Ixodes Tick-borne Borreliosis Research Articles

Zoonoses as factor of evolution, population dynamics, and speciation

The role of zoonoses in changes of animal populations and communities is considered. The analysis was carried out using examples of population dynamics of small mammals distributed in the Crimean Peninsula, under the influence of the main zoonoses common for this territory, in particular tularaemia, leptospirosis, Marseille fever, viral tick-borne encephalitis, Ixodes tick-borne borreliosis, Crimea-Congo fever, KU fever, HFRS, and many others. Such data were analysed according to databases on the state of small-mammal populations and zoonoses common in these populations, obtained by original studies over the past 40 years. The role of zoonoses as factors of evolutionary changes in populations of small mammals is considered, in particular as a factor of mortality leading to significant reductions in population numbers and fragmentation of species ranges, as well as factors determining co-evolution of pathogens, vectors (arthropods), and small-mammals as hosts. Both groups of factors lead to the formation of population diversity due to changes in character variability and the formation of new characters associated with adaptations to zoonoses.

Role of <em>Ixodes Pavlovskyi</em> (Acari, Ixodidae) in Borreliosis Epizootic Process at the Island Russky

The incidence of Ixodes tick-borne borreliosis (ITBB) at the Island Russky (Primorsk Territory) is higher than at the mainland. There is a bidominant structure of the tick population with mass occurrence of Ixodes persulcatus and I. pavlovskyi at the island. Due to the higher infectivity and aggressiveness of I. persulcatus, it is suggested that it plays a key role in high activity of the ITBB focus at the island.The aim of the study: to characterize the role of I. pavlovskyi in the borreliosis epizootic process based on the study of the structure of the borrelia genotype complex isolated from Ixodes ticks at the Island Russky.Materials and methods. The ticks were collected from vegetation at three sites. Ixodide species were determined morphologically and using PCR for mitochondrial gene cox1 and nuclear multicopy locus ITS2. Infection of 233 ticks was analyzed with the species identification confirmed by all methods. Borrelia genospecies were determined by multiplex two-round PCR with the primers specific to the gene fragments 5S and 23S rRNA of Borrelia burgdorferi sensu lato complex.Results and discussion. Coexistence of I. persulcatus and I. pavlovskyi at the island was confirmed, with different ratios in space and a gradual increase in the proportion of the latter species. The circulation of three etiological agents of ITBB: Borrelia garinii (predominantly in I. pavlovskyi), B. bavariensis and B. afzelii (in I. persulcatus) was identified. Thus, an active natural focus of ITBB has formed at the island, probably including two uninsulated chains of borrelia circulation. One chain combines I. persulcatus and small and large mammals as the tick feeders. The second – I. pavlovskyi that can feed on mammals and birds. Due to the spatial variability of the ixodide population structure at different sections of the island, the ratio of the circulating borrelia species can change, and this species becomes the main vector of the pathogenic agents in areas of I. pavlovskyi absolute dominance.

Clinical mimics and diagnostic challenges in tick-borne borreliosis: a systematic review

Background. Ixodes tick-borne borreliosis (TBB) is a clinically multifaceted disease posing a serious threat in most territories of the Russian Federation. New TBB outbreaks emerge and spread to the country’s south.Objectives. The review highlights the TBB clinical diversity to physicians in order to improve the diagnosis quality and opportune aid. It focuses on the early and late clinical presentation of localised and disseminated polysystemic TBB.Methods. Sources were mined in the MEDLINE, PubMed and national electronic databases (Сyberleninka, eLibrary, etc.) with keywords “tick-borne borreliosis” [клещевой боррелиоз], “Lyme disease” [болезнь Лайма], “Lyme arthritis” [Лайм-артриты], neuroborreliosis [нейроборрелиоз] for the period of 2014–2020. Selected impactive publications within 2007–2013 were also included. Research was considered eligible if borreliosis was diagnosed using specific techniques like immune-enzyme assays, immunoblotting or PCR.Results. TBB is a common and cross-disciplinary situation. The disease may progress occult or manifest in a variety of forms, from annular erythema to cardiac, peripheral and central nervous system involvement or arthritis. The polysystemic nature of lesions, often long-term of the tick bite, forces multiple specialist visits ending with misdiagnoses, late aetiotropic therapy and transition into a chronic phase through ignorance of the patient’s epidemiological record. Some patients may have the acute phase followed by irreversible neurological damage associated with memory loss, cognitive decline, arthrosis and sclerotic skin change reducing the quality of life.Conclusion. TBB can be mimicked by therapeutic, neurological, skin and ophthalmic illnesses, which warrants the physician’s attention to the epidemiological record and knowledge of specific diagnostic techniques. Further research is necessary into the pathogenesis and clinical presentation of chronic TBB and its residual manifestations.

