Academician I.N. Blokhina Nizhny Novgorod Scientific Research Institute of Epidemiology and Microbiology is one of the leading scientific institutions focused on obtaining new knowledge about current and socially significant infections and improving methods and means of diagnosing, preventing and treating them and one of the oldest in the country: the institute celebrates the centenary of its Foundation in 2019. Over such a long period of intensive activity for the benefit of the country's public health, the Institute has done a lot of work to combat such infections as rabies, measles, whooping cough, cholera, various intestinal, wound and other infections, provided assistance to practical health authorities both through direct participation of Institute employees in the elimination of accidents, outbreaks of infectious diseases, and through the introduction of scientific-methodical and information-methodical developments. Today, the Institute's scientific interests include issues of epidemiology, diagnosis and prevention of current bacterial and viral infections (viral hepatitis, HIV/AIDS, enterovirus infections, acute intestinal infections, HCAI, NGUI, HPVI, opportunistic, neuro-bronchial infections, including community-acquired pneumonia). New samples of probiotics for correction of microbiocenosis are being constructed. The GIS-project «Electronic Epidemiological Atlas of the Volga Federal District» has been developed and introduced into the practice of the bodies and organizations of Rospotrebnadzor and activity has begun on the creation of an «Electronic Epidemiological Atlas of Russia». The effectiveness and safety of vaccination are being studied. Works on design of Express test systems in the format of protein biochips are carried out to identify informative indicators for immuno-dependent risk assessment of various diseases. Having crossed the 100-year time-horizon the Institute is still demanded as a center for scientific-methodical and scientific-practical support for the epidemiological surveillance of the Nizhny Novgorod region, the Volga Federal District and Russia as a whole and successfully executes its noble and necessary work contributing to the protection of people from infectious diseases.

The article describes the main stages of the geoinformation project development «Electronic epidemiological Atlas of the Volga Federal district». Use of the Atlas allows to study the development of the epidemic process included in the database of Nosology Atlas in the space-time dynamics and present the results in the form of reports, thematic maps, tables or graphs. The Concept of creating a geographic information system (GIS) «Epidemiological Atlas of Russia» was developed as part of the further improvement of the existing geographic information system, expanding its functions for use in other Federal districts.

We researched the sensitivity to disinfectants and the ability to form a biofilm of coagulase-negative staphylococci circulating in a children's hospital in Nizhny Novgorod. It is shown that the most common resistance to disinfectants and a high degree of biofilm formation was observed in S. haemolyticus cultures. A comparison of testing sensitivity to the Avansept disinfectant planktonic cells of coagulase-negative staphylococci and the same strains in the form of a biofilm was performed. It was found that the resistance to «Advance» significantly increases in strains grown in the form of biofilm compared with plankton cultures.

We researched 26 K. pneumoniae ssp. pneumoniae strains, isolated from patients and objects of the environment during the epidemic ill-being period in the pediatric hospital. Identification of strains and their clustering, study of antibiotic sensitivity, detection of antibiotic resistance determinants, whole genome sequencing were carried out. It is established that one strain characterized by identical RAPD patterns and sensitivity to antibiotics from the groups of cephalosporins, monobactams, aminoglycosides, carbapenems, fluoroquinolones, sulfonamides and glycylcyclides circulates in the department.The strain is resistant to ampicillin (MIC > 16) and nitrofurantoin (MIC > 64). Whole genome sequencing made it possible to characterize the strain as K. pneumoniae ssp. pneumoniae ST 3181^K-54, the analysis of the whole genome sequence showed the presence of a fosomycin resistance gene (fosA) and virulence determinants namely a complex of siderophores (aerobactin and enterobactin), fimbria of the third type, iron utilization system kfu and cluster of genes responsible for allantoin utilization that allowed us to consider the strain as a microorganism with a high pathogenic potential capable to rapid prevalence and dissemination in tissues.

Type of enterovirus was detected in 2753 cases when examining 4122 patients with various clinical forms of enterovirus infection (EVI) during the 2017-2018 period. We identified viruses of 42 types belonging to Enterovirus A-B-С species. The ratio of EV-A: EV-B: EV-C species was 51.29 percent: 47.06 percent: 1.65 percent. In 413 environment samples 29 non-polio enteroviruses were identified, three of which, CA14, EVA76 and ECHO25, were not detected in the period in patients with EVI. The Coxsackie A6 virus, which caused a drastic increase in the morbidity of exanthema forms was the dominant agent in the etiological structure of EVI in 2017 in most areas; the leading etiological agents of enteroviral meningitis (ECM) were the ECHO30, ECHO9, ECHO18 viruses. There was a decrease in the morbidity of both all forms of EVI and computers due to a decrease in the activity of the circulation of epidemic variants of the Coxsackie A6 and ECHO30 viruses as a whole in Russia in 2018. The computer epidemic process in 2018 was supported by the become active or remained active viruses of ECHO6, Coxsacke B5, ECHO9, ECHO18 and other viruses of the Enterovirus B species. The remaining relatively high morbidity of exanthema forms of EVI in addition to the Koksaki A6 virus was supported by the activated viruses Koksaki A16, Koksaki A5 and other viruses of the Enterovirus A species. The results of phylogenetic analysis of genome sequences that dominated etiological agents of EVI indicate that in 2018 there was a multiple importation of enterovirus epidemic variants into the territory of the Russian Federation, which supported the EVI/ computer epidemiological process in the Russian Federation as a whole and caused a complication of the epidemiological situation in a number of subjects. It is possible that these events contributed to the arrival of a large number of fans at the 2018 FIFA World Cup and visa-free entry into the territory of the Russian Federation for this category of tourists until the end of the year.

