Date of Award

January 2025

Document Type

Open Access Thesis

Degree Name

Master of Public Health (MPH)

Department

School of Public Health

First Advisor

Peter Krause

Abstract

Post-Treatment Lyme Disease Syndrome (PTLDS) and persistent babesiosis are late-stage manifestations of two tick-borne diseases. Both are characterized by protracted symptoms despite the use of standard antimicrobial treatment. PTLDS is thought to be associated with immune dysregulation rather than active infection, while persistent and relapsing babesiosis is due to long-lasting infection caused by host immunodeficiency, pathogen antimicrobial resistance, and immune evasion. This thesis examines the immunological host deficits underlying both conditions, one too strong and the other too weak, and explores the mechanisms that contribute to prolonged disease states. Numerous studies suggest that Borrelia burgdorferi, the causative bacteria of Lyme disease, does not persist as an active infection. Rather, it appears that host immune dysregulation, including excessive toll-like receptor activation, persistent elevations of proinflammatory cytokines such as IFN-γ and TNF-α, and interference with the complement system likely play an important role in PTLDS. The adaptive immune response in PTLDS patients is marked by Th17 inflammation, autoantibody production, and antigen presentation by fibroblast-like synoviocytes, which suggests that PTLDS includes an autoimmune-like component. Other studies have shown that antigenic remnants like peptidoglycan and BbTox may persist in tissue, leading to a prolonged inflammatory response in PTLDS patients.

In contrast, persistent relapsing babesiosis is a long-term infection caused by Babesia microti that occurs in highly immunocompromised hosts with impaired immunity, especially in patients with an impaired antibody response. It also is driven by antimicrobial resistance and immune evasion. Through mutations in the CYTb gene and ribosomal components, Babesia microti can develop resistance to azithromycin-atovaquone therapy, leading to recurrent infections and persistence. The innate immune response in persistent babesiosis may be linked to Th1 and Th2 cytokine responses and impaired B cell responses in the adaptive immune system, contributing to persistence. Additionally, Babesia may adhere to vascular endothelium, which prevents circulation through the spleen where parasite-infected red blood cells are destroyed. Additional research is needed to fully understand each post-infectious condition.

Comments

This is an Open Access Thesis.

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