Background: April 21, 2021 marks the centenary of the birth of Irina N. Blokhina – a world­famous scien­ tist, Academician of the Russian Academy of Medical Sciences, Doctor of Medical Sciences, Professor, Laureate of the USSR State Prize, and Honorary Citizen of the city of Nizhny Novgorod. For 44 years, Dr. Blokhina headed the Nizhny Novgorod (Gorky) Research Institute of Epidemiology and Microbiology. The objective of this paper is to reflect and analyze the historical role of the personality in the development of new research areas, achievement of outstanding sci­ entific results, and education of younger generations of scientists on the example of the life path of Dr. Blokhina, whose name is associated with the most productive times in the history of the institute. Materials and methods: In preparing the present article, we analyzed extensive archival materials, scientific and media publications, and memoirs of contempo­ raries. Findings: We describe how the breadth of scientific outlook of this eminent scientist, her deep and comprehensive erudition, and a constant thirst for new knowledge allowed her to see and effectively solve the most pressing problems of fundamental science and practical health care. Professor Blokhina devoted her entire life to medical science by de­ veloping priority science trends in biochemistry, microbiology, immunology, biotechnology, and molecular biology. Conclusions: The personality of Academician Irina N. Blokhina demonstrates how purposefulness, creative attitude to assigned tasks, and a high degree of responsibility enable a person to achieve top results in science and life. Our findings may be particularly useful in education of the younger generation of scientists.

Introduction: Regulatory documents of the Russian sanitary legislation provide no standardization of microbiological indicators for urban public transportation. At the same time, extensive studies of public transport microbiome conducted in dif­ ferent countries demonstrated that the external environment (stations and platforms) and the interior of vehicles contain a large number of various microorganisms, the number of which is independent of air temperature, route duration, or the number of passengers. The objective of our work was to study the species composition of microbiota in urban buses and to assess its structure using methods of synecological and epidemiological analysis. Methods: We analyzed wipe samples from generally accessible bus interior surfaces. In total, 41 buses of 16 routes from three conditional groups (“Nagornaya” (Upland), “Zarechnaya” (Transverse) and “Interdistrict”) were examined. We applied methods of classical bacteriology, MALDI­TOF mass spectrometry for microor­ ganism identification, and synecological analysis. Results and discussion: We identified 85 types of microorganisms, 15 of which were found in all groups of routes. The bus microbiota followed the same ecological laws as natural microbiocenoses. The greatest number of species was represented by genera Staphylococcus (16), Acinetobacter (11), Bacillus (11), Pseudomonas (8), and Pantoea (5). The majority of identified microorganisms belonged to genera Acinetobacter, Enterobacter, and Pantoea. Among 15 species of micro­ organisms “common” to three groups of buses, 60 % were representatives of human microbiota. Microorganisms were found in large quantities on fabric seat backs (up to 18,600 CFU/cm³), seat back handles (up to 76,500 CFU/cm³), leather loop­holders (up to 6,400 CFU/cm³), and visually dirty surfaces (11,200 CFU/cm³). Conclusions: Our findings indicate the need to standardize micro­ biological indicators and develop guidelines for monitoring the efficiency of disinfection of interiors of public passenger vehicles.

