Russian Journal of Infection and Immunity

Journal "Infektsiya i immunitet" ("Russian Journal of Infection and Immunity") established by Northwest Branch of RAMS, St. Petersburg Pasteur Institute and the St. Petersburg branch of the Russian Association of Allergologists and Clinical Immunologists, with the participation of the St. Petersburg branch of All-Russian Practical Society of epidemiologists, microbiologists and parasitologists at St. Petersburg and Leningrad region.

The journal is devoted to numerous aspects of the interaction between different microorganisms and the host organism. Journal is of interest for microbiologists, immunologists, epidemiologists and clinicians. The most detailed discussion of the following questions: 

   • molecular basis of infections caused by pathogenic bacteria, fungi and parasites; 
   • mechanisms of pathogenicity of microorganisms; 
   • the impact of microbial virulence factors on host cells; 
   • factors and mechanism to protect the host from infection; 
   • factors of nonspecific and specific immunity; 
   • experimental models of infectious disease; 
   • development of vaccines and nonspecific anti-infectious defense. 

The editorial board of the journal includes leading Russian microbiologists, virologists and immunologists. Among them are 13 full members and 5 corresponding members of RAS, 19 professors. All published in the journal articles, reviews and lectures are subject to mandatory peer review by members of the editorial board. Traditional sections of the journal are: original articles, lectures, reviews, short communications, case studies.

Journal "Infektsiya i immunitet" ("Russian Journal of Infection and Immunity") was registered by the Federal Service for Supervision of Communications, Information Technology and Communications in St. Petersburg and Leningrad region, Registration certificate PI number78-00910 TU 24 June 2011, the International Standard Serial Number (ISSN) - 2220-7619. Journal quarterly (4 issues per year), the log volume - 12-14 conventional printed sheets (96-112 sheets of A4). From the second half of 2011 opened journal subscription, which can be issued through post offices.

Since its inception, the journal began to develop very fast. As a result it is fully meets the criteria for National Certification Comission (VAC) of the Russian Ministry of Education requirements to scientific journals. According the VAC decision №8/13 from 02.03.2012 the journal "Russian Journal of Infection and Immunity" is included in the "List of the leading peer-reviewed scientific journals and publications, in which major scientific results of the thesis for the degree of Doctor of Science or Candidate of Science should be published."

Since April 2014 journal "Russian Journal of Infection and Immunity" is included in the international database Ulrich's Periodicals Directory.

In 2012 the journal "Russian Journal of Infection and Immunity" was supported by grants from the Committee on Science and Higher Education of the Government of St. Petersburg.

In 2015 "Russian Journal of Infection and Immunity" was included in the list of national journals recognized as the most popular both in Russia and abroad and located on the Web of Science platform as part of a separate, but fully integrated with the Web of Science platform data base Russian Science Citation Index (RSCI).

Since 2017 journal "Russian Journal of Infection and Immunity" is included in Web of Science Core Collection (indexed by Emerging Sources Citation Index (ESCI))

Since March 2017 journal "Russian Journal of Infection and Immunity" is included in the international database Scopus

Currently, as of January 2014, according to an analysis of the "Russian Science Citation Index" (RISC) the two-year impact factor for the journal "Russian Journal of Infection and Immunity" was - – 0,676 while the self-citation index is 8% (details on the website:





Posted: 14.03.2019

Dear authors!

Since 2019, all manuscripts received in the Journal "Russian Journal of Infection and Immunity" should be checked using the ANTIPLAGIAT system.

Please note that in case of a high percentage of LOANS and a low percentage of ORIGINALITY, the article cannot be sent for review.


Posted: 13.03.2019

Dear authors!

We inform that since April 2019 of the article that has been reviewed and accepted for publication, we begin to publish in the form of preprints in the section "Online First". After the publication of the final version of the article in the next Issue of the Journal, the preprints from the specified section are deleted.

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Current Issue

Vol 13, No 3 (2023)

Cover Page

Full Issue


Autoimmune streptococcal glomerulonephritis: the problem of nephritogenicity of Streptococcus pyogenes
Burova L.A., Suvorov A.N., Pigarevsky P.V., Totolian A.A.

Acute post-streptococcal glomerulonephritis usually occurs as a complication after a streptococcal infection due to untimely or inadequate antibiotic therapy. The etiology of post-streptococcal glomerulonephritis has been studied rather comprehensively. Today, both clinicians and microbiologists do not deny the dominant role of Streptococcus pyogenes (streptococcus attributed to serological group A, GAS). Usually, emergence of acute post-streptococcal glomerulonephritis (APSGN) is associated with the so-called GAS-related "nephritogenicity" often judged by appearance and accumulation of antibodies to the antigens and extracellular products of streptococcal cells in patient blood. This interpretation is quite loose and most likely evidence about a link to the bacterial strain, rather than its nephritogenicity. Many studies refer and still attribute a leading role of "nephritogenic" factors to various streptococcal antigens and related biologically active products. Streptococcal nephritogenic factors include cross-reacting antigens, streptokinase, cysteine proteinase, endostreptosin – a GAS cell membrane protein as well as plasmin-tropic enzyme glyceraldehyde-3-phosphate dehydrogenase. Nephritogenicity of all such streptococcal products is suspected to result from the fact that they are found in renal biopsies like specific patient blood serum antibodies. Regarding a term of nephritogenicity, it has been evidenced that it cannot be attributed to any specific streptococcal cell product. This review attempted to analyze a number of bacterial products as starting factors triggering this process. APSGN can be reproduced experimentally in rabbits by intravenous administration of a heat-killed Streptococcus pyogenes culture. In our experiments, strains of serotypes 1, 4, 12, 15, 22 were used. They produced M-proteins and had the ability to bind human and rabbit immunoglobulin G by interacting with the Fc part of the IgG molecule. In numerous series of experiments, evidence was obtained regarding the initiating role of GAS IgGFc-receptor proteins in developing APSGN. Recent studies confirmed the role of streptococcal IgGFc-binding proteins in the initiation of glomerulonephritis after animals were inoculated with temperature-killed IgGFc-positive GAS. This approach excluded a large group of bacterial extracellular agents from the list of APSGN-initiating candidates. An unconventional view on the pathogenesis of GAS-infection-coupled complications may allow approaching their prevention or new treatment strategies.

Russian Journal of Infection and Immunity. 2023;13(3):409-429
pages 409-429 views


The impact of adjuvanted and non-adjuvanted influenza vaccines on in vitro lymphocyte immunophenotype
Khromova E.A., Akhmatova N.K., Kostinov M.P., Skhodova S.A., Stolpnikova V.N., Vlasenko A.E., Polishchuk V.B., Shmitko A.D.

Vaccination is the most effective method of influenza prophylaxis resulting in reduced frequency and severity of complications. Currently, for the prevention of influenza, inactivated split and subunit vaccines as the safest and promoting formation of protective level of strain-specific virus neutralizing antibodies are used. It is known that not all inactivated vaccines are effective enough for select human groups. While nowadays the level of public health is low, there is a need to improve the effectiveness of vaccines that should activate all chains of the immune system. In order to enhance intensity of influenza virus strain-specific antibody production, adjuvant vaccines exerting other mechanisms to activate humoral and cellular immunity compared to non-adjuvant vaccines have been used. The aim of the study was to examine lymphocyte immunophenotype in 27 healthy donors treated with polymer-subunit (immunoadjuvant) and non-adjuvanted split and subunit influenza vaccines.

Materials and methods. Peripheral blood lymphocyte subpopulations were studied in vitro by flow cytometer FC-500 Cytomics (Beckman Coulter, USA) using FITC- and PE-labeled monoclonal antibodies (mAbs).

Results. All examined influenza vaccines activate the effectors of cellular immunity, increasing the number of NK-cells (CD16/56), NKT-lymphocytes (CD3/CD16/56), B-lymphocytes (CD45/CD20), activated (CD3/HLA-DR) and cytotoxic (CD8/HLA-DR) T-lymphocytes, as well as cells bearing early activation marker (CD45/CD25). Among them the immunoadjuvant vaccine showed the greatest potential to induce cellular response eliciting regulatory mechanisms that prevent hyperactivation, stimulating growth of NK (CD16/56), NKT-cells (CD3/CD16/56), B-lymphocytes (CD45/CD20), activated (CD3/HLA-DR) and cytotoxic (CD8/HLA-DR) T-lymphocytes, T-regulatory cells (Tregs, CD4/CD25/Foxp3).

