The aim of this review was to assess the peculiarities of distribution and epidemiological risk of rabies in the extreme northeast of Asia. The systematic review was prepared through synthesizing publications on rabies over 1860–2022 (n=22) and previously unpublished data for 2009–2023. From the late 19th century until the 1980s, rabies epizootics were consistently observed in Chukotka and Kamchatka. A correlation was found between the time of occurrence of rabies in those territories with a lag period of 1–2 years (r=0.349; p=0.054). In 2009–2023, 24 animal rabies cases were confirmed in Chukotka; rabies has not been registered in Kamchatka since 1981. Until 1982, 5 confirmed human rabies cases were described in Chukotka, as well as 4 lethal cases presumably due to rabies (Chukotka – 3, Kamchatka – 1). The similarity of the spatial distribution of epizootics in different periods of time was established. Rabies was detected mainly in the area of the permanent polar fox (Vulpes lagopus) habitation, in the coastal tundra from the mouth of the Kolyma River to the Anadyr Gulf. Outside this territory (the valleys of the Anadyr and Penzhina Rivers, the Kamchatka Peninsula), rabies was reported in red foxes (Vulpes vulpes). At present, the importance of the polar fox in the spread of rabies in Chukotka has decreased, while the significance of the red fox has increased substantially. Due to vaccination, rabies among dogs is recorded sporadically. Rabies virus isolates from Chukotka belong to the Arctic genetic lineage (Arctic-3 group), which has a circumpolar distribution. The possibility of independent circulation of the rabies virus in the Kamchatka Peninsula is doubtful because of the limited size of the red fox population. Based on the mapping, possible directions for the introduction of rabies to Kamchatka from Chukotka have been identified. Barrier oral rabies vaccination of foxes is recommended during the years of high abundance of red and polar foxes in Chukotka.

The literature review presents an analysis of publications over the past five years on the global distribution of particularly dangerous (endemic) mycoses: coccidioidomycosis, histoplasmosis, blastomycosis, paracoccidioidomycosis. The causative agents of these mycoses are dimorphic micromycetes, which can cause a severe course of the disease, even death. These fungi exist in specific ecological niches, but in recent years there have been many reports of them occurring outside of regions of traditionally known endemicity. There are potential causes for these changes, such as global factors (climate change, migration) and extensive use of immunosuppressive drugs. Climate warming may provide favorable conditions for the growth of Coccidioides spp. in new areas, while prolonged dry spells and subsequent dust storms result in increased incidence of coccidioidomycosis in already established endemic areas. Currently, there is an assumption that not only the soil, but also rodents are the primary reservoir of Coccidioides in the external environment. Histoplasmosis is endemic in the countries of the Americas, but the extent of spread of the causative agents has not been fully defined. In Latin America, histoplasmosis is one of the most common infections in HIV-infected people, with a high mortality rate. Many epidemiological data on blastomycosis come from North America, with less information from Africa and Asia. Cases of endemic mycoses in immunocompetent travelers are usually diagnosed incorrectly, due to the absence of specific symptoms. There is also a risk of reactivation of infection in persons with acquired immunosuppression, even after a long period of time. Isolation of pathogens from environmental objects using conventional cultural methods is difficult, while the introduction of molecular-genetic studies will supplement the knowledge about the epidemiology of these mycoses.

