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Introduction. The Epstein–Barr virus (EBV) is one of the most common pathogens — it infects 90% of the world’s population. However, specific characteristics of the EBV infection epidemic process remain unidentified. The previous studies focusing on assessment of incidence rates for infectious mononucleosis (IM) tend to ignore the serological status of the population.The aim of the study was to identify epidemiological characteristics and assess the prevalence of serological markers for EBV infection for further epidemic control measures development.Materials and methods. In Moscow, the thorough analysis was performed using the data on IM incidence (Form 2 "Data on Infectious and Parasitic Diseases") and test results for 138,232 people checked for presence of VCA IgG, EBNA IgG, VCA IgM, EA IgG, and EBV DNA in their blood and saliva in 2011–2020.Results. The periodic pattern of IM incidence was discovered, demonstrating the repetitive peaks every 9 to 11 years and a strong direct correlative relationship with detection rates for active EBV infection markers. The intra-annual dynamics of IM incidence is characterized by a seasonal upswing during cold seasons of the year, reaching its peaks in October, November, or February and associated with a marked decrease in the VCA IgG and EBNA IgG seroprevalence. Children within the 1 to 17-year age range are groups at risk for acquiring primary infection, demonstrating significantly lower detection rates for chronic EBV infection (VCA IgG and EBNA IgG) markers and higher rates for VCA IgM and EBV DNA markers in blood compared to adults. The contribution of adult population to the epidemic process is formed through reactivation of chronic infection, which is observed primarily among women.Conclusion. The identified characteristics are essential for comprehensive understanding of the EBV infection epidemic process and can be used for developing preventive and anti-epidemic measures.

Nontyphoid strains of Salmonella enterica pose a great threat to human health. The problem of salmonellosis is aggravated compounded by the progressive spread of antibiotic resistance among clinical and agricultural strains of S. enterica. This literature review summarizes the current knowledge of the mechanisms of antibiotic resistance in S. enterica and illustrates the diversity and complexity of molecular systems providing antibiotic resistance. The spectrum of natural resistance is described and the adaptive (acquired) mechanisms of resistance to representatives of the main classes of antibiotics, including fluoroquinolones, aminoglycosides, tetracyclines, nitrofurans, sulfonamides, fosfomycin and chloramphenicol, are thoroughly characterized. Particular emphasis is placed on the analysis of the molecular genetic mechanisms of S. enterica resistance to representatives of the most important classes of antibiotics — β-lactams, and to reserve antibiotics — polymyxins (colistin). Genetic determinants of resistance, transmitted by a horizontal path route are also described. The review analyzes only those variants of the molecular mechanisms of antibiotic resistance where the clinical significance has been proven by a set of correct genetic (sequencing) and biochemical (confirmation of the spectrum of hydrolyzed β-lactams) studies. The main ways of regulating the expression of antibiotic resistance are also described. Many S. enterica strains exhibit a combination of different mechanisms of antibiotic resistance and have a multiple resistance. The question was raised about the heterogeneity of the distribution of resistance among different groups/serotypes within the S. enterica species. In particular, some clonal complexes with signs of resistance are more successful pathogens in humans and animals. Salmonella, like most other bacteria, exhibit a non-canonical type of antibiotic resistance — biofilm resistance, which is realized through several mechanisms, the main of which are the filtering/sorption capacity of the biofilm matrix and the transformation of biofilm cells into dormant and persistent forms.Despite the fact that the functional significance of the molecular assemblies that determine antibiotic resistance is the same for all enterobacteria, the specification of the mechanisms of resistance in Salmonella is a necessary link for the development of molecular diagnostic systems for assessing the sensitivity to antimicrobial drugs.

Introduction. Currently, the participation of women in space flights is increasing. In this regard, questions about the influence of space factors on the state of the female body arise inevitably. Model experiments, in particular, "dry" immersion, are most convenient for studying the influence of individual factors of space flight on the organism. The aim of this work is a comparative assessment of the state of the vaginal microbiota of 6 female volunteers before and after three-day "dry" immersion.Materials and methods. Microbial samples of all volunteers were stained according to Gram with a sequential culture study in accordance with the medical technology. The species identification of microorganisms was performed by MALDI-TOF-MS analysis using an Autoflex III time-of-flight mass spectrometer with Maldi BioTyper software.To assess changes in the state of the vaginal microflora and microflora of the cervical canal, eubiotic index was used. It reflects the number of positive states of microbiota to the number of negative ones.Results. After 3 days of "dry" immersion volunteers, who had high titer of aerobic microorganisms before isolation, had significant increase of the amount of aerobic microorganisms, while the number of lactobacilli decreased. The other group of volunteers showed activation of colonization resistance of the vaginal microflora. Volunteers, who had a significant contamination with anaerobic opportunistic microflora before isolation, had reduction of the number of all anaerobes, including lactobacilli. The eubiotic index, calculated for the cervical canal, decreased after 3 days of immersion. The data obtained indicate that after 3 days of isolation, the state of the microflora has deteriorated.

Introduction. Partially hydrogenated derivatives of xanthone, dihydroxanthones, are being intensively studied. They are of interest due to their antimicrobial, antitumor, and antioxidant effects. Many researches are focused on the study of the cytotoxicity of dihydroxanthones and very little information is available on their antimicrobial activity. Therefore, the study of the antimicrobial activity and mechanism of action of new synthetic derivatives of 4,4a-dihydroxanthone is relevant. Preliminary studies have demonstrated that 4,4a-dihydroxanthones are active against gram-positive bacteria and have a pronounced anti-staphylococcal effect. Namely, 5-bromo-4,4-dimethyl-7-chloro-4,4a-dihydroxanthone (BDC-DX) was shown to be the most active derivative.Aim of the study was to determine the possible target of action of the active derivative of BDC-DX in bacterial cells and its acute toxicity.Materials and methods. The method of measuring the intensity of absorption of the crystal violet dye by bacteria cells was used to prove the effect of BDC-DX on the permeability of the cytoplasmic membrane in bacterial cells. The plasma coagulase activity of Staphylococcus aureus was tested under the action of dihydroxanthone to determine the effect of dihydroxanthone on the process of protein synthesis. Plasmid DNA digestion method was used to study the effect of the compound on bacterial DNA. The acute toxicity of BDC-DX was determined by the express method of V.B. Prozorovsky.Results and discussion. BDC-DX increased the permeability of the cytoplasmic membrane of S. aureus. Dihydroxanthone did not directly affect the plasma coagulase activity of Staphylococcus and showed a weak damaging effect on bacterial DNA. The compound induced breaks in plasmid DNA at a very high concentration — 1 mM or 384 pg/ml and higher. BDC-DX is a low-toxic compound (the average lethal dose for oral administration of the compound is 1710 ± 170 mg/kg, the average lethal dose for intraperitoneal administration of the compound is 116.9 ± 13.3 mg/kg).Conclusion. For the first time, in-depth study of the possible mechanism of action of a new synthetic biologically active compound from the group of 4,4a- dihydroxanthones, BDC-DX, was conducted. A likely target of 5-bromo-4,4-dimethyl-7-chloro-4,4a-dihydroxanthone in S. aureus cells is the cytoplasmic membrane. BDC-DX did not affect the process of protein synthesis, namely the activity of the plasma coagulase enzyme. The compound had no pronounced damaging effect on bacterial DNA. It was found that 4,4a-dihydroxanthone refers to low-toxic compounds.

The objective of this study was to characterize and compare antigenic and genetic characteristics of Streptococcus pneumoniae strains isolated from patients with invasive and non-invasive pneumococcal infections (PIs) by using the data of high-throughput sequencing.Materials and methods. A total of 158 S. pneumoniae strains were studied. All of them were isolated during different stages of the PEHASus multicenter study performed in 2015-2020. The data analysis was based on the information about whole-genome sequences of 46 strains isolated during the above study. Real-time PCR methods and high-throughput sequencing (the Illumina platform) were used for identification of serotypes. The SeroBA, PneumoCaT software and PubMLST.org website resources were used in the data processing.Results and discussion. The serotypes of all the studied strains were identified. A number of discrepancies among serotypes in serogroup 6 and one discordant result were revealed by the analysis of whole-genome sequences using 2 programs. The PCR methods were effectively used to characterize serotypes in 87% and 69% of the pathogens of invasive and non-invasive PIs, respectively. The serotypes contained in PCV13 accounted for 59% and 37%, while PPV23 serotypes accounted for 78% and 53% of the strains isolated from patients with invasive and non-invasive PIs, respectively. The data analysis was unable to identify either the dominant sequence type (a total of 81 sequence types have been identified) or clonal complexes, except for serotype 3 strains, thus demonstrating consistency with the data from previous studies suggesting the absence of a well-represented clonal structure of S. pneumoniae associated with pneumococcal meningitis in Russia.Conclusion. The obtained data made it possible to identify the distribution of the circulating serotypes and genetic characteristics of the strains isolated from PI patients, thus being instrumental for assessment of the effectiveness of the existing polyvalent vaccines and providing information for improvement of the PCR-based methods of serotyping.