Lyme borreliosis: clinical and epidemiological features of its course in the territory of large industrial center of Western Urals

Objective. Since the territory of the Western Urals is widely known for its high morbidity and mortality rates associated with tick-borne infections, including ixodic tick-borne borreliosis, the study was aimed at estimation of the role of specific prevention in the prevalence of ITB.
 Materials and methods. A continuous retrospective clinical and laboratory analysis of 1214 adult patients admitted to Perm Regional Clinical Infectious Disease Hospital with lyme - borreliosis in 2012-2019 was carried out.
 Results. The disease is registered more often in persons over 50 years old, infection mainly occurs while visiting forests and park zones that requires the use of means of protection to reduce the number of the carriers of infection. Every third patient has mixed infection, where pathogens circulating in the ticks of the given territory of the Western Urals are combined. The increase in the number of non-erythemic forms in the recent years is probably associated with the development of immunodeficiency in the population of the industrial center, as well as with the use of more sensitive and informative methods of laboratory diagnostics.
 Conclusions. Specific prophylaxis is highly effective, helping to prevent infection in more than 90% of cases.

Emerging and re-emerging natural focal diseases of European Russia (typological classification of nosological profiles and dynamics of incidence)

This study considers an automated typological classification version by using the extensive factual material in analysis of emerging and re-emerging natural focal diseases of European Russia.The typological classification of nosological profile (a set of diseases) and the incidence dynamics for five nosological forms (hemorrhagic fever with renal syndrome, ixodic tick-borne borreliosis, tick-borne encephalitis, tularemia, and leptospirosis) was created using the formal methods of mathematical-cartographical modeling. This classification of the incidence in 1997–2015 yielded five types of the nosological profiles. These types vary by years, which is associated with the dependence of the incidence on climatic conditions in each specific year and on extent of deratization and preventive measures. The results obtained can be used to forecast potential epidemiological outbreaks and to develop targeted and appropriate for each region measures.

Cellular immune response in convalescents from Ixodes tick-borne borreliosis

Ixodes tick-borne borreliosis is a natural focal transmissive infectious multi-system disease featured with complex pathogenesis, which multiple aspects remain unclarified. The persistence stage during this infection associated with prolonged Borrelia presence in metastatic foci and repeated multiple dissemination is most complicated for clinical practice. It is assumed that the chronic process can be caused by an inadequate immune response associated with activated autoimmune mechanisms leading to emergence of permanent irreversible (degenerative and atrophic) changes in affected organs. Patients who experienced tick-borne borreliosis need dynamic observation for assessing disease prognosis providing a maintenance therapy. The purpose of the study was to evaluate an opportunity of using cellular immunity indices for predicting disease transition to a chronic course.Materials and methods. The study was carried out at the Medical Association of the Far East Branch of the Russian Academy of Sciences. Case report form data, serum and blood plasma samples collected from 22 patients aged 29–83 years old were examined. Immunological examination data from patients with ixodes tick-borne borreliosis (12–18 months after the onset of acute period) were analyzed. Specific IgM and IgG against Borrelia burgdorferi were determined by using the OMNICS diagnostic test system (St. Petersburg). Lymphocyte immunophenotyping was performed on BD FACSCalibur flow cytometer (Becton Dickinson, USA) by using doublelabeled monoclonal antibodies (Beckman Coulter, France).Results. A variability of activated peripheral blood lymphocytes was found in patients with tick-borne borreliosis evidencing about individual immune response. An imbalanced cellular immune response recorded in seronegative convalescents from tick-borne borreliosis, may be an indirect finding of ongoing Borrelia infection. Finding of specific serum IgG and IgM antibodies in convalescents at late stage coupled to impaired immune system is a warning sign presuming a risk to developing autoimmune reactions. Detection of specific IgM antibodies at late timepoint combined with increased immune cytotoxic potential may be referred to a marker of possible disease transition to chronic course.