The aim of this review was to investigate the use of the vaccines based on vaccinia virus, MVA stain, and adenovirus vectors for the prevention of Ebola virus disease. The recombinant MVA strains expressing antigen determinants of Filoviridae family representatives were assessed as possible candidates for vaccine preparations. Application of this virus as a vaccine vector is conditioned by the absence of herd immunity to smallpox and its safety for healthy adult volunteers, children, adolescents, individuals suffering from tuberculosis, persons aged 56–80 years, people with diagnosed atopic dermatitis, AIDS. Furthermore, immunization with the vaccine on the basis of vaccinia virus, MVA strain, does not cause complications associated with cardiovascular diseases. Preclinical trials on immunogenicity and protective efficiency were carried out on immune-competent and immune-compromised mice; guinea pigs adapted to Ebola virus; rhesus macaques and cynomolgus monkeys. Presented are the results of experiments on the creation of vaccines expressing either only viral glycoprotein or viral glycoprotein and structural protein Vp40. Given that Ebola fever and other filovirus infection outbreaks are hard to predict, multivalent vaccines that would be able to provide protection against all filovirus species were designed. Clinical trials on simultaneous use of the vaccines based on recombinant adenovirus vectors and MVA strain showed more pronounced safety of vaccines on the basis of recombinant MVA strain. Studies of humoral and T-cell immune responses have revealed that this vector is more suitable for booster vaccination in case of heterologous prime/booster immunization scheme. Vaccination regimens for forming strong durable immune responses have been analyzed. Epidemiological modeling provided evidence that preventive immunization leading to long-term immunity in healthy population in areas of high epidemic risk will be of greater benefit in terms of controlling future outbreaks compared to ring immunization that was effective during smallpox eradication campaign. Increased immunity level, induced by prime/booster vaccination, persisting for a long period of time, will have an advantage over accelerated ring immunization; when the duration of protection is more significant than the speed it is formed at.

Every year, the number of potentially life-threatening pathogenic biological agents (PBAs) is rapidly growing, which are represented by viruses, bacteria, rickettsia, chlamydia, protozoa, fungi, genetically engineered constructs and modified microorganisms, prions and toxins. The use of PBAs for the purpose of destroying society, the economic resources of the country, deteriorating the quality of food and water supplies, intimidating the population, provoking internal unrest, destabilizing government, and creating economic, socio-psychological and environmental crises is nothing more than biological terrorism. The numerous international agreements, treaties and protocols that have been developed and ratified to date, limiting the production and use of weapons of mass destruction, do not guarantee the elimination of the risks of illegal acquisition and use of biologically active substances by terrorist organizations, which does not exclude the possibility of committing acts of bioterrorism. In this regard, the preservation and strengthening of administrative-legal, medical-biological, sanitary-epidemiological, veterinary and phytosanitary and other measures should form the basis of the state policy of the Russian Federation to counter the use and spread of PBAs.

The aim of the present study was to evaluate the effectiveness of analysis of the high resolution melting curves obtained after amplification of VNTR loci for the identification and differentiation of Brucella strains.

Materials and methods. 16 strains of Brucella species – B. canis (n=1), B. abortus (n=9), B. melitensis (n=2), B. suis (n=4) – of different geographical origin were used as objects of the research. The MLVA-typing was performed using conventional PCR followed by separation of amplicons in agarose gel and real-time PCR with post-amplification analysis of the curves of VNTR loci melting in the presence of intercalating dye SybrGreen. Bioinformatics analysis was conducted with the help of Vector NTI 9.1, Mega 11 software (MUSCLE algorithm). Phylogenetic analysis was carried out applying UPGMA method using the Mega 11 program.

Results and discussion. MLVA approach based on the analysis of the melting point curves of the obtained after amplification of VNTR-loci PCR fragments has shown that each of the 16 strains of Brucella is characterized by a unique melting temperature profile. PCR followed by electrophoresis has demonstrated that despite the high variability of the used VNTR sequences (h=0.48…0.74), only post-amplification melting curves of the Bru7, Bru9, Bru18, Bru21 loci had sufficient information content to determine the genetic polymorphism of the studied Brucella strains. Based on the results of phylogenetic analysis of the Bru7, Bru9, Bru18, Bru21 sequences, it has been found that the majority of the studied Brucella strains are distributed in the dendrogram in accordance with their taxonomic and geographical position. Thus, HRM analysis of melting curves obtained after amplification of the Bru7, Bru9, Bru18, Bru21 loci has the potential to be used for differentiating Brucella strains.

The aim of the work was to analyze the results of investigating the field material obtained from natural plague foci of the Kyrgyz Republic (KR) in 2023, using modern diagnostic technologies.