Epidemic vector-borne viral infections pose a serious threat to public health worldwide. There is currently no specific preventive treatment for most of them. One of the promising solutions for combating viral fevers is development of vector vaccines, including MVA-based vaccines, which have virtually no adverse side effects. The safety of the MVA strain and absent reactogenicity of recombinant MVA vaccines have been supported by many clinical trials.The article focuses on test results for similar preventive products against viral fevers: Crimean-Congo hemorrhagic fever, Rift Valley fever, yellow fever, Chikungunya and Zika fevers.Their immunogenicity was evaluated on immunocompetent and immunocompromised white mice; their protective efficacy was assessed on immunocompromised white mice deficient in IFN-α/β receptors, that are used for experimental modeling of the infection. Nearly all the new recombinant vaccines expressing immunodominant antigens demonstrated 100% protective efficacy. It has been found that although the vaccine expressing Zika virus structural proteins induced antibodies against specific viral glycoproteins, it can be associated with high risks when used for prevention of Zika fever in individuals who had dengue fever in the past, due to the phenomenon known as antibody-dependent enhancement of infection, which can occur in diseases caused by antigenically related flaviruses. For this reason, the vaccine expressing non-structural protein 1 (NS1) was developed for vaccination against Zika fever.The yellow fever vaccine developed on the MVA platform had immunogenicity similar to that of the commercial 17D vaccine, outperforming the latter in safety.

Introduction. Cases of Chikungunya fever have been reported in more than 100 countries in Europe, Oceania, Africa, Asia, the Caribbean, and America. The musculoskeletal disorders typical for Chikungunya fever can last from several months to a year and even lead to disability. The infection is believed to provide lifelong immunity. This factor and the lack of specific therapy make vaccination the most promising method for preventing Chikungunya fever.Materials and methods. The purified inactivated preparation with the different doses of the CHIKV antigen was injected intramuscularly to BALB/c mice twice with an interval of 14 days. Indicators of humoral and cellular immunity were assessed in dynamics in ELISA, the neutralization test and proliferation test of splenocytes. Results. The purified preparation containing the CHIKV antigen inactivated by beta-propiolactone had pronounced immunogenic properties. The most prominent immune response in ELISA and neutralization test was registered for a dose of 40 μg. Stimulation with the specific CHIKV antigen caused a pronounced proliferation of animals' splenocytes. The peak values of specific humoral and cellular immunity parameters were registered 14 days after the second injection.Discussion. The purified preparation containing the CHIKV antigen inactivated by beta-propiolactone had demonstrated the sufficient immunogenic properties. The immunizing dose of 40 μg CHIKV selected as a result of the studies caused in BALB/c mice the development of the humoral immunity characterized by the specific IgG with neutralizing activity, and the specific cell immunity characterized by the animals' splenocytes proliferation after stimulation with CHIKV antigen.Conclusion. The purified β-PL inactivated preparation of the CHIKV antigen at a dose of 40 μg to demonstrated pronounced immunogenicity in BALB/c mice after two-dose immunization. The developed preparation can be considered as promising for the prevention of Chikungunya fever using the dose and scheme tested in this study.

Aim. Identification of epidemiological patterns of the SARS-CoV-2 spread among the population of St. Petersburg during the one-year COVID-19 pandemic period.Materials and methods. The performed analysis focused on the dynamics of COVID-19 cases in St. Petersburg from 2/3/2020 to 4/4/2021 and on the gender-age profile of patients. The information about patients (age, gender, type of the disease, hospitalization, social, and occupational status) was obtained from the database containing the materials from statistical data form No. 058/u.Results. After one year, the dynamics of reported cases of COVID-19 in St. Petersburg shows two cycles of seasonal surge (spring and autumn-winter) and 8 epidemic periods. It has been found that there are no gender-age differences among COVID-19 patients, which can be seen from the relatively similar number of cases among men and women per 100,000 people in each age group during specific epidemic periods. The strong association between clinical manifestations of COVID-19 and the patients' age was detected: Severe cases were more frequently diagnosed in patients over 70 years, regardless of their gender identity. Based on the social and occupational status, the people who were most exposed to the COVID-19 epidemic process were retirees and people whose occupation was associated with health and safety of St. Petersburg. Among the COVID-19 patients, retirees accounted for 13.69% (men) and 17.67% (women). The proportion of healthcare workers was 3.67% (men) and 9.41% (women).Conclusion. It has been assumed that COVID-19 tends to be a seasonal disease featuring annual autumn-winter epidemic cycles. The study addressed prospects of preventive vaccination against COVID-19 in Russia and the importance of tracking the complications pathogenetically associated with the acute phase of the disease in the system of epidemiological surveillance.

The COVID-19 pandemic continues, causing colossal damage to the population and the global economy. As COVID-19 is studied, new data are emerging regarding the risk of severe coronavirus infection in patients with α1-antitrypsin deficiency. α1 -Antitrypsin is the main inhibitor and key endogenous regulator of the serine leukocyte proteinase activitry released from the granules of activated neutrophils to the cell surface and into the extracellular space. It has been established that the number of cases of severe course and death of COVID-19 in the territories of 68 countries of the world correlates with the frequency of the spread of mutations in the proteinase inhibitor gene among the population of these countries, at which the concentration of α1-antitrypsin in the human blood plasma is 10 times lower than normal. All this contributes to the revision of a number of provisions of the pathogenesis and therapy of a new coronavirus infection.The review presents an analysis of the literature on the role of an inhibitor of serine leukocyte proteinases in protecting the body from COVID-19. The participation of α1-antitrypsin in the inhibition of SARS-CoV-2 penetration into the respiratory tract epithelial cells, in the protection of the vascular endothelium, blood plasma proteins and elastin of the lung tissue from the damaging effect of leukocyte elastase released during neutrophil degranulation and the formation of neutrophil extracellular traps (NETs) is considered. The role of a1-antitrypsin in suppressing inflammation by limiting the secretion of proinflammatory cytokines and neutrophil extracellular traps into the blood has been shown. The individual links in the pathogenesis of the new coronavirus infection have been detailed, which will allow revising the strategy for reducing the risks of severe course of COVID-19.

The review considers the nature of clinical and pathological disorders caused by highly pathogenic coronaviruses in the human body, analyzes the causes of systemic damage to various organs and tissues, the strategy of virus reproduction and the associated syndrome of cytokine reactivity with the development of specific immunodeficiency at the molecular level. The most developed approaches to the targeted therapy of cytokine reactivity syndrome and SARS including elements of theranostics - monitoring of molecular targets for targeted therapy - are described. An example of an innovative bioengineering technology associated with the reprogramming of cells of the primary “echelon of defense” with the ability to endow them with highly specific skills of directed destruction of cells infected with a virus is given. © 2021, Central Research Institute for Epidemiology. All rights reserved.

Rationale. Countries of Africa, especially countries in sub-Saharan Africa, represent a region characterized by high incidence of chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections. Methods for detection of HBV and HCV in low and middle-income countries differ from those that are used in countries having access to high-cost technologies. The Republic of Guinea is a region with high prevalence of hepatotropic viruses, however, the information on HBV and HCV prevalence in the area is extremely limited, thus emphasizing the significance of this study. The purpose of the study is to evaluate the need for improving laboratory diagnostics of parenteral HBV and HCV infections in the Republic of Guinea. Materials and methods . A total of 2,616 samples of blood serum were tested, the samples were collected from apparently healthy residents of the Republic of Guinea during the routine medical checkup. The testing included qualitative detection of HBsAg, anti-HBs IgG, anti-HBcore IgG, anti-HCV IgG antibodies as well as HBV DNA and HCV RNA. Results. The detection frequency of serological markers of HBV and HCV infections was 80.77% and 18%, respectively. However, HBsAg was detected only in 16.01% of individuals. Tests for detection of HBV DNA were performed among seropositive patients and patients seronegative by other HBV markers, HBV DNA was detected in 22.36% of cases, including 6.07% of HBsAg-negative cases. HCV RNA was detected in 2.2% of cases. Both HCV RNA and HBV DNA were detected in 27 people, including 19 HBsAg-negative cases, thus accounting for 1.03% of the examined group. Conclusions. The markers that are currently used for laboratory detection of HBV and HCV in the Republic of Guinea are not efficient enough to diagnose reliably all cases. Undoubtedly, there is an urgent need to improve laboratory diagnostics for timely detection of parenteral viral hepatitis. Routine laboratory operations need assays for additional serological and molecular markers of HCV and HBV infections.

The aim of the study — demonstration of the capabilities of new generation geographic information system software and agent-based modeling for solving epidemiological problems (on the example of the spread of measles in a metropolis).Materials and methods. Examples of the use of thematic layers and the functionality of the geoinformation platform, as well as the developed multi-agent model of measles spread in the megalopolis, are given. The measles spread model is presented as following three independent sub-models or nested models: behavior model, infection model, infectious process model. The modularity and independence of the sub-models allow the useof the necessary statistical and clinical data, both directly related to the studied disease and demographic indicators, which are analyzed and stored in the thematic layers of the platform.Results. The developed software tools allow visualizing, analyzing and short-term forecasting of the spread of the disease in the study area, with the ability to generate reports, which can be a useful and relevant addition to the daily work of specialists, contribute to the improvement and deepening of practical skills and abilities, in accordance with the types and tasks of professional activities, as well as expand opportunities for assistance in management decision making.