Conclusion. Vaccination against influenza besides the formation of specific antibodies render a transient, immunomodulating effect that is more noticeable after immunoadjuvant vaccine. It can be assumed that vaccination of people with dysfunctions of the immune system an additional prophylactic effect will be observed.

Russian Journal of Infection and Immunity. 2023;13(3):430-438
pages 430-438 views
The effect of Saposin D on the anti-tuberculosis immune response in experimental tuberculosis infection
Shepelkova G.S., Evstifeev V.V., Avdienko V.G., Bocharova I.V., Yeremeev V.V.

Saposins (Sap) are a subgroup of glycoproteins belonging to the Saposin-Like Proteins family. They are generated by the proteolytic processing of the common precursor prosaposin. Saposins localize primarily in the lysosomes and are required for the catabolism of glycosphingolipids. Saposins are involved in the presentation of lipid mycobacterial antigens on CD1 molecules. SapD is the most abundant saposin in normal tissues, where its concentration is three times higher than that of other saposins. SapD promotes the hydrolysis of ceramide by acid ceramidase in vivo, as evidenced by the accumulation of 〈-hydroxyl-ceramide in the kidneys and cerebellum of SapD-deficient mice. Accordingly, SapD-deficient animals show renal tubular degeneration and hydronephrosis, as well as progressive loss of Purkinje cells in the cerebellum, leading to ataxia. To date, no hereditary SapD deficiency has been identified in humans.Previously we had shown that macrophages derived from SAPD knockout mice suppress the growth of M. tuberculosis to a lesser extent than macrophages from wild-type mice. Moreover, compensation for the deficiency of SapD in knockout cells led to the restoration of their bactericidal function. Thus, SapD is an important component in the anti-TB immune response. However, it is not clear how SapD deficiency affects the in vivo antituberculosis immune response. In the model of experimental tuberculosis infection, it was shown that five weeks post infection the mycobacterial load in the lungs and spleens was significantly higher in SapD-ko mice than in wild-type mice. Analysis of the lung tissue cellular composition showed the differences between SapD-ko and B6 mice. Thus “naive” SapD-ko mice are characterized by a larger quantity of macrophages compared to B6 mice. It was also shown that five weeks after infection, SapD-ko mice differ from wild-type mice in a more pronounced neutrophilic infiltration of the lung tissue. A study of the propensity for apoptosis of cells in the lung tissue of SapD-ko mice showed that the content of apoptotic cells in the lungs of SapD knockout mice three weeks after infection was significantly higher than in wild-type B6 mice. Thus, SapD deficiency leads to a significant increase in inflammation during experimental tuberculosis infection, and also affects the predisposition of lung cells to apoptosis.

Russian Journal of Infection and Immunity. 2023;13(3):439-445
pages 439-445 views
Changes in in vitro GM-CSF-exposured monocyte subset composition and phagocytic activity in children with infectious mononucleosis
Savchenko A.A., Martynova G.P., Ikkes L.A., Borisov A.G., Kudryavtsev I.V., Belenjuk V.D.

The aim of the study was to investigate the features of changes in the monocytes subset composition and phagocytic activity in children with infectious mononucleosis (IM) exposed to granulocyte-macrophage colony-stimulating factor (GM-CSF) in vitro. We examined 84 children aged 3 to 11 years with Epstein–Barr virus (EBV) infection diagnosed by clinical signs, positive EBV DNA test in blood lymphocytes and ELISA data (EBV-VCAIgM (+), EBV-EA-DIgG (+)). The control group consisted of 40 apparently healthy age-matched children. Monocytes were obtained by the standard method on adhesion to plastic from mononuclear cells isolated from heparinized venous blood by density gradient centrifugation. The isolated monocytes were divided into two samples: control (without GM-CSF) and experimental (50 ng of GM-CSF per 1 ml of cell suspension). The monocyte subset composition and phagocytic activity in both samples were measured by flow cytometry after 1-hour incubation at 37°C in a CO2-incubator. It was found that in children with progressing IM, the blood monocyte subpopulation composition changes and their phagocytic activity is impaired. It was found that the subset composition and phagocytic activity of the blood monocytes changed in children during development of IM. Changes in the subset composition of monocytes in acute IM did not depend on the age group of children (3–6 and 7–11 years) and were characterized by increased number of pro-inflammatory (intermediate) monocytes and decreased level of anti-inflammatory (non-classical) monocytes. Features of altered monocyte phagocytic activity in children with IM depended on age. The phagocytic activity of all three monocyte subsets was reduced in children with IM 3–6 years old while children with IM 7–11 years old had reduced phagocytic activity only in intermediate and non-classical monocytes. The effect of GM-CSF in vitro on monocytes in patients with IM, regardless of the age of children, led to significantly increased level of anti-inflammatory monocytes while the phagocytic activity of cells changed less. An increase in the phagocytic number for classical monocytes after incubation with GM-CSF in vitro was noted in children with IM at the age of 3–6 years while the phagocytic index of this fraction of monocytes remained unchanged. The level of the phagocytic index increased only in classical monocytes of children with IM aged 7–11 years. The presented results determine the scientific and clinical value of studying the mechanisms of the effect of GM-CSF on cells of the immune system and prove that this cytokine can be used in a new immunotherapeutic strategy for the treatment of IM.

