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Keywords = untreated Lyme

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10 pages, 1421 KiB  
Case Report
Acrodermatitis Chronica Atrophicans in a Patient with Pulmonary Sarcoidosis: Case Report and Literature Review
by Simona Roxana Georgescu, Alexandra Florentina Dobrescu, Ela Ghiță, Iulia Maria Teodora Leulescu and Mircea Tampa
J. Mind Med. Sci. 2025, 12(1), 27; https://doi.org/10.3390/jmms12010027 - 3 May 2025
Viewed by 628
Abstract
Introduction: Acrodermatitis chronica atrophicans (ACA) is a late-stage cutaneous manifestation of Lyme borreliosis, primarily caused by Borrelia afzelii. It mainly affects the distal limbs and leads to progressive skin atrophy. Unlike other Lyme disease rashes, ACA does not resolve on its own [...] Read more.
Introduction: Acrodermatitis chronica atrophicans (ACA) is a late-stage cutaneous manifestation of Lyme borreliosis, primarily caused by Borrelia afzelii. It mainly affects the distal limbs and leads to progressive skin atrophy. Unlike other Lyme disease rashes, ACA does not resolve on its own and can worsen into severe atrophy and fibrosis if left untreated. Diagnosing ACA can be difficult due to its delayed onset and subtle symptoms, requiring clinical evaluation, multiple blood tests, and skin biopsy. Case presentation: We present the case of a 48-year-old female with a history of pulmonary sarcoidosis who presented to our clinic with multiple erythemato-violaceous patches over her left lower leg and was initially misdiagnosed with venous insufficiency. Histopathological and serological analyses confirmed ACA in its inflammatory phase. The patient responded well to a 30-day course of doxycycline, achieving complete resolution. This report underscores the importance of considering ACA in differential diagnoses and provides a comprehensive review of its pathogenesis, clinical progression, histopathological features, and epidemiology. Conclusions: This case emphasizes the need to consider acrodermatitis chronica atrophicans (ACA) in the differential diagnosis of chronic skin lesions. Clinicians should maintain a high index of suspicion for ACA, particularly in atypical presentations. When the diagnosis is uncertain but clinical suspicion persists, skin biopsy is recommended for histopathologic confirmation. Early diagnosis and appropriate antibiotic therapy are essential to prevent disease progression and irreversible cutaneous atrophy. Accurate diagnosis and effective management require a multidisciplinary approach, involving close collaboration between dermatologists, pathologists, and infectious disease specialists. Full article
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9 pages, 3839 KiB  
Article
Cerebrospinal Fluid Cytology in Lyme Neuroborreliosis Revisited—Role of Neutrophilic Granulocytes: A Retrospective Single-Center Study
by Ferdinand Otto, Peter Wipfler, Wolfgang Hitzl, Martin Preisel, Andrea Harrer and Georg Pilz
J. Clin. Med. 2024, 13(23), 7406; https://doi.org/10.3390/jcm13237406 - 5 Dec 2024
Viewed by 897
Abstract
Background/Objectives: diagnosis of Lyme neuroborreliosis (LNB) relies on medical history, clinical findings, and detection of pathogen-specific antibodies in the blood and cerebrospinal fluid (CSF). The chemoattractant CXCL13 serves as an additional marker for LNB acuity. During the diagnostic workup, cytomorphological examination of [...] Read more.
Background/Objectives: diagnosis of Lyme neuroborreliosis (LNB) relies on medical history, clinical findings, and detection of pathogen-specific antibodies in the blood and cerebrospinal fluid (CSF). The chemoattractant CXCL13 serves as an additional marker for LNB acuity. During the diagnostic workup, cytomorphological examination of immune cells in CSF provides early insights. Lympho-monocytic pleocytosis with plasma cells and activated lymphocytes is usually described as a typical feature of LNB. In contrast we frequently observe a cytological cell picture featuring neutrophilic granulocytes as well as activated mononuclear cells and plasma cells in patients with LNB, which we refer to as a mixed cell picture. We, hence, investigated the presence of granulocytes to determine their role as typical findings associated with LNB. Methods: we conducted a retrospective analysis of CSF cytology in patients diagnosed with definite LNB at the Department of Neurology, Christian Doppler Medical Centre, Salzburg between 2015 and 2021. CSF results of patients with more than 10 erythrocytes/µL were excluded to avoid the presence of granulocytes due to artificial blood contamination. Additionally, CXCL13 levels were recorded, where available. Results: a total of 75 patients (42 female; 56%) met the diagnostic criteria of definite LNB. Cytology revealed the presence of granulocytes in the CSF of 91% of the patients (68/75). CXCL13 elevation was found to be significantly associated with the presence of granulocytes in CSF (p = 0.0025, or 1.009 (95% CI: 1.003–1.016). Conclusions: we confirm a mixed cell picture with granulocytes, activated mononuclear cells and plasma cells being a typical finding in the CSF cytology of LNB. The association between granulocytes and elevated CXCL13 suggests that their presence is a specific feature of the acute, untreated phase of LNB. Full article
(This article belongs to the Section Clinical Neurology)
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8 pages, 230 KiB  
Review
Examining Infant and Child Neurodevelopmental Outcomes After Lyme Disease During Pregnancy
by Meagan E. Williams, David A. Schwartz, Roberta L. DeBiasi and Sarah B. Mulkey
Pathogens 2024, 13(12), 1029; https://doi.org/10.3390/pathogens13121029 - 22 Nov 2024
Cited by 1 | Viewed by 2137
Abstract
Lyme disease is the most common vector-borne disease in the United States. Recent environmental and socioecological changes have led to an increased incidence of Lyme and other tick-borne diseases, which enhances the urgency of identifying and mitigating adverse outcomes of Lyme disease exposure. [...] Read more.