Genospecies Diversity of Borrelia in Ixodes Ticks of the West Siberia

Objective : to determine genospecies composition of Borrelia in the ixodid ticks of various species in natural foci of Ixodes tick-borne borreliosis (ITB) in the South of Western Siberia. Materials and methods . A total of 1148 examples of ticks collected from vegetation and 2183 examples of ticks withdrawn from persons seeking medical help have been tested by bacteriological (sowing in BSK-H medium, SIGMA, USA) and Real Time PCR methods. Genotyping of Borrelia was performed by sequencing. Results and conclusions . Infection of Ixodes ticks with borrelia ranged from 22.4 % in the Altay Republic to 56.9 % in the Novosibirsk Region. Reliable differences in borrelia infection rates of ticks I. persulcatus and I. pavlovskiy have not been established (average levels of infection 40 % and 38.8 %, respectively). The study of isolates of borrelia sp. circulating in natural foci of the West Siberia showed the presence of at least four genospecies of pathogenic borrelia ( B. garinii, B. afzelii, B. bavariensis, B. miyamotoi ). 30 nucleotide sequences of the rrf (5S)-rrl (23S) intergenic spacer were submitted to GenBank database. The detection rate of genospecies B. garinii and B. afzelii of different types of ticks ( I. persulcatus and I. pavlovskiy ) has no significant difference. More frequent occurrence of B. garinii in comparison with that of B. afzelii was determined. The level of I. persulcatus ticks infection with B. miyamotoi was significantly lower than that with genospecies B. garanii and B. afzelii. DNA of B. spielmanii and B. miyamotoi was detected in ticks D. reticulatus . Further evaluation of the role of ticks D. reticulatus in the distribution of borrelia in ticks in natural foci of the Russian Federation is necessary.

Ixodic Tick-Borne Borreliosis in the Krasnodar Krai

Aim. Clinical, epidemic and laboratory characterisation of ixodic tick-borne borreliosis in order to improve the early diagnosis of the disease and the timely etiotropic therapy.Materials and methods. The medical histories of 257 patients with ixodic tick-borne borreliosis treated in the regional infectious diseases hospital in Krasnodar from 2004 to 2018 were analysed. The data of the epidemiological history, the clinical manifestations of the disease, the results of laboratory and instrumental studies, as well as the principles of therapy were analysed.Results. The incidence of ixodic tick-borne borreliosis in the Krasnodar Krai is characterised by spring-summer seasonality, the predominance among women over 45, and urban residents. The disease has an acute course (85.9%), occurs mainly in the erythema form with little pronounced symptoms of intoxication, a typical ring-shaped erythema, which large dimensions remain longer in women. During the non-erythemic form of the disease, the development of serous meningitis and encephalomeningitis with impaired cerebral blood fl ow as well as the changes in corticocortical relationships were observed. During the sub-acute course, radiculopathy and polyneuropathy, as well as diffuse changes of the myocardium with conduction disturbance and the development of atrioventricular block, arthralgia and arthritis/arthrosis were registered. The increase in LDH, CPK and transaminase was observed for all forms of the disease.Conclusion. In connection with the formation of a natural ixodic tick-borne borreliosis focus on the territory of the Krasnodar Krai, it is necessary to exclude this disease in patients with the signs of fever, weakness, and erythema at the site of tick suction. The tendency of ixodic tickborne borreliosis to the long course with the development of multiorgan pathology causes the need for follow-up observation of recovered patients both by an infectious disease specialist and narrow specialists (a neurologist, rheumatologist or cardiologist).

Epidemiological features of Ixodic tick-borne Borreliosis in children in the Ulyanovsk region

This paper presents materials on the incidence of children with ixodiс tick-borne borreliosis in the Ulyanovsk region for the period 1996—2017.28 cases of tick-borne borreliosis among children were recorded. Tick suction in April-May was observed in 6 (21.4%) children, in June—August — in 12 (42.9%), in September—November — in 10 (35.7%). Migratory erythema was detected in 15 patients (53.6%). In half of the cases, moderate intoxication symptoms were observed (57.1%). Borreliosis was confirmed laboratory early in 75% of cases.Thus, a feature of ixodiс tick-borne borreliosis in children in the Ulyanovsk region is: detection of the disease during the period of tick activity, that is, in the early stages; equal ratio of erythema and non-erythhema forms; the prevalence in the clinic of mild symptoms of intoxication; laboratory confirmation in 75% of cases in the early stages. The presence of migratory erythema in the patient gives reason for the diagnosis of ixodiс tick-borne borreliosis even in the absence of positive results of a serological examination.