The purpose of the study — to identify the factors contributing to the spread of the novel coronavirus infection within the territory of the Republic of Moldova and to develop measures aimed at their elimination.Materials and methods. In May 2020, experts of Rospotrebnadzor (the Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing), together with leading employees of institutions participating in planning and implementing measures aimed at prevention of COVID-19 spread, conducted a detailed analysis of epidemic control and curative measures in 10 healthcare organizations in the Republic of Moldova. They assessed the effectiveness of the undertaken actions in in-patient facilities, in laboratories, and in the country in general.Results. The existing approaches to treatment of patients with COVID-19 and to laboratory diagnostics were in line with the common practices; the adequacy of measures was evidenced by the hospital bed capacity and the stock of artificial lung ventilation machines. In the meantime, the experts came across the factors that obviously contributed to the infection spread. Their elimination could intercept some paths of infection and improve the situation.Conclusion. The analysis of the current measures and their results is important for planning and implementing actions aimed at improvement of the epidemic situation in different regions. The collaborative efforts helped slow down the outbreak in the Bender psychoneurological residential facility; outbreaks were prevented in other limited-access institutions; the incidence among healthcare workers decreased; the daily number of new COVID-19 cases decreased to 0–5 during the summer months in the Dniestrian Moldovan Republic. Presently, there is a clear picture of approaches that should be taken to decrease the incidence. Most likely, the experience obtained in the fight against the novel coronavirus infection will be of great use in future if any new variants of viruses emerge.

Introduction. The productivity of microbial synthesis of stable nanoparticles is determined by the growth stage of the populations of bacterial cultures used to obtain nanostructures. The study of the biocidal activity of biogenic nanoparticles of cadmium sulfide (NPsCdS), comparable in properties with nanomaterials obtained by physicochemical methods, is promising. The aim of this work was to evaluate the effect of the cell growth phase of the bacterial strains Bacillus subtilis 168 and Shewanella oneidensis MR-1 on the efficiency of biosynthesis of NPsCdS and to study their bactericidal properties against a number of gram-positive and gram-negative strains of microorganisms. Material and methods . Nanoparticles were obtained by introducing Na 2 S and CdCl 2 salts to a final concentration of 2 mM : 2 mM in liquid bacterial cultures with cells in different phases of growth. The efficiency of NPsCdS biosynthesis was evaluated by the optical density of aqueous nanoparticles solutions. The bactericidal properties of NPsCdS were determined by the diameter of zone of inhibition growth of gram-positive bacteria B. subtilis 168, B. amyloliquefaciens, Streptococcus salivarius, Rhodococcus rhodochrous and gram-negative S. oneidensis MR-1, Escherichia coli K-12, Pseudomonas putida. Results. It was found that the use of cells in the stationary phase of growth (18–24 hours) contributes to obtaining the maximum amount of NPsCdS corresponding to concentrations of 1.0–1.2 mg/ml. The high antimicrobial activity of NPsCdS was shown against gram-positive microorganisms, among gram-negative bacteria, P. putida strain showed insignificant sensitivity. Discussion. The experimental results expand scientific data about the effect of the phase of bacterial growth cycle on biosynthesis of nanoparticles. The stationary phase of growth of B. subtilis 168, S. oneidensis MR-1 is optimal for obtaining of NPsCdS. For the first time, the cytotoxicity of NPsCdS/Shewanella against bacteria of various taxonomic groups was demonstrated. Conclusion. An effective method for obtaining extracellular NPsCdS using bacteria B. subtilis 168, S. oneidensis MR-1 in the stationary phase of growth has been developed. The biocidal activity of biogenic NPsCdS was shown, which allows to consider them as a new class of antimicrobial agents.

Introduction . SARS-CoV-2 can be transmitted by infected people without or with mild symptoms of acute respira-tory infection (ARI). Monitoring based on nucleic acid amplification techniques is used to measure the prevalence of ARI pathogens and to assess the effectiveness of preventive measures. The aim is to measure the prevalence of pathogens causing ARIs of viral etiology, influenza, and COVID-19 among individuals without ARI symptoms throughout age groups, to trace changes in the epidemic situation by weekly monitoring pathogens during the inter-epidemic period and at the beginning of a typical ARI epidemic season, to assess the effectiveness of medical masks for prevention of the above infections. Materials and methods . A total of 14,119 people (including 4,582 children) without ARI symptoms went through examination, including questionnaire surveys, in 26 regions of Russia from August to October 2020. Nasopharyn-geal and oropharyngeal swabs were tested by using AmpliSens ARVI-screen-FL, AmpliSens Influenza virus A/B-FL, and AmpliSens Cov-Bat-FL reagent kits (The Central Research Institute of Epidemiology of Rospotrebnadzor, Moscow). Results. 11.1% of the tested samples showed positive results; the rhinovirus prevailed (7.32%), while SARS-CoV-2 was detected in 1.66%. In autumn, the proportion of SARS-CoV-2 infected cases increased from 0.49% to 4.02% (p < 0.001). The SARS-CoV-2 RNA concentration was up to 1010 copies/mL. Conclusions. Differences in the prevalence of SARS-CoV-2 and rhinovirus among the age groups and over time were found and analyzed. Using of medical masks reduced the risk of infection with respiratory viruses and with SARS-CoV-2 by 51% and 34%, respectively. In case of prolonged exposure to a COVID-19 patient, healthy people must use a respirator for more effective protection. The individuals whose work was associated with a high level of social contacts were infected more rarely than other individuals in the same age group (p = 0.001); this fact supports the importance of anti-epidemic measures and commitment to their adherence by people whose profession entails frequent social contacts.

Aim. To characterize the influence of azoximer bromide (polyoxidonium, PO) in cultivation conditions on the morpho- and nanomechanical cell surface properties of Y. pestis EV NIIEG vaccine strain and its derivatives Y. pestis КМ218 (pYT–, pYV–, pYP–), Y. pestis КМ216 (pYT–, pYV–, pYP+), Y. pseudotuberculosis, Y. enterocolitica by atomic force microsopy (AFM), as well as on the adhesion of cells Y. pestis EV NIIEG to human collagen type IV.Materials and methods. The measurements were carried out using the Solver P47-PRO probe microscope (NT-MDT, Russia), standard methods of semi-contact AFM and AFM imaging analysis program. The adhesion of Y. pestis EV NIIEG to type IV collagen was determined by the number of cells binding to glass slides covered with human collagen type IV.Results. The introduction of PO in the cultivation environment caused changes in the morphometric parameters of the cells of Y. pestis EV NIIEG vaccine strain and its isogenic derivatives (increase in volume, flatten ingested (S/H), index I (W/H). These changes were accompanied by the transformation of nanomechanical properties of the cell surface (reducing the root mean square, adhesion force), which countenance was associated with the plasmid profile. The lesser decrease of adhesion force in the absence of changes of the index I was observed in cells Y. pseudotuberculosis and Y. enterocolitica with plasmid pYV. In the strain Y. enterocolitica KM383 (pYV–) PO did not induce significant changes in the indicators studied. The introduction of the PO into the cultivation environment decreased the ability of Y. pestis EV cells to bind to human collagen type IV. Modification by PO the adhesive properties of the vaccine strain Y. pestis EV NIIEG was accompanied by an increase in its immunogenicity.

Aim. To determine the role of the acetate in the persistence of indigenous bifidobacteria in the colon biotope through the lysozyme resistance in model conditions of the acetylation–deacetylation of peptidoglycan.Materials and methods. The study was performed on 16 strains of the two indigenous bifidobacteria speсies: Bifidobacterium bifidum и Bifidobacterium longum subsp. longum. Bifidobacteria was cultivated in the 0.6% O2 and 9% CO2 atmosphere at the temperature 37ºС in CO2 incubator for 48 hours. The production of the acetate by the bifidobacteria was determined by gas chromatography. The effect of the acetate on the lysozyme resistance of non-indigenous gram-positive bacteria was determined on the Listeria monocytogenes ICIS-280 model strain by the cultivation in LB-Lennox broth with ammonium acetate added in the concentration range matching the concentrations produced by the studied bifidobacteria, in lysozyme serial dilutions at final concentrations 5 μg/ml to 40 μg/ml within 24 hours.Results. It was found that the acetate release of Bifidobacterium longum subsp. longum was on average two times higher that of Bifidobacterium bifidum (27.0 and 14.7 mmol/liter, respectively) and was quite consistent with the concentrations of acetic acid determined in the intestinal contents (up to 50 mmol/liter). Cultivation of bifidobacteria in a medium with lysozyme, ammonium acetate and their combination did not have a significant impact on their growth parameters at the maximum used concentrations of these substances. In the test strain, the addition of ammonium acetate in the range created by bifidobacteria caused a decrease in the minimum inhibitory concentration of lysozyme by more than two times — from 40 μg/ml to less than 20 μg/ml. In the control medium without lysozyme, no inhibition of the growth of the indicator culture was observed up to the maximum concentrations of ammonium acetate.Conclusion. The mechanism of persistence (survival) of indigenous bifidobacteria in the human intestinal biotope has been identified, which is associated with the production of acetic acid at a level that selectively suppresses lysozyme resistance of non-indigenous gram-positive microbiota viareversible deacetylation of peptidoglycan. This allows indigenous bifidobacteria to maintain a stable dominant position in the biotope.

