Clinical Manifestations Of Lyme Borreliosis Research Articles

Demographic patterns in Lyme borreliosis seasonality over 25 years.

Lyme borreliosis, the most common vector-borne disease in Europe and North America, is attracting growing concern due to its expanding geographic range. The growth in incidence and geographic spread is largely attributed to climate and land-use changes that support the tick vector and thereby increase disease risk. Despite a wide range of symptoms displayed by Lyme borreliosis patients, the demographic patterns in clinical manifestations and seasonal case timing have not been thoroughly investigated and may result from differences in exposure, immunity and pathogenesis. We analysed 25 years of surveillance data from Norway, supplemented by population demography data, using a Bayesian modelling framework. The analyses aimed to detect differences in case seasonality and clinical manifestations of Lyme borreliosis across age and sex differentiated patient groups. The results showed a bimodal pattern of incidence over age, where children (0-9 years) had the highest incidence, young adults (20-29 years) had low incidence and older adults had a second incidence peak in the ages 70-79 years. Youth (0-19 years) presented with a higher proportion of neuroborreliosis cases and a lower proportion of arthritic manifestations compared to adults (20+ years). Adult males had a higher overall incidence than adult females and a higher proportion of arthritis cases. The seasonal timing of Lyme borreliosis consistently occurred around 4.4 weeks earlier in youth compared to adults, regardless of clinical manifestation. All demographic groups exhibited a shift towards an earlier seasonal timing over the 25-year study period, which appeared unrelated to changes in population demographics. However, the disproportionate incidence of Lyme borreliosis in seniors requires increased public awareness and knowledge about this high-risk group as the population continues to age concurrently with disease emergence. Our findings highlight the importance of considering patient demographics when analysing the emergence and seasonal patterns of vector-borne diseases using long-term surveillance data.

The AxBioTick Study: Borrelia Species and Tick-Borne Encephalitis Virus in Ticks, and Clinical Responses in Tick-Bitten Individuals on the Aland Islands, Finland.

The AxBioTick study was initiated to investigate the prevalence of ticks and tick-borne pathogens and their impact on antibody and clinical responses in tick-bitten individuals on the Aland Islands. This geographical area is hyperendemic for both Lyme borreliosis (LB) and Tick-borne encephalitis (TBE). Blood samples and ticks were collected from 100 tick-bitten volunteers. A total of 425 ticks was collected, all determined to Ixodes ricinus using molecular tools. Of them 20% contained Borrelia species, of which B. garinii and B. afzelii were most common. None contained the TBE virus (TBEV). Blood samples were drawn in conjunction with the tick bite, and eight weeks later. Sera were analyzed for Borrelia- and TBEV-specific antibodies using an ELISA and a semiquantitative antibody assay. In total 14% seroconverted in Borrelia C6IgG1, 3% in TBEV IgG, and 2% in TBEV IgM. Five participants developed clinical manifestations of LB. The high seroprevalence of both Borrelia (57%) and TBEV (52%) antibodies are likely attributed to the endemic status of the corresponding infections as well as the TBE vaccination program. Despite the similar prevalence of Borrelia spp. detected in ticks in other parts of Europe, the infection rate in this population is high. The AxBioTick study is continuing to investigate more participants and ticks for co-infections, and to characterize the dermal immune response following a tick bite.