The bacteria of the Cutibacterium (formerly Propionibacterium) acnes species are representatives of normal microbiota of human skin on the one hand and they contribute to the development of inflammatory processes, such as acne, infectious complications in the post-traumatic and postoperative period of the eye (endophthalmitis), the cardiovascular system (endocarditis), central nervous system and musculoskeletal system (osteomyelitis), implant-associated infections on the other hand. To identify epidemically significant genotypes with high pathogenetic potential and genotypes of low pathogenic commensals the different molecular genetic approaches are used. The whole genome sequencing of C. acnes A1-14 strain isolated from the large intestine of a healthy person was carried out for the first time. As a result of alignment and collection, the nucleotide sequence of the genome was 2,484,560 pairs of nucleotides.The strain belongs to a phylotype II, a ribotype 6 and sequence-type 7 (McDowell A. et al. scheme) or 73 (Lomholt H. B., Kilian M. scheme) according to the results of genotyping. We showed that there are no mobile elements, determinants of pathogenicity and antibiotic resistance, mutations in the 16S rRNA, 23S rRNA, gyrA, gyrB, parC, parE genes and established the presence of CRISPR-Cas structure in the genome of C. acnes A1-14. An extrachromosomal sequence belonging to the genome of the Syphoviridae family bacteriophage was found. The morphological characteristic of the bacteriophage virion, the presence of that as extrachromosomal structure is typical to many C. acnes strains, is given using the electronic microscopic method of research. Thus, the obtained in our study results complement the understanding of the molecular genetic features of C. acnes strains isolated from various human biotopes and which are symbiotic microbiota representatives.

Urogenital mycoplasmas (Mycoplasma genitalium, Mycoplasma hominis and Ureaplasma spp.) currently prevail in the etiology of infections of the urogenital tract and are characterized by a high level of genetic polymorphism responsible for the occurrence of their antibiotic resistance. The review presents the data of domestic and foreign researchers on the resistance mechanisms of mycoplasmas and ureaplasmas to antibiotics and considers the acquisition by mycoplasmas of antibiotic resistance determinants. New knowledge of resistance mechanisms is important theoretical basis for improving measures to limit and prevent the spread of antibiotic resistant bacteria.

We studied mutations of HIV resistance to antiretroviral drugs during the period of widely use of antiretroviral therapy and the characteristics of the circulation of virus subtypes in the subjects of the Volga Federal District (VFD) from 2016 to 2018 on the plasma samples of HIV-infected patients. Genotyping of resistance mutations to antiretroviral drugs and statistical analysis were carried out. The most common mutations determining the resistance in the reverse transcriptase gene, the most common and specific mutations were identified. An analysis of the prevalence level of mutations in the virus resistance to different groups of antiretroviral drugs allows us to develop approaches to prevent the further occurrence of resistant strains of HIV and minimize their negative impact on the patient's body. With the development of the epidemic, there is an increasing diversity in the landscape of HIV-1 subtypes circulating on the territory of the Volga Federal District. Point mutation patterns associated with antiretroviral therapy failure in different subtypes vary.

Hepatitis A is a common cause of viral hepatitis. The pronounced autonomy of the epidemic process of infection, the polymorphism of its clinical symptoms and other factors make it difficult to apply universal approaches to predict the morbidity of hepatitis A. The aim of the study was to develop a complex approach for epidemiological risk assessment of hepatitis A. Short-term prediction of hepatitis occurrence rate was carried out with maximum stability and regression equation methods in Nizhny Novgorod during the 1994-2017 period. Concentration of the pathogen in waste water samples was made by adsorption method using non-woven bags with macroporous glass. Viral RNA was detected by real-time PCR method. Anti-HAV IgG prevalence rate was studied by ELISA (enzyme-linked immunosorbent assay) method among the relatively healthy population in the age from 1 to 60 years in Nizhny Novgorod. Accuracy of mathematic prediction of hepatitis A morbidity rate has been ineffective in the current conditions. It is necessary to supplement the analysis of recorded morbidity data by monitoring the activity of activation signs of the pathogen circulation and parameters of specific population immunity for an adequate assessment of the epidemiological risk of hepatitis A in current conditions. Such precursors are an increase in the detection rate of anti-HAV above a threshold value in the indicator age groups of children 1-4 years old and 5-9 years old, as well as the detection of pathogen RNA in wastewater before treatment.

The most important means of measles control is live measles vaccine, the high epidemiological effectiveness of which is confirmed by half a century of its use. There is a question of the need to further improve the effectiveness of vaccine prophylaxis, in particular, by increasing the immunogenicity of the used vaccine given the increase in the morbidity of measles in recent years. Investigation of effect features of existing vaccine variants is necessary to identify possible ways to increase their immunogenicity. We investigated the effect of measles culture live vaccine on the maturation of human dendritic cells - the most specialized antigen-presenting cells involved in the induction of an immune response. In vitro incubation of monocytic derived immature dendritic cells with the vaccine initiates the process of their partial maturation, which is manifested in an increase in the number of cells carrying molecules CD86, CD83 and ICOSL (CD275).At the same time they have a reduced expression level of the HLA-Dr molecule and chemokine receptors CCR7 and CXCR5 involved in the migration of dendritic cells to peripheral lymphoid organs. In our opinion, the relative weak side of measles vaccine effect on dendritic cell maturation is a factor limiting the immunogenicity of the vaccine, which must be taken into account when developing new measles vaccines.