Aim. Study of the effect of antibodies to agglutinogens 1 and 2, filamentous hemagglutinin (FHA) and pertussis toxin (PT) on the formation of biofilms by Bordetella pertussis strains on the abiotic substrate.Materials and methods. Vaccine-derived and freshly isolated strains of B. pertussis were used. Cultures of strains grown on a dense nutrient medium were used as an inoculum for obtaining biofilms. The intensity of biofilm formation in round-bottomed polystyrene 96-well plates in the presence of antisera to agglutinogens 1 and 2, antiserum to FHA, and monoclonal antibodies (MСА) to the S1, S2, and S3 subunits of PT was evaluated by staining with 0.1% gentian-violet solution.Results. Most of the studied strains were sensitive to antibodies, which was manifested in complete suppression of biofilm formation. All strains were sensitive to antiserum to agglutinogen 1, antiserum to FHA, and MCA to the S2 subunit of KT. Three out of 4 studied strains with this agglutinogen in their composition were sensitive to antiserum to agglutinogen 2: No. 475 (serotype 1.2.3), No. 317 (serotype 1.2.3) and No. 178 (serotype 1.2.0). Relative resistance to antiserum was detected only in serotype 1.2.0 strain No. 305, but with minimal dilution, the intensity of biofilm formation was 1.8 times lower than in the control group. Strains No. 703 (serotype 1.0.3) and No. 287 (serotype 1.0.3) that did not have agglutinogen 2 were resistant to antiserum. Four and 5 out of the 6 strains used were sensitive to the S1 and S3 subunits of PT, respectively. Strain No. 305 was resistant to MCA to the S1 and S3 subunits, and strain No. 287 to MCA to the S1 subunit. At the same time, the intensity of biofilm formation was 2 and 1.8 times lower than in the control at the minimum MCA dilution.Conclusion. These data indicate that the growth of biofilms of B. pertussis strains is suppressed by antibodies both to the surface structures of the microbial cell (agglutinogens 1 and 2, FHA) and to the S1, S2 and S3 subunits of PT.

The third part of the literature review on the role of intestinal microbiota disturbances in the pathogenesis of autism spectrum disorders (ASD) is devoted to the analysis of published literature on possible interventional approaches for intestinal microbiota in ASD and the evaluation of the effectiveness of various types of interventions that have been studied in experiment and in clinical practice. Presented are available data on the possibility of correcting the intestinal microbiota in ASD with diet, taking pre- and probiotics, antibiotic therapy, as well as the effectiveness of transplantation of intestinal microbiota. An analysis of published data suggests that further development of approaches for correcting intestinal dysbiosis in ASD may provide safe and probably effective strategy for behavioral symptoms, but this requires further randomized controlled trials to confirm efficacy and safety from the perspective of evidence-based medicine, since available to date studies are small and scattered, and therefore they can only be considered preliminary.

Introduction . Since the development of inactivated polio vaccines, different stages of the production process have been changed and improved. Current production of inactivated polio vaccines based on both wild and attenuated strains includes several technological stages, one of which is the concentration of the virus-containing liquid, which ensures poliovirus concentration, and purification of the virus-containing liquid from a significant part of the ballast components. Research objective is to compare the characteristics of ultrafiltration membranes and select the membranes that provide optimal value of purification and concentration of poliovirus type 1 (Sabin strain). Materials and methods . Laboratory ultrafiltration systems from two manufacturers with 50, 100, and 300 kDa membranes were used for the concentration. Results were evaluated by the content of total protein, which is the main stress for the subsequent purification stages, the value of infectious virus titer in the concentrate, and the content of D-antigen as the target product. Results and discussion . Obtained results demonstrated that the content of the target product (the highest D-antigen content) and purification from impurity proteins (the total protein content in the concentrate) were most optimal when a membrane with a cut-off of 300 kDa was used for concentration. The study also evaluated the real cut-off components by various membranes to determine the composition of the protein load on the target product. Conclusion . In terms of quality of the resulting target product and the manufacturability of the production process, the use of a 300 kDa membrane is the most appropriate when working out the technology for manufacturing inactivated polio vaccine based on Sabin strains of poliovirus and the Vero line as a producing culture.

The review provides information on single nucleotide polymorphisms (SNPs) in genes encoding some interleukins belonging to the interleukin-1 (IL-1) superfamily and on their association with different infectious and non-infectious human diseases. It also briefs on the history of SNP discovery and the progress in the related scientific studies till the present time. It gives an insight into some mechanisms of interaction between infectious agents and the human immune system, involving SNPs in some cytokines of the IL-1 superfamily. The review provides data on relationships of SNPs in genes encoding other factors of the immune system, which are associated with the specific characteristics of natural history of chronic hepatitis B and C. It explores the significance of assessment of the SNP-proportion in proinflammatory cytokines and their antagonists of the IL-1 superfamily among the healthy population as well as the ratio of individual SNPs in specific groups of patients as a monitoring parameter for epidemiological surveillance of infectious diseases.

Introduction . The role of neutrophils in the initiation and progression of atherosclerosis as well as in the development of its complications has received scientific attention only in the recent years. Today, there is growing evidence to support a role of the CXCL12/CXCR4 axis in sustained inflammation during different chronic inflammatory diseases by retaining neutrophils at inflammatory sites. The aim of the study is to assess the diagnostic and prognostic significance of circulating CD62L lo CXCR4 hi neutrophils in patients with carotid atherosclerosis. Materials and methods . A total of 75 patients (52% of men and 48% of women) aged 40 to 64 years were examined. None of them were diagnosed with atherosclerotic cardiovascular diseases. All the patients underwent carotid artery duplex scanning. The flow cytometry and CD16, CD11b, CD62L, CD182 (CXCR2) and CD184 (CXCR4) conjugated monoclonal antibodies were used for phenotyping and differentiation of neutrophil subpopulations. Results . Atherosclerotic plaques in carotid arteries were detected in 72% of the patients; most of the patients were diagnosed with stenosis development in more than one of the carotid arteries (CA). The elevated levels of circulating CXCR4 h neutrophils were associated with the levels of total cholesterol (r = 0.377; p = 0.001), low-density lipoprotein (LDL) cholesterol (r = 0.293; p = 0.014) and triglycerides (r = 0.388; p = 0.003). The study revealed direct correlation between the circulating CXCR4 hi neutrophil count and the cumulative percentage of CA stenosis (r = 0.300; p = 0.011), including the number of stenosed CA (r = 0.291; p = 0.034). It was also found that CXCR4 hi neutrophil counts demonstrated a statistically significant increase along with the increased number of stenosed CA (p = 0.025). The ROC analysis findings show that the elevated CXCR4 hi neutrophil counts ≥260 cells/μL made it possible to diagnose stenotic lesion of 4 CAs with a sensitivity of 71.4% and specificity reaching 76.6%. Conclusion . In patients with carotid atherosclerosis, the increased count of circulating CD62L lo CXCR4 hi neutrophils was associated with the increased number of stenosed CAs, while no significant changes were observed in the other examined subpopulations of neutrophil granulocytes. The increased CD62L lo CXCR4 hi neutrophil count made it possible to diagnose stenotic lesion of 4 CAs with a sufficient sensitivity and specificity.

Introduction . The concept of heterogeneity in obesity depending on the risk of developing cardiometabolic complications has garnered attention in recent decades, since not everyone with obesity goes on to develop metabolic dysfunction. The aim of the work is to study specific characteristics of colonic microbial communities in patients with different obesity phenotypes and in healthy individuals by employing metagenomics methods. Materials and methods . A total of 265 individuals (44 men and 221 women; mean age 47.1 ± 4.8 years) were enrolled in the study. They were further divided into clinical groups: Healthy normal-weight individuals (n = 129); patients with obesity (n = 136), including metabolically healthy obesity (n = 40) and metabolically unhealthy obesity (n = 55). Quantitative and qualitative assessment of the intestinal microbiome was based on metagenomic analysis. Fecal samples were used to isolate DNA and perform sequencing of the variable v3-v4 region of the 16S rRNA gene. Results . The study revealed statistically significant (p < 0.05) differences between quantitative and qualitative variables in studied phylotypes of colonic microorganisms in healthy individuals without obesity and in patients with different obesity phenotypes. Discussion . Patients with obesity had higher levels of Bacteroidetes, Proteobacteria and lower levels of Actinobacteria, Firmicutes, TM7 (Saccharibacteria), Fusobacteria, and more frequently detected phyla Tenericutes, Planctomycetes and Lentisphaerae compared to healthy individuals. Metabolically healthy obese patients had more rarely detected phylum Lentisphaerae in their colonic microbiome, increased numbers of Firmicutes and reduced numbers of Bacteroidetes compared to metabolically unhealthy obese patients. Conclusion . The findings demonstrate alterations in the colonic microbiome in patients with different obesity phenotypes.

