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Diagnosis of chronic Lyme disease is a challange for a clinician, even if there is modern laboratory and instrumental facilities at the hospital. Borreliosis is known for polysystemic and variable clinical picture. This article describes the clinical feachures and diagnosis of chronic borreliosis with central nervous system involvement. Various clinical variants of the disease and available methods of specific and nonspecific diagnosis are listed. The theoretical part of the work was carried out based on materials from 34 publications devoted to the problem of chronic neuroborreliosis. Also we describe the clinical case that illustrates the difficulties of managing this group of patients.

Relevance. Lyme disease (LD) remains an important public health problem, especially in Russia, where the incidence is consistently high. To date, there is still no available vaccine against LD, and prevention involves non-specific measures. Aim: to review the literature and summarise data on progress, approaches and strategies for LD vaccine development. Conclusions. The first LD vaccines were developed in the 1990s. An OspA-based vaccine (LYMErix) was commercially available in the early 2000s but not widely distributed. An important milestone in the development of LD vaccines was the shift from the development of monovalent vaccines based on a single type of outer surface protein to the development of multivalent combinations that provide protection against different Borrelia genospecies. A multivalent OspA-based vaccine (VLA15) is in phase III clinical trials and is likely to be the next LD vaccine available on the market. New genetic strategies for vaccine development, identification of new immunogens, and development of vaccines targeting different parts of the LD transmission cycle are of broad interest for further development of LD vaccines.

Introduction and Purpose: Accurate diagnosis of Lyme disease remains challenging due to its varied manifestations and the limitations of current diagnostic tests. This review examines the emerging role of artificial intelligence (AI) in enhancing the diagnostic accuracy for Lyme disease, aiming to understand how these technologies can be integrated into clinical practice. State of Knowledge: AI and machine learning techniques are increasingly applied to improve diagnostic processes. In Lyme disease, AI models have been developed to identify patterns in clinical data, enhancing early detection and accuracy. Studies have focused on using AI to interpret complex serological results and clinical symptoms more effectively than traditional methods. Additionally, AI has been utilized to analyze geographical and epidemiological data to predict Lyme disease risk areas, aiding in preventive strategies. Summary: AI holds significant promise in transforming Lyme disease diagnostics by increasing the speed and accuracy of detection. These technologies not only help in overcoming the limitations of current serological testing but also provide a framework for predictive analytics in epidemiology. As AI models continue to evolve, their integration into healthcare systems requires careful consideration of ethical implications and validation on broader scales. Future research should focus on refining AI algorithms, improving data inclusivity, and enhancing interoperability with existing medical systems to fully realize AI's potential in battling Lyme disease.

The study's objective was to reveal trends in tick-borne encephalitis (TBE) and Ixodes tick-borne borreliosis (ITBB) epidemic processes in Russia's Northwestern Federal District (NWFD) in 2002–2021. In the NWFD during the analyzed period, more than 1.1 million patients sought medical help following tick bites (14% of all cases registered nationwide). The long-term average tick bite incidence rate in the NWFD exceeded the nation-wide value: 409.5 and 280.7, respectively. In the NWFD, the highest long-term average tick bite incidence rates were recorded in Vologda Oblast, Pskov Oblast, and Novgorod Oblast. The tick bite incidence rate tended to grow in the NWFD, as well as nationally. The growth in tick bite incidence was statistically significant in the Republic of Komi, Kaliningrad Oblast, and Arkhangelsk Oblast. In 2002–2021, more than 6000 TBE cases were registered in the NWFD (11% of all cases registered nationwide), and the TBE long-term average incidence rate in the NWFD exceeded the national value: 2.3 and 2.0, respectively. The Republic of Karelia, Arkhangelsk Oblast, and Vologda Oblast were three NWFD subjects with high TBE epidemical hazard. TBE incidence in the analyzed period tended to decrease, both in the NWFD and nationwide. A statistically significant decrease in TBE incidence was revealed in St. Petersburg, in the Republic of Karelia, in Novgorod Oblast, and in Leningrad Oblast. About 22 000 ITBB cases were reported in the NWFD during the analyzed period (15% of all ITBB cases in Russia). The ITBB long-term average incidence rate in the NWFD exceeded the national value: 7.9 and 4.9, respectively. Vologda Oblast, Kaliningrad Oblast, and Pskov Oblast were three NWFD subjects with high epidemical hazard in terms of ITBB. ITBB incidence during the analyzed period tended to decrease, both in the NWFD and nationwide. The decrease in ITBB incidence was statistically significant in Vologda, Kaliningrad, Novgorod, Leningrad and Pskov Oblasts, as well as in St. Petersburg. In the Republic of Komi, in contrast to other NWFD subjects or national data, there was an uptrend in both TBE and ITBB incidence.

