Vol 98, No 5 (2021)

Cover Page

Full Issue


Assessment of the COVID-19 epidemiological situation in St. Petersburg

Akimkin V.G., Kuzin S.N., Kolosovskaya E.N., Kudryavtceva E.N., Semenenko T.A., Ploskireva A.A., Dubodelov D.V., Tivanova E.V., Pshenichnaya N.Y., Kalenskaya A.V., Yatcishina S.V., Shipulina O.Y., Rodionova E.N., Petrova N.S., Solov'eva I.V., Kvasova O.A., Vershinina M.A., Mamoshina M.V., Klushkina V.V., Korabel'nikova M.I., Churilova N.S., Panasyuk Y.V., Vlasenko N.V., Ostroushko A.A., Balmasov E.S., Mosunov A.V.


Aim. Identification of epidemiological patterns of the SARS-CoV-2 spread among the population of St. Petersburg during the one-year COVID-19 pandemic period.
Materials and methods. The performed analysis focused on the dynamics of COVID-19 cases in St. Petersburg from 2/3/2020 to 4/4/2021 and on the gender-age profile of patients. The information about patients (age, gender, type of the disease, hospitalization, social, and occupational status) was obtained from the database containing the materials from statistical data form No. 058/u.
Results. After one year, the dynamics of reported cases of COVID-19 in St. Petersburg shows two cycles of seasonal surge (spring and autumn-winter) and 8 epidemic periods. It has been found that there are no gender-age differences among COVID-19 patients, which can be seen from the relatively similar number of cases among men and women per 100,000 people in each age group during specific epidemic periods. The strong association between clinical manifestations of COVID-19 and the patients' age was detected: Severe cases were more frequently diagnosed in patients over 70 years, regardless of their gender identity. Based on the social and occupational status, the people who were most exposed to the COVID-19 epidemic process were retirees and people whose occupation was associated with health and safety of St. Petersburg. Among the COVID-19 patients, retirees accounted for 13.69% (men) and 17.67% (women). The proportion of healthcare workers was 3.67% (men) and 9.41% (women).
Conclusion. It has been assumed that COVID-19 tends to be a seasonal disease featuring annual autumn-winter epidemic cycles. The study addressed prospects of preventive vaccination against COVID-19 in Russia and the importance of tracking the complications pathogenetically associated with the acute phase of the disease in the system of epidemiological surveillance.

Journal of microbiology, epidemiology and immunobiology. 2021;98(5):497-511
pages 497-511 views

Antigenic and genetic characterization of Streptococcus pneumoniae strains isolated from patients with invasive and non-invasive pneumococcal infections by using high-throughput sequencing

Mironov K.O., Gaponova I.I., Korchagin V.I., Mikhailova Y.V., Shelenkov A.A., Kaptelova V.V., Chagaryan A.N., Ivanchik N.V., Kozlov R.S.


The objective of this study was to characterize and compare antigenic and genetic characteristics of Streptococcus pneumoniae strains isolated from patients with invasive and non-invasive pneumococcal infections (PIs) by using the data of high-throughput sequencing.
Materials and methods. A total of 158 S. pneumoniae strains were studied. All of them were isolated during different stages of the PEHASus multicenter study performed in 2015-2020. The data analysis was based on the information about whole-genome sequences of 46 strains isolated during the above study. Real-time PCR methods and high-throughput sequencing (the Illumina platform) were used for identification of serotypes. The SeroBA, PneumoCaT software and PubMLST.org website resources were used in the data processing.
Results and discussion. The serotypes of all the studied strains were identified. A number of discrepancies among serotypes in serogroup 6 and one discordant result were revealed by the analysis of whole-genome sequences using 2 programs. The PCR methods were effectively used to characterize serotypes in 87% and 69% of the pathogens of invasive and non-invasive PIs, respectively. The serotypes contained in PCV13 accounted for 59% and 37%, while PPV23 serotypes accounted for 78% and 53% of the strains isolated from patients with invasive and non-invasive PIs, respectively. The data analysis was unable to identify either the dominant sequence type (a total of 81 sequence types have been identified) or clonal complexes, except for serotype 3 strains, thus demonstrating consistency with the data from previous studies suggesting the absence of a well-represented clonal structure of S. pneumoniae associated with pneumococcal meningitis in Russia.
Conclusion. The obtained data made it possible to identify the distribution of the circulating serotypes and genetic characteristics of the strains isolated from PI patients, thus being instrumental for assessment of the effectiveness of the existing polyvalent vaccines and providing information for improvement of the PCR-based methods of serotyping.

