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Microorganisms
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Borreliosis and Other Tick-Borne Diseases in the Northern and Southern...
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Borreliosis and Other Tick-Borne Diseases in the Northern and Southern Hemispheres

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Medical Microbiology".

Deadline for manuscript submissions: 15 April 2025 | Viewed by 13487

Special Issue Editor

Prof. Dr. Giusto Trevisan

E-Mail Website
Guest Editor
Department of Medical Sciences, University of Trieste, 34151 Trieste, Italy
Interests: Lyme borreliosis; tick-borne infections; Adamantiades–Behçet disease; dermatomyositis; melanoma
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Borreliosis is divided into three groups: the Borrelia Lyme group (LG), echidna–reptile group (RepG), and relapsing fever group (RFG). According to current knowledge, only the Borrelia LG and RFG lead to infections in humans. There are several aspects that need to be clarified.

The current indirect diagnosis provides information on whether there has been an infection with the Borrelia LG, but it is less reliable in determining whether the infection is still microbiologically active or not. Therefore, innovative tests will be analyzed, which could provide us with more information concerning the presence or absence of active Borrelia, in addition to what the mechanisms are that can allow Borrelia to resist antibiotic treatment. A cultural examination in BSK or Kelly Pettenkhofer is the gold standard; however, this type of examination has a very high specificity but very low sensitivity, and it is therefore not frequently used in the clinic.

The Borrelia LG is widespread in the Northern Hemisphere, while little is known about the distribution of this disease in the Southern Hemisphere, where the Borrelia RFG is more frequent. New studies on Borrelia in Argentina, which will be published in this Special Issue, are ongoing, and a general survey will be carried out on the current knowledge of borreliosis in the Southern Hemisphere.

Prof. Dr. Giusto Trevisan
Guest Editor

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Keywords

  • lyme disease
  • borrelia
  • diagnosis
  • tick-borne infections
  • relapsing fever

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Published Papers (7 papers)

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12 pages, 1174 KiB  
Article
Twenty Years of Lyme Borreliosis in the Netherlands: Temporal Trends in Seroprevalence and Risk Factors
by B. J. A. Hoeve-Bakker, Oda E. van den Berg, H. S. Doppenberg, Fiona R. M. van der Klis, Cees C. van den Wijngaard, Jan A. J. W. Kluytmans, Steven F. T. Thijsen and Karen Kerkhof
Microorganisms 2024, 12(11), 2185; https://doi.org/10.3390/microorganisms12112185 - 30 Oct 2024
Viewed by 864
Abstract
Lyme borreliosis (LB) is not notifiable in many European countries, and the patchwork of surveillance strategies in Europe perpetuates knowledge gaps. In the Netherlands, LB incidence has been estimated from recurring general practitioner surveys since the 1990s. To complement the incidence data, this [...] Read more.
Lyme borreliosis (LB) is not notifiable in many European countries, and the patchwork of surveillance strategies in Europe perpetuates knowledge gaps. In the Netherlands, LB incidence has been estimated from recurring general practitioner surveys since the 1990s. To complement the incidence data, this study aimed to estimate the prevalence of antibodies against Borrelia burgdorferi sensu lato in the general population of the Netherlands in 1995/1996, identify risk factors for seropositivity, and compare these findings to data from 2016/2017 to identify temporal trends. Sera from participants (n = 8041, aged 0–80 years) in a cross-sectional nationwide surveillance study were assessed for the presence of antibodies against B. burgdorferi s.l., using a screening ELISA and immunoblot confirmation. Risk factors associated with seropositivity were evaluated using multivariable analysis. A significant difference in weighted seroprevalence was observed between 1995/1996 (2.8%) and 2016/2017 (4.3%). In both cohorts, the seroprevalence was significantly higher among men than among women, and increased with age and tick bite frequency. The upward trend in age-specific seropositivity in individuals over 50 was steeper in 2016/2017 than in 1995/1996, possibly due to improved fitness among contemporary elderly, allowing increased outdoor activities. This study highlights significant trends in the seroprevalence of B. burgdorferi s.l. antibodies in the general population of the Netherlands over 20 years. The doubling of seroprevalence underscores the increasing burden of LB, and the importance of continued surveillance. Targeted interventions, particularly for elderly populations, may help raise awareness to the risks of tick bites and reduce the growing disease burden and societal costs associated with LB. Full article
(This article belongs to the Special Issue Borreliosis and Other Tick-Borne Diseases in the Northern and Southern Hemispheres)
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8 pages, 933 KiB  
Article
Effects of Inosine-5′-monophosphate Dehydrogenase (IMPDH/GuaB) Inhibitors on Borrelia burgdorferi Growth in Standard and Modified Culture Conditions
by Eric L. Siegel, Connor Rich, Sanchana Saravanan, Patrick Pearson, Guang Xu and Stephen M. Rich
Microorganisms 2024, 12(10), 2064; https://doi.org/10.3390/microorganisms12102064 - 15 Oct 2024
Viewed by 1113
Abstract
Borrelia burgdorferi’s inosine-5′-monophosphate dehydrogenase (IMPDH, GuaB encoded by the guaB gene) is a potential therapeutic target. GuaB is necessary for B. burgdorferi replication in mammalian hosts but not in standard laboratory culture conditions. Therefore, we cannot test novel GuaB inhibitors against B. [...] Read more.
Borrelia burgdorferi’s inosine-5′-monophosphate dehydrogenase (IMPDH, GuaB encoded by the guaB gene) is a potential therapeutic target. GuaB is necessary for B. burgdorferi replication in mammalian hosts but not in standard laboratory culture conditions. Therefore, we cannot test novel GuaB inhibitors against B. burgdorferi without utilizing mammalian infection models. This study aimed to evaluate modifications to a standard growth medium that may mimic mammalian conditions and induce the requirement of GuaB usage for replication. The effects of two GuaB inhibitors (mycophenolic acid, 6-chloropurine riboside at 125 μM and 250 μM) were assessed against B. burgdorferi (guaB+) grown in standard Barbour–Stoenner–Kelly-II (BSK-II) medium (6% rabbit serum) and BSK-II modified to 60% concentration rabbit serum (BSK-II/60% serum). BSK-II directly supplemented with adenine, hypoxanthine, and nicotinamide (75 μM each, BSK-II/AHN) was also considered as a comparison group. In standard BSK-II, neither mycophenolic acid nor 6-chloropurine riboside affected B. burgdorferi growth. Based on an ANOVA, a dose-dependent increase in drug effects was observed in the modified growth conditions (F = 4.471, p = 0.001). Considering higher drug concentrations at exponential growth, mycophenolic acid at 250 μM reduced spirochete replication by 48% in BSK-II/60% serum and by 50% in BSK-II/AHN (p < 0.001 each). 6-chloropurine riboside was more effective in both mediums than mycophenolic acid, reducing replication by 64% in BSK-II/60% serum and 65% in BSK-II/AHN (p < 0.001 each). These results demonstrate that modifying BSK-II medium with physiologically relevant levels of mammalian serum supports replication and induces the effects of GuaB inhibitors. This represents the first use of GuaB inhibitors against Borrelia burgdorferi, building on tests against purified B. burgdorferi GuaB. The strong effects of 6-chloropurine riboside indicate that B. burgdorferi can salvage and phosphorylate these purine derivative analogs. Therefore, this type of molecule may be considered for future drug development. Optimization of this culture system will allow for better assessment of novel Borrelia-specific GuaB inhibitor molecules for Lyme disease interventions. The use of GuaB inhibitors as broadcast sprays or feed baits should also be evaluated to reduce spirochete load in competent reservoir hosts. Full article
(This article belongs to the Special Issue Borreliosis and Other Tick-Borne Diseases in the Northern and Southern Hemispheres)
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14 pages, 793 KiB  
Article
Ticks and Tick-Borne Pathogens in Popular Recreational Areas in Tallinn, Estonia: The Underestimated Risk of Tick-Borne Diseases
by Maria Vikentjeva, Julia Geller and Olga Bragina
Microorganisms 2024, 12(9), 1918; https://doi.org/10.3390/microorganisms12091918 - 20 Sep 2024
Viewed by 1104
Abstract
This study reveals a significant presence of ticks and tick-borne pathogens in urban recreational areas of Tallinn, Estonia. During the period of May–June 2018, 815 Ixodes ticks were collected from an area of 11,200 m2 using the flagging method. Tick density reached [...] Read more.
This study reveals a significant presence of ticks and tick-borne pathogens in urban recreational areas of Tallinn, Estonia. During the period of May–June 2018, 815 Ixodes ticks were collected from an area of 11,200 m2 using the flagging method. Tick density reached up to 18.8 ticks per 100 m2, indicating a high concentration of ticks in these urban green spaces. Pathogen analysis demonstrated that 34% of the collected ticks were infected with at least one pathogen. Specifically, Borrelia burgdorferi s.l., the causative agent of Lyme borreliosis, was detected in 17.4% of the ticks; Rickettsia spp. was detected in 13.5%; Neoehrlichia mikurensis was detected in 5.5%; Borrelia miyamotoi was detected in 2.6%; and Anaplasma phagocytophilum and tick-borne encephalitis virus were detected in 0.5% each. These findings indicate that the prevalence and abundance of ticks and tick-borne pathogens in these urban environments are comparable to or even exceed those observed in natural endemic areas. Given the increasing incidence of Lyme borreliosis in Central and Northern Europe, the risk of tick bites and subsequent infection in urban recreational sites should not be underestimated. Public health measures, including enhanced awareness and precautionary information, are essential to mitigate the risk of tick-borne diseases in these urban settings. Full article
(This article belongs to the Special Issue Borreliosis and Other Tick-Borne Diseases in the Northern and Southern Hemispheres)
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10 pages, 364 KiB  
Article
Pediatric Lyme Disease in Northern Italy: An 18-Year Single-Center Case Series
by Federica Forlanini, Raffaella Di Tonno, Roberta Caiazzo, Daniela David, Maria Sole Valentino, Sara Giordana Rimoldi, Gian Vincenzo Zuccotti, Giusto Trevisan, Francesca Wanda Basile and Vania Giacomet
Microorganisms 2024, 12(3), 455; https://doi.org/10.3390/microorganisms12030455 - 23 Feb 2024
Cited by 1 | Viewed by 1635
Abstract
Tracing the profile of pediatric Lyme borreliosis (LB) in Europe is difficult due to the interregional variation in its incidence and lack in notifications. Moreover, the identification of LB can be challenging. This study is an 18-year case series of 130 children and [...] Read more.
Tracing the profile of pediatric Lyme borreliosis (LB) in Europe is difficult due to the interregional variation in its incidence and lack in notifications. Moreover, the identification of LB can be challenging. This study is an 18-year case series of 130 children and adolescents aged under 18 years referred to the Pediatric Infectious Diseases Unit at L. Sacco Hospital, Milan, with suspicion of LB, between January 2005 and July 2023. The routine serological workup consisted of a two-step process: an initial screening test followed by Western blot (WB). Forty-four (34%) patients were diagnosed with LB. The median age was six years, and 45% were females. Of the children with erythema migrans (EM), 33 (57%) were confirmed as having true EM, and, of these, 4 (12%) were atypical. Ten (23%) patients had early disseminated/late diseases, including facial nerve palsy (n = 3), early neuroborreliosis (n = 1), arthritis (n = 3), relapsing fever (n = 2), and borrelial lymphocytoma (n = 1). No asymptomatic infections were documented. Over seventy percent of confirmed LB cases (n = 31/44) recalled a history of tick bites; in this latter group, 19 (61%) were from the area of the Po River valley in Lombardy. Almost half of the children evaluated for LB complained of non-specific symptoms (fatigue, musculoskeletal pain, skin lesions/rash, and persistent headache), but these symptoms were observed in only two patients with confirmed LB. Most LB cases in our study were associated with EM; two-tier testing specificity was high, but we found frequent non-adherence to international recommendations with regard to the timing of serology, application of the two-step algorithm, and antibiotic over-prescription. Most children were initially assessed for a tick bite or a skin lesion suggestive of EM by a family pediatrician, highlighting the importance of improving awareness and knowledge around LB management at the primary healthcare level. Finally, the strengthening of LB surveillance at the national and European levels is necessary. Full article
