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Epidemiology and Vaccinal Prevention

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Vol 23, No 3 (2024)
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PROBLEM-SOLVING ARTICLE

4-18 492
Abstract

Relevance. Altai Krai (AK) is one of the least prosperous subjects of the Russian Federation in terms of the incidence of acute respiratory infections (ARI). Results of studying long-term and intra-annual dynamics of the incidence of ARI and community-acquired pneumonia (CAP) in various population groups of the AK in 2011–2021 led to a conclusion about possible connection between the characteristics of the epidemic process of ARI and environmental factors, primarily air pollution, as well as the widespread distribution of natural and atropurgic foci of tick-borne transmissible and zoonotic infections in the territory of the AK, along with the problems of diagnostics. Aim. Assessment of the possible influence of environmental factors on the formation of a high level of registered incidence of ARI in the Altai Territory, as well as diagnostics of some natural focal and zoonotic infections with fever and respiratory symptoms. Materials and methods. A retrospective epidemiological study was conducted based on annual and monthly official statistical reporting during 2011–2021 about the morbidity of the population, demographic and environmental features of the territory of the AK for each of the municipalities (MU), the average long-term incidence rates of ARI, VBP, tuberculosis, Siberian tick typhus (STT), ixodid tick-borne borreliosis, tick-borne viral encephalitis were calculated; appeals of the population regarding tick bites; population density and annual average sulfur dioxide (SO2) emissions. Pearson correlation coefficient was used to assess the strength of the relationship between the analyzed indicators; and seasonality coefficients and the method of trend-seasonal decomposition were used to assess the intra-annual dynamics of the incidence of ARI and CAP (for the period 2011-2019). To study seroprevalence of antibodies to C. burnetii, R. sibirica and SARS-CoV-2 in febrile patients with symptoms of ARI blood samples were collected in October 2022 from ten rural districts of the AK. Results and discussion. It was established that there was a significant direct correlation between the incidence of ARI and the amount of SO2 emissions into the atmosphere (r = 0.61, p < 0.001), as well as between the incidence of ARI and population density (r = 0.53, p < 0.001). The largest share (69%) of the total number of ARI cases in the Altai Territory in 2011–2021 was attributed to the cities of Barnaul, Biysk, Rubtsovsk, Zarinsk and Novoaltaisk, which are characterized by maximum SO2 emissions and population density. An additional contribution (8% total) to the incidence of ARI in the Altai Territory was attributed to 7 rural areas with the highest levels of SO2 emissions. Regardless of the ranking for the incidence of ARI and CAP, in 9 out of 10 areas selected for the study, patients had both anamnestic and diagnostic titers of antibodies to C. burnetii and/or R. sibirica. At the same time, coxiellosis cases in these areas were not registered for 12 years, and the number of cases of STT was much less than the probable number based on the proportion of patients which were seropositive to R. sibirica and had symptoms of ARI. IgM to SARS-CoV-2 were detected in 5 out of 203 examined samples, IgG – in 188 out of 203 examined samples, moreover 13.8% of samples had 118 to 499 BAU/ml, 40.9% of samples had 500 to 5000 BAU/ml, and the rest of samples had more than 5000 BAU/ml. Conclusion. Among all the variables analyzed in the study, the greatest role in the formation of the high level of registered incidence of ARI in the AK for many years belong to the high level of air pollution with SO2 emissions, high population density and, especially, their combination. Underdiagnosis of tick-borne rickettsioses and coxiellosis is of particular importance due to the unavailability of test kits for laboratory verification. Starting from 2020, a new coronavirus infection made some contribution to the registered incidence of ARI.