Relevance. The Sverdlovsk district is a tense natural focus for Lyme borreliosis (LB) with a constantly recorded incidence that exceeds these indicators in the Russian Federation and the Ural Federal region several times. LB is registered on 56 of 59 administrative territories of the district. Currently, the count of LB in the Russian Federation includes both infections caused by Borrelia burgdorferi sensu lato group Borrelia and infections caused by Borrelia miyamotoi sensu lato group Borrelia.Aim. To characterize the epidemic process of LB in the territory of the Sverdlovsk district over a 20-year period (2002–2021).Materials and methods. The paper uses data from federal and regional statistical observations, reporting materials of the Department of Rospotrebnadzor in the Sverdlovsk district for 2002–2021, methods of statistical analysis.Results and discussion. During the follow–up period (2002–2021), the incidence rate of BL in the Sverdlovsk district exceeded the average long-term level in the Russian Federation by almost 3 times, and in the Ural Federal region – by 1.8 times. Among the mechanisms and ways of transmission of LB pathogens, the vector-borne mechanism dominated (84.5%), the share of the unidentified pathway was 15.4%, alimentary (when using raw goat's milk) – 0.1%. The duration of the epidemic season for LB in the district was 10 months (from March to December) with a peak incidence in June. Cases of LB were registered among people of different ages, with a predominance in the group of 60 years and older (39.1%). An analysis of the distribution of people with LB by social composition showed that pensioners prevailed among them – 36.3%, officials made up 27.8%, unemployed – 14.1%. Among the cases, a high proportion of schoolchildren and children under 7 years old were noted. It was found that erythematous and non-erythematous forms of LB are registered in the district, with a predominance of erythematous (64.5%). The main etiological agent of the erythematous form is Borrelia garinii, while the non-erythematous form is Borrelia miyamotoi and B. garinii. In the general structure of morbidity, the number of cases of LB is largely determined by the city inhabitants (92.9%). There were no fatal outcomes in LB in the territory of the district during the studied period.Conclusions. Due to the lack of vaccination of LB worldwide, the only strategy to reduce the incidence of LB is non-specific prevention and timely diagnosis of the disease, including data from epidemiological history, clinical and laboratory diagnostics. The long-term clinical and epidemiological and laboratory studies conducted by us in the Sverdlovsk district allowed us to characterize the main manifestations of the epidemic process of LB and to improve the diagnosis of the disease.

Relevance. The Sverdlovsk region is a highly endemic territory for infections transmitted by ixodic ticks. The possibilities of laboratory diagnostics of tick–borne infections in the routine practice of a clinician in the region today are limited mainly by testing blood serum for antibodies to the tick-borne encephalitis virus (TBE virus) and Lyme disease (LD) pathogens – Borrelia burgdorferi sensu lato complex, therefore, among tick-borne infections in the region currently mainly TBE and LD are registered. In case of negative results for antibodies to the pathogens of the above infections, the diagnosis may remain unknown. Aims. To study the etiological structure of infections transmitted by ixodic ticks in the Sverdlovsk region at the present stage, as well as to characterize the epidemiological and clinical features of the course of tick-borne infections detected in conditions of a combination of natural foci. Materials and methods. The study included 227 patients undergoing inpatient or outpatient treatment during the epidemic season of tick activity in 2021 (June-August) at LLS MO "New Hospital" (Urban Center of Natural Focal Infections). The case histories (epidemiological, clinical and laboratory indicators) were studied from each patient, as well as the material (blood) was examined prospectively and retrospectively using molecular biological (PCR) and serological (ELISA, planar protein biochip) methods. Results and discussion. During the study, six diseases were identified among the examined patients: TBE, LD (erythematous and nonerythematous forms), Borrelia miyamotoi disease (BMD), human granulocytic anaplasmosis (HGA), human monocytic ehrlichiosis (HME), as well as "Viral fever transmitted by arthropods" (VFTA). Among the examined patients, the proportion of patients with monoinfection was 49,5%, with mixed infection – 50,5%. Additional studies conducted by us using specific PCR for the presence DNA rickettsia and the causative agent of Q-fever in the blood of patients gave negative results. The general epidemiological characteristics for the above identified infections were the vector-borne mechanism, the prevalence of diseases in groups of middle-aged and elderly people, the largest number of cases of infection with pathogens of any tick-borne infection occurred in Yekaterinburg and its surroundings, for all infections, the duration of tick bite in most cases did not exceed one day; there were differences by sex, incubation period. Clinical symptoms were similar, except for the erythematous form of LD (the presence of erythema migrans at the byte site of tick), because the vast majority of patients had a general infectious syndrome; general laboratory indicators varied. Confirmation of the diagnosis was based on the results of the complex application of molecular biological and serological research methods. Conclusions. The modern etiological structure of infections transmitted by ixodic ticks in the Sverdlovsk region is represented not only by TBE and LD, but also by new disease to our country, such as BMD, HGA, HME, while a high proportion of mixed infections in various combinations has been revealed.

In rheumatology, the problem of infectious pathology is quite acute. This is primarily due to the participation of various infectious agents in the development of immuno-inflammatory rheumatic diseases (IIRD), in which microorganisms play a trigger role, triggering the immunopathological mechanisms of inflammation. Vivid examples of such diseases are acute rheumatic fever and reactive arthritis. The infectious etiology of Lyme disease has been proven. An equally difficult task is the fight against comorbid infection (CI), which often complicates the course of many IIRD due to a violation of the immune status caused by both the background disease and the use of immunosuppressive drugs. The predominance of respiratory tract lesions in the structure of CI in patients with IIRD makes it necessary to use influenza and pneumococcal vaccines in them, since the risk of deaths from these infections among these patients is quite high. During the development of the COVID-19 pandemic, which has become a challenge to all mankind, a large number of new fundamental and medical problems have been revealed concerning the relationship between viral infection and many widespread chronic non-communicable diseases, among which IIRDs occupy an important position. As one of the methods of combating the current COVID-19 pandemic, great hopes are pinned on the widespread use of vaccination. The possibility of using mo noclonal antibodies for pre-exposure prophylaxis of COVID-19, including in patients with IIRD, is discussed.