СРАВНЕНИЕ КЛИНИЧЕСКОЙ КАРТИНЫ ИКСОДОВОГО КЛЕЩЕВОГО БОРРЕЛИОЗА У ДЕТЕЙ И ВЗРОСЛЫХ В АМБУЛАТОРНЫХ УСЛОВИЯХ

The polymorphism of clinical manifestations of Lyme borreliosis (LB) creates significant problems in the study of this disease. In addition to the variability in classifications used in Russia and abroad, the spectrum and the frequency of symptoms in outpatient and hospitalized patients with LB differ significantly, which makes it difficult for a physician to understand the clinical picture of LB. The purpose of the study was to describe the clinical picture of LB in an outpatient infectologist appointment conditions according to the E. Asbrink, A. Hovmark classification of Lyme borreliosis in children compared with adults. Materials and methods of the research: a retrospective single-center cohort study was conducted based on the analysis of the data from 213 outpatient records of patients with confirmed LB diagnosis, consulted by infectologist at the Moscow Infectious Clinical Hospital No. 1 of the Moscow Department of Healthcare (Moscow, Russia) in Jan. 2018 - Sep. 2019. In order to compare the clinical features between children and adults the patients were divided into 2 groups by age: adults (18 years and older) and children (1 to 17 years old). The confirmation of the LB diagnosis was carried out according to the clinical and/or laboratory criteria using enzyme immunoassay and immune blotting. Results: in the group of children (n=52), the median age was 6 [3; 8] years old, the proportion of boys was 44% (n=23, 95% CI 30-57%), girls - 56% (n=29, 95% CI 43-70%). In the group of adults (n=161), the median age was 59 [49; 65] years old, the portion of males was 29.2% (n=47, 95% CI 22.2-36.0%), females - 70.8% (n=114, 95% CI 64.0-77.8 %). The most frequently diagnosed was LB at its early localized stage, both in children (n=44, 84.0%, 95% CI 74.0-93.0%) and adults (n=123, 76.4%, 95 % CI 69.7-82.6%). No statistically significant difference was found (p=0.248). Erythema migrans (EM) was the vast majority of early localized stage manifestations in children (95%, 95% CI 88-100%). The incidence of EM in adults was not statistically significantly different from that in children (94.3%, 95% CI 89.9-98.1%, p=1.000). EM in children was most often localized on the scalp (46%, 95% CI 31-60%), in adults the most common localizations were the skin of the trunk and lower extremities (total 92.9%, 95% CI 87.8-97.0; n=118). Differences in the typical localization of EM in children and adults were statistically significant (p<0.001). In the clinical picture of the early localized stage of LB the fever was rare in both children (7%, 95% CI 4-16%) and adults (8.9%, 95% CI 4.3-14.5%) (p=1.000). At the same time, the regional lymphadenitis was detected statistically significantly more often in adults than in children (50%, 95% CI 35-65% vs. 26.8%, 95% CI 19.3-34.5%, p=0.005). Both groups showed a lower incidence of regional lymphadenitis during examination by an infectologist if the patient was prescribed antibiotic therapy at the place of residence, while statistically significantly more often in the group of children (34%, 95% CI 23-46 vs. 15%, 95% CI 8-23, p=0.003). Conclusion: the authors have described the spectrum and frequency of the LB clinical manifestations according to the E. Asbrink, A. Hovmark classification in children vs. adults. The influence of research conditions and the previous antibiotic therapy on the spectrum and frequency of the LB clinical manifestations detected during the initial examination was demonstrated as well.

Persistent Borrelia burgdorferi Sensu Lato Infection after Antibiotic Treatment: Systematic Overview and Appraisal of the Current Evidence from Experimental Animal Models.

Lyme borreliosis is caused by spirochetes belonging to the Borrelia burgdorferi sensu lato group, which are transmitted by Ixodes tick species living in the temperate climate zones of the Northern Hemisphere. The clinical manifestations of Lyme borreliosis are diverse and treated with oral or intravenous antibiotics. In some patients, long-lasting and debilitating symptoms can persist after the recommended antibiotic treatment. The etiology of such persisting symptoms is under debate, and one hypothesis entails persistent infection by a subset of spirochetes after antibiotic therapy. Here, we review and appraise the experimental evidence from in vivo animal studies on the persistence of B. burgdorferi sensu lato infection after antibiotic treatment, focusing on the antimicrobial agents doxycycline and ceftriaxone. Our review indicates that some in vivo animal studies found sporadic positive cultures after antibiotic treatment. However, this culture positivity often seemed to be related to inadequate antibiotic treatment, and the few positive cultures in some studies could not be reproduced in other studies. Overall, current results from animal studies provide insufficient evidence for the persistence of viable and infectious spirochetes after adequate antibiotic treatment. Borrelial nucleic acids, on the contrary, were frequently detected in these animal studies and may thus persist after antibiotic treatment. We put forward that research into the pathogenesis of persisting complaints after antibiotic treatment for Lyme borreliosis in humans should be a top priority, but future studies should most definitely also focus on explanations other than persistent B. burgdorferi sensu lato infection after antibiotic treatment.