Materials and methods. 1435 biological samples from the Tien Shan, Alai and Talas high-mountain foci of the Kyrgyz Republic were studied using conventional methods of laboratory diagnosis of plague: microbiological, immunological, biological; as well as modern molecular-genetic methods. Testing of the obtained samples for the presence of plague pathogen DNA was carried out using RT-PCR; and the presence of antibodies to the plague microbe was detected by enzyme-linked immunosorbent assay (ELISA). Molecular identification of Yersinia pestis strains according to their appurtenance to subspecies, biovars, and phylogenetic lineages was performed by RT-PCR using the method of identifying single-nucleotide substitutions based on the analysis of melting curves of products.

Results and discussion. An approach to the molecular identification of Y. pestis strains from plague foci of the KR has been developed and validated through identifying singlenucleotide substitutions using the analysis of product melting curves (HMR-analysis) with a set of designed primers. It has been established that Y. pestis strains isolated in the Sarydzhaz autonomous focus of the Tien Shan high-mountain focus belong to the biovar antiqua of the main subspecies, phylogenetic branch 0.ANT5. The phylogenetic relation of Y. pestis strains isolated in 2023 was studied based on genome-wide SNP analysis. Areas of epizootic activity in Eastern Alai have been identified. The data obtained indicate the sustained activation of plague foci in the KR. Areas of the territory of the KR that are promising for paleogenomic research are also discussed.

Recently, pathogenic Leptospira culture isolation is an extremely rare phenomenon in Russia.

The aim of our work was to synthesize the lessons learned at the Irkutsk Anti-Plague Institute from Leptospira culture isolation and identification since 2011.

Materials and methods. Material from eight individuals with suspected leptospirosis and from 942 small mammals (SM) was examined using PCR and microscopic agglutination test (MAT), from humans and 260 SM, applying bacteriological method. Bacteriological temperature test, MAT, PCR, MLST and MALDI-TOF mass spectrometry with the original Leptospira protein profiles base were used to identify cultures. Six complete genomes were generated at the Central Research Institute of Epidemiology of the Rospotrebnadzor.

Results and discussion. Leptospira have not been isolated from humans against the background of taking antibiotics, despite the positive PCR and MAT results. Four cultures of Leptospira borgpetersenii of the Javanica serogroup and three L. kirschneri (Grippotyphosa) have been isolated from SM. The results of identification using MLST scheme No. 1 and MALDI-TOF MS are identical. MLST in silico has shown the uniformity of two Grippotyphosa serogroup strains from Primorie and Khabarovsk with a sequence-type (ST) profile 110:100:94. ST146 is determined in four Javanica serogroup strains according to scheme No. 1, and unique single nucleotide polymorphisms are detected according to schemes No. 2–3. Thus, in Siberia and the Far East, between 2012 and 2016, seven pathogenic Leptospira cultures were isolated from carriers in natural foci; carrier infection rate being12.0–48.9 %. Javanica serogroup strains differ in the MLST profile characteristics and adapt to nutrient media for a longer time than Grippotyphosa serogroup strains.

The aim of the work was to study the genetic diversity and spatial-temporal structure of Yersinia pestis in the Caspian sandy plague focus using MLVA25 and CRISPR typing methods.

Materials and methods. 98 Y. pestis strains isolated in the territory of the Caspian sandy plague focus in 1925–2015 were used in the study. Whole genome sequencing was performed on Ion GeneStudio S5 System (ThermoFisher Scientific) and MGI (DNBSEQ-G50RS) platforms. Fragment sequencing was conducted using “ABI PRISM 3500XL”. The search for VNTR and CRISPR loci with subsequent alignment of nucleotide sequences was carried out in the MEGA X program. The obtained sequences were entered into the created database in the Bionumerics v7.6 (Applied Maths) software. The phylogenetic tree was constructed using the UPGMA method.