The clinical case describes the difficulties of differential diagnosis of polyneuropathy that developed after Gam-Covid-Vac vaccination on the background of combined infectious pathology (HIV infection, tick-borne borreliosis, COVID-19) in a young woman. It is shown that various infectious and non-infectious diseases with similar clinical symptoms (peripheral nervous system affliction) occurring simultaneously in one patient can significantly affect each other’s course and complicate the establishment of the true cause of polyneuropathy. It should be noted that in this example, the establishment of a final diagnosis was carried out collectively, by consensus, and was based on the effectiveness of etiotropic (antibacterial) treatment, which in fact was an ex juvantibus therapy option, which made it possible to establish the most probable etiology of polyneuropathy – tick-borne borreliosis. In turn, HIV infection and possibly vaccination, according to the authors, could cause immunosuppression, which affected the degree of dissemination of Borrelia burgdorferi. It is also likely that the insufficient immune response in combination with the cascade plasma filtration session affected the initial dubious results of the serological tests, which further complicated the diagnosis.

Background. The relationship between pathogens of new diseases and tick-borne infections is an underinvestigated direction in the problem of infectious diseases.The aim. To show the features of identifying the markers of Borrelia burgdorferi, tickborne encephalitis and SARS-CoV-2 pathogens on the example of a case of a triple mixed infection (Lyme disease, tick-borne encephalitis and COVID-19) and using comprehensive studies.Methods. In 2019–2021, a comprehensive study of 7 blood samples from a patient with mixed infection was carried out. We used real-time polymerase chain reaction (PCR), enzyme immunoassay (ELISA) and determined antigen, IgM, IgG antibodies, and avidity index (AI) of IgG antibodies.Results. Ixodid tick-borne borreliosis was diagnosed in a patient 5 months after contagion. Only high-avid Lyme-IgG antibodies were detected. Low-avid Lyme- IgG antibodies appeared against the background of a reduced general condition. At the same time, high-avid IgG (cut-off index (COI) – 7.8) and IgM (COI = 1.2) antibodies to the TBE virus were detected. In July 2020, the patient was infected with SARSCoV-2. TBE virus which passed into the body simultaneously with Borrelia in the fall of 2019 was activated. Although the patient did not have specific symptoms of TBE, in subsequent blood samples (No. 4, 5, 6) we found TBEV antigen (optical density (OD) – 4.3; 1.9 and 2.0 respectively) and IgM (COI = 1.3; 0,9 and 0 respectively). These results were recognized as TBEV activation, which contributed to an increase in the avidity of IgG antibodies (AI = 65 %; 100 % and 63 % respectively). IgM antibodies to SARSCoV-2 virus were not detected, as opposed to the high levels of IgG (COI = 8.2; 8.1; 8.4 and 14.7 respectively).Conclusions. Therefore, using not only the common methods of diagnosing (PCR and ELISA), but also the determination of the antibody avidity degree, we have shown that when analyzing a case of a triple mixed infection, B. burgdorferi dominates in the human body and causes a long-term chronic course of the disease.

Introduction. Knowledge about tick-borne disease (TBD) distribution is necessary to improve prevention, whereas detection of human serum IgG antibodies against relevant pathogens is a method for monitoring TBD prevalence in local population. The study objective was to estimate seroprevalence of IgG antibodies against tick-borne encephalitis virus (TBEV), Borrelia burgdorferi sensu lato, Coxiella burnetii, Anaplasma phagocytophilum, and Ehrlichia chaffeensis/E. muris in healthy residents from the five territories of the Northwestern Federal District of the Russian Federation (Arkhangelsk Oblast, Leningrad Oblast, Pskov Oblast, the Republic of Komi and the Republic of Karelia). Materials and methods. In 20172019, a total of 1244 serum samples from healthy residents, not vaccinated against TBDs or other flavivirus-caused infections was studied by ELISA. Results. 21.7% of the sera samples contained IgG antibodies against a single TBD pathogen, whereas 2.1% showed signs of coinfection with two or more pathogens. The most common were IgG antibodies against TBEV (5 territories, 12.2%), followed by Borrelia burgdorferi sensu lato (5 territories, 3.5%), C. burnetii (4 territories, 2.9%), Anaplasma phagoсytophilum (3 territories, 1.6%), E. chaffeensis/E. muris (5 territories, 1.5%). The IgG antibodies were more common in men (55.2%) than in women (44.8%), being found virtually evenly in age-independent manner (from juniors under 18 to seniors over 60). Conclusion. The results of this first comprehensive serosurveillance study in the Northwestern Federal District of the Russian Federation assessing serum IgG antibodies against tick-borne diseases indicate a wide distribution of such pathogens. Moreover, infections caused by C. burnetii, Anaplasma phagocytophilum, and Ehrlichia chaffeensis/E. muris might be highly underdiagnosed.

Adverse drug reactions (ADRs) are recorded throughout the lifecycle of a medicinal product. In the post-marketing period, new ADRs are primarily identified via drug safety signals. In order to assess a signal and establish causality between an adverse drug reaction and a suspected medicinal product, it is necessary to evaluate the signal strength and quality.The aim of the study was to analyse the information submitted to Russian regulatory authorities by a patient and check it for a potential causal association of acute tubulointerstitial nephritis (ATIN) with the use of ceftriaxone and with the patient’s principal diagnosis, Lyme disease.Materials and methods: the authors analysed the patient’s submission received by the Ministry of Health of the Russian Federation in 2022 with a complaint that the treatment of Lyme disease with ceftriaxone had caused ATIN. The probability of a causal relationship between the medicinal product and the ADR was evaluated using the Naranjo algorithm.Results: according to the review of literature and the spontaneous reports collected in Pharmacovigilance 2.0, the database in the Automated Information System of the Russian Federal Service for Surveillance in Healthcare, both ceftriaxone and the underlying condition (Lyme disease) may cause renal abnormalities. Ceftriaxone is potentially nephrotoxic; it mainly affects the tubular system of the kidneys. Borreliosis may cause kidney damage as well; such damage manifests clinically as rapidly progressing and fatal damage to the glomeruli.Conclusions: the probability of a causal relationship between the development of ATIN in the complainant and the use of ceftriaxone was categorised as “possible”. However, the information available did not allow for establishing a definite relationship between kidney damage and the use of the medicinal product. Further monitoring of similar cases is necessary to minimise the risks of developing this pathology during treatment with ceftriaxone.