Lyme disease is the most common vector-borne disease in the United States. Recent environmental and socioecological changes have led to an increased incidence of Lyme and other tick-borne diseases, which enhances the urgency of identifying and mitigating adverse outcomes of Lyme disease exposure. Lyme disease during pregnancy, especially when untreated, may lead to adverse pregnancy and neonatal outcomes; however, long-term child outcomes following utero exposure to Lyme disease have not yet been systematically assessed. This concise review describes the current state of knowledge of Lyme disease as a congenital infection and the potential effects of in utero exposure to Lyme disease infection on the neurodevelopment of infants and children. We highlight the importance of distinguishing between acute Lyme disease and a chronic condition termed Post-Treatment Lyme Disease Syndrome, as the impacts of both conditions on the developing fetus and subsequent child development may differ. The importance of placental pathology for patients with acute or chronic symptoms of Lyme disease in pregnancy is explored. Future research aiming to understand and protect neurodevelopment after antenatal Lyme disease must carefully collect potentially confounding variables such as symptomatology and treatment, use clear and standard case definitions, and follow children into school-age and beyond. Full article
(This article belongs to the Special Issue The Future of Vector-Borne Diseases in a Changing World)
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13 pages, 573 KiB  
Review
Lyme Disease: A Review with Emphasis on Latin America
by Vanina Lucca, Sandra Nuñez, María Belen Pucheta, Nilda Radman, Teresita Rigonatto, Graciela Sánchez, Beatriz Del Curto, Dolores Oliva, Betina Mariño, Giuliana López, Serena Bonin, Giusto Trevisan and Nestor Oscar Stanchi
Microorganisms 2024, 12(2), 385; https://doi.org/10.3390/microorganisms12020385 - 13 Feb 2024
Cited by 7 | Viewed by 6723
Abstract
The spirochete Borrelia burgdorferi sensu lato (Lyme Group) is the causative agent of Lyme disease, transmitted to humans through tick bites carrying the bacteria. Common symptoms include fever, headache, fatigue, and the characteristic erythema migrans skin rash. If left untreated, the infection can [...] Read more.
The spirochete Borrelia burgdorferi sensu lato (Lyme Group) is the causative agent of Lyme disease, transmitted to humans through tick bites carrying the bacteria. Common symptoms include fever, headache, fatigue, and the characteristic erythema migrans skin rash. If left untreated, the infection can affect joints, the cardiac system, and the nervous system. Diagnosis relies on symptoms, clinical signs (such as the rash), and potential exposure to infected ticks, with laboratory tests proving valuable when appropriately employed with validated methods. Most cases of Lyme disease respond effectively to a few weeks of antibiotic treatment. In Latin America, knowledge of Lyme disease is limited and often confounded, underscoring the significance of this review in aiding medical professionals in recognizing the disease. This study delves explicitly into Lyme disease in Argentina, neighboring countries, and other Latin American nations. Full article
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7 pages, 554 KiB  
Case Report
Aseptic Meningitis Linked to Borrelia afzelii Seroconversion in Northeastern Greece: An Emerging Infectious Disease Contested in the Region
by Dimitrios Kouroupis, Maria Terzaki, Nikoletta Moscha, Anastasia Sarvani, Elisavet Simoulidou, Sofia Chatzimichailidou, Evangelia Giza, Georgios Sapouridis, Emmanouil Angelakis, Konstantinos Petidis and Athina Pyrpasopoulou
Trop. Med. Infect. Dis. 2024, 9(1), 25; https://doi.org/10.3390/tropicalmed9010025 - 19 Jan 2024
Cited by 1 | Viewed by 4362
Abstract
Borreliosis (Lyme disease) is a zoonosis, mediated to humans and small mammals through specific vectors (ticks), with increasing global incidence. It is associated with a variety of clinical manifestations and can, if not promptly recognized and left untreated, lead to significant disability. In [...] Read more.