Modern Epidemiological and Epizootiological Situation on Ixodic Tick-Borne Borreliosis in the South of the European Part of Russia

The aim is to analyze the current epidemiological and epizootiological situation on ixodic tick-bome borreliosis in the South of the European part of Russia. Materials and methods . The research materials were the epidemiological and epizootiological data for 2014-2018 provided by the Rospotrebnadzor Departments, the Hygiene and Epidemiology Centers of the North Caucasian and Southern Federal Districts, and regional anti-plague institutions: Stavropol, Volgograd and Rostov-on-Don research anti-plague institutes, Astrakhan, Dagestan, Kabardino-Balkar, Black Sea, North Caucasus, Elista plague control stations, as well as the plague control station of the Republic of Crimea. The data of scientific publications on epizooitological monitoring, the species composition of vectors and agents of tick-borne borreliosis involved in the epizootic and epidemic process in the region were studied. In the study descriptive, analytical epidemiological methods, retrospective epidemiological and cartographic analyzes were used. Results and discussion . It has been noted that in 1999, the incidence of tick-borne borreliosis in the South of the European part of Russia, has occurred in 11 of the 15 administrative regions. The incidence of tick-borne borreliosis in the Republic of Kalmykia, has not been recorded since 2007, in the Chechen Republic - since 2014. To clarify the sources of tick-borne borreliosis infection in the territory of the Krasnodar and Stavropol Territories, the Volgograd and Rostov Regions, the Republic of Dagestan and the Karachay-Cherkess Republic, and also, to determine the boundaries of natural and natural-anthropurgic foci of ixodic tick-borne borreliosis constant epizootiological monitoring is required. In addition, it is necessary to create a unified algorithm for monitoring natural foci, to analyze data using modern geographic information and statistical tools.

Erythematous ixodic tick-borne borreliosis in children over twenty-year monitoring period

We generalized the observed results obtained in the last twenty years from patients at the age of 1 to 14 years suffered from acute erythematous ixodic tick-borne borreliosis. Clinical characteristics of erythematous ixodic tick-borne borreliosis have not changed dramatically over twenty years. Key manifestations in children remain erythema at the site of a tick bite, fever, and regional lymphadenitis. These signs allow us to diagnose nosological form of the disease.

IX0DIC TICK-BORNE B0RRELI0SIS IN THE SAMARA REGION

The article is devoted to the identification of regional peculiarities of tick-borne borreliosis in the Samara region. Over the past 10 years, the Samara region has seen an increase in the number of cases of ticks sucking by 2.5 times, as well as an increase in contamination of ixodic ticks by Borrelia. Infection of patients with tick-borne borreliosis was observed not only in forest area, but also in the city. Cases of the disease were recorded from May to October. In this region asthenovegetative syndromes, exanthema, fever and regional lymphadenitis were revealed in patients diagnosed with ixodic tick-borne borreliosis.

EPIDEMIOLOGICAL FEATURES OF IXODES TICK-BORNE BORELIOSES IN THE KRASNOYARSK TERRITORY IN THE CONTEXT OF SEARCHING FOR THE CASES OF INFECTION CAUSED BY BORRELIA MIYAMOTOI

Aim. Estimation of the prevalence of Ixodes tick-borne borreliosis (ITBB) without erythema migrans in the Krasnoyarsk Territory in comparison with the prevalence of ITBB with erythema, that is Lyme disease (LD). Detection of cases of «new» infection caused by Borrelia miyamotoi (ITBB-BM) among patients with suspected tick-borne infection, primarily among patients with ITBB without erythema (ITBB-W/O-E). Materials and methods. We analyzed the database of Rospotrebnadzor containing individualized information about cases of ITBB officially registered in the Krasnoyarsk Territory in 2011 — 2016. Blood samples from 18 patients with suspected of tick-borne infection hospitalized in the Krasnoyarsk Emergency Hospital in 2017 were collected and studied. ITBB-BM was diagnosed if B. miyamotoi DNA was found in patient’s blood and/or the antibodies to specific antigens of B. miyamotoi were detected. Results. With an average annual incidence rate of ITBB of about 10 cases per 100,000 population, the proportion of ITBB-W/O-E among all ITBB in the Krasnoyarsk Territory is about 45%. Epidemiological characteristics of ITBB-W/O-E and LD are similar, but these diseases are very different clinically. All cases of ITBBW/O-E and some cases of tick-borne infections of unknown etiology, subjected to our enhanced laboratory diagnostics, were caused by B. miyamotoi. Conclusion. ITBB-W/O-E is a widespread disease in the Krasnoyarsk Territory, caused mainly by B. miyamotoi. The results of the study significantly expand the known geographic area of the ITBB-BM.