ORIGINAL ARTICLES

19-26 555
Abstract

Relevance. The development of antimicrobial drugs and alternative methods, technologies and means of prevention, diagnosis and treatment of human infectious diseases caused by antibiotic-resistant microorganisms is one of the priorities of ensuring the biological safety of the country. Aims. To evaluate the bactericidal activity of tetrapyrrole macroheterocycles (porphyrins) at different light irradiation durations in relation to staphylococci, in vitro. Materials and methods. Studied strains of microorganisms: museum strains of microorganisms – S. aureus ATCC 29213, S. epidermidis ATCC 14990 and antibiotic-resistant strains of bacteria of the genus Staphylococcus (n=18) isolated from clinical biomaterial and from environmental objects in a medical organization. The studied chemical compounds are three different compounds of water-soluble asymmetrically substituted porphyrins containing heterocyclic fragments on the periphery of the porphyrin cycle (residues of benzoxazole, N-methylbenzimidazole and benzothiazole). Results. The activity of all three porphyrin compounds in relation to museum strains of staphylococcus and 77.8% of clinical antibiotic-resistant strains (n=14; 95% CI 20.1-97.5) turned out to be maximal (complete lysis) after 10 minutes of irradiation. Conclusions. The tested tetrapyrrole macroheterocycles (porphyrins) exhibit bactericidal activity against museum and clinical strains of staphylococcus, with different levels of antibiotic resistance, which determines Keywords: antibiotic resistance, water-soluble porphyrin, photodynamic inactivation, photosensitizer, photochemistry, staphylococci No conflict of interest to declare.

27-37 585
Abstract

Relevance. Antibacterial drugs are widely used to treat and prevent infections of the upper and lower respiratory tract. The large-scale and unjustified use of antimicrobials to treat these infections has led to the emergence of resistance in most pathogens. The aim. To study antimicrobial susceptibility testing to erythromycin and azithromycin of strains of B. pertussis isolated in Russia. Materials & Methods. The research included 165 strains of B. pertussis isolated in January 2014 to June 2020. Antimicrobial susceptibility to erythromycin and azithromycin was determined by disk diffusion method and MIC test (HiMedia Laboratories Pvt. Limited, India). The A2047G mutation in the 23S rRNA gene was detected by PCR and subsequent sequencing. Results. Disk diffusion zone diameters for erythromycin in the studied strains ranged from 25 to 62 mm (median 44 mm) and disk diffusion zone diameters for azithromycin ranged from 22 to 80 mm (median 50 mm). Isolates with growth inhibition of more than 42 mm in diameter after 7 days of incubation were considered as susceptible. Among the studied strains, 57 (34.5%) were resistant to erythromycin and 23 (13.9%) to azithromycin. Then, MIC of erythromycin and MIC of azithromycin, respectively, were determined for these 57 and 23 strains using the MIC test. The comparison group included 79 isolates that were classified as sensitive to erythromycin (n = 31) and azithromycin (n=48) according to the results of the previous study. A MIC value of 0.12 μg/ml was considered as the cut-off for susceptible strains. All isolates were fully susceptible to erythromycin (MIC ≤ 0.01 μg/ml, median MIC 0.001 μg/ml) and azithromycin (MIC ≤ 0.01 μg/ml, median MIC 0.0001 μg/ml). An A-to-G mutation was not found at position 2047 in the 23S rRNA gene in 80 isolates that had a diameter of growth inhibition zone less than 42 mm. Conclusion. This study demonstrates no significant decrease in the susceptibility to erythromycin and azithromycin among B. pertussis strains isolated in Russia in 2014–2020. The studied B. pertussis strains exhibit a homozygous phenotype for macrolide resistance.