Borreliosis (Lyme disease) is a zoonosis, mediated to humans and small mammals through specific vectors (ticks), with increasing global incidence. It is associated with a variety of clinical manifestations and can, if not promptly recognized and left untreated, lead to significant disability. In Europe, the main Borrelia species causing disease in humans are Borrelia burgdorferi s.s., Borrelia afzelii, Borrelia garinii, and Borrelia spielmanii. The Ixodes ricinus tick is their principal vector. Although Lyme disease is considered endemic in the Balkan region and Turkey, and all three main Lyme pathogens have been detected in ticks collected in these countries, autochthonous Lyme disease remains controversial in Greece. We report a case of aseptic meningitis associated with antibody seroconversion against Borrelia afzelii in a young female patient from the prefecture of Thasos without any relevant travel history. The patient presented with fever and severe headache, and the cerebrospinal fluid examination showed lymphocytic pleocytosis. Serum analysis was positive for specific IgG antibodies against Borrelia afzelii. In the absence of typical erythema migrans, serological evidence of infection is required for diagnosis. Although atypical in terms of clinical presentation, the seasonality and geographical location of potential disease transmission in the reported patient should raise awareness among clinicians for a still controversial and potentially underreported emerging infectious disease in Greece. Full article
(This article belongs to the Special Issue From Bedside to Exposure: Infections of Leisure)
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13 pages, 2559 KiB  
Article
Comparative Evaluation of the Efficacy of Two Ectoparasiticides in Preventing the Acquisition of Borrelia burgdorferi by Ixodes scapularis and Ixodes ricinus: A Canine Ex Vivo Model
by Djamel Tahir, Virginie Geolier, Sophie Dupuis, Nouha Lekouch, Elisabeth Ferquel, Valérie Choumet and Marie Varloud
Microorganisms 2024, 12(1), 202; https://doi.org/10.3390/microorganisms12010202 - 18 Jan 2024
Cited by 1 | Viewed by 2108
Abstract
In dogs, tick infestation can cause damage ranging from a simple skin irritation to severe diseases and/or paralysis leading to animal death. For example, Ixodes ricinus and I. scapularis are among the tick species incriminated the most in the transmission of Borrelia burgdorferi [...] Read more.
In dogs, tick infestation can cause damage ranging from a simple skin irritation to severe diseases and/or paralysis leading to animal death. For example, Ixodes ricinus and I. scapularis are among the tick species incriminated the most in the transmission of Borrelia burgdorferi, the agent of human and canine Lyme borreliosis (LB). In this study, we aimed to compare the efficacy of two products designed for dogs—an oral systemic ectoparasiticide and a topical repellent ectoparasiticide—against the acquisition of B. burgdorferi by adult I. scapularis and I. ricinus using an ex vivo model. Thirty-two beagle dogs were included in a parallel-group-designed, randomized, single-center, negative-controlled efficacy study. The dogs were allocated to three groups based on gender and body weight: a fluralaner (F, Bravecto®) treatment group (n = 8), administered a single oral treatment on day 0 at the recommended dose; a dinotefuran–permethrin–pyriproxyfen (DPP, Vectra® 3D) treatment group (n = 8), topically treated on day 56 at the recommended dose; and an untreated control group (n = 16). Blood and hair were collected from each dog on days 58, 63, 70, 77, and 84. Hair was added to the silicone-based membrane separating two glass chambers forming the feeding unit (FU). Chamber 1 was filled with blood spiked with B. burgdorferi sensu stricto, strain B31 (105 cells/mL). Chamber 2, glued below chamber 1, was seeded with 20 adult I. scapularis or I. ricinus. The FUs (n = 240) were incubated at 37 °C with a humidity >90%. Tick survival, attachment, and feces presence were observed from 1 h up to 72 h after tick seeding. The uptake of B. burgdorferi was determined in ticks using nested polymerase chain reaction (nPCR). The acaricidal efficacy of DPP-treated hair was 100% within 1 h of tick release on every study day for both I. ricinus and