Journal of microbiology, epidemiology and immunobiology. 2021;98(5):512-518
pages 512-518 views

Immunogenic properties of the preparation containing the Chikungunya virus antigen inactivated by β-propiolactone

Ignatyev G.M., Kaa K.V., Antonova L.P., Atrasheuskaya A.V., Ishmukhametov A.A.


Introduction. Cases of Chikungunya fever have been reported in more than 100 countries in Europe, Oceania, Africa, Asia, the Caribbean, and America. The musculoskeletal disorders typical for Chikungunya fever can last from several months to a year and even lead to disability. The infection is believed to provide lifelong immunity. This factor and the lack of specific therapy make vaccination the most promising method for preventing Chikungunya fever.
Materials and methods. The purified inactivated preparation with the different doses of the CHIKV antigen was injected intramuscularly to BALB/c mice twice with an interval of 14 days. Indicators of humoral and cellular immunity were assessed in dynamics in ELISA, the neutralization test and proliferation test of splenocytes. Results. The purified preparation containing the CHIKV antigen inactivated by beta-propiolactone had pronounced immunogenic properties. The most prominent immune response in ELISA and neutralization test was registered for a dose of 40 μg. Stimulation with the specific CHIKV antigen caused a pronounced proliferation of animals' splenocytes. The peak values of specific humoral and cellular immunity parameters were registered 14 days after the second injection.
Discussion. The purified preparation containing the CHIKV antigen inactivated by beta-propiolactone had demonstrated the sufficient immunogenic properties. The immunizing dose of 40 μg CHIKV selected as a result of the studies caused in BALB/c mice the development of the humoral immunity characterized by the specific IgG with neutralizing activity, and the specific cell immunity characterized by the animals' splenocytes proliferation after stimulation with CHIKV antigen.
Conclusion. The purified β-PL inactivated preparation of the CHIKV antigen at a dose of 40 μg to demonstrated pronounced immunogenicity in BALB/c mice after two-dose immunization. The developed preparation can be considered as promising for the prevention of Chikungunya fever using the dose and scheme tested in this study.

Journal of microbiology, epidemiology and immunobiology. 2021;98(5):519-527
pages 519-527 views

Microbiota of the lower respiratory tract in community-acquired pneumonia, including cases associated with SARS-CoV-2

Kataeva L.V., Vakarina A.A., Stepanova T.F., Stepanova K.B.


Introduction. Many aspects of the pathogenesis and pathomorphology of pneumonia associated with novel coronavirus require a comprehensive study using modern diagnostic methods.
The aim of the study was to study the microbiota of the lower respiratory tract in community-acquired pneumonia associated with SARS-CoV-2, to assess the antibiotic and phage resistance of circulating strains of microorganisms.

Materials and methods. The analysis of biosamples from 486 patients undergoing inpatient treatment in five mono-hospitals in Tyumen and Tyumen region with a diagnosis of moderate and severe community-acquired pneumonia was carried out. In almost 90% of cases patients received oxygen therapy, about 8% of patients were connected to ventilators. The inoculation of the cultures with clinical samples was carried out for six months (from April to October 2020). The isolated bacterial strains were identified by mass spectrometry. The resistance to antimicrobial drugs and bacteriophages was assessed for identified isolated.
Results. Gram-positive cocci, mainly opportunistic microorganisms of the genus Streptococcus and Candida fungi predominated in the microbiota of the lower respiratory tract of patients diagnosed with community-acquired pneumonia associated with SARS-CoV-2. At the same time, bacteria of the Enterobacteriaceae family and nonfermenting gram-negative bacteria were less common compared to patients without coronavirus infection. In the structure of pathogens, the leading position was occupied by the bacteria K. pneumoniae and Acinetobacter spp. The analysis of the sensitivity of microorganisms to antimicrobial drugs showed the highest resistance rates in strains of Acinetobacter spp., Enterococcus spp., Coagulase-negative Staphylococcus. It has been established that in the group of patients with community-acquired pneumonia associated with SARS-CoV-2, the risk of infection with Streptococcus spp. with high level of antibiotic resistance was 1.5 times higher, and taking into account the 95% confidence interval, the value of this indicator ranged from 1.1 to 2.1 times.
Conclusion. The data obtained indicate that the microbiota of the lower respiratory tract in community-acquired pneumonia associated with SARS-CoV-2 is represented mainly by bacteria of the genus Streptococcus, which have a high level of resistance to antimicrobial drugs.

