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Life
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Lyme Disease—An Incompletely Solved Puzzle
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Lyme Disease—An Incompletely Solved Puzzle

A special issue of Life (ISSN 2075-1729). This special issue belongs to the section "Microbiology".

Deadline for manuscript submissions: closed (15 December 2023) | Viewed by 15039

Special Issue Editor

Dr. Stefan D. Momčilović

E-Mail Website
Guest Editor
Clinic for Reconstructive and Plastic Surgery, Clinical Center Niš, Niš 18 000, Serbia
Interests: lyme carditis; skin and soft tissue infections; surgery; molecular medicine

Special Issue Information

Dear Colleagues,

Lyme disease is a multisystem illness caused by spirochete Borrelia burgdorferi (named in honor of the microbiologist Dr. Willy Burgdorfer, who isolated it in 1982) and transmitted to a host through the blood meal of an infected Ixodes tick. This bacterial infection represents the most common vector-borne human disease in the northern hemisphere and can present with a variety of focal and non-focal symptoms and signs. Lyme disease is divided into three stages: early localized, early disseminated, and late stage. In patients who have not been treated with antibiotics, different clinical manifestations can occur in each stage of infection. Furthermore, the stages can overlap and, in some cases, late manifestations can be the presenting feature. In the majority of patients, the infection is cured after antibiotic treatment, while in a subset of cases, chronic health problems may persist for months and years. To date, the treatment of these persistent symptoms, defined as post-treatment Lyme disease (PTLD), is not well-understood and still remains the subject of a great deal of scientific dispute and controversy within the medical community. In the USA, the annual costs associated with Lyme disease and PTLD are estimated to be between USD 712 million and USD 1.3 billion. This Special Issue will provide an overview of all potential specific and non-specific manifestations of Lyme disease in children and the adult population. In addition, it will include papers that describe advances and potential challenges in further understanding the pathophysiology, diagnosis, and treatment of Lyme disease at molecular and clinical levels.

Potential topics include, but are not limited to:

  • Historical overview of Lyme disease
  • Molecular and immune aspects of Lyme disease
  • Lyme carditis
  • Neuroborreliosis
  • Borrelial lymphocytoma
  • Lyme arthritis
  • Dermatological manifestations of Lyme borreliosis
  • Psychiatric disorders related to Lyme disease
  • Nonspecific manifestations of Lyme disease that have been reported in other organ systems (e.g., ocular Lyme Borreliosis and vasculitis)

Dr. Stefan D. Momčilović
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Life is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • clinical manifestations
  • pathophysiological mechanisms
  • molecular mechanisms
  • diagnosis
  • treatment
  • post-treatment Lyme disease

Published Papers (5 papers)