Borelis Pro phytomedicine for the complex treatment of Lyme borreliosis in children

IntroductionLyme disease, also known as Lyme borreliosis (LB) (tick (Ixodes)borne borreliosis) is a transmissible, natural-focal disease characterized by damage of the skin, nervous system, heart.Material and methodsUnder observation were 68 children – residents of Ternopil region, who applied to Ternopil Regional Children Hospital, and whose age range was 8–17 years. Two schemes of complex treatment of patients were tested: the 1st – patients received Doxycycline (Unidox Solutab®), tablets 100 mg, 10 pcs. 2 time/day after meals for 14 days at a dose 4 mg/ kg; the 2nd – patients received the treatment regimen like the 1st group and phytomedicine “Boreliss pro” capsules, 28.56g, 60 pcs. (Duo Life Boreliss Pro., Poland) 1 capsule 2 time/day after meals for 14 days.ResultsResults showed that was significantly (p < 0.05) lower severity of LB in patients who received antibacterial therapy in combination with doxycycline hydrochloride and phytomedicine “Boreliss pro” (1 caps. 2 times/day, after meals), compared with individuals in another group, on the 30th day after treatment. Complex therapy of patients by phytomedicine “Boreliss pro” causes a decrease of pro-inflammatory levels of cytokines IL-1β in the serum.ConclusionsComprehensive treatment of patients with an erythematous form of LB by phytomedicine “Boreliss pro” contributes to a significantly (p < 0.05) faster disappearance of clinical manifestations of LB, shortening the duration of doxycycline hydrochloride use, and reducing the likelihood of side effects from this drug.

Seroprevalence of antibodies against Borrelia burgdorferi sensu lato in healthy blood donors in Romania: an update

BackgroundThe Borrelia burgdorferi sensu lato (s.l.) genogroup is the causative agent responsible for Lyme borreliosis, a common tick-borne infectious disease in some temperate regions of the Northern Hemisphere. In humans, the clinical manifestations of Lyme borreliosis vary from dermatological infection to severe systemic manifestations. In Romania, data on the seroprevalence of Lyme borreliosis and associated risk factors are scarce and outdated, as the only seroprevalence study with a large dataset was published more than 20 years ago. Therefore, the aim of the present study was to evaluate the seroprevalence for Borrelia burgdorferi s.l. in healthy blood donors from six Romanian counties and identify the associated risk factors.MethodsThe study was conducted among 1200 healthy blood donors aged between 18 and 65 years during November 2019 and September 2020 from six counties in the northwestern and central parts of Romania. A two-tiered testing strategy was applied. Positive and equivocal immunoenzymatic test results for IgG and IgM antibodies were further confirmed by Western blot.ResultsSerum samples from 20% of the blood donors had positive or equivocal IgG and IgM ELISA index values. In total, 2.3% of the serum samples for IgG and 1.8% for IgM were positive by Western blot. The seroprevalence for both antibodies varied between 1.5% (Satu-Mare) and 6.5% (Bistrița-Năsăud) in the six counties investigated. The highest seroprevalence was observed in men (4.7%), in blood donors performing their professional activities outdoors (4.2%), and in those aged ≥ 56 years (8%).ConclusionsThese findings confirm the presence of specific IgG and IgM antibodies to B. burgdorferi s.l. among healthy blood donors from Romania. Furthermore, potential risk factors, such as gender, age, and behavior, associated with the presence of positive B. burgdorferi s.l. antibodies among healthy blood donors were identified.Graphical

Modern condition of the problem of Lime Burreliosis of animals (systematic review)

Lyme borreliosis (LB) is the most common tick-borne disease in the temperate climate of the Northern Hemisphere. LB is caused by spirochetes, which are grouped in the complex Borrelia burgdorferi sensu lato, vectors – Ixodidae mites, dozens of species of small mammals and birds actas reservoir hosts, and the role of reservoirs of domestic animals, such as dogs and cats, is not excluded. Although the ecology and epidemiology of the disease have been extensively studied in Europe and North America, there is considerable uncertainty regarding the study of Lyme borreliosis in veterinary medicine. Search, selection andanalysis of scientific data on the research topic were carried out according to acceptable rules for systematic reviews of the literature. The scientometric database Web of Science Core Collection, the database of scientific articles Pub Med and the database Scientific Periodicals of Ukraine were used. Seventy-four scientific articles were used for the article, which contained the necessary set of data and met the set goal. The article highlights the main issues of the etiology of the disease, which describes the characteristics of the pathogen, its properties, genotypic composition of Borrelia, which cause Lyme disease, the spread of pathogenic genotypes of Borrelia in Europe and Ukraine. The connection of Lyme borreliosis spread with ecological factors, climatic changes and anthropogenic impact on biocenoses and biotopes, the role of vectors and reservoir hosts in the spread of LB is described. Data on the prevalence and degree of infection of Ixodes mites with Borrelia, as well as the spread of LB among the population of Europe and Ukraine are presented. The seroprevalence of each of the animal species (dogs, cats, horses, ruminants), clinical manifestations of LB, if documented and indicators of LB prevalence among animals in Europe and Ukraine, as well as currently known treatments, prevention and diagnosis of LB animals are considered. Key words: Borrelia Burgdorferi Sensu Lato, Lyme Diseases Etiology, Ixodidae.