Results and discussion. According to the results of MLVA25 and CRISPR analysis, 98 Y. pestis strains are divided into 60 genotypes (CS1 – CS60). Variability by 23 VNTR loci has been discovered. 7 new CRISPR spacers are described: 5 in YPa and 2 in YPb (size 31–33 bp, GC composition 34–58 %). The described spacers are designated as a108, a109, a110, a111, a112, b53, b54. The interrelation of changes in the copy number of VNTR loci depending on the place and time of isolation of strains has been revealed. The data obtained can be used to carry out molecular-genetic certification of the territory of the Caspian sandy plague focus and to study the routes and patterns of evolution and spatiotemporal circulation of Y. pestis populations in the Caspian plague foci.

State Scientific Center of Virology and Biotechnology “Vector” has been monitoring highly pathogenic influenza since 2005.

The aim of this work was to track the markers of highly pathogenic influenza in the blood sera of people who had a contact with infected and/or deceased birds, as well as of residents from regions where emergence of new variants of influenza A virus is most likely to occur.

Materials and methods. Sera were studied using hemagglutination inhibition test (HI test). HI-positive sera were subjected to virus neutralization reaction.

Results and discussion. In 2021, 2076 blood serum samples from 19 regions of Russia were collected. Only 7 samples demonstrated significant titers in HI test with A/H5N8 viruses. In 2022, 1620 blood serum samples from 23 regions were obtained; 25 of them were positive for influenza А/H5N8 and А/H5N1 viruses. In 2023 (January-August), 3335 serum samples from 31 regions of the Russian Federation were collected. 28 samples were positive for influenza А/H5N8 and А/H5N1 viruses. Furthermore, we monitored blood sera for low-pathogenic A/H9N2 virus. The number of positive samples in 2021 was lower than 1 % (13 out of 2076); in 2022, it reached 5 % (81 out of 1620); in 2023, the share was lower than 1 % (31 out of 3335). The data obtained suggest indirectly that currently there is no stable circulation of zoonotic influenza A/H5N8 and A/H5N1 viruses in Russia. Influenza viruses A/H9N2 have widely spread in many countries of the world and actively participate in evolution of highly pathogenic influenza A/H5Nx viruses. The Russian Federation demonstrates a gradual increase in the number of blood serum samples with antibodies to A/H9N2 virus.

The aim of our study was to investigate the antibiotic resistance profiles of Shiga toxin-producing Escherichia coli (STEC), Salmonella spp., Shigella spp., and Staphylococcus aureus strains.

Materials and methods. 660 samples were collected at two communal kitchens in Hanoi, Vietnam between 2021 and 2022. They included foodstuffs, environmental (food processing tools) and biological ones (swabs from the hands of personnel). The VITEK® 2 Compact system in combination with DNA sequencing was used to identify bacterial species. The antibiotic susceptibility test (AST) was performed according to Kirby-Bauer Disk Diffusion Susceptibility protocol following Clinical & Laboratory Standards Institute (CLSI) method (M100-Ed32).

Results and discussion. In total, 53 pathogenic bacterial strains have been detected, including 11 STEC, 24 Salmonella enterica, 9 Shigella sonnei, Shigella flexneri, and 8 S. aureus. AST of STEC has showed the highest resistance rates to tetracycline and chloramphenicol (90.9 %); trimethoprim+sulfamethoxazole (81.8 %); ampicillin, gentamycin and piperacillin (63.6 %). The STEC isolates were susceptible to carbapenem group. Among the Salmonella strains, 50 % demonstrated resistance to ampicillin, followed by tetracycline and piperacillin (45.8 %). Additionally, 25 % were resistant to ticarcillin+clavulanic acid, 20.8 % – to trimethoprim+sulfamethoxazole, and 16.7 % – to chloramphenicol. All Salmonella strains exhibited susceptibility to gentamicin, cefoxitin, imipenem, meropenem, and ceftazidime. AST of Shigella strains revealed the highest resistance rate for tetracycline (30 %), followed by cefazolin and ceftazidime (20 %). However, all Shigella strains were susceptible to cefoxitin, carbapenem groups, and chloramphenicol. Among the S. aureus strains, 50 % exhibited resistance to erythromycin, azithromycin, clindamycin, penicillin, telithromycin, and gentamicin, followed by ciprofloxacin, moxifloxacin, levofloxacin, and chloramphenicol (25 %). All S. aureus strains were still susceptible to trimethoprim+sulfamethoxazole, daptomycin, linezolid, doxycycline, minocycline, and vancomycin. Our findings reflect the current situation on antibiotic resistance among pathogenic bacteria strains circulating at the study sites during food processing. They are an evidence of potential risk of food poisoning. There is a need to undertake the proper containment measures on the part of authorities or policy makers.