The aim of the work is to clarify the clinical and laboratory features of Lyme disease in the Zaporizhzhia region on the basis of a retrospective clinical, epidemiological and serological analysis of this disease cases in the period from 2015 to 2019. Materials and methods. A retrospective analysis of 62 medical cards of stationary patients with Lyme disease for the period from 2015 to 2019 was carried out. The age of the patients ranged from 18 to 79 years. There were 38 men and 24 women. All the patients were given a traditional complex clinical-laboratory examination; ELISA was used to defined serum IgM and IgG to Borrelia burgdorferi. Results. According to the study results it was found that Lyme disease in the Zaporizhzhia region had a clear seasonal prevalence in summer (56.5 %) and spring (25.8 %). The vast majority of patients (80.6 %) clearly indicated the tick bite. The disease was mostly acute (90.3 %) with a predominance of erythema (94.6 %). In the acute course of the disease, patients were seropositive in 75.0 % of cases with simultaneous detection of both IgM and IgG to Borrelia burgdorferi, and positive IgM in the absence of IgG. Seronegative 25.0 % of patients required clear clinical and epidemiological data to confirm the diagnosis. Under prolonged and chronic conditions, patients had positive IgG to Borrelia burgdorferi (100 %) and IgM (50.0 %). Certain clinical and laboratory features at different course of Lyme disease were revealed. So, the acute course was characterized by the predominance of erythema (94.6 %), mild or no manifestations of general intoxication syndrome, lack of pathological changes in the hemogram in most patients (80.4 %). In the prolonged and chronic course, there was no history of erythema, clinical symptoms were polymorphic, half of the patients had increased erythrocyte sedimentation rate in the absence of changes in blood count, mild cytolytic syndrome and hyperbilirubinemia. Conclusions. As a result of the retrospective analysis of Lyme disease cases in the period from 2015 to 2019, certain patterns of epidemiological, clinical and serological changes in different courses of this infection in the Zaporizhzhia region were revealed, namely the clear seasonality of the disease, in the acute course – the predominance of erythema and different variants of serological profile in patients, and in prolonged and chronic course – polymorphism of all clinical symptoms and no history of erythema.

Lyme disease is an infectious zoonosis transmitted by ticks infected with Borrelia spirochetes. Condition affects multiple organ systems and typically has a protracted course. Although Lyme carditis is a comparatively rare symptom of Lyme borreliosis, it can cause major cardiac conditions, including death, if left untreated. Atrioventricular block of various degrees is the hallmark of cardiac involvement, although other manifestations of the disease are increasingly describe such as ventricular and supraventricular arrhythmias, pericarditis, acute coronary syndrome, mild heart failure, cardiac tamponade or individual cases of cardiomyopathy, degenerative valvular lesions and vasculitis. Cardiovascular conduction disorders have a good prognosis despite their abrupt onset and completely resolve after a few days of antibiotic therapy. Therefore, a wait-and-see attitude should be maintained. However, a temporary or permanent pacemaker may be required if the patient's clinical condition necessitates prompt intervention. Nevertheless, current recommendations suggest avoiding temporary stimulation wherever possible and limiting its use to the shortest treatment time possible.

In the presented case report, a patient with persistent atrial fibrillation developed due to borreliosis and grade III left atrial spontaneous echo contrast (SEC) according to transesophageal echocardiography, in order to rule out intracardiac thrombosis and concomitant Lyme carditis, contrastenhanced cardiac magnetic resonance imaging was performed. Given the rapid progression of heart failure on the background of tachycardia, the lack of evidence for left atrial appendage thrombosis and myocarditis, electrical cardioversion was performed with the restoration of sinus rhythm and without thromboembolic complications during further follow-up. The issues of the clinical and prognostic significance of SEC, the potential of various diagnostic methods, and the management of such patients are discussed.

Introduction: The most common tick-borne disease caused by the spirochete Borrelia burgdorferi is Lyme disease. It is characterized by a variety of disorders: dermatological, rheumatological, cardiological and neurological. Neuroborreliosis is defined as an involvement of the nervous system, and it is the second most common form of infection in children (10-15% of those infected). The aim of the study: To review the available materials and presentation of the current state of knowledge on the various manifestations of neuroborreliosis in children. Material and method: Databases such as PubMed and Google Scholar were searched. Literature was searched using the keywords: Lyme disease, neuroborreliosis, borreliosis, facial nerve paralysis, and pediatric population. The materials obtained in this way were analyzed in terms of compliance with the subject of the work. Results: Typical clinical manifestations of neuroborreliosis in children are facial nerve palsy and meningitis. Neuroborreliosis is the cause of 50% of all cases of bilateral facial nerve palsy in children. Multiple cranial and peripheral neuritis, myelitis, cerebral vasculitis and, consequently, the formation of intracranial aneurysms are less common manifestations of infection. Conclusions: The symptoms of neuroborreliosis are non-specific. This makes it difficult to make an accurate diagnosis. Even if no information on tick bite or erythema migrans has been obtained from the clinical history, neuroborreliosis should be considered in the differential diagnosis, especially in Lyme-endemic areas.