38-46 534
Abstract

Relevance. Serological monitoring of the state of the population's immunity to the rubella virus is one of the key elements of epidemiological surveillance of the infection, which makes it possible to assess the effectiveness of vaccine prevention, including the level of protection of the population from this infection. This article presents a comprehensive analysis of the results of this event in Russia for the period from 2015 to 2022 in individuals vaccinated against this infection, based on data from reports from regional centers and existing statistical models. The aim. To carry out a comprehensive analysis of data on serological monitoring of immunity among indicator groups of the population to rubella virus in the Russian Federation for the period from 2015 to 2022, taking into account the incidence and peculiarities of immunization tactics. Materials and Methods. Serological monitoring was carried out using standardized test systems and techniques, which ensured comparability of data throughout the entire study period (2015-2022). The contingent for the examination was selected with documentary confirmation of the fact of vaccination in the age groups 3–4 years, 9–10, 15–17, 25–29, 30–35 years. Only persons aged 40 years and older were examined without taking into account the vaccination history Results and Discussion. The conducted study confirmed a sufficient, stable level of immunity to the rubella virus in most age groups and regions of the country, which indicates the effectiveness of vaccination and the preservation (stabilization) of the infection elimination process. The slight increase in the average proportion of seronegatives among adults 30–35 and 40 years and older, revealed in the analysis, compared with other groups, requires further observation and clarification of the causes. Conclusions. The study confirmed the high level of immunity to rubella virus among the population of the Russian Federation, which indicates the effectiveness of the current program of vaccination against rubella infection and the infection elimination program. However, groups of the population have been identified, among which there is a slight decrease in the level of immunity, which requires additional attention from health authorities to maintain a stable rubella elimination status in the country. The results of the study will be used as additions to national and regional strategies aimed at maintaining the rubella elimination status.

47-56 435
Abstract

Relevance. The healthcare personnel’s adherence to hand antisepsis is а pressing problem during any epidemic outbreak. In the context of high biological hazards, the possibility of performing proper antiseptic procedures is reduced while nosocomial pathogen transmission and healthcare-associated infection (HAI) rate growth are promoted. Aims. Studying the factors determining the healthcare workers’ adherence to hand antisepsis during a pandemic infection spread (as exemplified by COVID-19). Materials and methods. The study was conducted during the entire COVID-19 pandemic. To estimate the rate of adherence rate by the healthcare personnel to hand hygiene, we conducted an anonymous questionnaire survey of the staff in infectious disease hospitals (2021–2022) as well as assessed the viral and bacterial contamination rates of the personnel’s hands and the hospital environment items (2021–2023). Epidemiological (descriptive-evaluation), bacteriological (conventional culture, AMR determination using a VITEK2 analyzer), molecular biological (RT-PCR, Sanger sequencing) and statistical (a questionnaire survey, building machine learning models) methods were used in the study. Results. Based on the results of the survey, the main factors influencing the formation of attitudes towards antiseptics among the staff of medical organizations with medical and non-medical education were identified. It was found that the pandemic spread of infections negatively affects the level of contamination of the hands of infectious diseases hospital staff, which amounted to 35.3% of doctors, 28.8% of nurses, and 25% of hospital cleaners. The spectrum of isolated pathogens included viruses (SARS-CoV-2) and opportunistic microorganisms (Enterococcus faecalis, Enterococcus faecium, Pantoea agglomerans, Acinetobacter baumannii, Klebsiella pneumoniae, Staphylococcus aureus, Escherichia coli), including those with a wide profile of antimicrobial resistance. Conclusion. During the COVID-19 epidemic, the rate of adherence to hand antisepsis in the infectious disease hospital was 82.3% in the staff with a medical background and 71.2% in the staff without one. The results confirm the significant role of staff hands in the in-hospital transmission of dangerous pathogens and indicate the need for systematic monitoring of the level of knowledge on antiseptics among all employees of a medical organization, regardless of specialization and level of education.