Ixodic tick-borne borreliosis: clinical and laboratory features.

For a differentiation of clinical forms of ixodic tick-borne borreliosis clinical laboratory assessment of features of the most often defined hemostasis and complete blood count (CBC) indicators is carried out. Ixodic tick-borne borreliosis in the territory of the Republic of Bashkortostan is characterized by mainly erythematous forms of a disease with a medium-weight current. At the same time some increase in quantity of platelets was noted that could be caused by irritation of a megakaryocytic sprout of bone marrow in the conditions of infectious process and have compensatory character whereas other indicators of CBC and hemostasis at this clinical form practically didn't change. Not numerous cases of the ixodic tick-borne borreliosis non-erythematous forms clinically proceeded more hard, with significantly more expressed toxicinflammatory syndrome. At the same time it was followed by significant shifts in biochemical parameters, indicators of CBC and hemostasis. The clinical laboratory features of erythematous and non-erythematous forms of ixodic tick-borne borreliosis revealed as a result of the conducted researches reflect character of a course of disease and can serve for assessment of severity, the forecast of the infection and justification of this treatment.

Clinical case of ixodes tick-borne borreliosis with development a-v blockade and implantation of the pacemaker

Borreliosis is an infectious transmissible natural-focal disease caused by borrelia of borrelia burgdorferi sensu lato group and transmitted by ixodic ticks. In the article a clinical case of chronic ixodic tick-borne borreliosis is described with the primary damage to the heart, joints and with polyneuropathy of extremities. The described clinical case is interesting on the one hand by demonstration of peculiarities of the heart damage associated with ixodic tick-borne borreliosis which finally lead to transient III degree A-V block with episodes of asystole up to 5.5 s and to implantation of continuous pacemaker. On the other hand, surprising in XXI century is the fact that despite a wide availability of high-tech methods of diagnostics and treatment in any field of medicine, the ixodic tick-borne borreliosis was identified only in 6 years after the moment of manifestations of clinical symptoms.

PCR Results of Vector and Carrier Investigations for the Presence of Tick-Borne Borreliosis, Human Monocytic Ehrlichiosis, and Human Granulocytic Anaplasmosis Agents in Natural Foci of the Rostov Region

Objective of the study is to detect the circulation of the agents of ixodic tick-borne borreliosis (ITB), human monocytic ehrlichiosis (HME), and human granulocytic anaplasmosis (HGA) in samples collected from carriers and vectors of transmissible tick-borne infections using PCR-assay. Materials and methods. Field material was studied in PCR for evaluating the rate of infection by causative agents of tick-borne infections (tick-borne borrelioses, ehrlichioses, anaplasmosis) in combined natural foci on the territory of the Rostov Region. Results and conclusions. The data obtained during epizootiological investigations carried out in 21 administrative districts and 10 cities of the Rostov Region between 2014 and 2016 were used in the study. The results were indicative of spontaneous infection in ixodic ticks by ITB causative agent on the territory of the Rostov Region, as well as of presence of corresponding natural focus. Since 2013 the activity of different components of ITB natural focus was confirmed by the detection and official registration of patients. Moreover, in the Rostov Region for the first time ever the circulation of HME and HGA causative agents was recorded and territorially combined foci of HME and HGA with ITB were identified. The results obtained allow assuming the genesis of a focus of ixodic tick-borne borreliosis and monocytic and granulocytic ehrlichioses owing to annual expansion of the areal of ticks, infected by these pathogens, and animals on which the ticks are feeding. PCR-analysis is of significant value for assessment of spread of causative agents of the “tick-borne” infections in the Rostov Region, forecasting of epidemiological situation, as well as implementation of preventive measures in the region.

Epidemiological features of ixodes tick-borne borrelioses in the regions of the center of the European part of Russia

The analysis of the level and long-term dynamics of the incidence of ixodic tick-borne borreliosis, the population's appeal for tick bites and the infection of mites with Borrelia burgdorferi sl. in the Moscow, Ryazan and Tula regions. An annual increase in the incidence of Lyme disease in the direction from the south to the north, from the forest-steppe to the southern taiga, was determined, due to the frequency of contacts of the population with Ixodes persulcatus Shulze 1930 and I. ricinus L. 1758. At the same time, a statistically significant relationship between the incidence of mites infection and the incidence of Lyme disease in The studied regions are not observed. The obtained results testify to a tense epidemic situation in the center of the European part of Russia and the need to implement all components of surveillance for the natural foci of the Lyme disease.

Microbiological Evidence of Etiology «Ixodes Tick-Borne Borreliosis without Erythema Migrans» - Infection Caused by Borrelia miyamotoi

Background. The spirochete Borrelia miyamotoi belongs to the group of borrelia causing tick-borne relapsing fevers. It is transmitted by the same tick species as Borrelia burgdorferi sensu lato and is widespread in temperate climate zones of Eurasia and North America. Previously we have shown by PCR that clinical cases presented as systemic febrile illness and diagnosed usually as «Ixodes tick-borne borreliosis without erythema migrans» were caused by B. miyamotoi. According to recent estimation in Russia there are several thousands human cases of B. miyamotoi infection annually. The investigation of this emerging human pathogen was hampered because the attempts to culture this bacterium directly from human blood failed. Results and conclusion: We here describe protocol - avoiding the inhibitory effects of anticoagulants on B. miyamotoi growth - enabling successful B. miyamotoi isolation from blood of Russian patients.

IMMUNOTHERAPY OF IXODES TICK BORRELIOSIS IN CHILDREN

The article presents the basic information relating to the clinical and immunological features of ixodes tick-borne borreliosis in children living in the Primorsky region. Research objective: to to analyze the effectiveness of the inclusion to the treatment scheme meglumine acridon acetate (cycloferon in pills) for the treatment of children with ixodes tick-borne borreliosis. The study included 55 children with ixodes tick-borne borreliosis at the age of 4–12 years: 25 children of the main group and 30 children of the comparison group who received traditional therapy. In the treatment scheme of children of the main group, the drug meglumine acridon acetate (cycloferon) was included. The use of cycloferon in the complex therapy of patients with ixodes tick-borne borreliosis resulted in a reduction in the duration of the manifestation of the main clinical symptoms of the disease, facilitated the synthesis of serum interleukine IL-10 by blood cells and inhibited the production of interleukine-1α and γ-interferon, which led to a faster formation of Th1 / Th2 type Immune response. Positive dynamics during treatment persisted in the study of the catamnesis of the patients observed for 5 years after the disease. There were no cases of chronic ixodes tick-borne borreliosis.

GENETIC POLYMORPHISM AND CYTOGENETIC CHANGES IN THE PERIPHERAL BLOOD T-LYMPHOCYTES OF PATIENTS WITH ARTHRITIS ASSOCIATED WITH IXODES TICK-BORNE BORRELIOSIS IN THE NORTHERN REGIONS OF SIBERIA

The authors have previously conducted studies that demonstrate the increased level of cytogenetic disturbances in patients with Ixodes tick-borne borreliosis (ITB). The severity of arthritis associated with ITB (AITB) is also ascertained to depend on whether the patient has certain HLA-DRB1 alleles. Objective : to assess the association between HLA-DRB1 gene polymorphism and cytogenetic changes in the peripheral blood T lymphocytes of patients with AITB. Subjects and methods . 146 patients with AITB, 100 clinically healthy convalescents with ITB (CITB), and a control group of 98 healthy blood donors (HBDs) without a history of tick-borne infections were examined using cytogenetic (micronucleus analysis of cytokinesis-blocked peripheral blood T lymphocytes) and molecular genetic (PCR analysis of HLA-DRB1 gene polymorphism) methods. Results and discussion. The frequency of cytokinesis-blocked lymphocytes with micronuclei in the AITB group was significantly higher than that in the CITB and HBD groups (p 0.05). The highest levels of lymphocytes with micronuclei were observed in AITB patients with the DRB1*17(03), *01, and *04 alleles as compared to those in the CITB and HBD groups (p 0.05). Thus, the patients with AITB had the highest frequency of cytogenetic disorders with the exception of individuals with the DRB1*10 allele.