Purpose: analysis of the arbovirus infections incidence in the south of the European part of the Russian Federation in 2015–2019.Materials and methods. Data from statistical documentation (epidemiological examination of the infectious disease cases, reports on the arbovirus infections incidence) reported by Departments of Rospotrebnadzor to Scientific and Methodological Center for monitoring pathogens of infectious and parasitic diseases of 1–3 risk groups for subjects of the North Caucasian and Southern Federal Districts were analyzed. The obtained data were processed using Microsoft Excel 2010 program.Results. In the south of the European part of the Russian Federation Crimean-Congo hemorrhagic fever (CCHF), West Nile fever (WNF), tick-borne viral encephalitis and dengue fever cases are registered annually.An expansion of the territory with registered epidemic manifestations of CCHF and WNF was noted, reflecting an increase in the area of circulation of their pathogens. An expansion of CCHF and WNF epidemic season with the involvement into the epidemic process of people from all age groups including young children was observed. Significant increase in number of imported cases of dengue fever was documented. Markers of tick-borne viral encephalitis, Batai, Inko, Sindbis, and Tyaginya fevers were detected in residents of a number of territories. A high levels of population humoral immunity to West Nile, Batai, Inko, Sindbis Tyaginya, Ukuniemi, Bhanja, Dkhori viruses were identified in the Astrakhan region.Conclusion. The data obtained indicate the need for epidemiological surveillance both for arbovirus infections with a pronounced epidemiological and clinical manifestations, and for infections, the proportion of which in the structure of infectious pathology in southern Russia has not been sufficiently studied, but carrying a potential risk of spreading.

Aim. This work was undertaken to assess the effect of 120-day isolation conditions in a sealed compartment with an artificial habitat on the formation of microbiocenosis and the system of signaling image-recognizing receptors of the Toll-like (TLR) family of innate immunity.Materials and methods. The microflora of the intestine and upper respiratory tract, as well as the content of monocytes and granulocytes expressing TLRs (TLR1, TLR2, TLR4, TLR6, TLR9) in the peripheral blood, and the basal production of cytokines (IL-1β, IL-6, IL-8, IL-10, TNF-α) by immunocompetent cells of six volunteers was studied. To prevent intestinal and upper respiratory tract dysbiosis, two groups of medication were used: commercial strains (Linex and Bifidumbacterin Forte) and autoprobiotics made on the basis of protective microflora representatives isolated from each individual before the experiment.Results. The studies showed that the stay of a healthy person in an artificial environment had a significant impact on the state of microflora and the system of TLRs of innate immunity cells. This work demonstrates for the first time unidirectional changes in the absolute content of monocytes in the peripheral blood expressing TLR1, TLR2, TLR4, TLR6, TLR9, and the total microbial count in the gastrointestinal tract and in the upper respiratory tract from the 30th to the 120th day of the experimental exposure. Oral administration of autoprobiotic medication contributed to a decrease in the content of opportunistic microflora, while maintaining a high level of protective intestinal microflora, as well as an increase in the production of TNF-α and IL-10 by immunocompetent peripheral blood cells in vitro.

Introduction. The coronavirus disease (COVID-19) pandemic was announced by WHO in February 2020. In the Khabarovsk Krai, the first three cases of the disease were diagnosed on March 19, 2020, these cases were imported from Argentina (transit through Italy). The epidemic process of COVID-19 in the Khabarovsk Krai is characterized by a slow increase in the incidence. During the period of time when the SARS-CoV-2 seroprevalence study was conducted the incidence rates varied from 35.9 to 39.1 per 100 thousand population. Within the next 5 weeks the incidence continued to increase, the maximum level was 67.3 per 100 thousand population. A statistically significant decrease in the incidence is noted in the first decade of August. The study of the SARS-CoV-2 seroprevalence among residents of the region was carried out from June 9 to June 21, 2020 during the period of increasing intensity of the epidemic process of COVID-19 infection.Aim. To determine the level and structure of herd immunity to SARS-CoV-2 virus among the population of the Khabarovsk Krai during the period of intensive spread of COVID-19.Materials and methods. The study was conducted as a part of the first stage of a large-scale Rospotrebnadzor project to assess the herd immunity to SARS-CoV-2 virus among the population of the Russian Federation, taking into consideration the protocol recommended by WHO. The selection of volunteers for the study was carried out by the method of questionnaires and randomization by random sampling. The results of a survey of 2675 individuals were included into analysis. The number of volunteers in all age groups was similar.Results. The results of the study showed that the herd immunity to SARS-CoV-2 in the total population of the Khabarovsk Krai was 19.6%. The maximum level of herd immunity was observed in children 14–17 years old (34.4%), children 7–13 years old (24.8%), and people over 70 years (22.6%). The highest level of seropositivity, except for the children and the elderly, was found among educational workers (26.7%). The lowest level of seropositivity was found in the military (8.7%) and the unemployed (8.3%). There were no statistically significant differences in the level of seroprevalence between men and women.Conclusions. The results of the seroepidemiological study demonstrated that in the Khabarovsk Krai, the presence of the contacts with COVID-19 patients is associated with the 1.4-fold increase in the likelihood of the seroconversion. Antibodies were detected in 58.9% of the past COVID-19 cases. In individuals with the previous positive PCR test result, antibodies were detected in 50% of cases. A high rate of asymptomatic infection, up to 93.7%, was observed among seropositive volunteers.

Allergen-specific immunotherapy (ASIT) has been used for more than a hundred years to treat patients with IgEmediated allergic diseases. The most common allergens have been obtained using molecular cloning technology in the past two decades. To increase the safety of immunotherapy, a large group of genetically modified allergens with reduced allergenic activity was created. The mechanism of action of these therapeutic allergens differs from natural allergen extracts, and more research is needed to understand how desensitization occurs in each case. The objective of this review is to introduce readers to new therapeutic allergy vaccines and their structural modification features as well as immunological effects on the body. To achieve this objective, we have analyzed and systematized the experimental developments presented in the literature on the main directions of creating new allergy vaccines: hypoallergenic derivatives of recombinant allergens, T cell epitope-based allergy vaccines and B cell epitope-based allergy vaccines, DNA vaccines.Summing up the results of the research presented in the literature, it is necessary to note the high heterogeneity of designs used to achieve the high efficiency of the developed therapeutic allergens. All allergy vaccines presented in the review solve the tasks set by the researchers: in experimental animal models they induce immunogenicity or tolerance, in clinical trials they reduce the symptoms of allergic reactions. The the effectiveness of the proposed medicinal products is quite high but its evaluation requires further long-term preclinical and clinical trials to confirm the safety and harmlessness of the created allergy vaccines.

The course of the Spanish flu on the territory of the former Russian Empire is not well studied. This is due to the state of the medical statistics during the times of the Civil War. The medical data was collected more diligently by the Soviet Russia rather than by the officials of the White Army.This article discusses the timeline, symptoms, morbidity and mortality of the Spanish flu. The materials used in this article were obtained from the regional hospital archives, printed publications, and personal memoirs.The virus of the Spanish flu has initially entered the territory of Russia at the end of August of 1918 through the demarcation line with the German army at the temporary western border defined by the Treaty of Brest. In the beginning of September the virus was carried out by the Allies army through the ports of Murmansk and Arkhangelsk. In the European part of Russia, the outbreak started around September–November of 1918. So far, there is not enough data regarding pandemic flu in Siberia and Far East region of Russia. The unknown illness that undermined the combat capability of the 11th Red Army at the end of the fall of 1918 was likely of viral etiology. There was no evidence found that pandemic flu in Russia had high mortality.The possible correlation between atypical malignant nature of typhus and relapsing fever, the epidemics of which began in the fall of 1918, and the previous exposure of the population to the influenza virus has been hypothesized. Another hypothesis under discussion is about the possible correlation between outbreaks of the malaria and measles and subsequent susceptibility to the pandemic Spanish flu virus.

The first part of the literature review on the role of intestinal microbiota dysbiosis in the pathogenesis of autism spectrum disorders (ASD) includes recent data published in the literature on the features of the quantitative and qualitative composition of the intestinal microbiota in patients with autism. It was shown that an excessive presence of Clostridium was detected in ASD, and evidence was presented showing the possible participation of these bacteria in the development of autism symptoms. Contradictory research results on an increase in a number of other pathogenic bacteria and, conversely, a decrease in the number of bacteria necessary to maintain the normal functioning of the intestine and the host organism as a whole are presented. The possible role of Candida albicans in ASD, requiring further study, is reported. Possible causes of contradictions in the results of studies on this topic are discussed.