57-66 536
Abstract

Relevance. The Altai Кray with its administrative center, Barnaul, is an endemic region for tick–borne rickettsioses. The contribution of other tick-borne infections (TBI) to the structure of overall morbidity in the subject is significantly lower. To assess the risks of complication of the epidemiological situation for bacterial TBI (tick-borne rickettsioses, borrelioses, human granolucytic anaplasmoses, human monocytic ehrlichiosis, coxiellosis) and understand the level of their diagnosis in the region, it is important to study the occurrence of their pathogens in ticks, comparing them with the officially registered incidence. The aim is the study of the epidemiological and epizootological situation in Barnaul for bacterial tick-borne infections as well as an analysis of the factors influencing the registration of the incidence of these infections. Materials and methods. The materials were official statistical reporting data, information, analytical materials, accounting and reporting documentation of the Department of Rospotrebnadzor and the Ministry of Health of the Altai Region. The infection of ticks collected in the biotopes of Barnaul with different landscapes by pathogens of tick-borne encephalitis, human granulocytic anaplasmosis (HGA), human monocytic ehrlichiosis (HME), borrelioses, rickettsioses, and Q fever were studied using molecular biological methods. The species of Rickettsia were determined by Sanger sequencing followed by phylogenetic analysis. Results. Rickettsia conorii subsp. raoultii detected in the Dermacentor ticks with a high occurrence (61.9%), DNA of R. helvetica detected in the Ixodes ticks (5.1%). R. sibirica was not been detected. The infection rate of ticks by Borrelia burgdoferi s.l. was 27.8%; 5.1% of imagos contained B. miyamotoi DNA. Pathogens of HGA, HME were founded in 6.2%, 1.0% of individuals of Ixodes ticks, respectively. In two copies out of 300, the causative agent of Q fever identified. The dynamics of the number of people affected by tick bite over the period 2014-2023 did not tend to decrease, and against this background, there is a continuing high incidence of Siberian tick typhus, in contrast to the incidence of borreliosis. Other bacterial TBI have not been noted in Barnaul officially. Conclusions. In Barnaul, high risks of complications of the epidemiological situation of ixodic tick-borne borreliosis (including non-erythemic forms) have identified, and underdiagnosis of the disease is likely. The question of the etiological structure of tick-borne rickettsiosis, the occurrence of infected individuals with an atypical picture remains unknown. The difficulty of diagnostic of tick-borne rickettsiosis without rash is aggravated by the shortage of reagent kits, primarily for the detection of specific antibodies. The landscape confinement of Dermacentor and Ixodes ticks should take into account when organizing long-term stationary observation sites for monitoring and forecasting the epidemiological and epizootological situation. The risks of Barnaul population infection by HGA, MECH and Q fever pathogens were also noted. Special attention should be paid to the introduction into clinical practice of reagent kits for complex laboratory verification of tick-borne infections. 

67-75 467
Abstract

Relevance. In Russia, phase III of clinical trials of the domestic trivalent vaccine Bubo®-Unigep, containing protective antigens that provide protection against “wild” forms of the hepatitis B virus subtypes ay and ad, as well as the determinant of serotype ay with the G145R mutation, has been completed. Аim. Evaluation of the effect of the new recombinant polyvaccine against hepatitis B «Bubo-Unigep» on vital functions and laboratory parameters in previously unvaccinated individuals in an adult healthy population. Materials and methods. A randomized multicenter clinical study was conducted to assess the reactogenicity, safety and immunogenicity of Bubo®-Unigep (CJSC NPC «COMBIOTECH») in previously unvaccinated healthy adults (n = 166). The study performed according to the protocol developed by the contract research organization «R&D Pharma» at eight clinical centers located in Russian Federation. Results and discussion. Analysis of the studied parameters throughout the study (frequency and severity of adverse events, physical examination data of volunteers with assessment of vital signs, laboratory test results, etc.) made it possible to establish a high safety profile of Bubo®-Unigep vaccine, which turned out to be virtually areactogenic without causing development of targeted local and systemic post-vaccination adverse events. Conclusion. The wide range of specificity of the immune response, along with the high safety and reactogenicity of the Bubo®-Unigep vaccine, the production of which can be carried out through a full technological cycle without the use of imported substances, will increase the effectiveness of hepatitis B prevention.