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11 pages, 1575 KiB  
Article
Lyme Borreliosis Serology: A Prospective Cohort Study of Forestry Service Workers in the Netherlands over 8 Years (2008 to 2016) of Follow-Up
by Hadewych ter Hofstede, Jeroen Haex, Michael Belias, Marije Oosting, Leo A. B. Joosten and Foekje F. Stelma
Life 2023, 13(5), 1143; https://doi.org/10.3390/life13051143 - 08 May 2023
Viewed by 1091
Abstract
There is little known about the dynamics within responses to Borrelia spp. upon repeated exposure to tick bites and the development of serological markers over time. Most studies have investigated antibody development in risk populations over a short period of time. Therefore, we [...] Read more.
There is little known about the dynamics within responses to Borrelia spp. upon repeated exposure to tick bites and the development of serological markers over time. Most studies have investigated antibody development in risk populations over a short period of time. Therefore, we aimed to study the dynamics of anti-Borrelia antibodies in forestry service workers over 8 years in association with tick bite exposure. Methods: Blood samples from 106 forestry service workers originally included in the 200 Functional Genomics Project (Radboudumc, Nijmegen, the Netherlands) were followed for 8 years and tested annually for anti-Borrelia antibodies (ELISA and Western blot). IgG seroconversion was related to the number of tick bites in the previous year, which was obtained through annual questionnaires. The hazard ratio for Borrelia IgG seroconversion was calculated using Cox regression survival analysis and a logistic regression model, both adjusting for age, gender and smoking. Results: Borrelia IgG seropositivity in the study population did not vary significantly between years and the average prevalence was 13.4%. Of the 27 subjects that underwent seroconversion during the study period, 22 reconverted from positive to negative. Eleven subjects seroconverted a second time. The total seroconversion rate per year (negative to positive) was 4.5%. Active smoking was associated with IgG seroconversion in the >5 tick bites group (p < 0.05). According to the two models used, the risks of IgG seroconversion in the >5 tick bites group were HR = 2.93 (p = 0.10) and OR = 3.36 (p < 0.0005). Conclusions: Borrelia IgG seroconversion in forestry service workers was significantly related to increasing tick bite exposure in a survival and logistic regression model adjusting for age, gender and smoking. Full article
(This article belongs to the Special Issue Lyme Disease—An Incompletely Solved Puzzle)
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17 pages, 956 KiB  
Article
Classical Borrelia Serology Does Not Aid in the Diagnosis of Persistent Symptoms Attributed to Lyme Borreliosis: A Retrospective Cohort Study
by Foekje F. Stelma, Anneleen Berende, Hadewych Ter Hofstede, Hedwig D. Vrijmoeth, Fidel Vos and Bart-Jan Kullberg
Life 2023, 13(5), 1134; https://doi.org/10.3390/life13051134 - 06 May 2023
Viewed by 1663
Abstract
Objective: The diagnosis of Lyme borreliosis is based on two-tier testing using an ELISA and Western blot. About 5–10% of patients report persistent symptoms of unknown etiology after treatment, resulting in substantial difficulties in further diagnostic workup. This paper presents a study aimed [...] Read more.
Objective: The diagnosis of Lyme borreliosis is based on two-tier testing using an ELISA and Western blot. About 5–10% of patients report persistent symptoms of unknown etiology after treatment, resulting in substantial difficulties in further diagnostic workup. This paper presents a study aimed at determining whether serology can differentiate between patients with persistent symptoms attributed to Lyme and other patients with Lyme borreliosis. Methods: A retrospective cohort study included 162 samples from four subgroups: patients with persistent symptoms of Lyme (PSL), early Lyme borreliosis with erythema migrans (EM), patients tested in a general practitioner setting (GP), and healthy controls (HC). ELISA, Western blots, and multiplex assays from different manufacturers were used to determine inter-test variations in PSL and to compare reactivity against Borrelia-specific antigens among the groups. Results: In comparing the IgG and IgM reactivity by Western blot, IgG was more often positive in the PSL group than in the GP group. The individual antigen reactivity was similar between the PSL and EM or GP groups. Inter-test agreement among the manufacturers was variable, and agreement was higher for IgG testing compared to IgM. Conclusions: Serological testing is unable to define the subgroup of patients with persistent symptoms attributed to Lyme borreliosis. Additionally, the current two-tier testing protocol shows a large variance among different manufacturers in these patients. Full article
(This article belongs to the Special Issue Lyme Disease—An Incompletely Solved Puzzle)
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11 pages, 502 KiB  
Article
Neuroborreliosis and Post-Treatment Lyme Disease Syndrome: Focus on Children
by Agnieszka Myszkowska-Torz, Magdalena Frydrychowicz, Mateusz Tomaszewski, Magdalena Figlerowicz, Anna Mania and Katarzyna Mazur-Melewska
Life 2023, 13(4), 900; https://doi.org/10.3390/life13040900 - 28 Mar 2023
Viewed by 1432
Abstract
Neuroborreliosis is a form of Lyme Borreliosis (LB) that affects various structures of the central and peripheral nervous system. Although most cases of LB can be cured with a course of antibiotics, some children can present prolonged symptoms, which may constitute post-treatment Lyme [...] Read more.