First Data on Human Lyme Borreliosis in Kosovo: Prospective Evaluation of the Disease from a Tick Bite Perspective.

Purpose: Lyme borreliosis (LB) occurs throughout Europe. No clinical and seroprevalence studies for LB in Kosovo have been publicly available thus far. Therefore, this study aimed to investigate LB from a tick bite perspective in the Pristina region, Kosovo. Methods: This single-center prospective observational study enrolled consecutive adult participants (≥18 years of age) with tick bite (embedded tick in the skin), who were examined at the Clinic of Infectious Diseases, Pristina, between January 2015 and August 2018. At the first visit related to the index tick bite, ticks (the complete ticks or parts of the ticks) were removed from the skin, blood samples were taken for serological tests, and antibiotic treatment was started when deemed necessary. The complete, undamaged ticks removed were proceeded for entomological identification. Participants were followed up at 2 months (serological tests were repeated) and 6 months after the index event for the development of clinical manifestations of LB and/or seroconversion against Borrelia burgdorferi. Results: A total of 380 subjects were included in the study. Most cases were seen in May and June in all study years. All 117 preserved ticks were identified as Ixodes ricinus. Immunoglobulin G seroprevalence among subjects during the first visit in the study was 28/380 (7.4%). Erythema migrans (EM) was clinically diagnosed in 74/380 patients (19.5%, 95% confidence interval 15.6-23.8). Only 15 clinically diagnosed EM (in seronegative patients) were serologically confirmed with seroconversion (2 months later), 3.9% of all subjects included in the study. There were three cases with clinical manifestation between the second and third visit: EM recidivans, multiple erythema, or several nonspecific systemic symptoms. Doxycycline and amoxicillin were mainly used for the treatment of borrelial skin lesions. Conclusion: This assessment can help indicate the need for disease awareness and reinforce the importance of primary prevention measures, early diagnosis, and appropriate treatment.

Epidemiology and molecular genetic characteristics of Lyme borreliosis pathogens circulating in tick’s population in the Almaty oblast of the Republic of Kazakhstan

Background. Information on the geographical distribution of different species of the Borrelia burgdorferi sensu lato (B. burgdorferi s.l.) complex is of great epidemiological importance, since different genospecies are associated with certain clinical manifestations of Lyme borreliosis. Although Almaty region of the Republic of Kazakhstan is considered to be endemic for tick-borne borreliosis, there is still no accurate data on the level of borrelia infection in ticks in the region, including information on the genotypes of circulating borrelia.The aim of this work was to study ticks collected from humans in the Almaty region of the Republic of Kazakhstan in 2018.Materials and methods. Ticks were tested for the presence of B. burgdorferi s.l. DNA, genotyping of the identified borrelia was done by sequencing of the fragment of 16S rRNA gene. The analysis of epidemiological data on the incidence of Lyme borreliosis in the Almaty region in 2013–2018 was performed.Results. Rhipicephalus turanicus (116/253), Haemaphysalis punctata (74/253), Dermacentor marginatus (28/253), and Ixodes persulcatus (23/253) were the predominant species of ticks taken from humans. The prevalence of B. burgdorferi s.l. infection in I. persulcatus ticks was 39.13% (9/23) It should be noted that the DNA of B. burgdorferi s.l. was also detected in single individuals of D. marginatus, H. punctata, and R. turanicus, although these species are not considered as competent B. burgdorferi s.l. vectors.Conclusion. As a result of sequencing of the positive homogenates of ticks, two genotypes of B. burgdorferi s.l. were identified: B. afzelii and B. garinii and/or B. bavariensis. Thus, at least two genospecies, B. afzelii and B. garinii and/or B. bavariensis, circulate in the territory of the Almaty region.