The aim of the study was to carry out whole-genome sequencing and comparative analysis of the original and benzalkonium chloride-resistant strains of Burkholderia pseudomallei.

Materials and methods. We used the strain B. pseudomallei 134 and resistant to benzalkonium chloride B. pseudomallei 134K. Whole-genome sequencing was conducted on the MiSeq Reagent Kit v3 platform (600-cucle).Genome assembly for both strains was performed with the help of SPAdes v3.11.1. In order to compare genome sequences of the studied strains, Snippy v4.6.0 software was applied. MEGA X program was used to align the nucleotide and amino acid sequences.

Results and discussion. The search and analysis of determinants responsible for the emergence of resistance to biocides in B. pseudomallei 134K have revealed two genes: the TetR transcriptional repressor gene and the AmrAB-OprA efflux pump gene. A single nucleotide polymorphism has been found in the TetR regulator, which led to the replacement of serine by proline in the mutant protein, and, as a result, a change in its secondary structure. It is believed that this mutation causes the loss of regulatory protein functionality, resulting in an increased expression of the efflux pump genes (AcrB/AcrD/AcrF) regulated by it. This follows by both, decrease in the level of sensitivity to benzalkonium chloride and the emergence of resistance to ceftazidime. In the AmrAB-OprA efflux pump gene, an insertion of 16 nucleotides has been detected at the position 544 of the amrA operon, which led to an increase in the length of the cistron, a shift in the reading frame, a change in the amino acid composition, and, as a result, a change in the secondary structure of the encoded protein. It is most likely that this mutation contributes to the loss of AmrAB-OprA operon function and the failure of normal outflow of xenobiotics from the cytoplasm of the microorganism. This assumption is evidenced by the loss of resistance to gentamicin in the mutant strain.

The aim of the work was to study the growth dependence on amino acids in Yersinia pestis strains of different phylogenetic branches of the antiqua biovar and to determine the genetic basis of auxotrophy of these strains.

Materials and methods. We used 38 strains of Y. pestis, the main subspecies of the antiqua biovar, isolated in various foci of the world in the period of 1928–2020. The nutritional requirements of the strains were determined by incubation on Difco minimal agar with different sets of amino acids. Phylogenetic analysis of the strains was carried out using the Wombac 2.0 and SeaView 5.0.5 programs. Comparative analysis of the nucleotide sequences of the genes was performed using the BLAST algorithm and the Mega 7.0 program.

Results and discussion. The phylogenetic appurtenance of the investigated Y. pestis strains of antiqua biovar to the phylogenetic branches 0.ANT3, 0.ANT5, 1.ANT, 2.ANT3, 3.ANT2, 4.ANT has been determined. It is established that all studied strains have a common dependence of growth on three amino acids – phenylalanine, threonine, and methionine. In the majority of the strains of antiqua biovar of all phylogenetic branches, growth is also dependent on the presence of cysteine in the medium, except for a part of the strains of the phylogenetic branch 4.ANT. In 14 genes of sulfur and cysteine metabolism, 19 mutations have been identified. Each phylogenetic group of the antique biovar has a distinct profile of mutations in genes involved in cysteine biosynthesis. The leucine requirement of the strains belonging to phylogenetic branch 0.ANT5 has been established, possibly caused by a frame shift in the leuA gene. Strains of the 1.ANT branch isolated in the Democratic Republic of the Congo demonstrate an additional proline-dependent growth. The defined nutritional requirements in the strains and the genetic causes of auxotrophy complement the phenotypic and genetic characteristics of the phylogenetic branches of the antiqua biovar and can be used as genetic markers for the differentiation of these strains.