Journal of microbiology, epidemiology and immunobiology. 2021;98(5):528-537
pages 528-537 views

Identification of Vibrio cholerae O1 strains of the El Tor biovar sensitive to polymyxin B and their molecular genetic analysis

Zadnova S.P., Krasnov Y.M., Plekhanov N.A., Kritskiy A.A., Kutyrev V.V.


The aim of the work was the identification and genetic characterization of Vibrio cholerae O1 strains of the El Tor biovar sensitive to polymyxin B among isolates imported to Russia.
Materials and methods. We used 56 toxigenic and non-toxigenic strains of V. cholerae isolated from patients and from the environmental samples on the territory of Russia in 1970-2020. Resistance to polymyxin B was determined according to MR4.2.2218-07. The ability of strains to form a biofilm on the abiotic surface was assessed by a photometric method. Nucleotide sequences of genes were determined using UGENE 1.32 and MEGA X software. Phylogenetic analysis and tree construction were performed using "maximum parsimony" method in MEGA X software.
Results and discussion. Two genetically modified strains of V. cholerae O1 biovar El Tor, M1509 and 3265/80, which were imported to Russia from India in 2012 and 2014, respectively, were identified. The analysis of 12 genes responsible for the resistance of V. cholerae O1 biovar El Tor strains to polymyxin B demonstrated that these strains contain the allele of the carRS gene, which is typical for all strains of cholera vibrio sensitive to polymyxin B. Study of V. cholerae M1509 and 3265/80 phylogeny based on SNP analysis showed that they fall into the same cluster with isolates containing the carRS allele isolated in India (2015) and Bangladesh (2018). V. cholerae M1509 and 3256/8 strains had the ability to form a biofilm similar to those observed in other genetically modified strains of cholera vibrio included into analysis.
Conclusion. Highly virulent strains of the cholera agent with altered diagnostically significant features are imported into Russia, which should be taken into account when identifying V. cholerae O1 biovar El Tor strains isolated from patients and environmental samples during monitoring studies.

Journal of microbiology, epidemiology and immunobiology. 2021;98(5):538-547
pages 538-547 views

Evaluation of mutagenicity, genotoxicity and chronic toxicity of antiviral drug imidazolyl ethanamide pentandioic acid in in vitro and in vivo test systems

Jain E.A., Pleimes D., Globenko A.A.


Introduction. The antiviral properties of imidazolyl ethanamide pentandioic acid (IPA), the active compound of the drug product, has been proven in various experimental models. However, the literature data on the toxicological properties of IPA are limited.
Purpose. To evaluate mutagenic and genotoxic properties in in vitro and in vivo models, as well as to study the toxicity of IPA following chronic oral administration to rats and dogs.
Materials and methods. Mutagenic and genotoxic properties of IPA were assessed using the Ames test, the test of chromosomal aberrations in human lymphocytes, and the micronucleus test in rats. The chronic toxicity of IPA was studied in Sprague Dawley rats and beagle dogs of both sexes, to which IPA was administered orally at doses of 30-300 mg/kg/day for 26 and 39 weeks, respectively.
Results and discussion. In the Ames test, the addition of IPA up to the maximum dose (5000 mcg/plate) did not result in the increase in the number of revertant colonies. At a concentration of up to 5000 mcg/ml, IPA did not cause chromosomal aberrations in human leukocytes. At doses doses ≤ 2000 mg/kg, IPA did not increase the amount of micronuclei in the bone marrow of rats. In chronic experiments, animals tolerated the administration of IPA well: the dose without an observed effect (NOEL) for rats and dogs was 300 mg/kg/day.
Conclusion. IPA did not show mutagenic and genotoxic properties in standard in vitro and in vivo tests. With chronic oral administration to rats and dogs, NOEL IPA equal to 300 mg/kg/day provided a systemic exposure that was 8-10 and 41-65 times higher than that in humans, respectively. The results obtained allow us to consider the safety profile of the prolonged use in humans as favorable.

Journal of microbiology, epidemiology and immunobiology. 2021;98(5):548-557
pages 548-557 views

Identifying possible target of action of 4,4a-dihydroxanthones in bacterial cells

Frolova V.V., Chernov N.M., Ivkin D.Y., Rumyantsev A.M., Gurina S.V.