Clinical and epidemiological features of lyme borreliosis

Lyme borreliosis (LB) is the most common transmissible disease of tick-borne origin. This disease is a significant medical challenge due to the damage to many organs and systems and the tendency to chronicity and long-term disability in the future. Currently, there is an upward trend in the incidence of Lyme disease in Sumy Oblast. Thus, in Ukraine in 2015 the incidence was 7.96 per 100,000 population, and in 2019 it increased to 10.62. The average level of indicators was exceeded in Kyiv Oblast (29.0), Cherkasy Oblast (25.4), Vinnytsia Oblast (23.09), Sumy (25.89) Oblast, and Kyiv (2.54). The peak of tick activity in Ukraine is registered in May and has increased by 4.23 times. The maximum number of patients falls within the working population and causes significant state financial damage. The increase in the number of cases indicates a spread of Lyme disease in Sumy Oblast. In order to prevent the spread, it is necessary to study all possible causes of this disease and find ways to eliminate them. This was the ground for the creation of a unified anonymous questionnaire, which covers the main issues regarding this disease from the standpoint of different population groups. A unified anonymous "Questionnaire for Lyme disease patients" contains 16 multiple choice questions and an option for comments. The first group of questions concerned gender, age, and social data of respondents (the largest part of patients fell within the working population – 42.86%). The next group of questions clarified the epidemiological features of this pathology (circumstances, date, time, location, body part bitten). Most often tick bites occurred during walks in the urban forests (42.86% of cases). Most respondents reported that tick bites had happened in June and July (39.29%). Other questions were designed to determine patients' awareness about Lyme borreliosis prevention. The next group of questions was aimed at clarifying the clinical features of the disease (lower extremities were the most frequent site of a tick bite) (46.43%), with erythema dominating among the clinical manifestations of Lyme borreliosis (91.07%). According to the anonymous questionnaire, we analyzed and evaluated awareness of diagnosis, clinical signs, and measures of Lyme disease prevention in the patients who were receiving treatment at Municipal Non-Commercial Enterprise of Sumy Regional Council "Medical Clinical Center of Infectious Diseases and Dermatology Named After Z. Krasovytskyi" and SSU University Clinic.

Facial palsy as a manifestation of early neuroborreliosis (clinical case)

Lyme borreliosis is a tick-borne transmitted infectious disease caused by the spirochete Borrelia burgdorferi sensu lato and spread by the bite of ticks of the genus Ixodes. Lyme neuroborreliosis is a clinical manifestation of Lyme borreliosis, which affects the central nervous system and peripheral nervous system in up to 15% of the affected patients. Nerve structures are affected by spirochetes both in acute and late phase of the disease. The clinical course of neuroborreliosis is highly variable. Although at least 80% of European patients present with facial nerve palsy and radiculitis, symptoms of neuroborreliosis may be quite unspecific or even mimic other neurological diseases. Idiopathic peripheral facial palsy has long been considered as the most common cause of prosopoparesis, but modern diagnosis significantly narrow the range of cases of unknown genesis. Neuroborreliosis is difficult to diagnose, especially when prosopoparesis is the only clinical manifestation, so practitioners should be mindful of possible etiology to avoid misdiagnosis. The article presents a clinical case of early neuroborreliosis in a woman of 57 years who manifested with peripheral facial palsy. The author describes in detail the course of the disease (the appearance of new symptoms on the background of standard medical therapy (poor response), the presence of additional criteria (erythema migrans, lymphocytoma (rarely), arthralgia), diagnosis (specific immunological examination of blood to Borrelia burgdorferi sensu lato). Antibiotic therapy made it possible to achieve complete recovery of facial nerve function and avoid future complications.

A Practical Approach to the Diagnosis of Lyme Borreliosis: From Clinical Heterogeneity to Laboratory Methods

Clinical evaluation of Lyme Borreliosis (LB) is the starting point for its diagnosis. The patient's medical history and clinical symptoms are fundamental for disease recognition. The heterogeneity in clinical manifestations of LB can be related to different causes, including the different strains of Borrelia, possible co-infection with other tick transmitted pathogens, and its interactions with the human host. This review aims at describing the heterogeneous symptoms of Lyme Borreliosis, as well as offering a practical approach for recognition of the disease, both in terms of clinical features and diagnostic/research tools.