The aim of the work was to compare the main socio-demographic and eco-epidemiological parameters of tick-borne viral encephalitis, tick-borne borrelioses and tick-borne rickettsiosis.

Materials and methods. The authors’ databases based on epidemiological investigation records were used for the study. All in all, 2974 cases (Irkutsk and the Irkutsk district) were analyzed during the periods of 1995–2022 for tick-borne viral encephalitis and tick-borne borrelioses, and 2001–2022 for tick-borne rickettsiosis.

Results and discussion. The following parameters were assessed: the timing of epidemic season; the geography of prevalence; localization of tick bite on the human body; incubation time; gender and age structure of patients; social composition and exposure conditions. It was shown, that the parameters had their own features for each disease, and part of them are common to all Eurasian area of these infections. The shared characteristics include: the early epidemic season onset for tick-borne rickettsiosis; the shorter incubation time for tickborne rickettsiosis as compared to tick-borne viral encephalitis and tick-borne borrelioses; the increased frequency of tick-borne rickettsiosis vectors’ bites near the head and neck, and tick-borne borrelioses vectors – on the torso; large percentage of older persons among patients with tick-borne borrelioses and children under 14 years of age among patients with tick-borne rickettsiosis; prevalence of male population over female one as regards all surveyed pathogens. Low incidence of tick-borne diseases among professional contingent (the work associated with staying in natural foci of infection), an increased risk of tick-borne encephalitis and rickettsiosis among social group “unemployed”, and tick-borne borrelioses – among retirees, can be attributed to regional specificity.

The circulation of a rather wide range of pathogens of natural-focal infectious diseases transmitted by ticks was detected in West Africa at different points of time: Borrelia, Rickettsia, Coxiella, Crimean-Congo hemorrhagic fever (CCHF), Bhanja, and bluetongue viruses, etc. Current epidemiological and epizootiological situation on natural-focal infectious diseases on the territory of the Republic of Guinea is not entirely clarified.

The aim of this work was to identify genetic markers (RNA/DNA) of natural-focal infectious disease agents in samples of Ixodidae ticks collected in the Republic of Guinea, and to determine the spectrum of pathogens circulating in various landscape-geographical zones of the country.

Materials and methods. To conduct research on the territory of all landscape-geographical zones of the Republic of Guinea, 4695 specimens of Ixodidae ticks of 11 species were collected. Taking into account the species appurtenance, gender, phase of development, as well as the site of collection, a panel of 1645 samples was compiled. Genetic markers of Crimean-Congo hemorrhagic fever and tick-borne encephalitis viruses, as well as Borrelia burgdorferi s.l., Ehrlichia chaffeensis, Ehrlichia muris, Anaplasma phagocytophilum, Coxiella burnetii, Rickettsia of the tick-borne spotted fever (TBSF) group, and Francisella tularensis were detected using polymerase chain reaction (PCR) and reverse transcription polymerase chain reaction (RT-PCR).

Results and discussion. The following markers of natural-focal disease agents were found in the Ixodidae tick suspensions: DNA of Rickettsia of the TBSF group (25.6 % of all samples studied), DNA of C. burnetii (6.2 %), cDNA of B. burgdorferi s.l. (9.1 %), and RNA of the CCHF virus (2.5 %). The listed spectrum of pathogens has been registered in all landscape-geographical zones of Guinea. Genetic markers of tularemia, anaplasmosis, ehrlichiosis and tick-borne encephalitis pathogens have not been identified in this study. The results obtained made it possible to clarify the probable spectrum of tick-borne diseases in the territory of the Republic of Guinea, determined the need for further study of the circulation of natural-focal infectious disease agents in West Africa and conducting regular epizootiological monitoring.

The aim of the study was to identify structural differences in the Brucella omp25 and omp2a genes, which make it possible to determine their taxonomic position.

Materials and methods. The objects of the study were the nucleotide sequences of the complete genomes of 48 Brucella strains presented in the GenBank NCBI database. To assess sequence homology, the BLAST algorithm and the MEGA 11 program were used.