Lyme disease (tick-borne borreliosis) is an infectious vector-borne natural focal disease that tends to a chronic and recurrent course with a predominant damage to the skin, nervous system, musculoskeletal system and heart. Cardiac features is manifested, as a rule, by a involvement of the conducting system as varying degrees of atrioventricular block, Bundle–branch block, dysfunction of the sinoatrial node. In case of untimely diagnosis and etiotropic treatment of tick-borne borreliosis, chronic lesions of the cardiac conduction system may occurs and implantation of a pacemaker may be required.

Lyme disease (LD) or tick-borne borreliosis affects thousands of people every year in different regions of the world, primarily in the United States and Europe. Given the great social and medical importance of this problem, an updated version of the clinical guidelines for the prevention, diagnosis and treatment of PD was published in November 2020 by a committee of experts of the Infectious Diseases Society of America (IDSA), the American Academy of Neurology (AAN) and the American College of Rheumatology (ACR). This article discusses the main issues of the use of antibacterial drugs in LD. The most commonly used medications are doxycycline, amoxicillin, cefuroxime axetil, and ceftriaxone. Patients with erythema migrans receive appropriate antibiotics for 7–14 days, depending on the medication used. In case of other clinical manifestations of LD, the duration of treatment is extended to 14–28 days. Antibiotic prophylaxis is carried out using a single oral dose of 200 mg doxycycline for adults and 4.4 mg/kg (with a maximum of 200 mg) for children. This treatment scheme is highly efficient, easy to administer, and has a relatively low risk of adverse events.

Lyme disease (LD) or tick-borne borreliosis affects thousands of people every year in different regions of the world, primarily the United States and Europe. In endemic areas, early LD is a common disease that requires high medical vigilance. Considering the extreme relevance of this problem for public health, in November 2020, the committee of experts of three American scientific societies published an updated version of the clinical guidelines for the prevention, diagnosis and treatment of LD, the main provisions of which are presented in this article. It is emphasized that in the absence of vaccines, the risk of LD and other diseases transmitted by ticks can be reduced by using personal protective equipment and repellents. Antibiotic prophylaxis is carried out by a single oral administration of doxycycline. In the laboratory diagnosis of LD, the determination of antibodies to B. burgdorfery in the blood serum is a first-line study. At the second stage, serum samples are examined using an immunoblot for IgM and IgG. The basis of treatment of LD is rational antibiotic therapy. The choice of an antibiotic depends on a number of factors, including the presence of extracutaneous manifestations of LD (neuroborreliosis, carditis, arthritis). The most commonly used are doxycycline, amoxicillin, cefuroxime-axetil and ceftriaxone.

Introduction: Lyme disease is the most common disease transmitted by ticks. In Poland, over 20,000 cases of this disease were diagnosed in 2019. The first vaccine approved to prevent this condition was Lymerix. Currently, we do not have any preparation registered for this purpose. Data from Phase 2 trials of VLA15 show strong immunogenicity in both adults and children, with an acceptable safety and tolerability profile in both study populations Aim: The purpose of this paper is to present the current state of the art in research into the VLA15 vaccine. Results: Phase 3 of the VALOR study has started. Ultimately, about 6,000 participants aged 5 and older are to take part in it. The experiment is conducted in a dozen or so sites located in areas where Lyme disease is highly endemic. Participants will receive three doses of VLA15 180 µg or a placebo in saline as the first series of vaccinations, followed by one booster dose of VLA15 or placebo in 0.9% NaCl (1: 1 ratio). Conclusion: Phase 2 studies on VLA15 showed promising results. Phase 3 of the research is ongoing. Key words: VLA15, Lyme disease, Borrelia

Borreliosis (Lyme borreliosis; Lyme disease) is a zoonotic disease caused by spirochetes from the genus Borrelia. In humans, the accidental host of ticks, the infection is transmitted by the bite of the tick - the spirochetes are present in the salivary glands of the tick. Any of the three forms of tick: larva, nymph and adult can be responsible for infection. The most common threats to humans are Borrelia burgdorferii sensu stricto, Borrelia garinii and Borrelia afzelii occurring mainly in Europe. Lyme disease is a complex, multi-stage disease and progresses in 3 stages. The targeted treatment of Lyme disease is based on the administration of antibiotics. The introduction of antibiotics in the early stages of Lyme borreliosis offers a good chance of a complete cure. Lyme disease is a major epidemiological problem in the world. In Europe, the average number of cases per year remains at 65,400. In Poland, the number of infections annually reaches several tens of thousands. According to the National Institute of Hygiene of Poland, which keeps statistics of epidemiological reports, a total of 83,495 people fell sick with Lyme disease in Poland between 2016 and 2019. Whereas in 2020, the number of cases of Lyme disease decreased to 12933. The reason for this is undoubtedly the COVID-19 pandemic, which has dominated health care and focused all the attention of medical workers. This review shows that Lyme borreliosis is a dangerous disease with a high risk of complications. A quick diagnosis is crucial in the therapeutic process. An algorithm should be developed in order to distinguish other diseases from Lyme disease and thus enable an early reaction and treatment.

