Novel Therapeutic Approaches for Lyme Disease

A special issue of Antibiotics (ISSN 2079-6382).

Deadline for manuscript submissions: closed (30 June 2023) | Viewed by 21792

Special Issue Editor


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Guest Editor
Department of Biology and Environment Science, University of New Haven, West Haven, CT 06516, USA
Interests: Lyme disease; spirochetes; infection; biofilm; persisters; antibiotic resistance; connection of cancer to bacterial infections
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Special Issue Information

Dear Colleagues,

Lyme disease is the number one vector-borne illness in the United States caused by Borrelia burgdorferi sensu lato species and transmitted via the bite of Ixodes species. The frontline treatment for Lyme disease is the administration of antibiotics such as doxycycline, minocycline, amoxicillin, cefuroxime, and ceftriaxone. Although treatment of early Lyme disease is generally successful, studies have shown that some patients are not successfully treated and go on to develop persistent Lyme disease symptoms.

One of the possible explanations for this clinical observation is the presence of different morphological forms of B. burgdorferi, such as round bodies, persisters, and biofilms with differences in sensitivity to antibiotics. While recent in vitro studies have suggested novel antimicrobial agents and their combinations to combat these resistant forms, there is still an urgent need to find a therapeutic treatment for Lyme disease whose effectiveness can be proven clinically.

This Special Issue seeks manuscript submissions for novel therapeutic approaches for Lyme disease, such as original research papers, short communications, reviews, case reports, and perspectives.

Prof. Dr. Eva Sapi
Guest Editor

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Keywords

  • lyme disease
  • spirochetes
  • infection
  • biofilm
  • persisters
  • antibiotic resistance

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Published Papers (3 papers)

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Review

16 pages, 341 KiB  
Review
Neuropsychiatric Lyme Disease and Vagus Nerve Stimulation
by Nicholas Biniaz-Harris, Mara Kuvaldina and Brian A. Fallon
Antibiotics 2023, 12(9), 1347; https://doi.org/10.3390/antibiotics12091347 - 22 Aug 2023
Viewed by 5572
Abstract
Lyme disease, the most common tick-borne disease in the United States, is caused by infection with the spirochete Borrelia burgdorferi. While most patients with acute Lyme disease recover completely if treated with antibiotics shortly after the onset of infection, approximately 10–30% experience [...] Read more.
Lyme disease, the most common tick-borne disease in the United States, is caused by infection with the spirochete Borrelia burgdorferi. While most patients with acute Lyme disease recover completely if treated with antibiotics shortly after the onset of infection, approximately 10–30% experience post-treatment symptoms and 5–10% have residual symptoms with functional impairment (post-treatment Lyme disease syndrome or PTLDS). These patients typically experience pain, cognitive problems, and/or fatigue. This narrative review provides a broad overview of Lyme disease, focusing on neuropsychiatric manifestations and persistent symptoms. While the etiology of persistent symptoms remains incompletely understood, potential explanations include persistent infection, altered neural activation, and immune dysregulation. Widely recognized is that new treatment options are needed for people who have symptoms that persist despite prior antibiotic therapy. After a brief discussion of treatment approaches, the article focuses on vagus nerve stimulation (VNS), a neuromodulation approach that is FDA-approved for depression, epilepsy, and headache syndromes and has been reported to be helpful for other diseases characterized by inflammation and neural dysregulation. Transcutaneous VNS stimulates the external branch of the vagus nerve, is minimally invasive, and is well-tolerated in other conditions with few side effects. If well-controlled double-blinded studies demonstrate that transcutaneous auricular VNS helps patients with chronic syndromes such as persistent symptoms after Lyme disease, taVNS will be a welcome addition to the treatment options for these patients. Full article
(This article belongs to the Special Issue Novel Therapeutic Approaches for Lyme Disease)
27 pages, 642 KiB  
Review
Disulfiram: Mechanisms, Applications, and Challenges
by Jenna Lanz, Nicholas Biniaz-Harris, Mara Kuvaldina, Samta Jain, Kim Lewis and Brian A. Fallon
Antibiotics 2023, 12(3), 524; https://doi.org/10.3390/antibiotics12030524 - 6 Mar 2023
Cited by 32 | Viewed by 10783
Abstract
Background: Since disulfiram’s discovery in the 1940s and its FDA approval for alcohol use disorder, other indications have been investigated. This review describes potential clinical applications, associated risks, and challenges. Methods: For this narrative review, a PubMed search was conducted for [...] Read more.
Background: Since disulfiram’s discovery in the 1940s and its FDA approval for alcohol use disorder, other indications have been investigated. This review describes potential clinical applications, associated risks, and challenges. Methods: For this narrative review, a PubMed search was conducted for articles addressing in vivo studies of disulfiram with an emphasis on drug repurposing for the treatment of human diseases. The key search terms were “disulfiram” and “Antabuse”. Animal studies and in vitro studies highlighting important mechanisms and safety issues were also included. Results: In total, 196 sources addressing our research focus spanning 1948–2022 were selected for inclusion. In addition to alcohol use disorder, emerging data support a potential role for disulfiram in the treatment of other addictions (e.g., cocaine), infections (e.g., bacteria such as Staphylococcus aureus and Borrelia burgdorferi, viruses, parasites), inflammatory conditions, neurological diseases, and cancers. The side effects range from minor to life-threatening, with lower doses conveying less risk. Caution in human use is needed due to the considerable inter-subject variability in disulfiram pharmacokinetics. Conclusions: While disulfiram has promise as a “repurposed” agent in human disease, its risk profile is of concern. Animal studies and well-controlled clinical trials are needed to assess its safety and efficacy for non-alcohol-related indications. Full article
(This article belongs to the Special Issue Novel Therapeutic Approaches for Lyme Disease)
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12 pages, 301 KiB  
Review
Disulfiram—Mitigating Unintended Effects
by Martha M. Grout and Kenneth B. Mitchell
Antibiotics 2023, 12(2), 262; https://doi.org/10.3390/antibiotics12020262 - 28 Jan 2023
Cited by 3 | Viewed by 4342
Abstract
Lyme disease caused by infection with a multitude of vector-borne organisms can sometimes be successfully treated in its very early stages. However, if diagnosis is delayed, this infection can become disseminated and, like another spirochetal infection syphilis, can affect multiple organ systems in [...] Read more.
Lyme disease caused by infection with a multitude of vector-borne organisms can sometimes be successfully treated in its very early stages. However, if diagnosis is delayed, this infection can become disseminated and, like another spirochetal infection syphilis, can affect multiple organ systems in the body, causing a wide variety of life-altering symptoms. Conventional antibiotic therapy may not be effective in eradicating the symptoms of the disease we know as Lyme disease. The recent literature has suggested that disulfiram (DSM) may be a potent drug in the armamentarium of physicians who treat chronic Lyme disease. The use of disulfiram in the treatment of Lyme disease started with a researcher who determined that DSM is bactericidal to spirochete. Encouraged by published case reports of apparent recovery from chronic Lyme disease, having prescribed DSM ourselves in the past for alcoholics who had a desire to stop drinking and prescribing it now for patients with chronic Lyme disease, we observed both predictable and potentially avoidable side effects not necessarily related to the ingestion of alcohol. We reviewed the published literature in PubMed and Google Scholar, using the following key words: Lyme Disease; Borrelia burgdorferi treatment; and disulfiram toxicity. This paper outlines the results of that research to help avoid some of the pitfalls inherent in this novel use of an old and established medication in the practice of clinical medicine. Full article
(This article belongs to the Special Issue Novel Therapeutic Approaches for Lyme Disease)
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