Results and discussion. In 13 species of Brucella and Brucella spp. with unknown species appurtenance, HindIII, EcoRV and EcoRI, AluI restriction profiles of genome regions have been reproduced in silico, including, omp25 and omp2a genes, flanked by primers 25A-25B and 2AB-2AA, respectively. In the omp25 gene, 11 non-synonymous and 24 synonymous mutations have been detected; two deletions: ∆103–108 bp – in В. nosferati, ∆562–597 bp – in В. Ovis; and ACT insertion after 585 bp – in В. vulpis. The variability of the omp2a gene in the studied Brucella strains was significantly higher. 138 SNPs have been identified, of which 60 lead to amino acid substitutions, 2 – form stop codons, and an additional deletion ∆424–561 bp – in В. abortus 1, 2, 4 biovars. Single mutations in the omp2a and omp25 genes had both group specificity – for several species, and unique – for a specific species or biovar of the pathogen. Allelic profiles of the omp25 and omp2a genes have greater resolution than their restriction profiles studied. The identified changes in the structure of the omp25 and omp2a genes correlate with the circulation of individual Brucella species and biovars in the organism of certain carriers. These genes show the presence of deletions, insertions and single polymorphic nucleotides specific to species, groups of species and, in some cases, biovars of the pathogen.

The aim of the study was to analyze the abundance, species composition, dissemination of mouse-like rodents and other small mammals in the settlements of the West Kazakhstan Region over the past 6 years and the factors contributing to the change in the numbers in the long-term aspect.

Materials and methods. We utilized the data obtained by employees of the Uralsk Plague Control Station, affiliated branch of the Republican State Enterprise “National Scientific Center of Particularly Dangerous Infections named after Masgut Aikimbaev” during a scheduled epizootiological survey of plague foci located in the West Kazakhstan Region.

Results and discussion. The average annual number of rodents and insectivores in the settlements on the plague-enzootic territory of the West Kazakhstan Region was 5.1 in spring season, 8.1 in autumn, with 30.0 % occupancy of the facilities. In outbuildings, the number of rodents was three times higher than in residential buildings and amounted to 11.5 (residential buildings – 3.7). The general species composition of small mammals caught in the settlements was represented by seven species, among which the house mouse was a predominant one (97.5 %). The second place was occupied by the small shrew (1.7 %). There is a downward trend in the number of rodents in the steppe foci of plague (over 18 years – an average of 22.0 %). A slight increase in the number of animals by 2.0 % has been registered in the sandy focus.

The World Health Organization declared COVID-19 a pandemic on March 11, 2020. While in March 2022, i.e. approximately two years later, the global dominance of the phylogenetic variant of SARS-CoV-2 Omicron with its associated milder clinical course of the disease was registered, and therefore an epidemiological forecast was made about the onset of a period of decline in the pandemic.

The aim of this work was to determine the duration and possibility of predicting the COVID-19 pandemic based on an epidemiological assessment of its dynamics in the context of the wave-like course, phase nature, and epidemiological significance of the phylogenetic transformations of the pathogen. Materials from a global source on the Internet about daily cases of infection/deaths of COVID-19, the results of phylogenetic studies of the pathogen and their interpretation using the epidemiological method were analyzed. The evaluation of the COVID-19 pandemic dynamics in the world revealed that it is a typical epidemiological variant of pandemics (epidemics) with its characteristic waves that last for months and do not coincide with the annual solar cycles. As of early March 2023, 7 waves were registered, of which the 1st–4th waves are the epidemic phase, caused by the consistent dominance of the Wuhan and Delta strains, the 6th–7th waves are the post-epidemic phase. The waves varied in duration from 4 to 7 months (M – 4.6 months) and in amplitude from 307205 to 4082344 (M – 1331389.14) peak values of the number of the infected and deaths – from 2997 to 20702 (M – 10506), accordingly. The post-epidemic phase was characterized by a steady trend of quantitative decrease in SARS-CoV-2 Omicron in the form of undulating dynamics with steadily decreasing amplitude of the waves of the number of infected people against the background of a sharp decrease in the number of lethal outcomes compared to the epidemic phase. The continuation of this trend is expected in the form of two more waves of small amplitude (8th and 9th) with a total duration of about 10 months; the completion of the postepidemic phase is predicted in the first half of 2024. Data on the phase nature of the pandemic, determined by genomic changes in the pathogen, are necessary to be prepared for future pandemics.