Introduction. Partially hydrogenated derivatives of xanthone, dihydroxanthones, are being intensively studied. They are of interest due to their antimicrobial, antitumor, and antioxidant effects. Many researches are focused on the study of the cytotoxicity of dihydroxanthones and very little information is available on their antimicrobial activity. Therefore, the study of the antimicrobial activity and mechanism of action of new synthetic derivatives of 4,4a-dihydroxanthone is relevant. Preliminary studies have demonstrated that 4,4a-dihydroxanthones are active against gram-positive bacteria and have a pronounced anti-staphylococcal effect. Namely, 5-bromo-4,4-dimethyl-7-chloro-4,4a-dihydroxanthone (BDC-DX) was shown to be the most active derivative.
Aim of the study was to determine the possible target of action of the active derivative of BDC-DX in bacterial cells and its acute toxicity.
Materials and methods. The method of measuring the intensity of absorption of the crystal violet dye by bacteria cells was used to prove the effect of BDC-DX on the permeability of the cytoplasmic membrane in bacterial cells. The plasma coagulase activity of Staphylococcus aureus was tested under the action of dihydroxanthone to determine the effect of dihydroxanthone on the process of protein synthesis. Plasmid DNA digestion method was used to study the effect of the compound on bacterial DNA. The acute toxicity of BDC-DX was determined by the express method of V.B. Prozorovsky.
Results and discussion. BDC-DX increased the permeability of the cytoplasmic membrane of S. aureus. Dihydroxanthone did not directly affect the plasma coagulase activity of Staphylococcus and showed a weak damaging effect on bacterial DNA. The compound induced breaks in plasmid DNA at a very high concentration — 1 mM or 384 pg/ml and higher. BDC-DX is a low-toxic compound (the average lethal dose for oral administration of the compound is 1710 ± 170 mg/kg, the average lethal dose for intraperitoneal administration of the compound is 116.9 ± 13.3 mg/kg).
Conclusion. For the first time, in-depth study of the possible mechanism of action of a new synthetic biologically active compound from the group of 4,4a- dihydroxanthones, BDC-DX, was conducted. A likely target of 5-bromo-4,4-dimethyl-7-chloro-4,4a-dihydroxanthone in S. aureus cells is the cytoplasmic membrane. BDC-DX did not affect the process of protein synthesis, namely the activity of the plasma coagulase enzyme. The compound had no pronounced damaging effect on bacterial DNA. It was found that 4,4a-dihydroxanthone refers to low-toxic compounds.

Journal of microbiology, epidemiology and immunobiology. 2021;98(5):558-566
pages 558-566 views


The role of plasma serine leukocyte proteinase inhibitor in the body's defense against COVID-19

Kravtsov A.L., Bugorkova S.A.


The COVID-19 pandemic continues, causing colossal damage to the population and the global economy. As COVID-19 is studied, new data are emerging regarding the risk of severe coronavirus infection in patients with α1-antitrypsin deficiency. α1 -Antitrypsin is the main inhibitor and key endogenous regulator of the serine leukocyte proteinase activitry released from the granules of activated neutrophils to the cell surface and into the extracellular space. It has been established that the number of cases of severe course and death of COVID-19 in the territories of 68 countries of the world correlates with the frequency of the spread of mutations in the proteinase inhibitor gene among the population of these countries, at which the concentration of α1-antitrypsin in the human blood plasma is 10 times lower than normal. All this contributes to the revision of a number of provisions of the pathogenesis and therapy of a new coronavirus infection.
The review presents an analysis of the literature on the role of an inhibitor of serine leukocyte proteinases in protecting the body from COVID-19. The participation of α1-antitrypsin in the inhibition of SARS-CoV-2 penetration into the respiratory tract epithelial cells, in the protection of the vascular endothelium, blood plasma proteins and elastin of the lung tissue from the damaging effect of leukocyte elastase released during neutrophil degranulation and the formation of neutrophil extracellular traps (NETs) is considered. The role of a1-antitrypsin in suppressing inflammation by limiting the secretion of proinflammatory cytokines and neutrophil extracellular traps into the blood has been shown. The individual links in the pathogenesis of the new coronavirus infection have been detailed, which will allow revising the strategy for reducing the risks of severe course of COVID-19.

Journal of microbiology, epidemiology and immunobiology. 2021;98(5):567-578
pages 567-578 views

Using the vaccinia virus MVA strain for developing recombinant vector vaccines against current arboviral infections

Stovba L.F., Krotkov V.T., Melnikov S.A., Paveliev D.I., Chernikova N.K., Borisevich S.V.


