suitable targets for novel repellents, acaricides, growth regulators, anti-tick vaccines, and potential genetic manipulations that block tick feeding and vector competence. However, determining the specific biological activities of individual saliva and other tick tissue molecules remains a challenge. RNA interference has been used extensively in attempts to link specific tick genes with biological activities (de la Fuente et al., 2007; Karim et al., 2008). The extent to which RNA interference is used in the study of ticks is reflected in the National Library of Medicine PubMed citations listing of 274 peer-reviewed manuscripts related to the topic (https://pubmed.ncbi.nlm.nih.gov/?term=tick+and+RNA+interference).

Opportunities

Lyme disease patients, and likely patients with other TBDs, are often unaware of a tick bite prior to the onset of symptoms (Eisen & Eisen, 2016). Emergence of novel products capable of killing undetected feeding ticks could therefore be of great value to complement existing personal protection measures. A novel compelling approach to achieve this is a skin lotion, shower soap, or shampoo containing an active ingredient, such as nootkatone, that is feasible to apply to human skin but also has acaricidal properties (Panella et al., 2005; Dolan & Panella, 2011; Evolva, 2021). Application of such a product must account for bites by different tick species and life stages being concentrated to different parts of the body (Falco & Fish, 1988; Falco et al., 1996; Felz & Durden, 1999; Gleim et al., 2016; Jordan & Egizi, 2019; Slaff & Newton, 1993; Xu et al., 2016, 2019). For example, females of the blacklegged tick and lone star tick tend to more frequently be found biting on the upper part of the body compared with nymphs, and females of the American dog tick are commonly found biting specifically on the head.

Similarly, an anti-tick vaccine that prompts removal of feeding ticks could also potentially reduce the risk of transmission but presents some challenges as well as opportunities. The findings described by Sajid et al. (2021) are a significant advance in efforts to replicate acquired tick resistance and to validate the concept of an anti-tick vaccine. Obviously, there is interest in creating a commercial vaccine based on this platform, given that a United States patent application (US 63/234,508) has been filed. Several points should be considered about this approach and study. Guinea pigs are highly responsive in developing acquired resistance to a tick bite. Similar experiments should be conducted with non-human primates to confirm the validity of the approach prior to any translational studies with human volunteers. Will individuals be accepting of skin inflammation and subsequent itch from the tick bite caused by vaccination to alert them to tick infestation? Cutaneous hypersensitivity, which is the degree of skin reaction, will increase with repeated exposures to ticks, and responses of humans will vary across the population. The same argument can be made about acceptability of this vaccine approach for companion animals. In companion animals, a tick bite may elicit potentially intense grooming. However, the potential for skin injury and secondary infections may be a concern. This vaccine approach might find greatest acceptability in vaccination regimens for cattle. Would FDA and the USDA Center for Veterinary Biologics approve this type of vaccine for human, companion animal, and/or livestock use?

There is increasing interest in developing multiple One Health approaches for design of vaccination strategies to protect humans from zoonotic diseases (Monath, 2013). Three vaccine deployment frameworks proposed by Monath (2013) include (1) vaccination of humans and economically valuable animals regardless of involvement, if any, in the pathogen transmission cycle; (2) vaccination of domestic animals to prevent disease in both those animals and humans; and (3) immunization of wild animals to prevent human and domestic, including companion, animal disease. The third framework also encompasses vaccination of wildlife to disrupt arthropod vector transmission of infectious agents to humans. Oral vaccination is a favored and established method for control of diseases of wildlife transmissible to humans and domestic animals, such as the widely deployed oral rabies vaccines that are effective for delivering prophylactic immunization of meso-carnivores and disrupting transmission to humans as well as levels of infection in enzootic cycles (Cross et al., 2007). A successful oral vaccination program in the field depends upon (1) an effective immunogen to drive the immune response; (2) an oral delivery system that ensures the integrity of the antigen in nature prior to uptake by the target species; and (3) a bait that is readily accepted and specific to the appropriate species (Cross et al., 2007). These technical considerations are being successfully addressed. Despite the limited home range of rodent hosts, current research projects aimed at mice include reservoir-targeted vaccines, oral acaricide baits, reservoir-targeted antibiotics, repurposing canine veterinary acaricides (such as oral isoxazolines) for rodents, anti-tick vaccines, and transgenic mice with suppressed potential for enzootic pathogen transmission. With any rodent-targeted approach, delivery, non-target consumption of oral products, issues with regulatory approvals for vaccine vehicles and licensing, cost, and impact on host-seeking tick populations will be important factors in adoption and implementation. Oral vaccination regimens for wildlife reservoirs of tick-borne pathogens and wildlife species that amplify tick populations are achievable objectives that have the potential to reduce infected tick populations. An example of a target species is the white-footed mouse (Eisen & Eisen, 2018), in which an oral vaccine consisting of B. burgdorferi outer surface protein A (OspA) was successfully used to immunize wild mice resulting in reduced numbers of B. burgdorferi-infected ticks (Richer et al., 2014; Stafford et al., 2020). Vaccination of reservoir mice in high-disease-risk areas with a baited vaccine is projected to reduce mouse-to-tick transmission of B. burgdorferi in a cost-effective manner (Carrera-Pineyro et al., 2020).

The oral OspA vaccine for delivery to white-footed mice meets all the criteria for successful delivery in diverse natural habitats and can be modified to deliver a diverse array of antigens, including anti-tick immunity-inducing epitopes. This oral vaccine, originally formulated for the OspA reservoir-targeted vaccine, has now evolved into a platform technology that can be readily adapted to any number of potential vaccines. Those successfully developed essential elements were described by van Oosterwijk (2021). Bait distribution must be sufficient to be available to the target species by broadcast, bait station, or other delivery formats. Distribution methods must take into account ways to avoid bait consumption by non-target wildlife species. Bait should be attractive to target wildlife species and preferably not have nutrient value; it should also be plentiful to ensure return visits for sufficient uptake for desired antigen exposure. Bait and antigen must be stable over the temperature and humidity ranges encountered in the climate of the deployed region. Finally, the vaccine formulation coating the bait must be sufficient to elicit a protective immune response in the target species.

Wildlife- and livestock-directed oral anti-tick vaccines are being developed, but an important consideration is that additional oral vaccines exist for white-tailed deer (such as tuberculosis and chronic wasting disease vaccines). Development of a deer anti-tick vaccine is an achievable objective. A major advance in tick research that resulted from years of organizational planning efforts, research, and data interpretation was the description of the 2.1 Gbp nuclear genome of the blacklegged tick (I. scapularis) with annotation of scaffolds representing approximately 57% of the genome and 20,486 protein-encoding genes (Hill & Wikel, 2005; Guila-Nuss et al., 2016; Pagel Van Zee et al., 2007). Those findings greatly expanded insights into genes involved in the tick biological processes of host detection, blood feeding, hemoglobin digestion and detoxification, hormonally regulated blood meal processing and water balance, egg production, cuticle synthesis, neurochemical signaling, and off-host survival physiological pathways. Opportunities are now greatly enhanced to identify unique tick genes and physiological processes that can be exploited to control ticks and the pathogens they transmit as a result of the wealth of new data derived from this first genome sequence for a medically important tick (Guila-Nuss et al., 2016).

Genomic analyses must continue for other human-biting tick disease vectors. An indication of the complexity of tick genomes is the diversity among tick species in their genome sizes (Pagel Van Zee et al., 2007). The first study of comparative genome sizes examined two Argasidae and seven Ixodidae species that were found to vary extensively across and within the species studied (Geraci et al., 2007). A major initiative reported by Jia et al. (2020) resulted in sequenced and assembled high-quality genomes of the six dominant ixodid species occurring across China: I. persulcatus, Haemaphysalis longicornis, D. silvarum, Hyalomma asiaticum, R. sanguineus and R. (Boophilus) microplus. This comprehensive study focused on how genetic complexity and genomic variation are linked to the geographic distributions, ecological adaptations, and vector capacities of these important vector species (Jia et al., 2020).

The concept of transgenic mosquitoes has been envisioned and anticipated as a component for integrated control of arboviral disease and malaria for many years, resulting in significant technological advances for manipulating the genomes of these important vector insects. Comparatively with other arthropods, the ability to generate transgenic mosquitoes is well developed, and transgenic applications for mosquito vector control are emerging. Genetic analyses of tick biology and tick-host-pathogen interface interactions have been limited by the functional genomic tools available that currently consist of RNA interference for gene knockdown studies (Karim et al., 2008). RNA interference can be limited by incomplete and transient knockdown; unsuitability for overexpression and transcript rescue experiments that are required to study down-regulated gene function; and difficulty of analyzing gene function in tick embryos and larvae (Agrawal et al., 2003; de la Fuente et al., 2007: Han, 2018; Nuss et al., 2021). In contrast to RNA interference, CRISPR-Cas holds great promise for absolute gene silencing and complete blocking of protein expression in ticks (Nuss et al., 2021).

A major impediment to genetic manipulation of ticks has been the need to understand the sequential patterns of early embryological events and development of an embryo injection technique to facilitate successful protocol development for CRISPR-Cas studies (Nuss et al., 2021). A presentation to the Tick Ecology Subcommittee of TBDWG by Dr. Monika Gulia-Nuss described her success in achieving germline transformation of ticks. A Sharma et al., 2022 preprint provided by Dr. Gulia-Nuss describes that, for the first time with any tick, a successful embryo injection protocol has been developed for blacklegged ticks (I. scapularis) and CRISPR-Cas9 has successfully been used to achieve genome editing to generate a mutation. Dr. Gulia-Nuss stated that this tick embryo injection technology has been shared with at least four other laboratories where gene editing studies are in progress in multiple tick species. These findings are a significant step forward in tick research. Transgenic tick research is essentially in its infancy. The potential benefits of transgenic tick basic research are significant, and sustained research funding support for this research area is encouraged.

Federal agencies, mainly CDC, DoD, and NIH, recently funded or are currently funding at least 20 research studies related to I. scapularis host-targeted control methods, with four studies on deer-targeted tick control (one fencing, two oral acaricide, one anti-tick vaccine), and 16 on rodent-targeted tick control (including two transgenic mice, six oral acaricides, two oral antibiotics, and six oral vaccines). Further evaluation is still needed of (1) proven tick-control measures (as evidenced by laboratory studies and small-scale field studies) at the scale of population-based prospective studies to validate these measures for preventing human tick bites and human disease, and (2) continued study and development of promising novel host-targeted tick and pathogen control measures, including molecular technologies for impacting pathogen prevalence in ticks and animal reservoir hosts.

Research focus tends to be applied on the development of host-targeted acaricides, vaccines, and antibiotics without a clear road to regulatory approval or commercialization. In addition, which Federal agency has regulatory authority with new, unique approaches related to vector hosts can be unclear. However, novel approaches will not become reality without field studies, appropriate regulatory approvals, and private and public partnerships to engage industry and other professionals to further develop novel and effective products based on early research that can be marketed to the public for tick-borne disease prevention.

Priority 2 Potential Actions

Potential Action 2.1. Fund research to validate the scale and degree of effectiveness of existing tick bite prevention and tick control strategies to reduce human tick bites and tick-associated disease.

The evidence for beneficial impact of existing personal protection measures is weak, with some studies indicating that regular use of these measures is associated with a reduction in tick-borne disease while other studies found no similar protective effect. In addition, evidence is lacking for environmental tick suppression methods to reduce either human tick bites or tick-borne disease. Additional research is needed to clarify the circumstances under which existing tick bite prevention and tick control strategies can reduce human tick bites and tick-associated disease.

Table 8: Vote on Potential Action 2.1

Number in Favor	Number Opposed	Number Abstained	Number Absent
11	0	0	2

Potential Action 2.2. Support development of novel concepts to prevent human tick bites or by reducing tick populations and their associated pathogens in the environment (for example, acaricide products such as nootkatone capable of killing undetected human-feeding ticks, anti-tick vaccines for humans or wildlife, or transgenic ticks to suppress population growth).

Given little to no evidence demonstrating that current tick control strategies can result in reduced human tick bites or human tick-borne illness, research funding is needed to use our expanding knowledge of the genes and molecules controlling tick feeding, tick reproduction, and transmission of tick-borne pathogens to precisely target and disrupt tick feeding, reproduction, and transmission of pathogens causing Lyme disease and other tick-associated diseases.

Table 9: Vote on Potential Action 2.2

Number in Favor	Number Opposed	Number Abstained	Number Absent
12	0	0	1

Table 11: Vote on Word Substitutions in Potential Action 2.2

Number in Favor	Number Opposed	Number Abstained	Number Absent
9	0	0	4

Potential Action 2.3. Define tick control strategies suitable for residential properties versus public properties and lands (for example, schools, parks, and high-use recreation areas) or entire communities.

Improved guidance for suitable tick control methods that can be implemented based on the targeted environment and tick species present would be valuable to stakeholders, including homeowners, pest control firms, and public health programs engaging in tick control.

Table 10: Vote on Potential Action 2.3

Number in Favor	Number Opposed	Number Abstained	Number Absent
12	0	0	1

Potential Action 2.4. Support the establishment of local public health tick management programs to implement proven control strategies, and to advise their communities on tick bite prevention and tick control.

This was an action suggested by the previous tick ecology and control subcommittees and remains an important goal. A public health management program would be, as previously noted: (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.

Table 11: Vote on Potential Action 2.4

Number in Favor	Number Opposed	Number Abstained	Number Absent
11	0	0	2

Minority Responses

There were no minority responses.

Priority 3. Define the primary drivers of tick populations, tick pathogen prevalence, and geographic expansion of ticks and tick-associated diseases.

 We are currently experiencing the emergence, resurgence, and geographic spread of tick-borne human diseases across the United States. The earth’s shifting climate as well as human land use and landscape management are critical drivers of these trends. In essence, temperature and relative humidity can strongly influence tick survival and reproduction. Moreover, changes in factors such as agricultural practices, forest cover, and plant species composition impact tick populations and tick-borne pathogen transmission. These impacts are both direct, through changes in local temperature and humidity, and indirect, by changing the community of available vertebrate blood hosts (such as mice, raccoons, and deer), which act as tick-borne pathogen reservoirs.

Ultimately, estimates of the local risk of human tick-borne disease and determination of the best strategies to minimize tick bites and suppress tick-borne disease can only be achieved through a quantitative assessment of the individual and combined effects of each variable on the different species of tick and parasites they may transmit. This will require (1) foundational research on the ecology of tick species of current public health concern in the United States and exotics of future concern and (2) accurate and early species identification of ticks and the parasites they may transmit. The combined results will provide needed predictive risk maps to inform actions as well as facilitate assessment of their outcome.

Background

Ticks are susceptible to their environment in multiple interconnected ways. Tick biology, ecology, geographic ranges, and population densities are influenced by variations in temperature, humidity, soil moisture, vegetation, leaf litter, shade, and availability of host species (Alkishe et al., 2021; Nuttall, 2021; Sonenshine, 2018). The tick life cycle frequently involves intervals of host attachment and blood feeding interspersed with significant off-host periods of months to years (Anderson & Magnarelli, 2008; Sonenshine, 2018). When ticks are off hosts, especially when they are reaching out for the next host on top of vegetation (termed “questing”), they are exposed to drier and warmer air, sometimes causing them to desiccate and/or overheat. This often curtails questing as they descend toward cooler humid environments nearer the soil surface (Schulze & Jordan, 2003). The need to rehydrate results in missed opportunities to latch on to a host and can impact tick distribution, abundance, and, critically, pathogen transmission.

Decreased rainfall and resultant drier environments due to climate change may, therefore, increase tick mortality and decrease local transmission of tick-borne pathogens (Ogden & Lindsay, 2016). However, for most populated areas of the United States, climate change is also associated with increased intensity of rain events with subsequent flooding, the effects of which on tick ecology are still basically unknown. Warmer temperatures can also increase the seasonal duration of tick and human activities, causing increases in tick bites and pathogen transmission (Gilbert et al., 2014).

In response to environmental warming in the northern hemisphere, the geographic ranges of native ticks may expand northward and to higher altitudes, and their current southern ranges may contract (Alkishe et al., 2021; Dantas-Torres, 2015; Sonenshine, 2018). However, climate change may also result in the establishment of Caribbean and Central American tick species in southern portions of the United States, with the potential to significantly affect local tick-borne pathogen epidemiology. Besides frequent reintroductions of cattle ticks across the southern border of the United States, detections of exotic ticks are not infrequent in southern states neighboring Mexico or in bird migratory pathways. Managing cattle fever ticks poses challenges similar to those of managing ticks biting humans such that, without resistant cattle breeds or an efficient vaccine against babesiosis or the ticks, eradication or management relies onintegrated tactics that include acaricide treatments delivered using different systems such as dipping, injectables, and cultural practices such as pasture rotations (Showleret al., 2021). The cost for managing a small state outbreak was nearly $123 million (Anderson et al. 2010). Equally concerning are the detections of exotic ticks on companion animals, such as dogs, or on people arriving at U.S. ports (Burridge, 2011), as well as the potentially common introduction of exotic ticks associated with the exotic pet commerce in amphibians and reptiles (Burridge, 2011). The implications of the exotic pet trade are unknown since these animals are not routinely checked for ticks and statistics are lacking. Of note, four exotic and broadly invasive species of ticks are currently present in the United States: two cattle ticks, R. (Boophilus) microplus and Rhipicephalus (Boophilus) annulatus; the brown dog tick, R. Sanguineus; and the Asian longhorned tick, H. longicornis. 

Summary of Evidence and Findings

Factors influencing geographic range and population size are dynamic and dependent upon the complex interplay among the following variables: micro and macro climate variations, vegetation patterns, land use, land fragmentation, habitat modification (agricultural, residential, recreational), host animal diversity (domestic, wild, and exotic species), human behavior, travel, commerce, economics, government policies, human and animal population growth, population movement, and evolutionary changes in ticks and tick-borne pathogens (Alkishe et al., 2021; Bouchard et al., 2019; Dantas-Torres, 2015; Sonenshine, 2018). Each of these continually evolving factors, to differing degrees, influences tick and pathogen ecology, enzootic cycles of tick-transmitted infectious agents, disease incidence, and epidemiology, and each is important to human disease risk and selection of appropriate control approaches (Ogden et al., 2021; Sonenshine, 2018; Wikel, 2018a; Wikel, 2018b).

Tick establishment in new regions may be accompanied by the introduction of the tick-borne pathogens for which that tick species is a competent vector (Paules et al., 2018; Wikel, 2018a; Wikel, 2018b). Physicians, veterinarians, public health workers, and the general public need to be made aware in a timely manner of these potential threats as they emerge in a new area. Knowing where ticks and tick-borne pathogens are present is foundational to understanding the health threats they pose.

Currently, data and maps describing occurrence and distribution of pathogens in field-collected ticks in the United States are limited, fragmented, and, in many instances, not published (Eisen & Paddock, 2021). In a changing environment, surveillance of tick populations and of the pathogens of medical significance they are capable of transmitting informs medical care providers and public health officials; alerts the public of disease risks and preventive measures that may be utilized; and informs the selection of effective vector control and disease interventions (Beard et al., 2019; Eisen & Paddock, 2021; Eisen & Stafford, 2021; Paules et al., 2018). Geographic degree of resolution, such as county- or census-level data, of ticks and pathogens across the range of a tick species is important for knowing variations of tick infection rate within the range of a tick species, which in turn more accurately informs risk, understanding of disease incidence, and identification of higher-disease-risk areas (Bisanzio et al., 2020; Diuk-Wasser et al., 2012). Such variations have significant implications for tick-borne pathogen incidence, characterization of enzootic cycles, and the selection of tick control measures because tick control suppression methods vary based on tick species present within a region (Stafford et al., 2017).

Significant geographic range expansions are occurring among human-biting tick species of North America. I. scapularis (the blacklegged tick) receives the most attention due to its role, along with I pacificus (the western blacklegged tick), as a primary vector of the causative agents of Lyme disease (Mead, 2015; Steere et al., 2016). I. scapularis is undergoing changes in ecology concomitant with its emergence as a vector of multiple pathogens and expansion of geographic range (Eisen & Eisen, 2018; Fleshman et al., 2021; Foster et al., 2022; Lehane et al., 2021). I. scapularis was elevated to an important human-biting tick when it was found to be a vector of B. microti and subsequently, over five decades, also B. burgdorferi, A. phagocytophilum, Powassan virus, E. muris eauclarensis, B. miyamotoi, and B. mayonii (Eisen & Eisen, 2018; Eisen et al., 2017). B. microti infection is present in approximately 20%of I. scapularis nymphs in endemic foci (Diuk-Wasser et al., 2014; Vannier et al., 2015). Coinfection of I. scapularis with multiple human pathogens is an established phenomenon (Little & Molaei, 2020; Zembsch et al., 2021). A recent prevalence study revealed that B. miyamotoi was detected in I. scapularis and I. pacificus in 19 U.S. states. Although detection rates were low (0.5-3.2%), 59% of infected ticks had from two to four coinfections (Xu et al., 2021).

From 1996 to 2016, the number of U.S. counties fulfilling the criteria for having an established population of I. scapularis increased by 45% (Eisen & Eisen) with further expansion in the upper Midwest (Alkishe et al., 2021) and south into the Tennessee Valley (Hickling et al., 2018). This likely resulted from a combination of range expansion, increased surveillance, and/or change in landscape features over time (Gardner et al., 2020). I. scapularis is established further north and expanding its range at a rate of approximately 46 kilometers per year in Ontario, Canada (Clow et al., 2017). As tick range expands, so does the incidence of disease.

The lone star tick, A. americanum, is expanding northward from its traditionally recognized southeastern United States range into the Mid-Atlantic states, New England, and the provinces of Ontario and Quebec in southern Canada (Gasmi et al., 2018; Molaei et al., 2019; Monzón et al., 2016; Rochlin et al., 2022; Sagurova et al., 2019; Sonenshine, 2018; Springer et al., 2015). Westward expansion of A. americanum includes the midwestern states of Michigan, Nebraska, and South Dakota while climate-change-induced range contraction could occur along the Gulf Coast and Lower Mississippi River region (Sonenshine, 2018; Springer et al., 2015). Significantly, the lone star tick is increasing in abundance while populations of the American dog tick, D. variabilis, decline in regions where both species occur (Jordan & Egizi, 2019; Molaei et al., 2019). Changes in population balance have significant implications for tick control measures because specific management strategies differ depending upon the tick species to be controlled (Eisen & Stafford, 2021).

The lone star tick is of increasing importance given its current and potential impact on human health. This tick is the primary vector for the largely under-recognized and under-reported ehrlichioses (E. chaffeensis and E. ewingii), which are appearing in regions where this tick recently expanded its range (Childs & Paddock, 2003; Eisen et al., 2017; Molaei et al., 2019). White-tailed deer are reservoir hosts for both Ehrlichia species, and, significantly, lone star tick larvae, nymphs, and adults readily acquire blood meals from white-tailed deer (Childs & Paddock, 2003; Lockhart et al., 1997; Yabsley et al., 2002). In addition to the Rocky Mountain wood tick, D. andersoni, and the American dog tick, the lone star tick also appears to be a vector of Francisella tularensis, causative agent of tularemia (Eisen et al., 2017; Zellner & Huntley, 2019).

Heartland virus transmitted by lone star ticksis an emerging human infection that is closely related to severe fever with thrombocytopenia syndrome virus, an emerging tick-borne hemorrhagic fever with a high fatality rate that is endemic in Central and East China, Korea, and Japan. White-tailed deer are implicated as a reservoir due to their widespread antibody seropositivity for Heartland virus (Brault et al., 2018; Clarke et al., 2018). Bourbon virus is another emerging pathogen transmitted by A. americanum (Godsey et al., 2021; Lambert et al., 2015; Savage et al., 2017). Human hypersensitivity to saliva proteins of A. americanum introduced during blood feeding can stimulate development of Alpha-gal (galactose-α-1,3-galactose) Syndrome, or red meat allergy, a unique food allergy of increasing frequency (Commins & Platts-Mills, 2013; Diaz, 2020).

Geographic range of the Gulf Coast tick, A. maculatum, is expanding in multiple directions (Benham et al., 2021). Historical range of this species in the United States was the southeastern states bordering the Gulf of Mexico to the Atlantic coast of South Carolina with 150 miles of inland extension along that range (Paddock & Goddard, 2015; Teel et al., 2010). A. maculatum moved northward into North Carolina, Virginia, eastern Maryland, and Delaware, accompanied by expansion further inland from the coast and into Kentucky, Tennessee, Arkansas, Oklahoma, and Kansas (Eisen & Paddock, 2020; Paddock & Goddard, 2015; Sonenshine, 2018). Recently, populations of this tick were found in Illinois (Phillips et al., 2020), Arizona and New Mexico (Hecht et al., 2020). The northward expansion of the Gulf Coast tickcontinues with detection of an established population in Connecticut (Molaei et al., 2021) and in Staten Island, NY (Bajwa et al., 2021).

The Gulf Coast tick is a vector and reservoir for Rickettsia parkeri, a spotted fever group rickettsia that was recognized as a human pathogen in 2002 (Paddock et al., 2004). R. parkeri has been detected in A. maculatum collected over much of the geographic range of this tick, including the northernmost reported established population in Connecticut (Bajwa et al., 2021; Eisen et al., 2017; Molaei et al., 2021). Although a vertebrate reservoir has not yet been determined, A. maculatum infected with R. parkeri have been collected from white-tailed deer, feral swine, and other wildlife species (Eisen et al., 2017), as well as found questing in the environment (Bajwa et al., 2021; Molaei et al., 2021; Ramirez-Garolalo et al., 2021). White-tailed deer, migratory birds, infested cattle, and the warming trend in the northeastern United States are all thought to be linked to the range expansion of A. maculatum (Teel et al., 2010).

However, the geographic expansion of tick species endemic to the United States is not the only threat for increased exposure to ticks and tick-borne diseases. Both human travel and the expansion of the legal and illegal plant and animal trades are important contributing factors for the potential importation, establishment, and expanded distribution of exotic ticks and their associated pathogens into new regions, possibly resulting in considerable medical and veterinary health concerns (Burridge, 2011; Keirans & Durden, 2001). Tick-borne diseases also pose a threat to the health of non-U.S. populations, as well as U.S. military personnel and civilians living and working abroad. While some of those diseases are not currently present in the United States, the establishment of exotic ticks that may vector existing or exotic tick-borne diseases is a concern. At least 140 tick species have been intercepted at U.S. ports of entry, with 63 of them documented to feed on humans, and 23 associated with human tick-borne diseases (Burridge, 2011; Keirans & Durden, 2001). The list of exotic tick incursions has undoubtedly grown in the years since these reviews.

Case in point, established populations of the exotic Asian longhorned tick detected in New Jersey in 2017, followed by the subsequent detection of this tick species across the eastern United States (detected in 17 states at the time of this writing) (Beard et al., 2018; Molaei et al., 2021; Rainey et al., 2018), illustrate the potential risks to humans and livestock associated with the introduction of an exotic tick species. H. longicornis is a known vector for several human disease agents in its native range and also for the cattlepathogenic Theileria orientalis Ikeda genotype, which is present in 13% of tested H. longicornis and also in cattle in Virginia (Oakes et al., 2019). Recent studies show that H. longicornis in Virginia are capable of transmitting this strain of the haemoparasite between infected and naïve cattle (Dinkel et al., 2021; Oakes et al., 2019; Thompson et al., 2020). While how this tick established itself in the United States remains unknown, this species was intercepted multiple times on imported horses and dogs at various U.S. ports of entry between 1969 and 2019 (Burridge, 2011; James W. Mertins, National Veterinary Services Laboratory, personal communication).

Other recent exotic tick introductions documented just in the state of Connecticut and associated with humans include H. truncatum, A. coelebs, A. oblongoguttatum, and R. capensis (Molaei et al., 2018, 2019, 2020; Stafford et al., 2022). These exotic tick interceptions highlight the ongoing challenges and risks associated with international travel and the animal trade that carry the potential for establishment of exotic vectors and pathogens in the United States. For example, Stafford et al. (2022) reported a new incursion of an exotic tick species with a limited endemic geographical distribution in South Africa on a human traveler returning to the United States and reviewed some similar historical exotic tick interceptions. In addition, several exotic tick-borne pathogens are listed on the CDC, USDA Federal Select Agent Program Select Agents and Toxins List, such as tick-borne encephalitis complex viruses (Far Eastern and Siberian subtypes) and CCHF virus, which pose some concern, and Kyasanur Forest disease virus and Omsk hemorrhagic fever virus, which pose a much lower risk for introduction. Critical to the identification of novel and emerging viruses, bacteria, and protozoa of unknown human pathogenicity is the application of increasingly powerful sequencing and bioinformatic analyses of tick microbiomes and viromes (Tijsse-Klasen et al., 2014; Tokarz & Lipkin, 2021). High-throughput sequencing of viromes of field collected A. americanum, D. variabilis, and I. scapularis resulted in identification of 24 novel viruses (Tokarz et al., 2018). Discovery of emerging infection threats will continue as more tick microbiomes and viromes are characterized and potential human pathogens identified (Bonnet & Pollet, 2021; Bonnet et al., 2017; Tokaz and Lipkin, 2021; Vayssier-Taussat et al., 2015). B. miyamotoi, an emerging relapsing fever spirochete (Branda & Rosenberg, 2013), was discovered in this manner and subsequently established to be a human pathogen. Initially isolated from I. persulcatus, B. miyamotoi is transmitted in North America by the blacklegged tick (I. scapularis) and western blacklegged tick (I. pacificus) (Eisen & Eisen, 2018; Krause et al., 2015).

Challenges

Although the primary drivers for establishment, growth, and expansion of tick populations are known (climate factors, habitat, and hosts for all tick life stages), the details of how they impact different tick species, or tick species that are widely distributed across particular ranges, are less well understood. Due to their roles as vectors of Lyme disease spirochetes, most research focuses on I. scapularis and I. pacificus (reviewed by Eisen & Eisen; Diuk-Wasser et al., 2021; Ogden et al., 2021). Even for these extensively studied species, much remains to be learned.

The blacklegged tick occurs widely across the eastern United States, as far west as the edge of the Great Plains (Eisen et al. 2016a). Within this vast geographical range, the tick encounters a variety of local climates, habitat types, and host communities, presenting different bottlenecks for population growth. As a result, basic aspects of tick biology and ecology varies across the eastern United States. A large number of studies have focused on the Northeast but the results from this area do not always apply to I. scapularis in the Southeast or Midwest, as geographical differences have been observed for seasonal activity patterns of different life stages, questing behavior of larvae and nymphs, and host utilization. These differences influence natural cycles of pathogen transmission as well as human risk of encountering questing ticks. Moreover, northern populations of I. scapularis, in which the nymphs are more prone to quest openly and encounter humans than in southern populations, appear to be expanding southward along the Atlantic coast with direct impacts on the incidence of tick-borne diseases associated with this tick (Arsnoe et al., Tsao, 2015).

The overall geographical range of I. pacificus in the far western United States covers a smaller area than that of I. scapularis (Eisen & Eisen); nevertheless, it includes considerable climatic and ecological diversity and has the potential to contact more people. Consequently, studies from north coastal California, where Lyme disease cases attributed to I. pacificus tend to be concentrated, may not accurately reflect the biology, ecology, and enzootic transmission cycles in Southern California, the Sierra Nevada foothills, or more northern locations in Oregon and Washington (McVicar et al., 2022).

Although I. scapularis and I. pacificus are closely related species, notable differences exist in the questing behavior of the immature stages. The nymphs of I. scapularis readily ascend vegetation to find a questing location, whereas I. pacificus nymphs tend to avoid ascending vegetation and instead are contacted by humans in leaf litter or on logs, tree trunks, or rocks, where they quest for lizard hosts.

These examples underscore the importance of conducting fundamental studies on the biology and ecology of ticks throughout their geographical ranges to better understand local dynamics of tick population establishment and growth, as well as pathogen transmission potential. For example, standard dragging techniques may underestimate the true diversity of ticks (Hacker et al, 2021), and averaging infection rates in ticks across all counties in any one state, particularly large states such as California, could be misleading (Salkeld et al., 2021). The challenge lies in that research studies are now needed for a large number of tick species and their numerous associated pathogens, in some cases over vast geographical ranges (Action 3.1). Until such research is accelerated, data will be lacking to inform (1) local public health messaging regarding when and where people are most at risk for bites by different tick species and life stages and (2) modeling of tick populations and pathogen transmission dynamics.

Tick surveillance at U.S. borders to intercept invasive ticks or for native ticks is fragmented across different Federal agencies, state and local public health entities, the research community, and commercial tick identification and pathogen testing companies. Moreover, fundamental surveillance approaches, such as active versus passive tick surveillance or collection of ticks by drag/flag sampling versus from host animals, have different strengths and weaknesses (Eisen & Eisen, 2021). This presents challenges for both compiling comprehensive surveillance data and making decisions about which types of data are considered of sufficient quality to be included as the basis for surveillance reports and map outputs. Another key challenge lies in developing improved capacity for accurate detection of tick species, including exotic ticks intercepted at U.S. borders or discovered on returning travelers, and the pathogens they carry, including exotic pathogens (Action 3.2).

A final challenge lies in presenting surveillance findings in user-friendly, dynamic formats while still making the data limitations clear to the user. There is distinct value in creating browsable maps of estimated distributions and local abundances of tick species and presence and local prevalence of tick-borne pathogens so stakeholders can assess risk (Action 3.3). However, the technological potential for developing and visualizing browsable fine-scale map outputs must be weighed against the quality of the underlying tick and pathogen data and the finest scale at which the output is considered reasonably accurate. Efforts are needed to work with stakeholders, including the public, to better understand how they would use such browsable fine-scale maps and which spatial scales are most meaningful to them.

Opportunities

New funding initiatives related to climate change and One Health initiatives or stemming from an emerging national public health framework for the prevention and control of vector-borne diseases in humans may help to provide the resources needed for the potential actions outlined under this priority. Interagency collaborations could stimulate progress in building further capacity for national surveillance of ticks and tick-borne pathogens as part of the problem lies in ineffective data sharing and lack of a shared vision at the national scale. Opportunities can also be found in supporting academic institutions—especially entomology departments that are historically more likely to develop operational research—in the training of students in basic science related to tick ecology, physiology, and behavior. Novel data storage, data processing, and map visualization technologies provide opportunities for making information accessible to stakeholders in interactive and easily understandable ways.

Priority 3 Potential Actions

Potential Action 3.1. Fund critical research on the effects of environmental variables on tick biology and ecology (for example, survival, reproduction, and ability of ticks to transmit pathogens that impact public health). 

Reducing the incidence of established and emerging tick-borne diseases requires an understanding of how ecological, environmental, and social factors contribute to the increased risk of tick bites and tick-borne diseases. Temperature and precipitation are considered the two most important climate variables that directly influence tick distribution and abundance and, ultimately, their ability to transmit human pathogens. However, for most tick species of public health concern, the effects of these factors have not been formally quantified. This omission prevents the development of models to predict the effects of current and future climate as well as impact of land management (for example, agricultural practices, fire suppression, invasive plants, and urban greening) on tick populations and the local risk of tick-borne diseases.

Table 12: Vote on Potential Action 3.1

Number in Favor	Number Opposed	Number Abstained	Number Absent
12	0	0	1

Potential Action 3.2. Fund capacity for rapid identification of tick species and discovery of the pathogens they may transmit to allow early detection and rapid response.

Exotic ticks, range expansion of native ticks, and expansion of seasonal tick activity with climatic and landscape changes all increase the risk of exposure to tick-borne pathogens. Accurate tick identification is critical to early detection and effective action but is currently limited by (1) a small (and diminishing) cadre of trained tick taxonomists; (2) the current use of geography (local taxonomic keys) for identification; and (3) the need to identify any tick life stage, some of which may lack diagnostic characters. The adoption of alternatives to morphology such as DNA, RNA, or protein analysis will allow rapid, high throughput processing as well as the concurrent detection of tick-borne pathogens. While technology is broadly available, a curated molecular database of accurately identified tick species of public health concern as well as tick-borne pathogens is needed before implementation is possible.

Table 13: Vote on Potential Action 3.2

Number in Favor	Number Opposed	Number Abstained	Number Absent
12	0	0	1

Potential Action 3.3. Create browsable maps of current and forecasted distributions of tick species and tick-borne pathogens of public health significance so stakeholders can assess risk.

Updated documentation of tick and tick-borne pathogen species ranges, range expansions and contractions, and geographic overlap as noted in Action 3.2 will allow CDC and other partners to create maps available to public health authorities, researchers, pest management professionals, and the public. These will inform immediate actions (such as repellent use, warnings, and interventions) and facilitate measures of the outcomes of those actions.

Table 14: Vote on Potential Action 3.3

Number in Favor	Number Opposed	Number Abstained	Number Absent
12	0	0	1

Minority Responses

No Minority responses.

Priority 4. Expand knowledge and increase adoption of tick bite prevention and tick control methods.

This priority has been elevated from a similar action item in the 2020 Tick Ecology, Biology, and Control Subcommittee Report to provide education and training to all stakeholders with an increased focus on minority, inequity, and occupational issues. Collectively, studies indicate that some members of the public take actions to prevent tick bites. Previous studies also show mixed results for education interventions aimed at increasing knowledge of personal protection measures against tick bites; improved knowledge does not always lead to increased usage of these measures. In addition, no national workplace hazard assessment requirements or standards exist for the prevention of tick bites among employees in outdoor workplaces.

Background

Exposure to human-biting ticks can occur while spending time on residential or public properties, in neighborhood green spaces, and during recreational or occupational activities on public lands (Fischhoff et al., 2019a; Hahn et al., 2018; Jordan & Egizi, 2019; Mead et al., 2018; Stafford et al., 2017). During occasional recreational activities on public lands, protection against tick bites can be achieved using existing personal protection measures. Occupational exposures may be more frequent but can still be addressed with existing personal protection measures, such as permethrin-treated clothing, particularly if established occupational mitigation standards for employers are in place. Tick bite prevention for the public on residential properties and in neighborhood green spaces with daily or near-daily human use is much more challenging because avoiding tick habitats is not feasible in these settings and maintaining daily vigilance with personal protection measures may not be realistic during many months of every year.

Summary of Evidence and Findings

Studies spanning more than three decades collectively indicate that members of the public do take action to prevent tick bites, most frequently by wearing untreated protective clothing or conducting tick checks (done routinely by 30-70% of respondents in most studies of the public). Showering/bathing after being outdoors or using repellents on skin/clothing are moderately common (done routinely by 15-40% of respondents) and wearing permethrin-treated clothing is the least frequently used tick bite prevention method (done routinely by <5-20% of respondents) (selected references from the last decade include Beck et al., 2021; Bron et al., 2020a; Gupta et al., 2018; Hook et al., 2015;  Kopsco & Mather, 2021; Nawrocki & Hinckley, 2021; Niesobecki et al., 2019). Similar information is available for outdoor workers (Donohoe et al., 2018; Jones et al., 2015; Kopsco & Mather, 2021; Magnavita et al., 2022; Noden et al., 2020; Schotthoefer et al., 2020; Valente et al., 2015) and other distinct population groups, including Hispanic persons (Beck et al., 2021; Hu et al., 2019).