I. scapularis. The speed of kill associated with DPP was sufficiently fast to prevent tick attachment and engorgement, and, consequently, to prevent the acquisition of B. burgdorferi. In the F-treated group, the acaricidal efficacy observed at 12 h, throughout the study, was <20% and <28% for I. scapularis and I. ricinus, respectively. Furthermore, tick feces were observed in the FUs, and several female ticks (I. scapularis (n = 55) and I. ricinus (n = 94)) tested positive for B. burgdorferi. The results provide proof of concept for the use of an ex vivo model based on an artificial feeding system to compare two ectoparasiticides against the acquisition of B. burgdorferi by I. ricinus and I. scapularis. In addition, our results demonstrate the superiority of DPP compared to F in the speed of acaricidal activity against ticks, as well as in preventing the acquisition of B. burgdorferi. Full article
(This article belongs to the Special Issue Ticks and Tick-Borne Diseases in Animals)
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22 pages, 5367 KiB  
Article
The Development of a Rabies Virus-Vectored Vaccine against Borrelia burgdorferi, Targeting BBI39
by Shantel Rios, Bibek Bhattachan, Kruthi Vavilikolanu, Chrysoula Kitsou, Utpal Pal and Matthias J. Schnell
Vaccines 2024, 12(1), 78; https://doi.org/10.3390/vaccines12010078 - 12 Jan 2024
Cited by 4 | Viewed by 3073
Abstract
Lyme disease (LD) is the most common tick-borne illness in the United States (U.S.), Europe, and Asia. Borrelia burgdorferi, a spirochete bacterium transmitted by the tick vector Ixodes scapularis, causes LD in the U.S. If untreated, Lyme arthritis, heart block, and [...] Read more.
Lyme disease (LD) is the most common tick-borne illness in the United States (U.S.), Europe, and Asia. Borrelia burgdorferi, a spirochete bacterium transmitted by the tick vector Ixodes scapularis, causes LD in the U.S. If untreated, Lyme arthritis, heart block, and meningitis can occur. Given the absence of a human Lyme disease vaccine, we developed a vaccine using the rabies virus (RABV) vaccine vector BNSP333 and an outer surface borrelial protein, BBI39. BBI39 was previously utilized as a recombinant protein vaccine and was protective in challenge experiments; therefore, we decided to utilize this protective antigen in a rabies virus-vectored vaccine against Borrelia burgdorferi. To incorporate BBI39 into the RABV virion, we generated a chimeric BBI39 antigen, BBI39RVG, by fusing BBI39 with the final amino acids of the RABV glycoprotein by molecular cloning and viral recovery with reverse transcription genetics. Here, we have demonstrated that the BBI39RVG antigen was incorporated into the RABV virion via immunofluorescence and Western blot analysis. Mice vaccinated with our BPL inactivated RABV-BBI39RVG (BNSP333-BBI39RVG) vaccine induced high amounts of BBI39-specific antibodies, which were maintained long-term, up to eight months post-vaccination. The BBI39 antibodies neutralized Borrelia in vaccinated mice when challenged with Borrelia burgdorferi by either syringe injection or infected ticks and they reduced the Lyme disease pathology of arthritis in infected mouse joints. Overall, the RABV-based LD vaccine induced more and longer-term antibodies compared to the recombinant protein vaccine. This resulted in lower borrelial RNA in RABV-based vaccinated mice compared to recombinant protein vaccinated mice. The results of this study indicate the successful use of BBI39 as a vaccine antigen and RABV as a vaccine vector for LD. Full article
(This article belongs to the Section Vaccine Design, Development, and Delivery)
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10 pages, 272 KiB  
Review
An In-Depth Review of the Benefits of Antibiotic Use in the Treatment of Borreliosis in Pregnancy
by Michael J. Cook, David Moynan, Gordana Avramovic and John S. Lambert
Appl. Microbiol. 2023, 3(2), 312-321; https://doi.org/10.3390/applmicrobiol3020022 - 23 Mar 2023
Cited by 3 | Viewed by 3482
Abstract
Evidence of congenital transmission of Lyme disease from mother to fetus has been investigated since the 1980s. This study reports the results of a retrospective analysis of 31 studies described in 27 papers published in a 2018 review article. Analysis of these identified [...] Read more.
