Posted May 6, 2020

Dr. J. Stephen Dumler, M.D., Uniformed Services University of the Health Sciences
Dr. Noel Elman, Ph.D., GearJump Technologies, LLC
Dr. Rebecca Smith, Ph.D., D.V.M., University of Illinois at Urbana-Champaign

Lyme disease, first identified in symptomatic patients in 1975, was subsequently attributed to a tick-transmitted spirochete bacteria in 1981 that was later named Borrelia burgdorferi (1). Since then, researchers have sought to investigate B. burgdorferi transmission and pathogenesis, Lyme borreliosis treatment strategies, and tick- or rodent-targeted infection prevention and control interventions. Though much has been learned over the past 45 years, significant gaps in fundamental knowledge and patient care still exist.

For example, it is unclear why individuals with Lyme disease can experience such a wide array of symptoms ranging from fever, rash, and headache to arthritis, neurological impairments, heart arrhythmia, and other severe and debilitating conditions (2). For some, infection can be controlled with a single course of antibiotics, while others can experience prolonged infections that require multiple rounds of various treatment regimens (3). Additionally, following treatment some patients develop Post-Treatment Lyme Disease Syndrome (PTLDS) and experience continuous or relapsing debilitating symptoms. Despite decades of research, there are currently limited treatment options for Lyme disease and resulting pathologies and no proven treatment for PTLDS (4).

Moreover, it is anticipated that the number of Lyme disease and other tick-borne disease (TBD) cases will continue to grow due to the geographic expansion of tick and rodent reservoir populations and the identification of new tick-species and tick-borne pathogens (5). In support of this notion, the number of counties with an incidence of more than 10 confirmed Lyme disease cases per 100,000 persons has increased over the past 10 years from 324 in 2008 to 415 in 2018, demonstrating that the geographic distribution of high-incidence areas with Lyme disease is unfortunately expanding (6,7). 

May is Lyme Disease Awareness Month, which aims to bring increased public attention to the ongoing struggles of Lyme disease patients, their physicians, and caregivers. Since its inception in FY16, the Congressionally Directed Medical Research Programs’ TBDRP has executed approximately half of its total research budget to support Lyme disease research focused on prevention and reducing public health burden, improving treatment options and diagnostic assays, and understanding pathogenic mechanisms. 

Brief summaries of FY18 TBDRP awards seeking to answer challenging questions and address critical gaps in the field of Lyme disease are provided below:

Dr. J. Stephen Dumler, Uniformed Services University of the Health Sciences, is building upon his expertise in in vitro microvessel and capillary network models to develop new tools for Lyme disease research. Physiological models that replicate human vasculature are critical for addressing fundamental questions about the entry, dissemination, and pathogenesis of TBDs. With his team of experienced collaborators, Dr. Dumler is developing 3-D human brain and skin microvessels to investigate the role of specific cellular and molecular components derived from the pathogen, host, and tick during B. burgdorferi and A. phagocytophilum infection and transmigration through the mammalian dermis and vasculature. The newly developed 3-D vascular models will be used to identify genes and gene products that are linked to intravasation and extravasation of B. burgdorferi and A. phagocytophilum and that ultimately, could serve as targets for future vaccine or drug development efforts. 

Dr. Noel Elman, GearJump Technologies, LLC, is developing the Adaptive Barrier Controlled Release Device (AB-CRD) that relies on Micro-Electro-Mechanical Systems technology to provide controlled and sustained release of spatial and contact tick repellents. The goal is to build upon his team’s experience with previous wearable mosquito repelling devices to develop a personal protective device against tick bites thus preventing TBDs. Dr. Elman has partnered with experts including Dr. Sebastian D’hers from the Department of Mechanical Engineering at the Instituto Tecnológico de Buenos Aires for device design and simulations, Dr. Stephen Rich from the Department of Microbiology at the University of Massachusetts Amherst for investigation of the effects of AB-CRDs on tick behavior and entomological studies, Dr. Andrew Li from the Invasive Insect Biocontrol & Behavior Laboratory at the Agricultural Research Service, US Department of Agriculture for efficacy experiments, Mr. Meredith Metzler from the Quattrone Nanofabrication Facility at the University of Pennsylvania for device microfabrication, as well as Ms. Melynda Perry from the US Army Combat Capabilities Development Command-Soldier Center for expertise in military equipment for device integration and design input. These collaborative partnerships enable efforts to optimize repellent combinations for integration into the AB-CRD, test tick repellent efficacy, and obtain valuable stakeholder feedback on design. The AB-CRD will offer a number of advantages over existing repellent products, including broad-spectrum efficacy, low toxicity, integration into Soldier and civilian wearable devices, and portability for use in tents, sleeping bags, and vehicles. If successful, Dr. Elman and his colleagues hope AB-CRD will help prevent future Lyme disease cases by improving compliance-related issues associated with current topical repellents.

Dr. Rebecca Smith, University of Illinois at Urbana-Champaign, is bringing her extensive experience in building epidemiologic models to the field of TBDs. Dr. Smith is a co-investigator for the Midwest Center of Excellence for Vector-Borne Disease and is involved with the Illinois Tick Inventory Collaboration Network. In her TBDRP-funded award, she is leveraging tick ecology and behavioral data from these networks, in combination with human behavioral data and TBD case reports from the Illinois Department of Public Health, to build validated, simulation models for Lyme disease and other TBDs. These models will predict Lyme disease (or other TBD) risk in humans and determine the relative efficacy of potential vector or reservoir control programs. It is anticipated that Dr. Smith’s simulation models will be incorporated into web-based vector-borne disease prediction platforms that will be accessible by public health departments and policy makers to aid in the implementation and evaluation of prevention and control strategies.

References

1. https://irp.nih.gov/accomplishments/discovery-of-the-disease-agent-causing-lyme-disease
2. https://www.cdc.gov/lyme/signs_symptoms/index.html
3. https://www.cdc.gov/lyme/treatment/index.html
4. https://www.cdc.gov/lyme/postlds/index.html
5. https://www.cdc.gov/media/dpk/diseases-and-conditions/lyme-disease/index.html
6. https://www.cdc.gov/lyme/datasurveillance/tables-recent.html
7. https://www.cdc.gov/lyme/datasurveillance/recent-surveillance-data.html

 

Links:

Public and Technical Abstracts: Human 3D Microvessels for Analysis of Tick-Borne Pathogen-Blood Vessel Interactions

Public and Technical Abstracts: Warfighter Adaptive Barrier Controlled-Release Devices (CRDs) for Active Protection Against Ticks

Public and Technical Abstracts: Critical Control Points for Tick-Borne Disease Control

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