Epidemic vector-borne viral infections pose a serious threat to public health worldwide. There is currently no specific preventive treatment for most of them. One of the promising solutions for combating viral fevers is development of vector vaccines, including MVA-based vaccines, which have virtually no adverse side effects. The safety of the MVA strain and absent reactogenicity of recombinant MVA vaccines have been supported by many clinical trials.
The article focuses on test results for similar preventive products against viral fevers: Crimean-Congo hemorrhagic fever, Rift Valley fever, yellow fever, Chikungunya and Zika fevers.
Their immunogenicity was evaluated on immunocompetent and immunocompromised white mice; their protective efficacy was assessed on immunocompromised white mice deficient in IFN-α/β receptors, that are used for experimental modeling of the infection. Nearly all the new recombinant vaccines expressing immunodominant antigens demonstrated 100% protective efficacy. It has been found that although the vaccine expressing Zika virus structural proteins induced antibodies against specific viral glycoproteins, it can be associated with high risks when used for prevention of Zika fever in individuals who had dengue fever in the past, due to the phenomenon known as antibody-dependent enhancement of infection, which can occur in diseases caused by antigenically related flaviruses. For this reason, the vaccine expressing non-structural protein 1 (NS1) was developed for vaccination against Zika fever.
The yellow fever vaccine developed on the MVA platform had immunogenicity similar to that of the commercial 17D vaccine, outperforming the latter in safety.

Journal of microbiology, epidemiology and immunobiology. 2021;98(5):579-587
pages 579-587 views

Epidemiologic characteristics of Campylobacter infections in high-income countries: a systematic review

Gill G.


Introduction. The Campylobacter is the most common bacterial cause of foodborne illnesses in high-income countries. In contrast to other infectious diseases, the number of Campylobacter cases has increased in developed countries over the last ten years. A systematic review has been conducted to identify the factors contributing to incidence of Campylobacter infection in developed countries and to estimate it by age, sex, geography, and season.
Materials and methods. The review was limited to studies published in English from 2010-2021; eight nationwide surveillance and register-based cohort studies, which met the selection criteria, were included in the review.

Results. While the highest incidence of Campylobacter infection was reported among young children living in rural areas, the highest number of Campylobacter cases among adults was recorded in urban settings. Nevertheless, population-wise, children and older adults are most affected, while the incidence rates are higher in males than in females, with cases peaking every summer.
Conclusion. Campylobacter infection is a public health concern in high-income countries, being difficult to eradicate and having become an urgent challenge to the existing well-developed surveillance systems. Additionally, the threat of antibiotic resistance in Campylobacter is growing at an alarming rate. The reasons behind Campylobacter affecting more men than women as well as the age and geographic distribution of the infection still need thorough research.

Journal of microbiology, epidemiology and immunobiology. 2021;98(5):588-596
pages 588-596 views


Academician V.D. Belyakov is the creator of the modern domestic theory of epidemiological science: on the centenary of the birth of an outstanding scientist, teacher and military epidemiologist

Belov A.B., Kuzin A.A., Zobov A.E.


The article analyzes the results of life and creative heritage of Prof. Vitaly D. Belyakov (1921-1996), Academician of RAMS and RANS in connection with the 100th anniversary of his birth and the 85th anniversary of the Department of General and Military Epidemiology at the Kirov Military Medical Academy. S. M. Kirov Military Medical Academy. He was an outstanding scientist-epidemiologist, organizer and teacher, who headed this department for 18 years, and then for 14 years headed the epidemiology department of the 1st Sechenov Moscow Medical Institute. In these years he created two epidemiological schools of his own and made an invaluable contribution to the epidemiological science, professional training of personnel for the military medicine service and national public health as well as improving the system of anti-epidemic support of troops (fleet) and preventive medicine. The principal contributions of V.D. Belyakov and his pupils are: the development of the self-regulation theory of parasitic systems, recognized as the biological basis of the epidemiology of infectious diseases; the introduction of the epidemiology of non-infectious diseases and epidemiological diagnosis methodology teaching in medical universities; substantiation of modern epidemiological surveillance systems for population morbidity and epidemic process management of actual infections. He and his collaborators made a great contribution to the study and prevention of infections significant for troops (fleet) and population; improvement of immuno- and emergency prevention; reform of preventive directions of higher medical education system and health care structures.

Journal of microbiology, epidemiology and immunobiology. 2021;98(5):597-606
pages 597-606 views


Review of the textbook of the academician of the Russian Academy of Sciences R.M. Khaitov "Immunology"


Учебник «Иммунология», 4-е издание, подготовил известный советский и российский учёный с мировым именем, иммунолог, доктор медицинских наук, профессор, академик РАН Рахим Мусаевич Хаитов.

Journal of microbiology, epidemiology and immunobiology. 2021;98(5):607-609
pages 607-609 views

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies