Tick-Borne Disease
Lyme Disease Awareness Month – Spotlight on Tick-Borne Disease Research Program Fiscal Year 2020 Lyme Disease Initiatives
Posted May 31, 2022
Dr. Lise Nigrovic, M.D., Ph.D., Boston Children’s Hospital
Dr. Naeha Subramanian, Ph.D., Institute for Systems Biology
Dr. Vanessa Ante, Ph.D., Texas A&M University System Health Science Center, College Station
Dr. Ronald Wooten, Ph.D., University of Toledo, Health Science Campus
Dr. Monica Embers, Ph.D., Tulane University
May is designated as Lyme Disease Awareness Month to increase public awareness and help reduce the burden of Lyme disease on patients and their families, physicians, and caregivers. It has recently been estimated that approximately 476,000 people contract Lyme disease in the United States each year.1 Patients with Lyme disease may experience varying symptoms, including a rash with a characteristic “bull’s-eye” appearance, fever, swollen lymph nodes, chills, dizziness, shortness of breath, severe headaches and neck stiffness, fatigue, heart palpitations/irregular heartbeat, arthritis, neuroinflammation, and pain in muscles, tendons, bones, joints, and nerves.2 While some cases of Lyme disease may be diagnosed and resolved within several weeks of treatment with antibiotics, if treatment is administered too late or if the treatment protocol fails, patients may develop Post-Treatment Lyme Disease Syndrome (PTLDS) and experience long term symptoms of burdensome pain, fatigue, and/or difficulty thinking.2 Failed diagnosis or misdiagnosis of Lyme disease, resulting in lack of treatment or improper treatment, may also lead to other severe complications such as Lyme arthritis, Lyme carditis, and/or neurological problems.
The Congressionally Directed Medical Research Programs’ Tick-Borne Disease Research Program (TBDRP) funds research addressing several important factors of Lyme disease and tick-borne illnesses including disease pathogenesis, prevention, diagnosis, and treatment. Since its inception in 2016, the TBDRP has received $41 million, with approximately half of the appropriations funding research on Lyme disease both with and without common co-infections. The TBDRP distinguishes itself from other funding agencies by emphasizing the impact of the research on addressing the burden of tick-borne illnesses on military Service Members, Veterans, and their beneficiaries. Brief summaries of five Fiscal Year 2020 TBDRP awards focused on addressing important needs in the field of Lyme disease are described below.
Dr. Lise Nigrovic at Boston Children’s Hospital aims to derive and validate a novel Lyme disease blood-based biomarker in children and adults. Discovery and validation of this novel serum proteomic biosignature will assist in distinguishing between Lyme disease patients and those with analogous symptoms. Early detection of Lyme disease is critical to rapidly target appropriate therapies for patients. This important work will help inform the future development of a sensitive and accurate point-of-care diagnostic test for Lyme disease that will prevent misdiagnosis and greatly improve patient care and quality of life.
Dr. Naeha Subramanian at the Institute for Systems Biology hypothesizes that potential changes in the immune system of patients with Lyme disease may result in infection-induced immune dysregulation, contributing to the development of PTLDS. Dr. Subramanian proposes to characterize the acute immune response to Lyme disease in a longitudinal cohort of patients by utilizing high-density flow cytometry. Characterization will include monitoring immune mediators and immune cell populations in the blood of patients and age-, sex-, and ethnicity-matched healthy controls at different time points after Lyme disease diagnosis. Results from this study will inform disease prognosis and provide clinically relevant information targeted at understanding the immune response to Borrelia infection and yield further insight into why some patients develop PTLDS.
Dr. Vanessa Ante at Texas A&M University Health Science Center aims to elucidate the role of the adenylate cyclase cyaB and the second messenger cyclic adenosine monophosphate (cAMP) in the pathogenesis of Borrelia burgdorferi, the causative agent of Lyme disease. The signaling molecule cAMP is produced by the enzyme adenylate cyclase and involved in numerous distinct pathways including regulation of virulence in many human pathogens. Dr. Ante and her team hypothesize that B. burgdorferi regulates cyaB and intracellular cAMP upon exposure to the mammalian host to promote host adaptation and dissemination. The team plans to utilize a combination of in vitro and in vivo approaches to examine cyaB in virulence factor regulation and cAMP production, and the overall host-borrelia interaction in relation to these factors. The proposed research will provide a greater understanding of B. burgdorferi environmental sensing and pathogenesis, and may identify potential new targets in this signaling pathway for therapeutic intervention.
Dr. Ronald Wooten at University of Toledo and his team are working to develop an attenuated vaccine for B. burgdorferi that would allow significant production of antibodies against novel targets to prevent the development of Lyme disease in vertebrate hosts. The investigators posit that a mutant B. burgdorferi strain with impaired motility chosen for vaccine development should be able to survive within a host long enough to express previously unidentified virulence proteins necessary to stimulate a host immune response for protection and survival, but not long enough to cause clinical disease. If successful, Dr. Wooten’s research could potentially aid in the development of clinically available recombinant protein vaccines to prevent Lyme disease and help reduce infection and the burden of disease on military Service Members, their beneficiaries, and the American public.
Dr. Monica Embers at Tulane University aims to build on previous in vitro and murine studies that suggest that co-infection of Lyme disease and Anaplasma phagocytophilum facilitates the migration of B. burgdorferi through brain endothelial cells and contributes to pathogen burden, antibody responses, and pathology compared to single infections. Dr. Embers and team will test the hypothesis that Borrelia/Anaplasma co-infection results in the suppression of acquired immune responses, thereby increasing pathogen burden and disease in primate hosts. This research will aid in further translating and validating earlier studies that co-infection of Borrelia/Anaplasma can enhance pathogenicity, especially with respect to invasion of the central nervous system. A greater understanding of co-infection as it relates to diagnosis and treatment of tick-borne illnesses is essential to protect individuals from serious and chronic disease. A greater understanding of co-infection as it relates to diagnosis and treatment of tick-borne illnesses is essential to protect individuals from serious and chronic disease.
References:
1 Centers for Disease Control and Prevention: Data and Surveillance
2 Centers for Disease Control and Prevention: Signs and Symptoms of Untreated Lyme Disease
Links:
Last updated Tuesday, May 31, 2022