Introduction: Staphylococcal infections rank high among healthcare­associated infections. Coagulase­negative staphylococci, especially S. epidermidis and S. haemolyticus, often induce inflammatory processes in newborns. In this regard, it is important to study the persistence of these microorganisms in pediatric hospitals using intraspecific differentiation based on the comparison of spectra of their extracellular proteins. Our objective was to study circulation of S. epidermidis and S. haemolyticus strains in a children’s hospital by electrophoretyping of their extracellular proteins. Materials and methods: We studied 277 strains of S. haemolyticus and 267 strains of S. epidermidis isolated from patients and various objects of the hospital environment by obtaining extracellular proteins of the isolates, analyzing them using polyacrylamide gel electrophoresis, and determining their antibiotic resistance and ability to form biofilms. Results: The analysis of electrophoregrams of extra­ cellular proteins of staphylococci revealed groups of identical strains. Isolates from different patients were combined into 21 S. haemolyticus groups comprising of 69 strains and 13 groups of S. epidermidis comprising of 38 strains. All the cultures were methicillin­resistant, with the exception of one group of two S. haemolyticus strains. More than half of the cultures grouped by spectra of extracellular proteins were multidrug resistant. The absolute majority of S. haemolyticus strains (97.2 %) and three quarters of S. epidermidis strains (76.0 %) were able to form biofilms. The average values of the degree of film formation in S. haemolyticus strains were significantly higher than those in S. epidermidis. Conclusions: Of all the studied cultures of staph­ ylococci, 25 % of strains and 14 % of S. epidermidis strains persisted and were endemic in the children’s hospital, including 88.4 % of hemolytic and 42.1 % of epidermal staphylococcus strains for more than a month, and 21.7 % of S. haemolyticus and 21.1 % of S. epidermidis strains for almost a year. The strains were resistant to methicillin, and the isolates of S. haemolyticus had a high ability to form biofilms.

Introduction: Cytomegalovirus (CMV) infection is a serious problem of modern health care. It belongs to the category of socially significant infections and is characterized by polymorphism of clinical manifestations and high child mortality. Abroad, much attention is paid to virus genotyping, determining the role of various genotypes in the development of certain clinical forms of CMV infection, and developing a vaccine against congenital human cytomegalovirus infection. The objective of our study was to assess the genetic diversity of cytomegaloviruses in children of Nizhny Novgorod. Materials and methods: We analyzed clinical CMV isolates from body fluid samples (blood, urine, and saliva), viral DNA and its fragments in 580 children aged from 15 days to 16 years. Molecular biology (PCR, RT­PCR, and sequencing), bioinformatics and statistical methods were applied in the study. Results: We established that CMV detection rates in children varied from 3.8 % to 18.9 % depending on the form of the dis­r ease. We assessed various method approaches to genotyping human cytomegalovirus clinical isolates, were first to determine prevalent gB1, gB2, and gN4a CMV genotypes in children in the Russian Federation, and revealed infected cases caused by two and three genotypes simultaneously. The phylogenetic analysis of UL55 and UL73 gene sequences indicates genetic diversity of Russian CMV isolates from children in the Nizhny Novgorod Region. Conclusions: New data on the prevalence of various CMV genotypes in children living in Nizhny Novgorod may be used in the system of epidemiological surveillance of cytomegalovirus infection while the results of genotyping and phylogenetic analysis of clinical CMV isolates may contribute to domestic vaccine development.

Introduction: Studying the possibility of using geoinformation technologies to analyze the epidemiological situa­ tion in the Volga Federal District (VFD) dates back to early 2000s. The experience of creating and maintaining the electronic epidemiological atlas of the Volga Federal District confirmed the relevance of this research direction for ensuring sanitary and epidemiological wellbeing of the population and showed the importance of its results for activities of healthcare and Rospotrebnadzor institutions. The purpose of our work was to consider the main stages of formation and development of geoinformation technologies in epidemiological surveillance of infectious diseases as a research direction of Academician I.N. Blokhina Nizhny Novgorod Scientific Research Institute of Epidemiology and Microbiology. Materials: The article de­ scribes the development of medical geography and gives characteristics of classical scientific schools and some of their results. It presents main results of research work carried out within the framework of the Rospotrebnadzor Sectoral Re­ search Program for 2016–2020 as well as methodology and main stages of development of the geographically distributed geoinformation software complex “Electronic Epidemiological Atlas of the Russian Federation” (GIS “Epidemiological Atlas of Russia”) and its structure. Conclusions: Geographic information systems in epidemiological surveillance as an up­to­date scientific direction of research activities of the Institute enabled implementation of the geoinformation project “Epidemiolog­ ical Atlas of the Volga Federal District”, the development of which began in 2000–2005 by specialists of the Institute and JSC Upper Volga Air Geodetic Enterprise, and development of GIS “Epidemiological Atlas of Russia”.