Introduction: Lyme disease is an infectious disease caused by Borrelia bacteria. Characteristic symptoms are erythema migrans, facial nerve palsy, aseptic meningitis, acquired heart blocks, chronic arthritis and radiculitis. The psychiatric manifestations of Lyme disease are known. They include cognitive, emotional and behavioral symptoms and syndromes. Purpose: The aim of the review was to present psychiatric disorders caused by Borrelia infection. State of knowledge: There are three basic types of infections causing neuropsychiatric symptoms: the meningovascular form associated with cerebrovascular infarcts; infection within the central nervous system which is the atrophic form of Lyme meningoencephalitis and is associated with cortical atrophy, gliosis and dementia and the last is infection outside the CNS causing immune and other effects within the CNS that contribute to neuropsychiatric symptoms. A range of psychiatric manifestations of borreliosis include psychosis, sleep disorders, anxiety disorders, depression, obsessive-compulsive disorder, intrusive symptoms, cognitive impairments and rapidly developing dementia. Summary: Lyme disease is a common problem in medical practice of many health professionals. It is important that physicians of different specialties, including psychiatrists, consider Lyme disease in differential diagnosis. Appropriate pharmacotherapy can stop the progression of the disease and improve the patient's quality of life.

Borreliosis after sucking ticks is an acute problem in the world. People do not go to doctors after that often, which leads to the development of various complications. Thrombosis of veins of various localization can be one of them. Thrombosis of the portal vein represents a significant problem too with high morbidity and mortality. The risk factors for splanchnic vein thrombosis include infections, but its relationship with borreliosis has not been studied. А 34-year-old man with chronic helicobacter-associated gastritis and gallstones was hospitalized due to development during the last 11 days of epigastric pain and fever to 38.7 °C after a picnic at the forest without a registered tick bite. The blood leukocytes were increased to 11.2*109/l, lymphocytes 70%, C-reactive protein 34.6 mg/l, procalcitonin 0.195 ng/ml. The multispiral computed tomography of the abdominal cavity revealed thrombosis of portal, lienalis and superior mesenteric veins. D-dimer was 1.98 mcg/ml, antithrombin III 75%. JACK2V617F, oncological, rheumatic, thrombophilia markers, blood and urine cultures were negative. A high concentration of anti-Borrelia burgdorferi IgM 62.2 U/ml and its increasing to 190 U/ml in dynamics was revealed at the immunofluorescence assay. Anti-Borrelia IgM to OspA, p31 and OspC, p25 were detected at the immunoblotting assay. Anticoagulation, doxycycline, detoxification therapy reduced pain and normalized temperature and inflammation markers. Vein thrombosis was not detected at the control tomography after 2 weeks. Despite that the combination of thrombosis and borreliosis is rare, it is necessary to screen for Borrelia antigens in patients with splanchnic vein thrombosis and fever.

Background. Early detection of tick-borne pathogens in blood samples of infected people prevents the disease before clinical manifestations using antibiotic and immunoglobulin treatment. As far as tick-borne diseases are associated with significant activation of innate immune response, the changes in the cytokine profile soon after a tick bite could be used as an indicator of early tick-borne infection. Aims. The goal of this study was to characterize the production of cytokines during first 2-4 days after a tick bite in asymptomatic people infected with tick-borne pathogens. Materials and methods. The infection of tick-borne encephalitis virus, B. burgdorferi sensu lato, A. phagocytophilum and E. chaffeensis / E. muris was detected in blood of bitten humans using appropriate commercial real time RT-PCR and ELISA assays. Concentration of 14 cytokines in plasma of 89 infected and 45 non-infected people was established using quantitative ELISA kits. Results. Between 2nd and 4th days after tick bite, the prevalence and concentration of certain cytokines in blood of infected people significantly differed from those of the control group. Bacterial pathogens exhibited very similar patterns of cytokine profiles with induction of IL-1a, IL-8 и IFN-a and suppression of SOD, IL-1Ra и IL-17A. For virus infection the increased concentrations of IL-1 a, IL-8, IL-10, IL-17A, IFN-y and SOD were detected. The only suppressed cytokine was IL-1Ra receptor antagonist. Conclusions. The results suggest that evaluation of innate immune response between 2nd and 4th days after the tick bite could be a useful tool for evaluation of the risk of tick-borne disease for the humans bitten by ticks.

Purpose of the study: To investigate the role and clinical inflammatory (IL-17A, IL-23, IL-33) and anti-inflammatory (IL-35) cytokines in patients with of form without erythema of Borrelia infection. Materials and methods: We studied 30 patients with of form without erythema of Lyme borreliosis. The diagnosis was based on epidemiological, medical history, clinical and laboratory, serological data. The blood serum interleukins level was detected from patients at admission to the infectious hospital and on the 10th day of hospitalization, as well as from 30 healthy donors. Groups of investigated persons were matched by sex and age. Blood serum analysis was carried out in the laboratory of directed regulation inter microbe interactions in the exo- and endoecological systems in Kirov State Medical University. Statistical analysis was performed using StatSoft Statistica v 10.0. Results: Patients with form without erythema of Lyme borreliosis oft have lesions of the respiratory system (60,0%), nervous system (53,3%), cardiac disorders (40,0%), rarely – liver disease (26,7%), joints (10,0%). In blood serum of patients with form without erythema at admission and at hospital discharge concentrations of IL-17A, IL-23, IL-33 are authentically higher compared with healthy donors. The content of anti-inflammatory IL-35 in patients with a form without erythema during hospitalization and at discharge is authentically lower than in healthy donors. Conclusion: Patients with form without erythema of Lyme borreliosis have early combined Th1-Th2 immune response (increased content of blood serum IL-23 and IL-33). Elevated concentrations of IL-17A and IL-33 serum in patients with form without erythema indicate the presence of autoimmune or allergic reactions. Patients with form without erythema have inflammatory processes limited moderately by inflammatory reactions on the part of Treg-system (lack of IL-35 production).

Ixodid ticks are the vectors of many pathogens including tick-borne encephalitis virus and the Lyme disease agent Borrelia burgdorferi sensu lato. In Pribaikalye, Ixodes persulcatus, Dermacentor nuttalli, D. silvarum and Haemaphysalis concinna are regarded as main vectors of the diseases. Recently, significant changes in world tick fauna have been reported and this affects the spread of tick-borne pathogens. We studied the current species diversity, population structure and the number of attacks of hard ticks (Acari:Ixodidae) on humans in Irkutsk region and nearby territories during the season 2015. Long-term trends of changes in attack rate were analyzed as well. In total, 4268 individual ticks were identified and analyzed during the season 2015. The majority (86 %) of victims was bitten by I. persulcatus; 13.55 % of attacks on humans were caused by D. nuttalli and D. silvarum; whereas H. concinna was documented only in 2 cases (~0.05 %). No non-endemic or invasive tick species were documented in 2015. The seasonal activity and the age/gender structure of tick population that bite human hosts were described as well. The comparison of the results of 2015 with previously reported datasets on tick bite ratesfrom 1992-2001 andfrom 2007-2014 indicates that, after the burst of tick bites in 1992-2001, there are no significant increase of attack rate since 2007. Possible implications to human health and epidemiology of tick-borne infections are discussed.

The urgent detection of tick-borne pathogens in attached ticks or in human blood followed by the prophylaxis of infection with specific immunoglobulin and/or antibiotics is one of the most reliable measures to prevent human disease. The aim of this work was to evaluate the usability of real-time PCR (RT-PCR) assay in early detection of tick-borne infections. Using commercial RT-PCR assay (Amplisens, Russia) we studied 361 Ixodes persulcatus ticks, 33 Dermacentor sp. ticks and 448 samples of human blood delivered by people attacked by ticks in Irkutsk region during 2013-2014for presence of DNA/RNA of tick-borne encephalitis virus (TBEV), Borrelia burgdorferi sensu lato (B.b.s.l.), Anaplsma phagocytophilum and Ehrlichia chaffeensis/E. muris. The ELISA assay and direct microscopy were used to validate the detection of TBEV and B.b.s.l. respectively. The highest prevalence of tick-borne infections was observed for I. persulcatus ticks - 6,9; 23,8; 6,9; and 11,9 % for TBEV, B.b.s.l., A. phagocytophillum and E. chaffeensis/E. muris respectively. The Dermacentor sp. ticks were less frequently infected with abovementioned pathogens - 3,0; 6,1; 3,0 and 9,1 % respectively. The prevalence of infection in blood samples was lowest and comprised 2,5; 4,2; 2,2 and 4,5 % respectively. Mixed infections were documented in 6,5 % of ticks and 0,7 % of human blood samples. The testing of blood samples in ELISA and testing of ticks in ELISA and direct microscopy corresponded to the results, obtained by RT-PCR. Thus, RT-PCR is valuable and reliable approach for urgent detection and prophylaxis of tick-borne infections.

Ixodes tick-borne borrelioses found both in Europe, Asia and in America. It has long been known that the disease is transferred ticks. It has been proven, and the assumption of transplacental transmission of Borrelia. But so far not proved the existence of congenital borreliosis. Numerous studies conducted in various countries have not been able to prove or disprove the possible impact of infection on prenatal development of the child. In spite of this, the world’s developed principles of chemoprophylaxis borreliosis in pregnant women after tick bites. Also developed an effective therapy borreliosis in pregnant women. Russia is a country with a high incidence of Lyme disease. Meanwhile, in the domestic literature is almost no descriptions of cases of suspected congenital Lyme. The results obtained in other countries, need to continue to explore the possible impact on the fetus borreliosis. Before domestic doctors and scientists continue to study the task, begun counterparts in other countries.

Borreliosis, encephalitis, anaplasmosis, ehrlichiosis and babesiosis belongs to tick-borne transmissive diseases. These diseases are dangerous for human and animals as well. Moreover, some animals can have no clinical signs of these diseases. These diseases are widely spread across Russian Federation, although only encephalitis and borreliosis (Lyme disease) are being monitored nowadays. At the same time anaplasmosis, ehrlichiosis and babesiosis (pyroplasmosis) are not being monitored. Thus a goal of monitoring of these diseases appears. The main vector for these diseases are ticks. Ticks can carry and transmit causative agents of the diseases to domestic and wild animals. Thus a goal of monitoring transmissible diseases in different population of ticks gathered in our country appears. In this study PCR was chose. This method is perspective and is widely used to detect infectious diseases nowadays. Moreover this method allows getting results in quite short period of time. The goal of this work is to determine the presence of causative agents of tick-borne diseases in ticks of different species gathered in different areas of Kirov region in 2010–2015 with the help of PCR. Moreover the goal was to determine if there is a relation between a number of infected ticks and its species. To solve these goal a primers, PCR conditions, method of extraction of total nucleic acid from fixed and alive ticks were engineered. Method of extraction of total nucleic acids allowed with the help of a reverse transcriptase to determine tick-borne encephalitis virus in samples. Analyzed ticks were gathered in Kirov region. It was determined that main vectors in these region are of an Ixodes persulcatus and a Dermacentor reticulatus species. It was prooved that the number of infected ticks can vary in time. It was also proved that there is no significant difference in the number of infected with TBEV and Lyme disease causative agents but there is a significant difference in the number of infected ticks with anaplasmosis, ehrlichiosis and babesiosis causative agents.