76-87 550
Abstract

Relevance. It is known that the immune response to the administration of immunobiological drugs is variable and depends on the individual characteristics of the organism. Host immunogenetic factors have a significant impact on the effectiveness of vaccination. In this study, the frequencies of alleles of the HLA class I (HLA-A, B, C) and class II genes (HLA-DRB1, DPB1, DQB1) were studied in groups of participants with different levels of antibodies (anti-HBs) after vaccination against viral hepatitis B. Aims of the work was to determine the possible relationship between alleles of HLA genes and the intensity of post-vaccination immunity against hepatitis B. Materials and methods. The study included 271 apparently healthy adults who were divided into 3 groups depending on the specific concentration of post-vaccination antibodies (anti-HBs) using ELISA. All calculations were made relative to the groups anti-HBs >100 mIU/ml (n=82), 10-100 mIU/ml (n=98) (protective antibody level) and anti-HBs <10 mIU/ml (n = 91). To type alleles of the HLA class I (HLA-A, B, C) and class II (HLA-DRB1, DPB1, DQB1) genes, we used a panel we developed for whole-genome next-generation sequencing (NGS). Statistical analysis was performed using Pearson's χ2 goodness-of-fit test using the FDR multiple correction method with an initial target of p < 0.05. Results. When typing the six genes studied, the total number of alleles identified at least once was 189 variants that were distinct from each other. We identified 3 alleles (B*38:01:01, DQB1*06:03:01 and DRB1*13:01:01), which were significantly more common (FDR p < 0.05) in the group with a protective level of anti-HBsS. Also in this group there was an increased frequency of occurrence of alleles A*26:01:01, A*32:01:01, C*12:03:01, DPB1*04:01:01 and haplotypes DQB1*06:03:01 -DRB1*13:01:01 and B*38:01:01-C*12:03:01. In the group of seronegative patients, alleles A*02:01:01, A*03:01:01, B*44:02:01, B*44:27:01, C*07:04:01, DPB1*04 were more common :01:01, DQB1*05:01:01, DRB1*01:01:01 and DRB1*16:01:01. It was shown that the identified associations were more significant in the group of individuals with a concentration of post-vaccination anti-HBs above 100 mIU/ml. Conclusion. The results obtained indicate that the HLA alleles we identified may influence the level of anti-HBsS production, and that the genetic factor may, to a greater extent, determine whether the antibody level exceeds 100 mIU/ml. defined as an anti-HBS level of 10 mIU/ ml. The development of an integrated approach to the organization of vaccine prevention, including the determination of genetic markers, will improve the quality of immunization of the population. Information about the association of HLA gene alleles can be used to develop predictive scenarios for the development of the hepatitis B epidemic process. 

PRACTICAL ASPECTS OF EPIDEMIOLOGY AND VACCINE PREVENTION

88-97 636
Abstract

Relevance. The improvement of the surveillance of evolution of influenza viruses and the refinement of the capacity of prognostics of their evolutionary tendencies would lead to the better understanding and control on influenza epidemics. Aim. Establish the etiological nature of influenza epidemics in 2020–2023 in Russia and the antigenic properties of influenza viruses of the types A and B which circulated on its territory in 2020–2023. Methods. Isolation of influenza viruses from PCR+-clinical materials (nazo-pharingeal swabs and post-mortem tissue samples) in the cell lines MDCK and MDCK-Siat1; antigenic analysis by means of the reaction of hemagglutination-inhibition (HI) and micro-neutralization (MN) with the cell-ELISA detection using the post-infectious ferret antisera and rat polyclonal antisera; antigenic cartography. Results and discussion. The season 2020–2021 – the 1st season of pandemic of COVID-19, was characterized by quasi-total disappearance of influenza viruses from human population on the territory of REussia, probably as a consequence of stringent sanitary-hygienic measures worldwide due to COVID-19 pandemic. In the next epidemic season we could observe the domination of influenza viruses A(H3N2) during all season with the slight growth of the proportion of influenza B in the second part of the season. We could not isolate influenza viruses A(H1N1)pdm09 in that season due to their low epidemic activity, and the majority of isolated strains were А(H3N2) viruses – 94,4% of the total number of isolates. Influenza Вvic consisted 28 % of all number of isolates. The season 2022-23, opposite to the previous one, was characterized by the domination of influenza viruses of the sub-type А(H1N1)pdm09 what made it different from the epidemic in Europe and North America, where the A(H3N2) were prevalent, particularly in the first half of the epidemic season. Later on, the situation in Europe has changed and, as in Russia, influenza B actively introduced in circulation. The proportion of isolation of influenza viruses A(H1N1) pdm09 in Russia was 69,2 %, of influenza A(H3N2) – 3,5 %, of influenza Вvic – 27,3 %. Activation of A(H1N1)pdm09 viruses was probably a result of emergence of drift-variants of this sub-type during the epidemics what was supported by the data of antigenic and genetic analyses. Thus in 2020 the first isolates of a genetic clade 6В.1А5а were discovered. They possessed the key substitution N156K in the antigenic site Sb of НА1. The results of genetic analysis have shown that among the A(H1N1)pdm09 viruses of the last season which belonged to the clade 6В.1А.5а.2а, a group of viruses carrying the substitutions P137S, K142R, D260E, T277A in HA1 could be found, which are also present in the new vaccine strain А/Victoria/4897/2022 (genetic sub-group 6В.1А.5а.2а.1). This virus was recommended for the next season 2023-2024 for the Northern Hemisphere. Concerning the antigenic properties, the viruses having such substitutions practically did not differ from the majority of strains A(H1N1)pdm09 in circulation during the last season. So influenza A(H1N1)pdm09 viruses, that circulated in Russia in 2022-2023 represented the antigenic cluster of A/Victoria/2570/2019-like strains. They were also similar to the strain A/Victoria/4897/2022, which was recommended by the WHO experts for the composition of vaccines for the season 2023–2024. The majority of viruses A(H3N2) have preserved the ability to agglutinate erythrocytes of mammals in the presence of 20 nM oseltamivir carboxylate, that is why we applied for their characterization the HI-test. The strains under study were very close to the strain A/Darwin/09/21, recommended by the WHO as the vaccine strain for the season 2022-2023. They belonged to the most wide-spread in the World genetic group 3С.2а1b.2a.2. All studied influenza B viruses belonged to the Victoria lineage and were B/Austria/1359417/2021-like. According to the phylogenetic analysis, all modern Victoria strains clustered into the sub-clade V1A.3a.2, coding the substitutions A127T, P144L и K203R in HA1. Inside this clade one can determine two genetic sub-groups: the 1st include viruses with the substitution in the HA1-protein D197E and the second – a group of viruses with the substitutions E128K, A154E, S208P in НА1. Strains of the Yamagata lineage were not registered on the territory of Russia since 2021, so the problem of their antigenic drift and possible return into circulation stays opened. The very low level of circulation of influenza viruses in 2020-2021 complicated the prognostics and selection of vaccine strains. According the results of HI- and MN-tests we could conclude that in 2021-2022 there was a partial consistency between the vaccine strain A/Cambodia/е0826360/20 (H3N2) and the strains in circulation which were more like to the reference strain A/ Darwin/9/21. We could also observe a mismatch of influenza viruses B in circulation and the vaccine variant B/Washington/02/19. As a result of the propagation of drift variants, the substitution of vaccine strains was made for the Northern Hemisphere for 2022/23. For the H3 component the strain A/Darwin/09/21 was introduced, and for Bvic component –B/Austria/1359417/21. Conclusion. In the period under consideration the relative homogeneity of population was observed inside each type and sub-type of influenza viruses and their fitness to the actual vaccine strains. However the selection of the strains – candidates for seasonal vaccines still remains a serious problem. Thus, in the season 2019-2020 one could observe a mismatch of the vaccine strain and the viruses in circulation in Russia for the component A(H3N2) and partial mismatch for the component B Victoria. In the season 2021-22 was evident a mismatch for Bvic and partial conformity for the component A(H3N2) and only in the last season 2022-23 we could confirm a complete fitness of the vaccine composition and the viruses in the circulation. The timely submission of data and samples to the WHO CCs promotes decision-making on the selection of strains and their introduction into influenza vaccines for the future epidemic season. The sustainability of the epidemiologic surveillance and the refinement of the methods of analysis of antigenic, genetic and other biological properties of circulating viruses would enhance the level of preparedness of healthcare system to the yearly influenza epidemics in the country.