(This article belongs to the Special Issue Borreliosis and Other Tick-Borne Diseases in the Northern and Southern Hemispheres)
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10 pages, 372 KiB  
Article
Microbiologic Findings in a Cohort of Patients with Erythema Migrans
by Eva Ružić-Sabljić, Vera Maraspin, Petra Bogovič, Tereza Rojko, Katarina Ogrinc, Martina Jaklič and Franc Strle
Microorganisms 2024, 12(1), 185; https://doi.org/10.3390/microorganisms12010185 - 17 Jan 2024
Cited by 1 | Viewed by 1131
Abstract
Erythema migrans (EM) is the initial and the most frequent clinical manifestation of Lyme borreliosis (LB). Herein, we report on the capacity of culture and serology for the demonstration of Borrelia infection in a cohort of 292 patients diagnosed with typical EM at [...] Read more.
Erythema migrans (EM) is the initial and the most frequent clinical manifestation of Lyme borreliosis (LB). Herein, we report on the capacity of culture and serology for the demonstration of Borrelia infection in a cohort of 292 patients diagnosed with typical EM at a single medical center. The median duration of EM at diagnosis was 12 days, and the largest diameter was 16 cm; 252 (86.3%) patients presented with solitary EM, whereas 40 (13.7%) had multiple EM. A total of 95/292 (32.5%) patients had positive IgM, and 169 (57.9%) had positive IgG serum antibodies; the Borrelia isolation rate was 182/292 (62.3%). The most frequent species by far was B. afzelii (142/148, 95.9%) while B. garinii (2.7%) and B. burgdorferi s.s. (1.4%) were rare. IgM seropositivity was associated with a younger age, multiple EM and the absence of underlying chronic illness; IgG seropositivity was associated with the duration of EM at diagnosis, the diameter of the EM, having had a previous episode of LB and the absence of symptoms at the site of the EM. Furthermore, the Borrelia isolation rate was statistically significantly lower in patients with positive Borrelia IgM antibodies. Although microbiologic analyses are not needed for the diagnosis of typical EM, they enable insights into the etiology and dynamics of the immune response in the course of early LB. Full article
(This article belongs to the Special Issue Borreliosis and Other Tick-Borne Diseases in the Northern and Southern Hemispheres)
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12 pages, 1863 KiB  
Article
Estimated Incidence of Symptomatic Lyme Borreliosis Cases in Lublin, Poland in 2021
by Emily Colby, Julia Olsen, Frederick J. Angulo, Patrick Kelly, Kate Halsby, Andreas Pilz, Urszula Sot, Tomasz Chmielewski, Katarzyna Pancer, Jennifer C. Moïsi, Luis Jodar and James H. Stark
Microorganisms 2023, 11(10), 2481; https://doi.org/10.3390/microorganisms11102481 - 3 Oct 2023
Cited by 5 | Viewed by 1615
Abstract
Lyme borreliosis (LB), the most common tick-borne disease in Europe, is endemic to Poland. Despite public health surveillance with mandatory reporting of LB cases by physicians and laboratories, many symptomatic LB cases are not included in surveillance in Poland. We estimated the extent [...] Read more.
Lyme borreliosis (LB), the most common tick-borne disease in Europe, is endemic to Poland. Despite public health surveillance with mandatory reporting of LB cases by physicians and laboratories, many symptomatic LB cases are not included in surveillance in Poland. We estimated the extent of the under-ascertainment of symptomatic LB cases via surveillance in the Polish province of Lublin to better understand Poland’s LB burden. The number of incident symptomatic LB cases in Lublin in 2010 was estimated from two seroprevalence studies conducted among adults in Lublin, as well as estimates of the proportion of asymptomatic LB cases and the duration of LB antibody persistence. The estimated number of incident symptomatic LB cases was compared to the number of surveillance-reported cases in Lublin to derive an under-ascertainment multiplier. This multiplier was applied to the number of surveillance-reported cases in 2021 to estimate the number and population-based incidence of symptomatic LB cases in Lublin in 2021. We estimate that there are 5.9 symptomatic LB cases for every surveillance-reported LB case in Lublin. Adjusting for under-ascertainment, the estimated number of symptomatic LB cases in Lublin in 2021 was 6204 (population-based incidence: 467.6/100,000). After adjustment for under-ascertainment, the incidence of symptomatic LB in Lublin, Poland, is high. Full article
(This article belongs to the Special Issue Borreliosis and Other Tick-Borne Diseases in the Northern and Southern Hemispheres)
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Review

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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 4 | Viewed by 4719
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
(This article belongs to the Special Issue Borreliosis and Other Tick-Borne Diseases in the Northern and Southern Hemispheres)
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