Background: Coxsackievirus A10 (CV-A10) is currently one of the most common etiological agents of enterovirus infection (EVI). Over the past decade, severe and fatal cases of CV-A10 infection have become more frequent while clinical manifestations of the disease are similar to those of Enterovirus A71 infection. The objective of our study was to characterize circulation of Coxsackievirus A10 in the Russian Federation in 2008–2019 and to study the phylogenetic relationships of strains isolated in Russia and Vietnam. Materials and methods: In 2008–2019, 220 CV-A10 strains were isolated from patients with various clinical manifestations of EVI and from sewage water samples taken in the Russian Federation and then studied using molecular genetic methods. In addition to that, we analyzed 26 CV-A10 strains isolated from patients with hand, foot, and mouth disease (HFMD) and acute flaccid paralysis in South Vietnam in 2018–2019. Results: We established a two-year periodicity of CV-A10 active circulation in Russia. In the structure of clinical forms of CV-A10 infection, herpetic angina prevailed (30.8 %), followed by minor illness (25.25 %), respiratory diseases (15.66 %), exanthema (14.65 %), gastrointestinal disorders (8.08 %), and asymptomatic infections (2.02 %). Symptoms of CNS damage (meningitis, meningoencephalitis) were observed in 3.53 % of cases. Most CV-A10 strains from Vietnam were isolated from patients with CNS affection of varying degrees of severity. During the study period, CV-A10 strains of genotypes C, E, and F3 circulated in the territory of the Russian Federation whereas the strains from South Vietnam were represented by genotypes F3 and F1. The studied strains showed a genetic relationship with those of CV-A10 circulating in different countries. Vietnamese and some Russian strains of the F3 genotype were genetically close to the strains isolated from severe cases. Conclusions: Molecular monitoring of CV-A10 circulation is an important component of the global epidemiological surveillance of EVI.

Introduction: A large number of infectious processes are associated with opportunistic microorganisms. The phenotype of antibiotic resistance of such pathogens is multidrug-resistant strains with the presence of various β-lactamases. Our objective was to determine the phenotypic and genotypic features of antibiotic resistance of staphylococci, enterobacteria, and non-fermenting Gram-negative bacteria – the cause of infectious diseases in patients of various health facilities of Nizhny Novgorod. Material and methods: Using classical microbiological methods and molecular genetic studies, we analyzed 486 strains of microorganisms isolated from the upper respiratory tract, intestines, urine, and wound discharge of patients in 2019–2020. In all isolates, the phenotype of antibiotic resistance was determined by the disco-diffusion method (Bioanalyse, Turkey) and using the Multiscan FC spectrophotometer (ThermoScientific, Finland) with Microlatest tablets (PLIVA-Lachema, Czech Republic), along with molecular features of resistance mechanisms by PCR on the CFX96 device (BioRad, USA) using AmpliSens kits (Russia). Results and discussion: The results showed that the most prevalent causative agents of infectious diseases (40.7 %) were Gram-negative bacteria, of which Enterobacteriaceae and non-fermenting bacteria accounted for 27.1 % and 13.6 % of cases, respectively. Staphylococci were isolated in 37.6 % of patients: S. aureus and coagulase-negative staphylococci induced 13.4 % and 24.2 % of cases, respectively. The analysis of antibiotic resistance of the isolates showed a high level of antimicrobial resistance in all hospitals, regardless of the isolation locus. The phenotype of methicillin-resistant strains was found in 26.3 % and 37.9 % of S. aureus and coagulase-negative staphylococci, respectively; the mecA gene was found in 89.0 % of methicillin-resistant staphylococci. The highest number of antibiotic-resistant strains among Gram-negative microorganisms was observed in K. pneumoniae, A. baumannii, and P. aeruginosa. We established that 61.7 % of K. pneumoniae, 75.1 % of A. baumannii, and 58.2 % of P. aeruginosa were resistant to carbapenems. The results of molecular genetic studies confirmed the presence of serine carbapenemases KPC and OXA groups in all multidrug-resistant K. pneumoniae and A. baumannii; genes of the metallo-β-lactamase of VIM group were found in 40.9 % strains of P. aeruginosa. The production of numerous β-lactamases and the presence of determinants of antibiotic resistance in the genome determine the virulent properties of opportunistic microorganisms. Conclusion: The antibiotic resistance of opportunistic microorganisms is the cause of developing a chronic infectious process. Today, a wide spread of antibiotic-resistant infectious agents is a serious public health problem, which determines the need for constant microbiological monitoring and studies of molecular mechanisms of resistance to identify the most potent antibiotics and to determine the ways of eradication of multidrug-resistant strains.

Introduction: Solution of the problem of prevention of the spread of HIV infection among adolescents and young adults is associated, inter alia, with systemic implementation of primary prevention strategies in educational establishments aimed at developing the necessary level of expertise in health risk management in students. The objective of our study was to determine the level of competence of adolescents in the field of HIV spread prevention Materials and methods: The technique of an online survey was used to establish the competence of high school students aged 15–17 living in the Nizhny Novgorod Region and to compare its level between boys and girls. Results: The level of competence was determined by four basic scales (emotional, cognitive, practical, and the scale of actions) and the additional scale of erudition. The level of general competence of the respondents was found to be high. Girls had significantly higher scores by all scales (p < 0.001) compared to boys. The erudition component was most prominent in both subgroups. The emotional component (empathy) was more important for girls. We noted differences in the significance of individual aspects of the assessed competence. Of the four priority strategies of HIV epidemic spread prevention, the respondents chose health care management and effective interaction of responsible structures as key factors in disease spread stop (р < 0.001). Conclusion: Promoting competence in HIV spread prevention among students for their effective social interaction in HIV related issues is an important outcome of preventive activities at schools. The content and forms of their implementation should facilitate students’ ability and readiness to self-protection, self-improvement, and mastering skills of predictive behaviour. Evaluating the level of competence and intensity of its components, setting priorities in choosing areas of applying efforts to reduce the risk of HIV epidemic growth can make prevention efforts more targeted.

Introduction: Establishing the reasons for the decrease in the effectiveness of anti-Helicobacter pylori therapy and proton pump inhibitors in the treatment of acid-dependent diseases is an urgent task due to high prevalence of these disorders undermining population health. Our objective was to conduct a literature review to assess the influence of the genetic polymorphism of cytochrome P-450 CYP2C19 on the eradication rate of Helicobacter pylori and the metabolism of proton pump inhibitors, to evaluate the effectiveness of their use, and to determine possible ways of overcoming refractoriness to these drugs in the clinic. Materials and methods: We analyzed published studies found in domestic (eLibrary, CyberLeninka.ru) and international (PubMed, Cochrane Library) databases. Results: We revealed a genetic polymorphism CYP2C19 of cytochrome P-450, according to which different types of drug metabolism were identified: fast, intermediate, slow, and ultrafast. The relationship of this polymorphism with biotransformation of proton pump inhibitors was then analyzed. In Russia, the predominance of fast and intermediate metabolism in individuals of the Caucasian race decreases the efficacy of acid-suppressive therapy and the Helicobacter pylori eradication rate. Correction of the daily dose and frequency of drug administration are necessary to increase the antisecretory effect of proton pump inhibitors. Discussion: The dependence of proton pump inhibitor biotransformation on the CYP2C19 polymorphism determines the differences between patients with different types of metabolism in the effectiveness of these drugs, the success of anti-Helicobacter pylori treatment, and clinical outcomes. Pharmacogenetic testing is useful for predicting the response to proton pump inhibitors, the likelihood of developing adverse events, and the possibility of personalized prescriptions in patients with acid-related diseases. Conclusion: Genetic testing of cytochrome CYP2C19 helps optimize the use of proton pump inhibitors, overcome refractoriness, and improve the quality of treatment of acid-dependent diseases and the overall Helicobacter pylori eradication rate.

Introduction: Cytomegalovirus (CMV) infection is a common beta-herpesvirus infection widely spread in the human population. The proportion of infected population increases with age and approaches 100 % in elderly people. The infection is usually latent but is capable of reactivation when immunosuppression develops. The mechanisms of reactivation are not fully understood. The objective of our study was to evaluate the role of soluble molecules CD25, CD38, CD95 in the development of immunosuppression in CMV infection. Materials and methods: We used 18 serum samples from cases of CMV disease in the stage of reactivation, all confirmed by clinical and laboratory data. The patients received treatment in Nizhny Novgorod Infectious Disease Hospital No. 2. The serum content of the total and oligomeric soluble molecules CD25, CD38, and CD95 was identified by ELISA using monoclonal and polyclonal antibodies against human peripheral blood mononuclear cell proteins. The results were recorded spectrophotometrically and evaluated by converting optical density units to conventional units (U/mL). Results: We established an increase in the serum content of total and oligomeric fractions of soluble molecules CD25, CD38, and CD95 in the cases of CMV disease. While the serum content of the total and oligomeric fractions of molecules CD25 and CD38 increased equally, the oligomeric fraction of molecules СD95 demonstrated a more pronounced increase compared to the total fraction of these molecules. Our findings suggest the immune response suppression mechanism associated with initiation of apoptosis of effector T lymphocytes involving oligomeric form of molecules CD95. Conclusion: Changes in the content, structural and functional state of soluble differentiating molecules CD25, CD38, and CD95 indicate their involvement in immunosuppression mechanisms in patients with CMV infection.

Introduction: Today, we are witnessing the process of forming a fundamentally new epidemiological situation on infectious mononucleosis. Over the past decade, a general increase in the incidence of infectious mononucleosis, its proportion in the structure of respiratory tract infections, and economic importance was noted in Russia. Information about the epidemic process of infectious mononucleosis in different areas is limited. Our objective was to study the features of the epidemic process of infectious mononucleosis in the Nizhny Novgorod Region in 2010–2019. Methods: We conducted a retrospective epidemiological analysis of the incidence of infectious mononucleosis in the Nizhny Novgorod Region for 2010–2019 based on official statistics using standard statistical approaches. Results and discussion: The long-term incidence rate of infectious mononucleosis in the Nizhny Novgorod Region was stable (+0.6 %) with the long-term average rate of 12.6 ± 0.6 ‰оо. An autumn-winter-spring seasonality with two distinct peaks (in November–December and May) was revealed. The majority of cases were children aged 0–14 years (72.8 ± 2.2 %). The highest incidence rates were registered in the age groups of 1–2 and 3-6 years. We established a reverse trend in the disease incidence among children aged 0–6 (decrease) and 7 years and older (increase). Adolescents aged 15–17 demonstrated the most pronounced growth rate (+7.5 %). The typical annual dynamics in adults was distinguished by a clear spring-summer seasonality, the absence of a characteristic growth in the autumn months, and a low rate in December. The identified features of the epidemic process in different age groups require clarification and detailing. Conclusions: We established recent patterns and features of the epidemic process of infectious mononucleosis in the Nizhny Novgorod Region. This work is an important component of epidemiological surveillance of infection and a scientific basis for improving the existing system of preventive and anti-epidemic measures.

Introduction: Vaccines are one of the most effective means of preventing infectious diseases. Their effectiveness and safety are guaranteed by studies of vaccine properties, during their development and during the mandatory preclinical and clinical trials of each new vaccine. Additional information on the mechanisms of vaccine action on human immune system cells can be obtained using in vitro immune response models. The objective of the study was to determine applicability of certain methods of studying human dendritic cells in vitro to assessing the effect of vaccines. Dendritic cells are the most active antigen presenting cells, which play a key role in triggering a primary immune response to an infection or vaccine. Materials and methods: We studied the effect of vaccines on the maturation of dendritic cells, their phagocytic activity and the ability to stimulate T­lymphocytes in vitro. Results: To test the methods, we used vaccines with a known pattern of action on the immune system. All the vaccines induced the expression of dendritic cell maturation markers. At the same time, different vaccines induced a different set of markers and the degree of expression of these molecules. Quantitative methods for assessing phagocytosis and stimulating activity of dendritic cells are described. Conclusion: Methods for evaluation of phagocytosis, phenotypic maturation and functional properties of dendritic cells have been shown to be useful for evaluation of vaccine action. In our opinion, these methods, as a complement to traditional methods for evaluating the immune response, can be used to investigate the action of prototype vaccines at the stage of their development and preclinical trials.