98-106 405
Abstract

Relevance. Studying the experience of working under the conditions of COVID-19 allows us to more effectively assess the functioning of anti-epidemic measures in the event of the occurrence or threat of new pandemics, including those caused by new pathogens. The risk of contracting COVID-19 among employees of medical organizations is higher compared to the rest of the population of the metropolis, which determines the need to develop additional measures in medical organizations to protect workers. Timely assessment of risks and preventive measures during a pandemic allow building a system to protect medical institutions from various biological threats when providing medical care. Aim. Assessment of the risks of contracting COVID-19 among employees of a large anti-tuberculosis medical organization in a metropolis. Materials & Methods. A survey of employees of a large anti-tuberculosis medical organization in Moscow was conducted. The survey was conducted on 46 key questions of epidemiological history, compliance with the requirements of the sanitary and anti-epidemic regime, alleged sources of infection, prognostic risks of the occurrence and course of COVID-19. During the period from August 1 to October 1, 2022, 1225 employees of the institution were surveyed (43.8% of the total number). The survey was conducted on a voluntary basis and was anonymous. When answering questions, participants provided information about demographic factors (age, gender), place of actual residence, the fact of contracting a new coronavirus infection, frequency of laboratory testing for SARS-CoV-2, immunization against COVID-19, possible places of contact with patients with COVID-19, the use of personal protective equipment (PPE) at home and at work, the regular use of skin antiseptics, as well as other information that allowed us to establish the risks of infection of workers at home and at work. To assess the risks of infection, respondents were divided into two groups depending on the presence of a positive test for SARS-CoV-2 (group I) or its absence (group II) as of October 1, 2022. The material for testing was nasal/oropharyngeal swabs. The research of employees was carried out on the basis of the laboratory of the anti-tuberculosis medical organization, as well as in other accredited laboratories of the metropolis using the molecular genetic method, and since February 2022 also using the express method that determines the SARS-CoV-2 antigen. Results. Among the survey participants and according to the questionnaire data, 797 employees suffered from the new coronavirus infection COVID-19, and 138 (17.3%) of them had repeated cases of the disease. Factors that increase the risk of COVID-19 among personnel of anti-tuberculosis medical organizations directly involved in the fight against the new coronavirus infection have been identified. The results of the study demonstrated that important factors influencing the incidence of workers were the frequency of examination for COVID-19, the regular use of skin antiseptics, contact with sources of infection, the use of glasses for vision correction, the use of public transport and eating at work. Conclusion. The need to study the risks of contracting COVID-19 among employees of medical organization and, based on them, develop a set of additional anti-epidemic protection measures was confirmed.

107-119 848
Abstract

Relevance. According to the World Health Organization (WHO), it is not yet possible to effectively stop the spread of new strains of coronavirus [1]. At the same time, most experts and analysts in the field of medicine publicly admit that at the moment vaccination is the most powerful weapon in the fight against COVID-19 [2–6]. While vaccination, like the entire health care system, has now become an element of politics and economics, the creation of proprietary vaccine in each country has become an element of national security [7]. Aims. To evaluate the safety of the inactivated booster vaccine «BelCovidVac» in immunized study subjects from 18 to 60 years old (day 28). Materials and methods. A prospective, randomized, double-blind phase I/II trial evaluated the safety of an inactivated whole virion booster vaccine against the SARS-CoV-2 virus in two doses in healthy study subjects aged 18 to 60 years who had completed a full course of vaccination with the SARS-CoV-2 virus and/or recovered from COVID-19, which included 129 subjects (24 in phase 1 and 105 in phase 2). Results. The study reported 195 adverse reactions in 94 study subjects. The study reported 80 adverse reactions in 24 (100%) study subjects at Phase 1, and 115 adverse reactions in 70 subjects at Phase 2. The study detected mild adverse reactions in 77,50% of cases at Phase 1, and in 71,30% at Phase 2. Moreover, the study found one serious adverse reaction in 1 subject at Phase 2, which occurred as a result of taking placebo. The incidence of adverse reactions with the use of the candidate vaccine in two doses is comparable to placebo (χ2 = 3,15, p = 0,08). Conclusion. The vaccine candidate demonstrated good tolerability at both Phase 1 and Phase 2.

