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Relevance. H. influenzae is a common cause of bacterial meningitis in children worldwide. Significant data have been accumulated worldwide on the use of H. influenzae type b conjugate vaccines over the past three decades. In the Russian Federation, constant monitoring of hemophilic meningitis is carried out, but data on the incidence of hemophilic infection are limited.Target. To consider global changes in the epidemiology of invasive forms of H. influenzae in the world and in the Russian Federation.Conclusions. The use of conjugate vaccines has resulted in a steady decline in invasive Hib infections. However, there has been a significant increase in invasive infections with non-typeable H. influenzae and non-b serotypes. In the Russian Federation, the incidence of meningitis caused by H. influenzae does not tend to increase or decrease; the majority of cases occur in children under 5 years of age.

Relevance. The decrease in the number of cases of invasive diseases caused by N. meningitidis, S. pneumoniae, H. influenzae and in the world has been associated with measures against the spread of the 2019 coronavirus disease (COVID-19).Aim. Presentation of the epidemiological features of purulent bacterial meningitis (PBM) in the Russian Federation at the present stage.Materials and methods. On the basis of the Russian Reference Center for Monitoring Bacterial Meningitis (RCMC), an in-depth personalized system for recording PBM cases has been established. Since 2010, all territories of the Russian Federation have been included in the monitoring system. In 2022, the RCMC received information on 1596 cases of PBM. The descriptive-evaluative epidemiological method was used in the work: a retrospective analysis.Results. The increase in the incidence of a generalized form of meningococcal infection (GFMI), which began in 2017, was recorded in 2018 and 2019, but in 2020–2021 growth was interrupted: the indicator dropped sharply, amounting to 0.26–0.21 per 100 thousand of the population, which is most likely due to the disunity of the population as a result of measures aimed at combating the new coronavirus infection. Measures to combat COVID-19 were canceled in 2021, and already in 2022 the incidence rate of GBM increased by 1.4 times, while the GFMI by 2 times, amounting to 0.44 per 100 thousand of the population. A sharp decrease in the incidence of PBM caused by S. pneumoniae and H. influenzae in 2020-2021 was replaced in 2022 by an increase in the incidence of pneumococcal meningitis, however, the incidence of meningitis caused by H. influenzae remained at the same level.Conclusion. Continued monitoring of the incidence of PBM and the properties of the pathogen are extremely important tasks in order to identify risk groups and areas for the timely optimization of vaccination measures, given that the three infections that cause bacterial meningitis are vaccine-controlled, and vaccination is recognized as the most effective measure to combat meningococcal, pneumococcal and hemophilic infections.

Relevance. The success of vaccine prophylaxis of meningococcal infection depends on the composition and properties of vaccine preparations and the strict implementation of recommendations on vaccine prophylaxis tactics by the territorial epidemiological characteristics of meningococcal infection. Despite the high burden of B-meningococcal infection, especially among young children, the design of B-meningococcal vaccines has faced serious difficulties. Aim. The literature review presents the history of the development of B-meningococcal vaccines and provides characteristics of two immunologically effective and safe new generation B-meningococcal vaccine preparations. Conclusion. The licensing of the two new B-meningococcal vaccines presented in the review (Bexsero and Trumenba) was based on immunogenicity and safety. The inclusion of vaccines in national vaccination programs requires careful analysis, including analysis of the antigenic characteristics of circulating strains.