Currently, a lot of attention is given to SARS-CoV-2 subpopulations and their coexistence with different genomic variants within the same patient. In this study, we performed next-generation whole-genome sequencing and assembly of viruses from samples representing swabs or autopsy specimens obtained from patients diagnosed with СOVID-19, which were initially confirmed by the real-time polymerase chain reaction (Ct = 10.4–19.8). Samples were prepared for sequencing by using the SCV-2000bp protocol. The obtained data were checked for presence of more than one SARS-CoV-2 genetic variants in a sample. Variants of nucleotide substitutions, coverage for each variant, and location of the variable position in the reference genome were detected with tools incorporated in the CLC Genomics Workbench program. In our search for variable nucleotide positions, we assumed that the sample had two genetic variants (not more); the threshold value ≥ 90% was set for probability of the identified variant. Variants represented by less than 20% of the reads in the total coverage were not taken into consideration. The obtained results showed that 5 samples had variability, i.e. they had several genetic variants of SARS-CoV-2. In 4 samples, both of the detected genomic variants differed only in one nucleotide position. The fifth sample demonstrated more substantial differences: a total of 3 variable positions and one three-nucleotide deletion. Our study shows that different genetic variants of SARS-CoV-2 can coexist within the same patient.

Introduction . Listeriosis is a foodborne infection, especially dangerous for people in at-risk groups. Susceptibility to listeria infection is determined by a complex of reasons: environmental factors, host immune status, and pathogen virulence. The susceptibility to listeriosis can also be aggravated by previous infections, especially viral infections, which demonstrate a steadily increasing number of identified pathogens. The aim of our study was to present molecular and genetic characterization of pathogens causing sporadic invasive listeriosis in a megalopolis, primarily during the peak of influenza and ARVI incidence. Materials and methods . Listeria monocytogenes isolates were collected from 18 hospitalized patients at hospitals in Moscow, from November 2018 to October 2019. The first comparison group was represented by isolates from food products and fish preserves. The second comparison group included previously examined environmental isolates. The clinical isolates were examined by using multilocus sequence typing techniques, including the standard MLST scheme extended by loci of internalin genes. Isolates of the autochthonous genotype (ST7) were compared through whole-genome sequencing and subsequent analysis of the core genome (cgMLST). Results . In cases of invasive listeriosis, 44% of isolates were isolated from patients with listeriosis; 27% of isolates were obtained from patients with meningitis. L. monocytogenes of phylogenetic lineage II prevailed in these groups of cases that occurred when the epidemic threshold for influenza was crossed during the 2018/2019 season. Listeria pneumonia identified in the senior age group occurred during the season of autumn ARVI and was primarily caused by L. monocytogenes of phylogenetic lineage I. The examination of genomes of ST7 isolates demonstrated identity between the core genomes of bacteria isolated from the mother-infant pair. Out of ST7 food isolates most closely related to the clinical ones was the isolate from meat (23 locus differences, the common deletion in the MFS transporter locus). Analyzing invasive listeriosis, the comparison between the list of the identified genotypes and the data from European countries showed that each country had its own specific range of genotypes, though ST7 was detected in all the examined samples. Conclusions . Along with the monitoring of food manufacturing and storage, timely vaccination against seasonal respiratory infections and use of personal protective equipment in public spaces can reduce the risk of listeriosis incidence in at-risk groups.

To maintain viability under stressful conditions of existence and the implementation of protective strategies, bacteria must receive signals and respond quickly to extreme changes in environmental parameters. The results of recent experimental studies complement the paradigm that has dominated since the 1970s on the predominant role of phospholipids (PL) as molecular building blocks in the formation of the cell wall of bacteria. Specific transformations of these lipid domains have shown to have a significant effect on the shape and function of cells, membrane remodeling, and the ability of bacteria to adapt to environmental stresses. The physiological role of bacterial PLs is pleiotropic and determines both cell integrity and cell function. In addition to the key structural role of membrane PL in the cell, their intermediate metabolites are able to act as secondary messengers and perform important signaling and regulatory functions. Modern studies of the mechanisms of detection and integration of signals from the environment that cause stationary-dynamic changes in phospholipid homeostasis and form pleiotropic resistant cellular bacterial phenotypes are of fundamental and practical interest. PL homeostasis was proved to be crucial for the pathogenesis of bacterial infections and is necessary not only to maintain the viability of bacteria, but also to ensure their growth during infection. The suppression of the biosynthesis of these macromolecules reduces the viability of bacteria. In recent decades, one of the main advances in the concept of "liquid mosaic" model of biological membranes has been the understanding of their domain structure. This discovery is of fundamental and practical interest, since phospholipid domains are a promising target for modern antimicrobial strategies. The aim of this review is to summarize modern ideas about the structural, metabolic and signaling role of membrane PL in the implementation of the protective mechanisms of bacteria and maintaining their viability in adverse environmental conditions.

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.

The review considers the regulatory capabilities of the human microbiota to preserve human health. The problem is not new, but it has expanded with the inclusion of new “findings” since the time of I.I. Mechnikov, a staunch supporter of the useful (protective) function of the normal flora. The study of the integration of human metabolism and microbes inhabiting human body revealed the participation of microbial metabolites — “signaling molecules” — in providing the homeostasis of the host. Particular attention is paid to the metabolic products aromatic amino acids as regulators of the physiological functions of humans and microbes. “Signal” molecules regulate the microbial “quorum”, the immune system (its cellular and humoral components). Opiates, hormonal peptides, in particular, natriuretic hormone, hypothalamic nonapeptides (oxytocin and vasopressin), which have both a direct antimicrobial and an indirect effect in the host's body, are not ignored. Researchers are also showing interest in the products of adipose tissue — “adipokines” (in particular, leptin), which turned out to be a multipurpose regulator showing a pro-inflammatory nature. The category of “signaling” molecules also includes cytokines that interact with gram-positive bacteria, which is actively discussed in the literature. In the evaluation of the material presented on various models of infections, a general pattern is observed: under the conditions of symbiosis, a “single regulatory environment” is formed, in which a variety of connections from immediate (direct) interactions are noted, i.e. the destruction of “signaling” molecules, induction of physiological functions due to the presence of similar receptors with ligands and, finally, modification of “signaling” molecules, i.e. expansion of the spectrum of action. The combination of this variety of integration mechanisms in this “single regulatory environment” (microorganism-host) probably leads to the formation of homeostasis, i.e. dynamic balance of the “signaling” systems of the microbiota and humans in the conditions of associative symbiosis, where an infection is its model system. This concept fits well our method of intermicrobial recognition of friend-foe in the dominant-associate pair and the described triangle: microbiota-hypothalamic-pituitary neurosecretion-oxytocin, organically constituting the gut-brain axis.

Introduction . The comprehensive assessment of the herd immunity to measles in Russia can be challenging, as Russian subject-related studies tend to focus on seroprevalence in various cohorts of different sizes. The systematic review and subsequent meta-analysis of different research findings increase the total number of observations and statistical significance of the studies, thus enhancing the reliability of conclusions. The purpose of the study is to assess the status of herd immunity to measles in Russia by analyzing the findings of studies published by Russian researchers. Materials and methods . The conducted systematic review and meta-analysis covered 13 Russian studies (the total number of the examined was 15,353, from birth to 79 years of age) published in 2011-2020 and addressing the assessment of herd immunity to measles in population of different regions in Russia. Results. It was found that the principal approach in all the studies was assessment of herd immunity through examination of adult people, including healthcare workers, with no regard for their vaccination history. The proportion of seronegative cases among young people (18-30 years) — 27.3% (95% CI 25.7-27.3%) and among children under 17 — 38.3% (95% CI 35.8-40.8%), who were born after the two-time vaccination had been included in the National Immunization Calendar, was larger than in older age groups — 19.8% (95% CI 17.8¬21.8%). The level of herd immunity among healthcare workers representing a decreed group — 84.5% (95% CI 83.7-85.3%) was higher than that of relatively healthy population — 75.4% (95% CI 74.1-76.6%), which can be explained by stricter vaccination requirements. Conclusion. The high proportion of seronegative cases among children and young adults of under 30 years of age is a risk factor associated with measles spread among the population and can be seen as the result of insufficient vaccination coverage.