120-128 524
Abstract

Relevance. The production of brucellosis diagnosticums is currently being established in the medical and veterinary practice of the Republic of Uzbekistan. However, due to the lack of a national standard serum in the country and the high cost of analog standard serums on the market, problems may arise in the production of diagnostic tools. In addition, the lack of national standard serums causes problems in quality control of commercial and local antigens, hinders the development of local drugs – brucellosis diagnostics, which reduces the effectiveness of serological diagnosis of brucellosis in humans and animals. Given the above, it becomes necessary to develop and produce a standard serum with a high level of safety, which will improve the methods of laboratory diagnosis of various forms of brucellosis in patients and animals to identify hidden foci of infection in Uzbekistan. The aim of the study is to obtain and characterize experimental standard diagnostic brucellosis rabbit sera for the development of national and industry standard serum with appropriate titers. Materials and Methods. The experiments were carried out in full compliance with the European Council Directive 2010/63/EU on compliance with ethical principles in working with laboratory animals and the experiments were carried out on the basis of the methodological manual «Methods and rules of work» approved by the Ministry of Health of the Republic of Uzbekistan in 2016 with laboratory animals in experimental microbiological and immunological studies. To obtain positive standard sera against brucellosis pathogens, 12 rabbits weighing from 2.2 kg to 4.6 kg, aged 6 to 12 months, were used. The animals were kept under identical conditions on a standard vivarium diet. For the experiment, animals adapted to the conditions of the study were selected and kept in quarantine for 21 days. The maintenance and conduct of the studies followed international rules for the humane treatment of animals. Results and Discussion. During the evaluation of the heterologic specificity of the obtained sera for 23 collection and hospital strains, a weakly positive response (+) was observed in 16.7% of cases. Rabbit sera positive for heterologic specificity were adsorbed on suspensions of inactivated microorganisms (Citrobacter spp. and Enterobacteriaceae spp.) - no significant drop in titer was observed, and cross-agglutination was eliminated. A significant increase in the total protein level was noted after the first and fourth immunizations. Before the first immunization, the total protein level was 59.57 g/l, and after the fourth immunization, it increased threefold to 157.17 g/l. There was also an increase in albumin and globulin (33.2 g/L and 26.37 g/L, respectively) to 79.37 g/L and 77.43 g/L, respectively. IgM levels remained almost unchanged, increasing 3.5-fold after the second immunization and decreasing to 0.24 mg/ml after the fourth immunization. An increase in the level of IgG after the second and third immunizations was revealed, followed by a decrease after the fourth immunization. Conclusion. The obtained national and industry standard diagnostic polyvalent brucellosis sera, as well as the developed methods of laboratory control of its quality and efficiency testing will make it possible to produce candidate standard serum samples for agglutination reaction test and detection of Brucella strains. The obtained standard serum samples will be further used for control of the produced immunobiological diagnostic preparations and provision of unified requirements to their quality. The goal was achieved – improving the serological diagnosis of brucellosis, laying the foundation for further study and standardization of serum. 

OVERVIEW

129-136 436
Abstract

Relevance. Gonorrhea is a widespread infection. More than 80 million cases of this disease occur annually. The problem is compounded by the growing resistance of gonococcus to antibiotics worldwide. The only way out in this situation may be the immunization of certain groups of the population against this infection. Despite the numerous efforts of specialists, there is currently no registered vaccine against gonorrhea, which is due to the characteristics of the pathogen. However, over the past 30 years, reliable observations have accumulated that vaccines containing N. meningititidis serogroup B outer membrane proteins (OMP), developed for prophylaxis meningococcal infection, can also prevent a significant proportion of gonorrhea cases. Aims. To give a brief overview of publications on the reduction of the incidence of gonorrhea in individuals who received vaccines containing N. meningitidis serogroup B outer membrane vesicles, followed by an analysis of information about the nature of these proteins and methods of their study, as a promising platform for creating a vaccine against gonococcus. Conclusions. There is a theoretical and real possibility of creating a preventive drug against gonorrhea. Our analysis of literature sources showed that during the period 2006–2016 from 31% to 59% of those vaccinated with the protein meningococcal vaccine В were protected from gonorrhea. It is necessary to continue studying meningococcal OMV in terms of their preventive properties against gonorrhea, improve the set of models to identify their protective effect, and find adjuvants that enhance the immunogenicity of potential vaccine candidates. 

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ISSN 2073-3046 (Print)
ISSN 2619-0494 (Online)