Andrew Schindler

Background:  Lyme Disease is a vector-borne disease carried by the Ixodes family of ticks that has been deemed by the Center for Disease Control and Prevention as one of the top zoonotic diseases of national concern. An estimated 300,000 individuals develop new cases each year, while over the past 20 years, reported cases have increased by over 200%¹. Chronic Lyme Disease (CLD), or Post-treatment Lyme Disease Syndrome (PTLDS), occurs in between 0.5 and 13.1% of these patients, and its mechanism is still largely unknown². This paper will serve to explore various research areas in treating and diagnosing CLD/PTLDS. After reviewing the literature, insights will be drawn to identify potential research gaps and provide insights on how current research could impact the diagnosis and treatment of CLD.

Research Objectives:  Currently, there are no guidelines or recommendations for treatment of CLD. This literature review will provide insights to the many facets of research surrounding CLD treatment and diagnosis.

Methods:  PubMed was utilized in order to find appropriate articles with the MeSH Database and key words such as “Lyme Disease, Chronic Lyme Disease, Chronic Lyme Disease; diagnosis, Chronic Lyme Disease; treatment.” Further search refinement was made utilizing filters to narrow the search to articles less than five years old, published in english.

Results:  Current research has found a distinct microbiome signature in PTLDS patients, which suggests that the gut microbiome may be altered in patients with CLD³. The finding of a unique microbiome in patients with CLD reinforces the validity of PTLDS and cement the disease as a condition related to a biological basis. Other research found that patients with PTLDS have a distinct metabolic response compared to those without PTLDS⁴. This finding suggests that there may be underlying physiological differences between these groups of patients that could inform the development of targeted treatments for PTLDS and confirm the controversial diagnosis. Additionally, a gene set predictor for PTLDS has been developed using machine learning approaches and could serve as a powerful tool to predict and diagnose CLD⁵. Advances in vaccine development are being made and refined, such as DNA vaccine development and the isolation of specific target sites on the CspZ protein^6,7.

Conclusion:  The emerging areas of research surrounding related biomarkers in PTLDS hold great promise for the development of targeted therapies and diagnostic tools for this complex syndrome. By identifying specific biomarkers associated with PTLDS, it may be possible to develop a more objective and accurate diagnostic test for the syndrome. This would be a significant improvement over the current subjective and controversial diagnostic criteria for PTLDS, which rely on the presence of subjective symptoms such as fatigue, joint pain, and cognitive impairment. Further research must be done to refine the diagnostic capabilities of these modalities and to explore the treatment potential in each case.

Works Cited:

1. Marcinkiewicz AL, Lieknina I, Yang X, et al. The Factor H-Binding Site of CspZ as a Protective Target against Multistrain, Tick-Transmitted Lyme Disease. Infect Immun. 2020;88(5):e00956-19. Published 2020 Apr 20. doi:10.1128/IAI.00956-19
2. Wong KH, Shapiro ED, Soffer GK. A Review of Post-treatment Lyme Disease Syndrome and Chronic Lyme Disease for the Practicing Immunologist. Clin Rev Allergy Immunol. 2022;62(1):264-271. doi:10.1007/s12016-021-08906-w
3. Morrissette M, Pitt N, González A, et al. A Distinct Microbiome Signature in Posttreatment Lyme Disease Patients. mBio. 2020;11(5):e02310-20. Published 2020 Sep 29. doi:10.1128/mBio.02310-20
4. Fitzgerald BL, Graham B, Delorey MJ, et al. Metabolic Response in Patients With Post-treatment Lyme Disease Symptoms/Syndrome. Clin Infect Dis. 2021;73(7):e2342-e2349. doi:10.1093/cid/ciaa1455
5. Clarke DJB, Rebman AW, Fan J, Soloski MJ, Aucott JN, Ma’ayan A. Gene set predictor for post-treatment Lyme disease. Cell Rep Med. 2022;3(11):100816. doi:10.1016/j.xcrm.2022.100816
6. Klouwens MJ, Trentelman JJA, Wagemakers A, Ersoz JI, Bins AD, Hovius JW. Tick-Tattoo: DNA Vaccination Against B. burgdorferi or Ixodes scapularis Tick Proteins. Front Immunol. 2021;12:615011. Published 2021 Feb 25. doi:10.3389/fimmu.2021.615011
7. Marcinkiewicz AL, Lieknina I, Yang X, et al. The Factor H-Binding Site of CspZ as a Protective Target against Multistrain, Tick-Transmitted Lyme Disease. Infect Immun. 2020;88(5):e00956-19. Published 2020 Apr 20. doi:10.1128/IAI.00956-19