Evidence of congenital transmission of Lyme disease from mother to fetus has been investigated since the 1980s. This study reports the results of a retrospective analysis of 31 studies described in 27 papers published in a 2018 review article. Analysis of these identified statistically probable transmission in 13 (42%) of the 31 studies and possible transmission in 2 (6%). Most studies included mothers who had been treated with antimicrobials. When no antimicrobials were used, 74% of the pregnancies had adverse outcomes. When oral antimicrobials were used, 29% of pregnancies had adverse outcomes. When intravenous (IV) antimicrobials were used, adverse outcomes dropped to 12% of the pregnancies. This is a six-fold reduction in risk compared with no antimicrobial treatment. Some studies did not define whether oral or IV antimicrobials were used. When these results were included, adverse outcomes were 30 times higher for untreated mothers. Adverse outcomes included deaths, heart anomalies, and preterm births. Full article
52 pages, 5781 KiB  
Review
Lyme Disease in Humans
by Justin D. Radolf, Klemen Strle, Jacob E. Lemieux and Franc Strle
Curr. Issues Mol. Biol. 2021, 42(1), 333-384; https://doi.org/10.21775/cimb.042.333 - 11 Dec 2020
Cited by 97 | Viewed by 8067
Abstract
Lyme disease (Lyme borreliosis) is a tick-borne, zoonosis of adults and children caused by genospecies of the Borrelia burgdorferi sensu lato complex. The ailment, widespread throughout the Northern Hemisphere, continues to increase globally due to multiple environmental factors, coupled with increased incursion of [...] Read more.
Lyme disease (Lyme borreliosis) is a tick-borne, zoonosis of adults and children caused by genospecies of the Borrelia burgdorferi sensu lato complex. The ailment, widespread throughout the Northern Hemisphere, continues to increase globally due to multiple environmental factors, coupled with increased incursion of humans into habitats that harbor the spirochete. B. burgdorferi sensu lato is transmitted by ticks from the Ixodes ricinus complex. In North America, B. burgdorferi causes nearly all infections; in Europe, B. afzelii and B. garinii are most associated with human disease. The spirochete's unusual fragmented genome encodes a plethora of differentially expressed outer surface lipoproteins that play a seminal role in the bacterium's ability to sustain itself within its enzootic cycle and cause disease when transmitted to its incidental human host. Tissue damage and symptomatology (i.e., clinical manifestations) result from the inflammatory response elicited by the bacterium and its constituents. The deposition of spirochetes into human dermal tissue generates a local inflammatory response that manifests as erythema migrans (EM), the hallmark skin lesion. If treated appropriately and early, the prognosis is excellent. However, in untreated patients, the disease may present with a wide range of clinical manifestations, most commonly involving the central nervous system, joints, or heart. A small percentage (~10%) of patients may go on to develop a poorly defined fibromyalgia-like illness, post-treatment Lyme disease (PTLD) unresponsive to prolonged antimicrobial therapy. Below we integrate current knowledge regarding the ecologic, epidemiologic, microbiologic, and immunologic facets of Lyme disease into a conceptual framework that sheds light on the disorder that healthcare providers encounter. Full article
20 pages, 934 KiB  
Concept Paper
Chronic Lyme Disease: An Evidence-Based Definition by the ILADS Working Group
by Samuel Shor, Christine Green, Beatrice Szantyr, Steven Phillips, Kenneth Liegner, Joseph Jr. Burrascano, Robert Bransfield and Elizabeth L. Maloney
Antibiotics 2019, 8(4), 269; https://doi.org/10.3390/antibiotics8040269 - 16 Dec 2019
Cited by 41 | Viewed by 27594
Abstract
Objective: Chronic Lyme disease has been a poorly defined term and often dismissed as a fictitious entity. In this paper, the International Lyme and Associated Diseases Society (ILADS) provides its evidence-based definition of chronic Lyme disease. Definition: ILADS defines chronic Lyme [...] Read more.
Objective: Chronic Lyme disease has been a poorly defined term and often dismissed as a fictitious entity. In this paper, the International Lyme and Associated Diseases Society (ILADS) provides its evidence-based definition of chronic Lyme disease. Definition: ILADS defines chronic Lyme disease (CLD) as a multisystem illness with a wide range of symptoms and/or signs that are either continuously or intermittently present for a minimum of six months. The illness is the result of an active and ongoing infection by any of several pathogenic members of the Borrelia burgdorferi sensu lato complex (Bbsl). The infection has variable latency periods and signs and symptoms may wax, wane and migrate. CLD has two subcategories, CLD, untreated (CLD-U) and CLD, previously treated (CLD-PT). The latter requires that CLD manifestations persist or recur following treatment and are present continuously or in a relapsing/remitting pattern for a duration of six months or more. Methods: Systematic review of over 250 peer reviewed papers in the international literature to characterize the clinical spectrum of CLD-U and CLD-PT. Conclusion: This evidence-based definition of chronic Lyme disease clarifies the term’s meaning and the literature review validates that chronic and ongoing Bbsl infections can result in chronic disease. Use of this CLD definition will promote a better understanding of the infection and facilitate future research of this infection. Full article
(This article belongs to the Special Issue Antibiotics Resistance of Borrelia)
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