The aim of the work was to assess the possibility of using disposable polymeric containers in the production technology of the live plague vaccine.

Materials and methods. We deployed the vaccine strain Yersinia pestis ЕV NIIEG for the work. A standard disposable 10 L Flexboy type polymeric container manufactured by Sartorius Stedim Biotech, equipped with Sartopore 2 filter capsules, was used for submerged cultivation of plague microbe inoculum. This method was compared to the regulated technology for obtaining seed cultures using glass bottles with a volume of 20 liters. The control of the produced seed cultures of the vaccine strain EV was performed in accordance with FS.3.3.1.0022.15. The cultivation of the seed culture in a disposable polymeric container was carried out in a liquid nutrient medium at a temperature of 26 to 28°C with continuous barbotage and mechanical agitation with a platform oscillation frequency of 80 to 90 per minute. For aeration, compressed air with a pressure of 0.3 to 0.4 kgf/cm² was used. The volumetric flow rate of sterile air supplied for aeration ranged from 0.9 to 1.0 l/min.

Results and discussion. The use of disposable polymeric containers made it possible to reduce the duration of the technological stage of obtaining a seed culture by 1.7 times and increase the yield of live microbes per unit volume of the nutrient medium by 2.8 times, as compared to the regulated production technology. Thus, the possibility and prospects of using disposable polymeric containers in the production technology of live plague vaccine at the stage of preparation of sowing cultures is evidenced.

Mutations in the SARS‑CoV‑2 genome make it possible to effectively escape defense mechanisms of the host, which explains the spread of infection among vaccinated or previously affected by the virus individuals.

The aim of the study was to investigate the dynamics of mutations in the SARS‑CoV‑2 virus genome during the rise of the seasonal incidence in the Chuvash Republic.

Materials and methods. Under conditions of the clinical diagnostic laboratory of the Federal Center for Traumatology, Orthopedics and Endoprosthetics of the Ministry of Health of Russia (Cheboksary), samples, containing SARS‑CoV‑2 RNA, taken in January-February and July-October, 2022 were tested using reverse transcription PCR. The “MBS-Test SARS‑CoV‑2 RNA” (Technical Specifications 21.20.23-068-26329720-2021, Russia) and “AmpliTest SARS‑CoV‑2 VOC v.3” (Series V017, Certificate of Registration No. 2022/16307, Russia) were utilized in compliance with the manufacturer’s instructions.

Results and discussion. Variations in the sets of SARS‑CoV‑2 S gene mutations have been revealed in the studied samples obtained during different periods of the spread of SARS‑CoV‑2 coronavirus. Timely detection of various mutations in the virus genome at the beginning of the epidemiological season and the alleged rise in the incidence of coronavirus infection is valuable information for forecasting the rate of virus transmission. It can also be used to create vaccines (taking into account changes in the virus genome) and to choose the adequate tactics for treating coronavirus infection.

The spread of Vibrio cholerae strains with multiple antibiotic resistance necessitates the search for alternatives to antibiotics. Cholera bacteriophages can become such means.

The aim of the work was to study the safety of a mixture of cholera bacteriophages using an experimental animal model.

Materials and methods. We used a composition based on cholera phages Rostov-M3, Rostov-13, FB1. The toxicity of the drug, cytotoxic and apoptogenic effects in experimental animals were assessed.

Results and discussion. It has been shown that a single administration of the maximum defined dose of the mixture of phages does not cause negative effects on the body of laboratory animals. Comparison with the control group has not revealed statistically significant differences in the histological picture in the organs of the experimental animals after long-term administration of the drug. Also, after a single and repeated seven-day administration, these phages do not cause apoptosis and necrosis of immune competent cells in experimental animals. The results of the studies indicate the safety of the 3-component phage composition and can be used for the further development of new biological products based on cholera bacteriophages in the future.