The Crimean Peninsula is located in the Northern part of the Black sea, from the East it is washed by the Sea of Azov, to the South and West by the Black Sea. The unique geographical and climatic conditions facilitate leptospirosis, tularemia, tick-borne encephalitis, Lyme disease, intestinal yersiniosis, pseudotuberculosis, hemorrhagic fever with renal syndrome, Crimean-Congo hemorrhagic fever, Mediterranean fever, Q-fever and other infectious diseases natural foci formation on the territory of Crimea Republic. Tick-borne natural focal infections have the most significance due to favorable epidemiologic conditions especially on the background of high raid ticks attacks on people. A leading role in the epizootology and epidemiology of tick-borne natural-focal infections of the Crimea are playing Ixodidae that occur in different landscape-climatic zones, with the greatest their species diversity is observed in mountain-foothill, forest and forest-steppe regions. There are about 30 species in Ixodidae fauna of the Crimean Peninsula. Ticks species composition identification shows that over 50% of people attacks episodes in the Crimea on recent years is caused by Ixodes ricinus ticks species, the remaining are associated with Haemophisalis punctata, Rhipicephalus sanguineus, Hyalomma marginatum, Dermacentor marginatus and other. Refusal of treatment in medical institutions of the people affected by tick bites, and the possibility of an attack on people subtle phases of mites are lubricates the real picture of the frequency of contacts of the population with ticks and complicates the forecasting of the epidemiological situation. This review summarizes the available information about spreading of tick-borne encephalitis, Lyme disease, Mediterranean and Crimean-Congo haemorrhagic fevers on the territory of Crimea Republic and demonstrates the modern trends and manifestations of epidemic process of these nosological forms. The results obtained in the analysis of our investigations and literature data, showed that the conditions of globalization lead to an increase in the frequency of contacts of the population with natural foci, and one of the most common tick-borne natural focal infections on the territory of the Peninsula are Lyme disease and the Mediterranean fever. Epidemiological analysis of the prevalence of tick-borne encephalitis and Crimean-Congo haemorrhagic fever in Crimea revealed a decrease in the activity of natural foci of these infections at the present stage. The problem of tick-borne natural focal infections in Crimea Republic requires further careful study.

For the first time the current situation with tick-borne infections in recreational places of the Republic of Buryatia is evaluated. According to the data of the Center for diagnostic and prophylaxis of tick-borne infections (Irkutsk) collected in 2007 - 2014 the tick-borne encephalitis, Lyme disease, monocytic ehrlichiosis and granulocytic anaplasmosis are widely spread in most popular recreational places of south coast of the Baikal Lake and Tunka valley.

Detection of clinico-epidemiological features of the mixed tick-borne infections – tick-borne Lyme disease and a human granulocytic anaplasmosis was the purpose of the conducted research. During the spring – summer period 146 patients with tick-borne borreliosis were surveyed. As a result at 45 (30,82%) patients authentically diagnosed the mixed tick-borne infection. Features of clinical manifestations of a mixed tick-borne infection revealed: catarrhal phenomena (20%), liver defeats (33%), nephros (31, 7%), frequent secondary erythems (20%). Changes in haemogram defined: thrombocytopenia (42,2%), anemia (20%), leukopenia (13,3%).

This review present current immunological, microbiological and molecular genetic features of Lyme disease. The mechanisms of borrelia’s dissemination and adaptation in the macroorganism are describe. The role of B. burgdorferi s.l. in the development of autoimmune diseases and non-Hodgkin-lymfomas is describe.

The article presents the results of a survey of 77 patients with confirmed acute tick-borne infection in the age of 1 year to 17 years. Three patients (5%) selected Borrelia miyamotoi. Identified clinical and laboratory features of infection caused by Borrelia miyamotoi. It is shown that Borrelia miyamotoi causes the development of recurrent febrile conditions without erythema migrans at the background of marked cerebral symptoms. In this regard, necessary to carry out a differential diagnosis of this disease with tick borne encephalitis.

During 1999-2011 we conducted the collaborative research in Northern, Central and Eastern Mongolia. Several tick-borne infections were revealed in ticks and. human patients. Most important of them are tick-borne encephalitis, Lyme disease, tick-borne rickettsiosis, human granulocytic anaplasmosis and. babesiosis. The importance, risk of infection and. spread of tick-borne diseases in Mongolia are discussed in the paper.

The aim of this work was creation of recombinant chimeric protein using TAKARA expression system Brevibacillus choshinensis with fused gene dbpAAG, which include the parts of dbpAA and dbpAG genes coding the major antigenic determinants of decorinbinding proteins А (DbpA) from two species of borreliosis agents - Borrelia afzelii and Borrelia gаrinii. Such plasmid should be able to support the synthesis of recombinant chimeric polypeptide consisting immunogenic domains of DbpA Borrelia afzelii and Borrelia gаrinii in the stable and soluble forms, that important for effective using in Lyme diseases serodiagnosis. We chose the TAKARA expression system based on the strain Brevibacillus choshinensis and plasmid pNCMO2. It give us possibilities to obtain the scale quantity of the secreted soluble target proteins with native conformation in particular with conserve antigenic determinants. As results, the plasmid pNCMO2 with a fusion gene dbpAAG was constructed. Recombinante plasmide DNA pNCMO2/dbpAAG was used for Brevibacillus choshinensis trasformation. We were able to show that during cultivation in a liquid medium recombinant cells of В. choshinensis/pNCMO2/dbpAAG produced secreted chimeric 30кD protein with high immunoreactivity to Lyme borreliosis patient's serum., Competing Interests: The authors declare no conflict of interest.