Epidemiology of Lyme Disease in a Highly Endemic European Zone.

Background and objective: Lyme disease, also known as Lyme borreliosis (LB), is a tick-borne infectious disease caused by the spirochete bacteria Borrelia. The risk of infection depends on the geographical area, ecological factors, and human behavior. Clinical manifestations of Lyme borreliosis have a wide range, but the most frequent clinical symptom, which is also a diagnostic symptom, is a skin rash called erythema migrans (EM). The disease is very common worldwide. In Lithuania, the disease frequency is 99.9 cases per 100,000 population (Centre for Communicable Diseases and AIDS, Lithuania, 2017). The main aim of this study was to obtain the baseline characteristics of the disease regarding the infected Lithuanian population. Materials and Methods: We analyzed data from the Centre for Communicable Diseases and AIDS about all Lyme disease (A69.2) diagnosed patients over a three-year period (from 2014 to 2016) in Lithuania. Results: In 2014–2016, 7424 (crude incidence rate 85.4) cases with LB were diagnosed in Lithuania. Most of them (4633 (62.4%)) were identified in women. Older people were more likely to suffer from LB. Urban residents were 2.6 times more often affected that those living in villages. Tick bites were primarily observed in high season months, from May to September (90%), with the highest peak in July. There was a higher number of observed tick bites (p = 0.003) in the urban residents. Erythema migrans occurred in 75.6% LB cases, while other symptoms did not exceed a quarter of all LB cases. There were 7353 (99.6%) cases where LB was confirmed via clinical symptoms and/or laboratory tests. Also, 1720 (23.2%) patients were tested for LB immunoglobulins. Conclusions: This study found a high incidence of Lyme disease in Lithuania. We elucidated the baseline characteristics regarding the infected Lithuanian population which may ease medical clinicians’ work on new Lyme diagnoses.

Association of Seropositivity to Borrelia burgdorferi With the Risk of Neuropsychiatric Disorders and Functional Decline in Older Adults

Exposure to Borrelia burgdorferi (Bb) has been reported to be associated with certain neuropsychiatric disorders. To establish the association between seropositivity to Bb and incidental neuropsychiatric disorders (eg, cognitive decline, incident dementia, and depressive symptoms) as well as functional decline. This prospective, 6-year follow-up cohort study was conducted in a rural southwestern region of France and included 689 retired farmers 65 years or older randomly recruited from the Farmer Health Insurance System who agreed to submit a blood sample and were participants in the Aging Multidisciplinary Investigation study, an ongoing epidemiological prospective study of aging initiated in 2007. The data were analyzed from April to May 2019. Borrelia burgdorferi serology testing was performed in a 2-tiered approach. During the follow-up period, cognitive decline, incident dementia, depressive symptoms, and functional decline were repeatedly assessed. Diagnosis of dementia relied on a 3-step procedure; cognitive decline was determined using the Mini-Mental State Examination and depressive symptomatology was assessed using the Center for Epidemiologic Studies Depression scale. For disability, scores on instrumental and basic activities of daily living were investigated. Of 689 participants, 432 (62.2%) were men and the mean (SD) age was 75.8 (6.4) years. The seroprevalence rate of Bb was 6.5%. At baseline, compared with Bb- participants, those who were Bb+ were older, predominantly men, and had lower depressive symptoms. No association between seropositivity and any of the studied outcomes (ie, cognitive decline, depressive symptoms, or functional decline) was found in the crude analysis and after adjusting for confounding variables. Regarding incident dementia, no increased risk was found among Bb+ participants (hazard ratio, 0.42; 95% CI, 0.1-1.17; adjusted for diverse confounders). To our knowledge, this is one of the few longitudinal studies exploring the risk of neuropsychiatric disorders and functional decline associated with exposure to Bb. Despite its limitations (eg, a lack of information if clinical manifestations of Lyme borreliosis existed, date of exposure, or treatment received), this study suggests that seropositivity to Bb is not a risk factor for incidental neuropsychiatric disorders and functional decline.

Psychosis in Borrelia burgdorferi infection - part I: epidemiology, pathogenesis, diagnosis and treatment of neuroborreliosis.