Introduction. An increasing incidence of pertussis among different groups of population and shortcomings of the existing preventive solutions pinpoint urgency of development of new safe vaccines suitable for immunization of infants and for booster immunization of adolescents and adults.The purpose of this study is evaluation of safety, immunogenicity and protective activity of the new constructed attenuated Bordetella pertussis bacteria 4MKS by infecting immunized Macaca mulatta monkeys intranasally with virulent bacteria of the pertussis pathogen.Materials and methods. Five adult, clinically healthy Macaca mulatta monkeys aged 3–4 years were used for immunization and experimental infection. The re-immunization was performed in 6 months. Three non-immunized animals of the same age were used as controls.Results. The intranasal single-dose inoculation and re-inoculation of attenuated B. pertussis bacteria did not cause any nasopharyngeal inflammation in the rhesus monkeys and any changes in the blood lab test values after the nonhuman primates had been infected with virulent bacteria. No elevation of total IgE was detected in blood serum of the Macaca mulatta monkeys after the single-dose and double-dose immunization. When the monkeys were intranasally immunized with attenuated and virulent B. pertussis bacteria, they developed a defensive reaction to re-infection, namely suppression of the bacterial growth, increased rates of elimination of bacteria from the animals’ nasopharynxes and development of a humoral immune response to the infection. The development of immunity against pertussis re-infection is accompanied by a pronounced booster effect.Discussion. The obtained results suggest common mechanisms of development both of post-vaccination immunity after intranasal vaccination of animals and infection-acquired immunity against pertussis. Both of them provide protection against re-infection with B. pertussis bacteria and prevent development of clinical symptoms of pertussis.

Multicellular organisms and the saprophytic flora form complex, highly integrated chimeric systems (associative symbioses, metaorganisms) characterized by interplay between pro- and eukaryotic components. To be able to interact symbiotically microorganisms (MO) need a whole body.When grown on artificial media for a long time, symbiotic MO have to adapt to the artificial environment and gradually, though reversibly, lose their ability of associative interaction with the human body, thus causing a decrease in the therapeutic efficacy of MO-derived probiotic products. To increase the therapeutic activity of probiotic MO, they must be functionally rehabilitated.A pathological process induces development of a secondary metabolic dysbiosis; as a result, changes in the regulatory processes of an individual interfere with the restoration of the normal microflora. Therefore, functional rehabilitation of probiotic MO must take place during cultivation, while the cultivation process must replicate the whole-body conditions.

The review presents the basic information available in literature on the use of gas chromatography-massspectrometry. Issues concerning the significance of this method for the identification of microorganisms are discussed. The prospects of creating domestic software and databases of mass spectra of microorganisms are noted.

The purpose of the study is to adjust the tactics of immunization of children exposed to HIV and HIV-infected people on the basis of studying modern vaccination practices within the framework of the National Calendar of Preventive Vaccinations (NCPV).Materials and methods. According to the information in the patient's outpatient card, the card of preventive vaccinations and the history of the child's development, the completeness and timeliness of immunization of 216 children exposed to HIV and 198 HIV-infected children were analyzed. The control group consisted of 100 children born to mothers with negative HIV status. In order to study adherence to vaccines, a survey was conducted among 160 parents of children registered in the dispensary for HIV infection.Results. It was established that, despite the delayed immunization, the coverage of vaccination against the major infections from NCPV among children ranged from 94.4% to 97.5%. The greatest difficulties in the implementation of the NCPV arose when immunizing children under 2 years of age. The “missed opportunities” during immunization subsequently led to a violation of the calendar terms of vaccinations and their implementation at an older age. The number of “missed vaccinations” in the study cohort did not exceed the criteria recommended by WHO (10%) and amounted to 5.8% for certain types of vaccines (DTP and polio).The proportion of children vaccinated against tuberculosis in the maternity hospital in the HIV-exposed group was 2 times less compared to the control group, however, there were no differences in the incidence of vaccine induced allergy.During the vaccination of children with HIV on the highly active antiretroviral therapy (HAART), the number of CD4 lymphocytes corresponded to the parameters of the age norm. Compared to baseline data, no changes in the immune status of vaccinees were recorded.Organizational omissions in immunizing children with HIV infection were the use of live polio vaccine, a 3-dose vaccination schedule against viral hepatitis B in children at risk, and vaccination against tuberculosis in the absence of a three-stage chemoprevention of mother-to-child transmission of HIV.When assessing parental vaccine adherence, it was found that 85% of respondents considered vaccination necessary for the prevention of infectious diseases, 11.3% found it difficult to answer, due to the possible risk of vaccine reactions and the lack of guaranteed protection, and 3.8% were against vaccination, citing own opinion.The most authoritative source of information for most respondents, both positive for vaccination and those who doubted its need, was medical workers (98.5 and 72.7%, respectively). In 33.3% of those who are negatively related to vaccines, health workers were also a source of information.Conclusion. The analysis of the completeness and timeliness of vaccinations in a cohort of HIV-infected and exposed to HIV revealed the most problematic issues regarding vaccinations within the time periods regulated by the NCPV. Children with HIV infection who have the 1st category of immune disorders on the background of HAART are subject to vaccination in the framework of the National calendar of vaccinations to full extent. The use of combined vaccines will make it possible to reduce the manipulation load in this cohort, overcome the identified inconsistencies and optimize the vaccination calendar.

The SARS-CoV-2 virus is a pathogen causing the coronavirus infection that culminated in a worldwide pandemic in 2020. It belongs to β-coronaviruses and has high genetic similarity to the SARS-CoV virus that is responsible for an outbreak of severe acute respiratory syndrome in 2002–2003. The analysis of molecular interactions shows that SARS-CoV-2 has higher virulence due to lower binding free energy in interaction with the angiotensin-converting enzyme 2 (ACE2), which is used by the virus to enter the host cell. At the time of the global coronavirus pandemic, the thorough study of ACE2 as a key component of the disease pathogenesis comes to the fore. The detailed study of the enzyme, which is a receptor located on the surface of different tissues and which normally catalyzes the conversion of angiotensin II to angiotensin (1–7), led to diverging conclusions. Being non-tissue specific, the receptor is abundantly present in the heart, kidneys, small intestine, testes, thyroid, and adipose tissue. Besides regulating blood pressure, it suppresses inflammation, mainly in the lung tissue, participates in amino acid transport and maintains the activity of the gut microbiome. With all its essential positive functions, the role of ACE2 is highly ambiguous, specifically in coronavirus infection. The influence on the renin-angiotensin system can be seen as a promising therapeutic route in treatment of coronavirus infection. The preliminary data on using of ACE2 inhibitors, soluble forms of ACE2, and angiotensin II receptor blockers demonstrate their effectiveness and, consequently, improvement in symptoms and prognoses for patients with coronavirus infection. The review presents information about ACE2 distribution in human tissues, explores its interaction with SARS-CoV-2, provides a theoretical basis for medications involving ACE2 metabolic pathways and for using them in treatment of coronavirus infection and its prevention.

Introduction. Rotavirus infection (RVI) is the most common cause of severe gastroenteritis in infants and young children worldwide: 600,000 children die annually; it accounts for approximately 3 million hospitalizations and 25 million physician visits each year among children. Preventive vaccination is universally recognized as the most effective measure against this infection.The purpose of the study is assessment of reactogenicity, safety and immunogenicity of the pentavalent live vaccine for RVI prevention in childhood immunization.Materials and methods. The first multicenter prospective, randomized, double-blind, placebo-controlled clinical trial of the pentavalent live vaccine for RVI prevention was conducted in Russia among healthy infants aged 2 months at the time of the first vaccination.Results. The vaccine had a satisfactory safety profile and high immunologic activity when administered in a threedose series for childhood immunization. No negative changes in the children’s health condition were detected during the surveillance monitoring.Discussion. The seroconversion rates, the seroconversion factor and the geometric mean antibody titer were consistent with the results obtained during trials of the above vaccine and its equivalents in other countries.

Introduction . In a number of countries, including Russia, there is no systematic registration and reporting of parvovirus infection cases; the extent of its spread can be estimated by using humoral immunity rates. Purpose of the study : Assessment of seroprevalence of parvovirus B19 (B19V) in different age groups of population of Russia, Central Asia, and West Africa. Materials and methods . A total of 1,732 blood serum samples from residents of St. Petersburg and Nur-Sultan, migrant workers from Uzbekistan and Tajikistan, residents of the Republic of Guinea were studied for IgG antibodies to B19V. Results . The highest seroprevalence rates were identified in St. Petersburg and Nur-Sultan (62–65%); the lowest rates were registered among migrant workers from Uzbekistan and Tajikistan (47%). The results for the Republic of Guinea showed a B19V seroprevalence rate of 53%. It was found that there is an increasing trend of seropositivity with age; the percentage of seropositive individuals clearly increases in older age groups: up to 55% — among migrant workers from Central Asia and residents of the Republic of Guinea; up to 80–85% — among residents of St. Petersburg and Nur-Sultan. Discussion . The obtained results confirm the worldwide occurrence of parvovirus infection. People susceptible to infection can cause infection spreading in high-risk groups — among pregnant women, immunodeficient patients, blood product recipients, and cancer patients.