Relevance. Unencapsulated strains of meningococcus (NmNG) very rarely cause invasive meningococcal disease. A new ciprofloxacin-resistant strain NmNG ST-175 cc175, which has recently caused several cases of invasive meningococcal infection in Europe, has been discovered in the Russian Federation.Aim. To compare the new Russian strains of NmNG ST-175 with the already characterized NmNG ST-175 and to analyze the genetic markers associated with antibiotic resistance.Materials and methods. The nucleotide sequences of NmNG ST-175 strains of more than 2 million base pairs were exported from the PubMLST database. Comparison was carried out for 1605 core genome loci using the N. meningitidis cgMLST v1.0 ". Genetic relationships of 127 NmNG ST-175 strains, including 8 Russian carrier strains, were visualized using the SplitsTree software (version 4.16.2).Results. Of the eight Russian strains, six found themselves in a cluster with German and Swedish isolates that caused invasive meningococcal infection. Two more Russian strains were closest to the isolates of the cluster, including carrier isolates from England. Seven strains showed resistance to ciprofloxacin and possessed the gyrA-187 and gyrA-152 alleles, which, based on the phylogenetic analysis of the alleles, belonged to the genetic branches of Neisseria cinerea and Nm.Conclusion. Protein vaccines alone could potentially provide protection against ST-175 NmNG. It seems promising to study the antigenic characteristics of Russian Nm strains, including NmNG ST-175, to assess the potential vaccination coverage with existing protein vaccines, the possibility of their registration on the territory of the Russian Federation, as well as the development of domestic vaccines.

Relevance. Population migration can play a crucial role in the spread of invasive strains of meningococcus, initiating outbreaks of meningococcal infection, and changing the incidence at the local level.Aim. To assess the prevalence of meningococcal carriage among migrants arriving in Moscow and to characterize the antigenic and genetic properties of carrier strains of meningococcus.Materials and methods. The study was conducted in March 2020 at the bases of the Multifunctional Migration Center of Moscow and the Federal Budget Institution of Science «Central Research Institute of Epidemiology». Samples of nasopharyngeal mucus were collected from 352 people. Nasopharyngeal strains of meningococcus were identified and identified using microbiological, serological, and molecular biological methods.Results. The overall level of the carriage was 5.7%. Of the twenty selected strains, 10 have a serogroup defined: Y – 5 strains, W - 3, A, and B – 1 each. The obtained genetic and antigenic characteristics do not allow talking about the import into the RF of representatives of known hypervirulent clonal complexes. In this study, strains were identified that are part of the clonal complex ST-175 complex, which has not been previously described in the Russian Federation.Conclusion. It seems promising to continue the dynamic monitoring of carriage of meningococcus in various groups, including among people entering the country to obtain a migration patent, as well as identifying risk factors for acquiring carriage. The data obtained will supplement current information on the incidence of the generalized form of meningococcal infection and will be crucial for determining the epidemiology at the country level, the population groups responsible for the transmission of the disease, and the need for targeted vaccination.

Aims. The purpose of this study was to identify current epidemiological features of meningococcal infection in Moscow.Materials and methods. Cases of invasive meningococcal disease in Moscow from 2014 to 2018 and the biomaterial from patients with an invasive meningococcal disease were analyzed.Results. The features of the epidemic process of meningococcal disease in Moscow were revealed: increasing in the incidence rate involving teenagers and young adults into the epidemic process; meningococcal strains of serogroups W and A increased in the etiology of the invasive meningococcal disease; high mortality rate.Conclusions. It seems reasonable to recommend vaccination against meningococcal disease by including adolescents, young adults and persons over 65 years old.