Borreliosis is a multisystem, bacterial, zoonotic infectious disease with diversified spectrumof symptoms, which may also include psychotic disorders. Clinical picture of the disease is often unspecific, which makes the diagnosis relatively difficult. Uncharacteristic process of borreliosis is a result of complex molecular strategies used by spirochetes to infect, disseminate and survive in host organism. Part I of the article is focused on the current knowledge about pathogenesis of Lyme Borreliosis (LB), especially neuroborreliosis. Additionally, epidemic situation in Poland and in Europe was presented. Also, typical clinical manifestations of LB were described. In the article, the crucial pathogenic cell mechanisms were depicted. The processes of infection and dissemination of Borrelia in host were presented. The most important strategies of evading the response of host immune system were also discussed. These mechanisms are probable cause of the chronic and uncharacteristic clinical picture of the disease, as they significantly impair host immune response to bacteria. Also, there were presented molecular processes of neural cells impairment, which may lead to observed clinical symptoms of neuroborreliosis. Furthermore, diagnostic methods, treatment guidelines and some of diagnostic problems were discussed.

Combining primary care surveillance and a meta-analysis to estimate the incidence of the clinical manifestations of Lyme borreliosis in Belgium, 2015–2017

Lyme borreliosis (LB) is an important tick-borne disease which can cause a broad range of symptoms mainly affecting the skin, the nervous system and the joints. This study aims to estimate the incidence of the different clinical manifestations of LB in Belgium. The incidence of erythema migrans (EM) was estimated through the network of sentinel general practices at 97.6/100,000 inhabitants (uncertainty interval [UI] 82.0–113.0) for the period 2015–2017. This result was used to estimate the incidence of other LB manifestations based on their proportional distribution (ratios) to EM reported in the neighboring countries of Belgium. To estimate these ratios, we performed a systematic review of studies published between February 1, 2008 and January 31, 2018 and pooled the results using a random effects meta-analysis. Six studies were retained in the systematic review, and the meta-analysis estimated the occurrence ratios for Lyme neuroborreliosis/EM, Lyme arthritis/EM and other manifestations/EM at 0.024 (95% confidence interval [CI] 0.016–0.037), 0.022 (95% CI 0.020–0.024) and 0.014 (95% CI 0.012–0.016) respectively. Applying these ratios to the EM incidence in Belgium resulted in an incidence estimation of 2.4/100,000 inhabitants (95% UI 1.5–3.7) for Lyme neuroborreliosis, 2.1/100,000 (95% UI 1.7–2.6) for Lyme arthritis and 1.4/100,000 (95% UI 1.1–1.7) for other less frequent manifestations. Some of these LB manifestations, other than EM, are more severe, hence these estimates are essential to assess the health burden and economic cost of LB which would be highly relevant for patients, healthcare providers and policymakers. As both over- and underestimation of different clinical LB manifestations remain possible due to characteristics of the primary surveillance systems and the disease itself, future studies to validate these estimates would be of great value.

Infection Kinetics and Tropism of Borrelia burgdorferi sensu lato in Mouse After Natural (via Ticks) or Artificial (Needle) Infection Depends on the Bacterial Strain.

Borrelia burgdorferi sl is a complex of pathogen bacteria transmitted to the host by Ixodes ticks. European Ixodes ricinus ticks transmit different B. burgdorferi species, pathogenic to human. Bacteria are principally present in unfed tick midgut, then migrate to salivary glands during blood meal and infect a new host via saliva. In this study, efficiency of transmission in a mouse model of three pathogen species belonging to the B. burgdorferi sl complex, B. burgdorferi sensu stricto (B31, N40, and BRE-13), B. afzelii (IBS-5), and B. bavariensis (PBi) is examined in order to evaluate infection risk after tick bite. We compared the dissemination of the Borrelia species in mice after tick bite and needle injection. Location in the ticks and transmission to mice were also determined for the three species by following infection kinetics. After inoculation, we found a significant prevalence in the brain for PBi and BRE-13, in the heart, for PBi, in the skin where B31 was more prevalent than PBi and in the ankle where both B31 and N40 were more present than PBi. After tick bite, statistical analyses showed that BRE-13 was more prevalent than N40 in the brain, in the bladder and in the inguinal lymph node. When Borrelia dissemination was compared after inoculation and tick bite, we observed heart infection only after tick inoculation of BRE-13, and PBi was only detected after tick bite in the skin. For N40, a higher number of positive organs was found after inoculation compared to tick bite. All European B. burgdorferi sl strains studied were detected in female salivary glands before blood meal and infected mice within 24 h of tick bite. Moreover, Borrelia-infected nymphs were able to infect mice as early as 12 h of tick attachment. Our study shows the need to remove ticks as early as possible after attachment. Moreover, Borrelia tropism varied according to the strain as well as between ticks bite and needle inoculation, confirming the association between some strains and clinical manifestation of Lyme borreliosis, as well as the role played by tick saliva in the efficiency of Borrelia infection and dissemination in vertebrates.