With regard to control of host-seeking ticks, recent surveys of the public in Lyme disease-endemic areas indicate that 5-25% of homeowners treat their properties (themselves or via pest control firms) with conventional synthetic acaricides or natural product acaricides (Bron et al., 2020b; Kopsco & Mather, 2021; Niesobecki et al., 2019). No similar recent data are available for hardscaping/xeriscaping or vegetation management. The level of use for methods to control host-seeking ticks may be improved through education provided by trusted local organizations, such as local public health or environment departments or university extension services.

Challenges

In most individual studies focusing on the public and evaluating routine use of multiple personal prevention measures, the level of use is greater for non-chemical approaches, such as wearing untreated protective clothing or conducting tick checks, than for applying repellents. However, details of how personal prevention measures are used (for example, how often a protective action is taken, which parts of the body are protected, and how tick checks are conducted) are scarce in the published literature. Numerous studies have presented information on factors that influence use of personal protection measures (Bron et al., 2020a; Donohoe et al., 2018; Kianersi et al., 2020; Niesobecki et al., 2019; Omodior et al., 2020, 2021; Schotthoefer et al., 2020).

Previous education intervention studies in the United States aiming to improve knowledge of tick bite prevention measures and increase the use of such actions have focused on outdoor workers and the public, including children (Hornbostel et al., 2021; Shadick et al., 2016). Although these education interventions universally led to increased knowledge of personal protection measures against tick bites, the results for how well this translated to increased use of the measures are mixed. This speaks to the need for further studies to determine which types of messages are most effective in leading to behavioral change, including for different types of risk groups and for underserved communities.

Risk of exposure to ticks and tick-borne diseases, prevention, diagnosis, access, and education of minority groups were largely not addressed in either the 2018 or 2020 Reports to Congress, although the TBDWG 2018 Report to Congress noted that under-represented minority populations need to be included in tick-borne disease studies. According to Nelson et al. (2016), Hispanic persons were more likely than non-Hispanic persons to have signs of disseminated Lyme disease infection and onset during fall months. As the authors noted in their conclusion, “Direct and more in-depth assessments regarding prevention practices, knowledge, and Lyme disease epidemiology on local and national scales will further the understanding of Lyme disease risk in this population and guide future targeted prevention and education efforts.”

While specific circumstances that underlie tick encounters are not well documented (Eisen & Stafford, 2021), up to three quarters of tick bites in Connecticut and the Northeast are estimated to be acquired in residential settings where forested tick and host habitat is present (Mead et al., 2018; Stafford et al., 2017). By contrast, around 20% of tick bites appear to be acquired in activities away from the home, likely through neighborhood and recreational activities associated with walking a dog, playing near edges of school grounds, hiking or camping at parks and state forests, or engaging in outdoor occupational activities.

Outdoor occupational workers can be at higher risk of tick exposure. Lyme disease cases are greatly under-reported and data on tick bite exposure or tick-borne disease specifically related to ethnic or minority populations is even less readily available. However, both Black and Hispanic populations have been reported to have increased signs of late or disseminated infection, suggesting a lack of available prevention information or disparities in early diagnosis and provider follow-up (Fix et al., 2000; Nelson et al., 2016). The key to reducing the potential impacts of tick-borne disease under climate change is to evaluate prevention options and identify vulnerable communities. Communities with lower socioeconomic status and limited access to public health services and information on preventive measures are at greater risk of contracting tick-borne diseases or not receiving appropriate diagnosis and treatment. Increased targeted and culturally appropriate educational efforts for these groups are needed.

Employers and their employees with occupational risk of exposure to ticks and tick-borne disease should have access to the most current tick bite and tick-borne disease prevention information available. While prevention information and recommendations are available from the National Institute for Occupational Safety and Health (NIOSH) and many other sources, OSHA currently has no workplace national hazard assessment requirements or standards for employees in outdoor workplaces relating to exposure to ticks and tick-borne pathogens. Implementing a robust employer tick bite prevention program as part of an employer’s safety and health program could provide a significant reduction in exposure and convey confidence that protective measures are being taken. An effective program would include training, policies and procedures, habitat awareness, understanding of high- versus low-tick-density areas, personal protective equipment, and the use of the wide variety of repellants available.

Opportunities

Extensive existing resources offer information on how to prevent tick bites. Nevertheless, more in-depth studies are required to fully understand reasons for choosing not to take action to prevent tick bites (Action 4.1) and how to optimize and most effectively deliver information materials about tick bite prevention to high- risk groups, such as children, animal health professionals, hunters, farmers, park rangers and other outdoor workers, and, particularly, underserved communities (Action 4.3).

Broader urban/suburban/exurban community planning solutions to reduce human contact with tick habitat have received only limited attention to date (Kaup, 2018; MacDonald et al., 2019). This is a topic that merits more attention to achieve sustainable community-based solutions to reduce tick-borne disease, taking into consideration both health equity issues and climate adaptation (Action 4.2). Given sufficient funding, current development or the potential development of new tick management tools that may be more effective and environmentally acceptable (Priority 3) can provide new opportunities for residential and community-level efforts to reduce the risk of tick-borne disease. While workplace requirements or standards for employees in outdoor workplaces related to ticks is needed, OSHA and NIOSH have provided interim guidance on protecting workers from occupational exposure to Zika virus, a mosquito-transmitted disease pathogen. Many of the employer and worker actions this guidance includes, such as proper use of repellents, would also apply to ticks. Similar guidelines should be implemented to reduce the risk of tick bites and tick-associated illnesses. Increased awareness of measures to prevent exposure to and transmission of tick-borne disease pathogens is especially needed now, given the potential introduction of exotic tick species, range expansion of native vector species, and expansion of seasonal activity with warming temperatures.

Priority 4 Potential Actions

Potential Action 4.1. Clarify the reasons behind the public’s limited use of tick bite prevention methods (such as repellents) and tick control methods (such as backyard treatments to kill ticks) and pursue solutions to overcome roadblocks.

Without a clear understanding of why some members of the public choose not to protect themselves and their families against tick bites, generating impactful messages to increase the use of tick bite prevention and tick control measures will not be possible.

Table 15: Vote on Potential Action 4.1

Number in Favor	Number Opposed	Number Abstained	Number Absent
12	0	0	1

Potential Action 4.2. Charge the U.S. Occupational Safety and Health Administration (OSHA) to work with employers to develop standards to mitigate occupational risk for ticks and tick-borne disease and educational requirements for occupational physicians.