A significant mortality rate from infectious diseases is largely mediated by the widespread and uncontrolled use of antibiotics, which has led to the emergence of drug-resistant strains of bacteria. The rapid evolution of bacterial resistance to antimicrobials is a serious challenge for modern health care, mediates the need to create new antibiotic agents, as well as to intensify the study of molecular mechanisms underlying the formation of microorganism resistance. One of these mechanisms is bacterial persistence, manifested by the formation of persistent cells in the culture, which are a phenotypic variant of the isogenic population. The persistence of bacteria can occur spontaneously, regardless of exposure to antimicrobials or environmental reasons, such as lack of nutrients, oxidative stress or hypoxia. This small cell subpopulation is able to maintain viability even in the presence of antimicrobial agents at concentrations many times higher than therapeutic. The presence of persistent cells of pathogenic bacteria in the host organism reduces the effectiveness of antibiotic treatment, not due to the genotypic drug resistance of the microorganism, but due to the presence of phenotypic resistance of persister cells. The difference is fundamental, since cell-persisters are insensitive to any antibiotics and the development of fundamentally new antimicrobial strategies is necessary for their eradication. Persister cells are phenotypic variants of the maternal culture of bacteria that are present in all populations of microorganisms, and after the onset of favorable conditions, they are able to reclaim and form a new generation of vegetative bacteria. This review discusses modern concepts of the molecular genetic mechanisms of bacterial persistence with an emphasis on their clinical significance for the occurrence of persistent infections, and discusses innovative technologies for the eradication of resistant cell forms of microorganisms.

Objective. To designate the nasopharyngeal carriage of bacterial pathogens among children and adults diagnosed with recurrent respiratory diseases residing in the Khabarovsk city during a four-year period.Materials and methods. Nasopharyngeal and oral swabs obtained from 7,043 children and adults were tested using classical bacteriological methods. In order to grow “difficult-to-culture” microorganisms a columbian agar with addition of 5% defibrinated sheep blood, incubation in the atmosphere rich with CO2 (5%), bacteriological analyzer Vitek 2 Compact were used. Real-time PCR was used to confirm the identification of S. pyogenes.Results. A high level of nasopharyngeal pathogens carriage (47%) was detected. The most prevalent microorganisms were as follows: S. pneumoniae (47%), M. catarrhalis (30.4%), H. influenzaе (17.5%), S. pyogenes (5.2%). The age groups at risk were children aged 0–6 years for S. pneumoniae and children aged 7–12 years for S. pyogenes. An emerging trend it the level of nasopharyngeal carriage of S. pneumoniae observed in 2018 was followed by the increase of registered incidence of pneumococcal pneumonia.Conclusion. Nasopharyngeal carriage of S. pneumoniae imposes a high risk of community-acquired pneumonia and other pneumococci-associated diseases, predominantly in children.

The Central Research Institute of Epidemiology of Rospotrebnadzor presents priority data obtained from the largescale population PCR-based study of the changes in the rates of circulation of SARS-CoV-2 among relatively healthy residents of Moscow and Moscow Region.

Objective. To study the role of influenza viruses in the development of severe acute respiratory infections (SARI) in patients admitted to Yekaterinburg hospitals during 2017-2018 epidemic season.Materials and Methods. A retrospective epidemiological analysis of influenza incidence in Yekaterinburg was conducted, 403 influenza and acute respiratory viral infections case sheets were studied, and PCR analysis of clinical samples from the patients for respiratory viral infections was performed.Results. During the epidemic period a total 27.0% of the Yekaterinburg population were reported with influenza and other SARI, with 1.8% patients hospitalized. 5.6% of the total number of patients admitted with influenza and SARI in Yekaterinburg hospitals were included in the study. The rate of the detection of influenza A and B viruses RNA in the clinical samples from the patients with SARI was 28.3%. The rates of the detection in PCR of influenza B/Yamagata, A(H1N1)pdm09 and A(H3N2) were 46.5, 20.2 and 10.5%, respectively.Conclusion. The study results indicated that influenza viruses remain significant pathogens of respiratory infections that required hospitalization. Among patients with SARI the highest incidence was observed in children of a younger age group and was mainly associated with influenza B virus of Yamagata lineage and influenza A virus (H1N1)pdm09. According to the results of a molecular genetic study, influenza A (H1N1) pdm09 viruses belonged to clade 6B.1, carried characteristic amino acid substitutions in hemagglutinin S84N, S162N (with the acquisition of a potential glycosylation site) and I216T and were similar to the A/Michigan/45/2015 vaccine strain. The influenza B viruses studied belonged to the Yamagata lineage, clade 3. The influenza B/Ekaterinburg /RII-4723S/2018 virus differed from the reference strain B/Phuket/3073/2013 by two amino acid substitutions in the hemagglutinin gene M251V and L172Q.

Aim. Development of technology for the manufacture of cell-free pertussis vaccine (CPV) from a freshly isolated strain of B. pertussis No. 211 serotype 1.2.3 and the study of its protective activity and safety in comparison with the preparation of vaccine strains. Materials and methods. Following B. pertussis strains were used: freshly isolated strain No. 211, serotype 1.2.3; vaccine strains No. 305, serotype 1.2.0, and No. 475a, serotype 1.2.3. According to the original method, a CPV was obtained from the supernatant of the liquid culture medium of B. pertussis strain No. 211 and its protective and toxic properties were studied. Results. Studies have shown that the use of enriched nutrient media for the cultivation of the strain and the increase in the duration of the the detoxification period of the protective antigen complex isolated from the culture medium are needed to obtain a CPV vaccine consisting of antigens of a freshly isolated strain. CPV obtained from the freshly isolated strain had protectivity 1.7 times higher compared to those of CPV obtained from vaccine strains, was nontoxic and had a low sensitizing properties. The results indicate that the freshly isolated strain No. 211 is a promising candidate for use in the development of pertussis vaccines.

Introduction. In Bulgaria, mold allergies are common, and sensitization to different fungal species is found in many patients with atopy. The objective of this study is to explore sensitization to the most widespread mold species in Bulgaria, and to determine the extent of sensitization to Alt a1, a major allergen of Alternaria alternata, by using component-resolved diagnosis. Materials and Methods. 21 patients (14 males and 7 females, age range 5-40 years), with respiratory allergy participated in the study. All patients are sensitized to mix of fungal allergens containing: Alternaria alternata, Aspergillus sp., Cladosporium herbarum, Penicillium notatum, proved by in vivo and in vitro methods. All patients underwent the ImmunoCAP test and were assessed for sIgE to individual fungal allergens: m1 Penicillium notatum, m2 Cladosporium herbarum, m3 Aspergillus fumigatus and m6 Alternaria alternata. The component-resolved diagnosis to Alt a1 was performed for 10 patients with increased sIgE to m6 Alternaria alternata. Results. All studied patients (100%) had elevated sIgE to Alternaria alternata. Eight (38%) patients were sensitized to Penicillium notatum. 11 (52%) and 10 (48%) patients were sensitized to Cladosporium herbarum and to Aspergillus fumigatus, respectively. Ten patients (48%) were monosensitized to Alternaria alternata. Nine (90%) patients with sensitization to Alternaria alternata demonstrated elevated levels of IgE to Alt a1. Conclusion. Alternaria alternata most often causes sensitization in patients with respiratory allergy. The component-resolved diagnosis using Alt a1 is a precision marker to prove species-specific sensitization to Alternaria alternata.

Aim. To study the genetic stability of the measles virus strain Leningrad-16 (L-16) used for the production of vaccine at JSC NPO Mikrogen.Materials and methods. A series of production and sowing strains of L-16 (JSC NPO Mikrogen), ready-made series of measles vaccines from various manufacturers, and the strain of measles virus genotype D6 were studied. Molecular genetic study of the strains was performed using RT-PCR followed by restriction analysis and sequencing.Results. The complete genome sequences of the production and sowing strains of L-16 that are used for vaccine production were obtained. The sequence of the vaccine strain was deposited in GenBank. Strain L-16 was confirmed to be genetically stable. The obtained data demonstrated the possibility of using the RT-PCR method with subsequent restriction analysis to confirm the authenticity of the vaccine strain L-16 in finished mono and three component vaccines.Conclusion. The results of the study suggest the applicability of the molecular genetic methods to confirm the authenticity of the studied strains not only at the production stages, but also in the finished series of vaccines.

The review presents retrospective data on six cholera pandemics and current views on the causative agent of the seventh pandemic V. cholerae El Tor, which caused a pandemic infection with the formation of true persistent and temporary intermediate endemic foci that provide the longest pathogen circulation in the history of the disease. One of the possible explanations for such a long course of the cholera pandemic is associated with an extremely high variability of the genome and the development of a number of adaptive reactions that allow cholera vibrios to adapt and remain in the environment. Due to the development of molecular genetic research methods, the ability of cholera vibrios to form biofilms which increases stress resistance, the ability to spread by attachment to abiotic (plastic) and biotic substrates (zooplankton and phytoplankton) has been discovered. Biofilm formation is also directly related to overcoming the antagonistic action of members of aquatic ecosystems. Another strategy for the survival of cholera vibrios is the transition to an uncultured state that proves a low level of death in the population. Published data on the possible effects of temperature increasing due to the climate change on cholera outbreaks in Africa (Democratic Republic of the Congo, Nigeria, Angola, Zimbabwe, Sierra Leone), Southeast Asia (Thailand, Malaysia), Central Asia (Pakistan, Afghanistan, Kazakhstan) and South Asia (Nepal) are overviewed. Based on the publications of recent years, an analysis is made of the current state of the studied problem in the Russian Federation and, in particular, in the Rostov region.