Relevance. Vaccines based on capsular polysaccharides of pneumococci are not active against serotypes that are not included in the vaccine, non-capsulated strains and do not protect against carriage caused by other serotypes. Their use leads to the replacement of dominant serotypes of pneumococci, the appearance of highly virulent strains, changes in the microbial landscape of mucous membranes due to the appearance of other etiologically significant pathogens of respiratory tract diseases. This requires the creation of intraspecific anti-pneumococcal immunity, which will be facilitated by the development of serotype-dependent drugs, which will include protein-containing antigens of pneumococci.Objective. Study of serotype-independent activity of protein-containing antigenic components obtained from freshly isolated and archival strains of S. pneumoniae.Materials and methods. Strains of three serotypes of S. pneumoniae were used: archival strains of serotypes 6B N296, 19F N 298 and 10A N297 and freshly isolated serotypes 6B N 1121, 19F N 1055 and serogroup 10 N 1193 (from the cerebrospinal fluid of patients with purulent meningitis).. In the experimental protein-containing preparations EPCP obtained, the protein content was determined. Protective activity of EPCP and virulence of strains were determined in the model of intraperitoneal immunization and infection of BALB/c mice; LD50 was calculated using the generally accepted modified Kerber formula. The immunophenotype of lymphocytes previously isolated from donor-mice whole blood was studied by flow cytometry. Statistical analysis of the materials was carried out using parametric and nonparametric methods using the application package «Statistica for Windows», ver. 7.0 (Stat Soft, Inc); in statistical analysis, the significance level of p was assumed to be < 0.05.Results and discussion. During cultivation there was the analysis of growth dynamics showed intensive accumulation of biomass of the archival strain N296 with low virulence, and lower - by virulent strain N 1121 isolated from the patient's cerebrospinal fluid. The protein content of drugs from serotype 6B strains did not differ. The strains of other serotypes isolated during the generalized infectious process were also more virulent than the archival strain. The effect on the immunophenotype of human lymphocytes of fractions of 50-100 kDa isolated from the initial preparations obtained by culturing serotype 6B, significantly increased only under the influence of the preparation from the archival strain. In the study of protective activity of the initial preparations from strains of serotype 6B and fractions with MM 50-100 kDa only triple immunization with the initial preparation from strain N 296, at a dose of 20 micrograms of protein per mouse, led to significantly greater survival of immunized mice from infection with the newly isolated virulent strain N 1121 of homologous serotype. A fraction of 30-100 kDa provided protection of mice twice immunized with 50 mkg of protein per mouse, with a high efficacy index of 8.9, even after infection with a freshly isolated strain of heterologous S. pneumoniae serotype 3 N 10196.Conclusion. The protein-containing fraction with MM 30-100 kDa obtained from a low virulent archival strain of S. pneumoniae serotype 6B N296 possessed protective activity against a newly isolated virulent strain of heterologous serotype after double immunization. Under the action of the studied protein-containing fractions, activation of the cellular component of immune system with the involvement of innate immunity effectors and T-lymphocytes is shown. These data can be considered as a evidence for further study of EPCP to assess the possibility of their use in the design of anti-pneumococcal drug with serotype-independent protective activity.

The aim. of the work was to evaluate the cost-effectiveness of vaccination with the 13-vaIent pneumococcal conjugate vaccine (PCV13) and its combination with the 23-valent pneumococcal polysaccharide vaccine (PPV23) of immunocompetent adult patients with different levels of risk of pneumococcal infection.Material and methods. Cost-effectiveness analysis was carried out by a modeling method, with a horizon of 15 years from the position of the healthcare system, and. taking into account the social perspective. The analysis was performed, for 20, 40, and 60 year oId patients with 1, 2, and 3 risk factors. In accordance with national recommendations, the vaccination. regimen included, the introduction, of PC 1 dose of PPV23 one year later. In addition, the analysis was performed, for vaccination, with 1 dose of PCV13.The efficacy of PCV13 and PPV23 in different age groups corresponded, to the results of foreign studies, taking into account the data of a Russian study of the serotypic landscape of pneumococci with community-acquired, pneumonia, which required, hospitalization.The cost of treating pneumococcal infections was calculated. on the basis of the mandatory medical insurance rates in St. Petersburg for 2019. The cost of vaccination, for federal programs was calculated, on the basis of the PCV13 price of 1199 rubles per dose, and. for regional programs — 1518.63 rubles per dose. The cost of PPV23 in both, cases corresponded. to the weighted average price of auctions for 2019 (1639 rubles per dose).Indirect costs were calculated, on the basis of data on average wages in the Russian Federation, and. employment of citizens of various age groups.Costs and. life expectancy were discounted, at 3.5% per year.Results. The number of cases of infection prevented, and. the amount of costs averted, increase with increasing risk level. Moreover, with age, the number of deaths caused, by these diseases increases significantly. The volume of prevented, direct medical and. general costs per 1 vaccinated, patient varies from 0.41-2.95 thousand, rubles and. 1.00-6.82 thousand, rubles, respectively. Vaccination, of patients with 3 risk factors is most cost-effective.Conclusion. When analyzed, from the perspective of the healthcare system., vaccination, against pneumococcal infection with PCV13+PPV23 in 60-year-old. patients with at least 1 risk factor and. patients of any age with at least 2 risk factors can be considered as cost-effective. Vaccination with 1 dose of PCV13 of patients of any age with at least 1 risk factor in the analysis from the perspective of the healthcare system, can be considered, as a cost-effective intervention.