Neuroborreliosis is a form of Lyme Borreliosis (LB) that affects various structures of the central and peripheral nervous system. Although most cases of LB can be cured with a course of antibiotics, some children can present prolonged symptoms, which may constitute post-treatment Lyme disease syndrome (PTLDS). The aim of our analysis was the long-term observation of children with NB and the determination of their risk of PTLDS. The clinical observation was supplemented by a laboratory study based on the assessment of the dynamics of anti-VlsE (variable major protein-like sequence, expressed) IgG antibodies in children with NB after antibiotic therapy. The prospective survey based on 40 children presented 1–2 forms of NB. The control group consisted of 36 patients with analogical symptoms for whom LB was excluded. Our long-term observation showed a low risk of developing long-term complications in children who received antibiotic therapy in accordance with the recommendations. The concentration of anti-VlsE IgG demonstrates a statistical significance for differences between the control and the study groups for each measurement period. Higher values of anti-VlsE IgG were observed in the study group, and the concentration decreased from the first measurement period to the next. The article emphasizes the importance of the long-term follow-up of children with neuroborreliosis. Full article
(This article belongs to the Special Issue Lyme Disease—An Incompletely Solved Puzzle)
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8 pages, 705 KiB  
Communication
Myositis Autoantibodies in Patients with Suspected Post-Treatment Lyme Disease Syndrome
by Kristyna Sloupenska, Barbora Koubkova, Pavel Horak, Beata Hutyrova, Mojmir Racansky, Jan Mares, Martina Miklusova, Jan Schovanek, Jana Zapletalova, Milan Raska and Michal Krupka
Life 2023, 13(2), 527; https://doi.org/10.3390/life13020527 - 15 Feb 2023
Cited by 2 | Viewed by 1903
Abstract
Most patients suffering from Lyme disease are effectively treated with antibiotics. In some patients, however, problems persist for a long time despite appropriate therapy. The term post-treatment Lyme disease syndrome (PTLDS) is currently used for this condition in scientific literature. The pathogenesis is [...] Read more.
Most patients suffering from Lyme disease are effectively treated with antibiotics. In some patients, however, problems persist for a long time despite appropriate therapy. The term post-treatment Lyme disease syndrome (PTLDS) is currently used for this condition in scientific literature. The pathogenesis is still not precisely known, but the involvement of immunopathological mechanisms is assumed. In our study, we analyzed the presence of autoantibodies including myositis-specific (MSA) and myositis-associated autoantibodies (MAA) in patients with laboratory proven history of Lyme disease and with clinical symptoms of PTLDS. A total of 59 patients meeting the criteria for PTLDS were enrolled in this study. The control group consisted of 40 patients undergoing differential diagnosis of neurological disorders without clinical and/or laboratory-proven history of Lyme disease. The presence of autoantibodies was determined by immunoblot methods and positive samples were further tested for serum creatine kinase (CK) and myoglobin levels. The presence of myositis autoantibodies was detected in 18 subjects with suspected PTLDS (30.5%), but only in 5% of control subjects exhibiting no evidence of Lyme disease history. The difference was statistically significant (p = 0.002). The subsequent biochemical analysis of muscle-damage markers in positive subjects found a mild elevation in six MSA/MAA-positive PTLDS patients. The study detected raised MSA/MAA autoantibodies formation in the group of PTLDS patients raising the question about their involvement in the pathogenesis of this syndrome. Full article
(This article belongs to the Special Issue Lyme Disease—An Incompletely Solved Puzzle)
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11 pages, 1849 KiB  
Case Report
Cutaneous Manifestations of Lyme Borreliosis in Children—A Case Series and Review
by Agnieszka Myszkowska-Torz, Mateusz Tomaszewski, Michał Kotowski, Cezary Witczak, Magdalena Figlerowicz and Katarzyna Mazur-Melewska
Life 2023, 13(1), 72; https://doi.org/10.3390/life13010072 - 27 Dec 2022
Cited by 1 | Viewed by 8135
Abstract
The occurrence of skin lesions is the earliest symptom of Lyme disease, and the diagnosis of these lesions and appropriate treatment may prevent complications of the disease, which are mainly neurological. The cutaneous presentation in borreliosis is heterogeneous. There are typical lesions that [...] Read more.
The occurrence of skin lesions is the earliest symptom of Lyme disease, and the diagnosis of these lesions and appropriate treatment may prevent complications of the disease, which are mainly neurological. The cutaneous presentation in borreliosis is heterogeneous. There are typical lesions that constitute the basis for the diagnosis of Lyme disease, and atypical ones, which cause significant diagnostic difficulties especially when the patient does not remember the tick bite. This study aims to describe the heterogeneous skin symptoms of Lyme borreliosis, as well as offer a practical approach for the recognition of the disease. Based on pediatric cases from clinical practice, rare cutaneous presentations of Lyme disease at various stages of illness and therapy are presented. Diagnostic recommendations for recognizing individual forms are discussed. Full article
(This article belongs to the Special Issue Lyme Disease—An Incompletely Solved Puzzle)
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