Currently, no national workplace hazard assessment requirements or standards related to ticks and tick-borne disease exist for employees in outdoor workplaces. Employers should be required to implement a tick bite prevention program as part of their safety and health programs to provide training and appropriate resources to reduce the risk of tick bites and tick-borne disease.

Table 16: Vote on Potential Action 4.2

Number in Favor	Number Opposed	Number Abstained	Number Absent
12	0	0	1

Potential Action 4.3. Develop information materials for tick bite prevention and tick control targeted to high-risk groups for tick bites (for example, children, animal health professionals, hunters, farmers, and park rangers and other outdoor workers) in multiple languages and styles to reach underserved communities. 

Although a variety of information materials are currently available, room for improvement remains, specifically for high-risk groups and underserved communities.

Table 17: Vote on Potential Action 4.3

Number in Favor	Number Opposed	Number Abstained	Number Absent
12	0	0	1

Potential Action 4.4. Incorporate tick-borne disease prevention strategies in livable environment design considering health equity issues and climate adaptation.

The key to reducing the potential impacts of tick-borne disease in the face of climate change is to evaluate prevention options, including solutions based on community planning, and identify vulnerable communities. Communities with lower socioeconomic status and limited access to public health services and information on preventive measures are at greater risk of contracting a tick-associated disease or not receiving appropriate diagnosis and treatment.

Table 18: Vote on Potential Action 4.4

Number in Favor	Number Opposed	Number Abstained	Number Absent
12	0	0	1

Minority Responses

No minority responses.

Discussion and Big Picture Summary

Ticks and tick-borne pathogens are persistent global public health threats that are increasingly challenging due to expanding geographic ranges; emergence of previously unrecognized tick-transmitted infectious agents; and the complex dynamic interactions among biotic (that is, living) and abiotic (for example, climate) factors that influence the tick-host-pathogen triad (Dantas-Torres, 2015; Sonenshine, 2018; Tsao et al., 2021; Wikel, 2018a). Among arthropod vectors, ticks transmit the greatest diversity of infectious agents to humans and livestock (Jongejan & Uilenberg, 2004). Within the United States, 75%of reported vector-borne human infections are attributed to ticks (Eisen & Eisen, 2018; Rosenberg et al., 2018) and cases of tick-borne bacterial and protozoan diseases more than doubled in the United States during the period from 2004 to 2016 (Rosenberg et al., 2018). Among human tick-borne diseases, Lyme disease is the most commonly reported tick-transmitted infection in North America (Mead, 2015). Thus, it has become a major research focus since its discovery. During the period from 2010 to 2018, the annual estimated frequency of human Lyme borreliosis in the United States was 476,000 cases (Kuguler et al., 2021). The annual medical cost burden of Lyme borreliosis is estimated from $786 million (Mac et al., 2019) to potentially $1.3 billion (Adrion et al., 2015). For each case of Lyme disease, the average annual cost to the individual patient is $12,070. Given that approximately 470,000 Americans are diagnosed with Lyme disease each year, the total annual public health burden of Lyme disease in the United States is $5.7 billion, which does not include the cost burden of other tick-borne diseases. 

The problem of significantly increasing numbers and diversity of tick-borne infections in the United States, along with weak evidence showing the impact of existing personal protection measures and environmental tick control methods on human tick bites and tick-borne disease, has increased calls for a national strategy to address vector-borne disease threats (Beard et al., 2021). A national strategy for tick-associated diseases should:

• Raise awareness of the need for focused and areawide ITM programs
• Increase incentives to academia and industry to develop, test, and register new tick control technologies
• Update strategies to address the increasingly complex tick and disease threats occurring in a changing landscape
• Expand educational initiatives for both professions and the public (Eisen, 2020; Eisen & Stafford, 2021; Little et al., 2020;)

Selection of appropriate tick control or suppression methods will require ongoing monitoring because approaches differ based on the different human-biting tick species in a given area and whether the effort focuses on a limited area, such as an individual residential or public property, or a larger geographical area (Eisen & Stafford, 2021). Public health impacts of all tick-transmitted infections remain largely unquantified (Rochlin and Toledo, 2020). However, research has established that the direct effects of tick infestation and tick-borne infectious diseases have broad economic and societal repercussions (Rochlin and Toledo, 2020).

Limitations

Several notable roadblocks to achieving reduction in human tick bites and tick-associated disease persist. Despite progress made in the last 5 years to conduct national surveillance for human-biting ticks and the disease agents they carry, gaps remain in our knowledge of where and when humans are most at risk for tick bites and pathogen exposure, especially at fine spatial scales. Linked to this problem is the fact that several native tick species are expanding their ranges in the United States, placing new human populations at risk for tick-borne pathogens. Funding continues to be a major limitation and many of the goals and recommendations in previous reports remain unresolved. Few tick control options are currently available, and there is no or limited evidence of their impact on tick bites or human disease, even for those that are effective in killing ticks. This underscores the need for continued evaluation of existing strategies, development of new, more targeted methodologies, and a better understanding of the public’s limited use of current methods to reduce the risk of tick bites.

We are also threatened by exotic invasive ticks and their associated pathogens, with limited ability to detect or eliminate invasive ticks should they escape notice at U.S. borders and become established. A national strategy for tick and tick-borne disease response should include preventative biosecurity measures to detect and prevent introductions as well as strategies for early detection and response. The likelihood of success in eliminating an invasive tick species from the United States is greatest if it has a narrow host range and thus can be targeted on host, whereas we are unlikely to succeed against a generalist tick species with a broad host range, such as the Asian longhorned tick. Exotic tick-borne pathogens, some of which are known to cause serious disease and death, are also of concern, as national and international health authorities have noted. Perhaps most urgently, attention is needed to address pathogens that can be hosted by major native human-biting tick species that are likely to serve as natural vectors. One such virus is TBE, which most likely would be effectively transmitted by the blacklegged tick in the eastern United States and the western blacklegged tick in western states. Another example of a potential invasive tick-borne pathogen of significant biosecurity concern as noted by WHO and DHS is CCHF virus.

Studies to clarify how existing personal protection measures need to be used and how environmental tick control methods should be implemented to result in reduced human tick bites are urgently needed. These efforts should be complemented by the pursuit of novel approaches to tick bite reduction and tick control, together with a more effective and timelier pathway from novel concept to marketed product, a process that currently takes too long and does not effectively engage industry. Another problem is the lack of a local public health workforce engaged in protecting the United States from tick-borne disease, serving as a stable market for tick control products, and acting as a conduit to the tick control industry. A final imperative is to achieve increased use of tick bite prevention methods and tick control methods, which will likely require a stronger evidence base to show their beneficial health impacts, intensified education campaigns, and the support of a local public health workforce tasked with helping communities address the pervasive problem of ticks and tick-borne diseases.

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