Vaccination against pneumococcal infections by 13-valent conjugate vaccine (PCV13) can significantly reduce morbidity and mortality.The study has been aimed to evaluate the social and pharmacoeconomic aspects of PCV13 vaccination of 65-year-old patients with various risks of pneumococcal infection.Material and methods. Markov model with 5 and 15 years time horizon was used for the analysis from the position of the health care system.The analysis was carried out for 65-year-old citizens with low (absence of immunocompromized conditions and chronic diseases), moderate (patients with chronic diseases without immunodeficiency) and high (immunocompromized conditions) risk of pneumococcal infection as well as for the entire population of 65-year-old citizens, regardless of the risk level.In base-case assumption has been made that 1 dose of PCV13 should be administered for the patients from low and moderate risk groups and in the high-risk group 1 dose of PCV13 and in 8 weeks a dose of polysaccharide pneumococcal vaccine (PPV23) should be given.The treatment and physician visit costs have been calculated using CHI rates for St. Petersburg in 2018. Vaccination cost was calculated using the auction price to purchase PCV13 and PPV23 in 2018.Results. Vaccination of 1 cohort of 65-year-old citizens in Russian Federation within 5 years will result in prevention of 2200 deaths, 3900 cases of invasive pneumococcal diseases (IPD) and 48700 cases of community-acquired pneumonia. In 15 years prevention of about 4,3 thousand deaths, 6,6 thousand IPD and 101,1 thousand cases of CAP will be provided.Within 15-year horizon the cost-effectiveness ratio will be RUR 30,3, 82,4 and 410,0 thousand per QALY in high, moderate and low risk groups, respectively. Even if the time horizon is reduced to 5 years the PCV13 vaccination can be considered as an economically high-efficient intervention in moderate and high risk groups (cost-effectiveness ratio - RUR 279,2 and 221,7 thousand / QALY, respectively).In the 15-year-horizon noting the distribution of 65-yearolds by risk levels the cost-effectiveness ratio of PCV13 in population as a whole will be RUR 216,4 thousand / QALY. If moderate and high risk groups only are vaccinated, the average cost-effectiveness ratio will drop to RUR 67,6 thousand /QALY. At universal PCV13 vaccination of 65 years old in 5 year time horizon return of investment to the health care system budget will be 33.2% and at vaccination of persons with moderate and high risk return of investment will be 44.0%. With the assumption of vaccination during the planned physician visit (without additional visit) the return to the budget will be 46.8% and 60.9% for vaccination of all 65-year-olds and patients from the moderate and high risk groups, respectively.Conclusions. Vaccination of the 65-year-old persons against PCV13 pneumococcal infection in Russian Federation can be considered as a highly socially and economically effective intervention resulting in significant reduction of pneumococcal infection incidence and related mortality. The cost-effectiveness of vaccination is increasing along with the level of the risk. PCV13 vaccination of patients with moderate and high risk only provides a significant reduction in the burden for the health care budget in comparison with the vaccination of the entire population of 65-year-olds.

The aim. The study of phenotypic characteristics and dynamics of sensitivity to antibiotics Russian invasive strains H. influenzae. Materials and methods. Studied 89 Russian invasive strains H. influenzae for the period 13-year period (2004 - 2016). To study metabolic, enzymatic activity and beta-lactamase and biotype characteristics H. influenzae strains. Studied H. influenzae sensitivity to antibiotics. Results. Most strains related H. influenzae serotype b (86,1%), biotype II (69,7%), VII (16,9%), I (13,5%). Ampicillin-resistant strains accounted for 10.1%. All of them produced the enzyme beta-lactamase. Conclusion. The population of the Russian invasive ampicillin-resistant H. influenzae strains accounted for 10.1%. The mechanism of resistance to ampicillin is the production of the enzyme beta-lactamase.

Introduction. Pneumococcal meningitis (PM) refers to severe manifestations of pneumococcal disease with high mortality and frequent post-infectious complications. In the context of the introduction of vaccination against pneumococcal infections in the Russian Federation healthcare practice increases the importance of close monitoring of the spread of the PM in the country, identifying areas of concern, the definition of risk and serotype structure of pneumococcus, which is an essential component of the assessment of the effectiveness of vaccination. Materials and methods. We collected 1380 cases identified by the PM on the territory of the Russian Federation in 2010 - 2014. We analyzed the incidence, mortality, mortality, age distribution, social belonging PM patients in the whole country, and in the federal districts. Determined serotype affiliation 35 pneumococcal strains isolated from patients with PM in Russia in 2015. Results. The proportion of pneumococci in the etiological structure of bacterial meningitis during the 2010 - 2014 fluctuated in the range of 18.4 - 24.8% and averaged 22.1%. The incidence of the PM in the Russian Federation in 2010 - 2014 determined at the level of 0.19, the death rate - 0.03. The level of mortality in pneumococcal meningitis in the Russian Federation in 2010 - 2014 increased from 13 (2010) to 21.1% (2014), the average was 17.1%. The most vulnerable age groups were adults over 25 years old and children up to 6 years. Among children under the age of 6 years mortality was 10.7%. The study of serotypes of 35 pneumococcal strains showed that in 2015 serotype structure of invasive pneumococcal vaccine serotypes maintained dominance, the proportion reached 75% for PCV13 and 54% for PCV10. Conclusion. The problem of pneumococcal meningitis remains valid in the Russian Federation. Active use of vaccines, especially in children, will reduce the incidence of this infection and the severity of its consequences.

Relevance. One of the prognostic criteria meningococcal infection (MI) epidemic status process is the increasing number of resistant to antibiotics meningococcal strains. Aim of this study was to investigate the dynamics of invasive strains of N. meningitidis susceptibility to antibiotics in Moscow in 2006 - 2015. Materials and methods. Studied 98 strains of N. meningitidis, isolated from blood and cerebrospinal fluid of patients with MI. The study changes of sensitivity N. meningitidis to antibiotics was occured in two periods: first -2006 - 2011 and second - 2012 - 2015. The MIC was determined by E-test. Results. In the present study revealed for the first time the Russian strains of N. meningitidis, moderately resistant to penicillin (5 strains) and resistant to rifampicin (3 strains). Among the studied strains were not found resistant to ceftriaxone, ciprofloxacin, tetracycline and chloramphenicol. Discussion. Comparison results two study periods allowed to reveal the dynamics of increasing the sensitivity of N. meningitidis to antibiotics, which confirms the decline in meningococcal virulence, and as a result, continued interepidemic MI period. Conclusions. Despite the decline antibakterial resistance is required continuous monitoring.

Invasive pneumococcal serotypes landscape in various Russian regions studied. The study showed dominance (in decreasing order of importance) serogroups/serotypes 3, 6, 19, 4, 23, 18, 14, 15, 7, 11 and 9, which accounted for 88% of all identified serogroups/ serotypes. Among children under 5 years occupied a leading position serogroups/serotypes 19F, 18, 14, 6, 3, 7F and 23F, whereas among adults older than 45 years was dominated by serogroup/serotype 3, 6, 19F, 11, 4, 18, 23, 7, 15 and 14. The most frequently encountered material samples sectional serotypes 4, 23F, 14, 11A, 19F and 3.