Multilocus sequence typing of clinical Borreliella afzelii strains: population structure and differential ability to disseminate in humans

BackgroundLyme borreliosis in humans results in a range of clinical manifestations, thought to be partly due to differences in the pathogenicity of the infecting strain. This study compared European human clinical strains of Borreliella afzelii (previously named Borrelia afzelii) using multilocus sequence typing (MLST) to determine their spatial distribution across Europe and to establish whether there are associations between B. afzelii genotypes and specific clinical manifestations of Lyme borreliosis. For this purpose, typing was performed on 63 strains, and data on a further 245 strains were accessed from the literature.ResultsAll 308 strains were categorized into 149 sequence types (STs), 27 of which are described here for the first time. Phylogenetic and goeBURST analyses showed short evolutionary distances between strains. Although the main STs differed among the countries with the largest number of strains of interest (Germany, the Netherlands, France and Slovenia), the B. afzelii clinical strains were less genetically structured than those previously observed in the European tick population. Two STs were found significantly more frequently in strains associated with clinical manifestations involving erythema migrans, whereas another ST was found significantly more frequently in strains associated with disseminated manifestations, especially neuroborreliosis.ConclusionsThe MLST profiles showed low genetic differentiation between B. afzelii strains isolated from patients with Lyme borreliosis in Europe. Also, clinical data analysis suggests the existence of lineages with differential dissemination properties in humans.

Reduction in human Lyme neuroborreliosis associated with a major epidemic among roe deer

Lyme neuroborreliosis is the most severe clinical manifestation of Lyme borreliosis. In most of Denmark, and also Europe, the overall prevalence of Lyme borreliosis seems to be stabilising. This is not the case on the island of Funen, Denmark, where the number of human Lyme neuroborreliosis cases has markedly declined throughout the last decade. We propose the reason for the decline is a major epidemic among roe deer, killing almost half of their population, resulting in a reduction in the tick population which make it less likely to get a tick bite and therefore to contract Lyme neuroborreliosis. This is the first time such a relationship is described as a naturally occurring phenomenon in Europe.

The HUMTICK study: protocol for a prospective cohort study on post-treatment Lyme disease syndrome and the disease and cost burden of Lyme borreliosis in Belgium

BackgroundIn Belgium, different routine surveillance systems are in place to follow-up Lyme borreliosis trends. However, accurate data on the disease and monetary burden for the different clinical manifestations are lacking. Despite recommended antibiotic treatment, a proportion of Lyme patients report persisting aspecific symptoms for six months or more (e.g. fatigue, widespread musculoskeletal pain, cognitive difficulties), a syndrome now named “post-treatment Lyme disease syndrome” (PTLDS). Controversy exists on the cause, incidence and severity of PTLDS. This study aims to estimate the incidence of PTLDS in patients with Lyme borreliosis and to quantify the disease burden and economic costs associated with the different clinical manifestations of Lyme borreliosis in Belgium.MethodsThe project is a prospective cohort study in which about 600 patients with an erythema migrans and 100 patients with disseminated Lyme borreliosis will be followed up. Questionnaires, including the SF-36 vitality and pain subscale, the Cognitive Failure Questionnaire and the EQ-5D-5L, will be used to collect information on acute and persisting symptoms and the impact on quality of life. Symptom frequency and severity will be compared with self-reported pre-Lyme health status, a control group and existing Belgian population norms. Additionally, information on the associated costs and possible risk factors for the development of PTLDS will be collected.DiscussionA study of the health burden will allow evaluation of the relative importance of Lyme borreliosis in Belgium and information on the economic cost will help to formulate cost-effective measures. There are only few prospective studies conducted estimating the incidence of PTLDS and even though discussion exists about the prevalence of subjective symptoms in the general population, a control group of non-Lyme borreliosis participants has often not been included.