First in Russia prospective non-interventional hospital-based study on Streptococcus pneumoniae serotypes causing meningitis and acute otitis media (AOM) in children and community-acquired pneumonia (CAP) in children and adults, as well as serotype coverage by pneumococcal conjugate vaccines (PCV’s) of different composition has been conducted. Serotypes 19F, 14 and serogroup 6 are the leading in meningitis; serotype coverage is 70,6% for PCV7, and 76,5% – for PCV10 and PCV13. Among S. pneumoniae serotypes causing AOM 19F, 3, 23F and serogroup 6 have been the most prevalent in Saint Petersburg. PCV7 and PCV10 provide equal serotypes coverage in AOM – 63,2% among children 0–2 years old, and 32,5% among children 5–17 years old. PCV13 covers up to 79% of serotypes in infants. In CAP PCV7 and PCV10 provide 57,1% serotype coverage in children and 56,1% – in adults. Serotype coverage in CAP for PCV13 has been 14,3% and 34,5% higher for children and adults, correspondingly. Obtained data supports PCV inclusion in children immunization program in Saint Petersburg, whereas PCV13 provides the broadest serotype coverage. In the course PCV’s implementation continued pneumococcal infection surveillance is advisable.

The article is dedicated to prevention of pneumococcal infections, which remain among the most common diseases in infants. The authors analyze international approaches to vaccination effectiveness assessment in light of predicting the expected effect of cohort immunization, given introduction of vaccination against this infection to the Russian National Immunization Calendar. The article presents a discussion of difficulties in interpreting epidemiological, immunological and clinical data in the absence of studies on directcomparison of drugs. The authors demonstrate the need in multicomponent approach to immunization program effectiveness analysis, which would include optimization of epidemiological vigilance, adoption of the standard definition of a case, registration of results of prelicensure clinical trials of vaccines and postlicensure follow-up in similar groups of patients.

Aim: cost-effectiveness assessment and budget impact analysis for 13-valent pneumococcal conjugate vaccine (PCV13) in infant immunization program in Russian Federation. Materials and methods: 10 year modeling with social perspective (direct medical and indirect costs and life expectancy with discounting by 3,5% per year) and population effect based on results of clinical studies, global PCV13 use and Russian epidemiological data has been established. Budget impact has been analyzed without discounting. Direct effect was assessed by influence on pneumococcal meningitis, bacteremia, pneumonia and acute otitis media (AOM) incidence, population effect — by pneumococcal meningitis and hospitalized all-cause pneumonia incidence. Results: Possible PCV13 effectiveness was estimated as 76,6% for invasive pneumococcal diseases (IPD) and 23,7% for hospitalized cases of AOM. Vaccination (per 100 000 vaccinated infants) can prevent 13,8 lethal cases in vaccinated population and 171,1 — in unvaccinated population. Cost-effectiveness ratio for PCV13 is estimated as 32,400 rubles / LYG and 32,400 rubles / QALY. Cost of 1 lethal case prevention is 140 100 rubles, additional cost for 10 years is 111,5 rubles per child. Conclusions: PCV13 mass vaccination of infants in Russian Federation is highly cost-effective and will significantly cut expenses due to pneumococcal diseases treatment.

As it was reported by World Health Organization, the annual number of deaths caused by pneumococci reaches 1,6 million people including 700 thousand of children of 0–5 years old. Pneumococcal meningitis is one of the most severe manifestations of pneumococcal infection. S. pneumoniae keeps one of the leading positions in aetiological structure of bacterial meningitis. Data on serotypes distribution of pneumococci in children of the early age in the Russian Federation are limited. In this study serotypes of pneumococci from pediatric patients with pneumococcal meningitis (children aged 0–7 years, n =35) isolated in 1981–2010 in Moscow were identified. Screening for sensitivity of strains to penicillin was performed, as well as molecular typing by MLST approach. The most frequent serotypes causing pneumococcal meningitis in children aged 0–7 years were 19F, 7F, 14 and 1. Most of MDR-strains were collected in 2007–2009. Among MDR-strains and those demonstrating increased resistance to antibiotics, several new allelic patterns were described.