Russian Journal of Infection and Immunity. 2023;13(3):446-456
pages 446-456 views
Evaluation of virus-neutralizing antibody level after novel coronavirus infection COVID-19: development of an instant assay assessing protective antibodies using a pseudovirus-based reaction
Funtikov A.A., Litvinova N.A., Zuev E.V., Kulemzin S.V., Shukurov R.R.

The continued emergence of SARS-CoV-2 variants with immune evasion properties of concern, such as Delta (B.1.617.2) and Omicron (B.1.1.529), calls into question the extent of the antibody-mediated immune response from the virus. The presence of virus-neutralizing antibodies against SARS-CoV-2 in the blood serum of recovered and immunized volunteers is the most accurate indicator of the level of protective activity. Methods for reliable, sensitive and rapid detection of anti-SARS-CoV-2 nAbs are needed for preclinical and clinical vaccine research. In addition, quantification of virus-neutralizing antibodies in recovered COVID-19 subjects may be useful in identifying potential donors for passive immunization and therapeutic use of class G immunoglobulins. Pseudoviruses are actively used as an alternative to infectious viral isolates of pathogenicity groups I–II in serological studies to determine the titers of neutralizing antibodies formed in vaccinated or infected volunteers. In addition, using several pseudotypes with different reporter genes, it is possible to simultaneously detect antibodies to different types of viruses in one biological sample. Currently, the pseudolentiviral system is widely used, in which pseudoviral particles are obtained by transfection of producer cells with vectors of a multiplasmid system of 4–5 plasmids: one for the vector genome, the second for Gag-Pol, the third for Rev, and one or two for protein(s) envelope, or for the co-expression of a labeled viral protein such as GAG-GFP or VPR-GFP, the main advantage of which is safety due to the minimal risk of generating a replication-competent virus. The article discusses the development of a technique that allows to determine the presence of virus-specific neutralizing antibodies to the SARS-CoV-2 antigen in the blood serum of volunteers who have had a new coronavirus infection COVID-19 and/or immunized with specific prophylaxis drugs, healthy volunteers in a neutralization reaction on a HEK 293-cell culture. T-hAce2 using pseudotyped viral constructs based on human immunodeficiency virus. The results of the development and validation of the method, as well as its subsequent prospects for use, are shown.

Russian Journal of Infection and Immunity. 2023;13(3):457-468
pages 457-468 views
Various reagent kits for comparatively analyzed effectiveness of humoral immune response after vaccination “Sputnik V"
Kazakov S.P., Reshetnyak D.V., Davydova N.V., Efimushkina О.А., Putkov S.B.

Modern methods of vaccination have confirmed their high effectiveness in fighting against the pandemic of a novel coronavirus infection. However, the use of various types of vaccines requires studying the effectiveness of the post-vaccination immune response (PIO), first of all, assessing the specificity and amount of production of antibodies to the surface and internal antigens of the SARS-CoV-2 virus, in particular, after the use of the most promising domestic vaccine “Gam-Covid-Vac” (“Sputnik V”). In particular, the data on the effectiveness of PVIR (increased antibody level) for the most promising domestic vaccine “Gam-Covid-Vac” (“Sputnik V”) need to be confirmed. It is also necessary to evaluate the effectiveness of the laboratory methods used for this purpose. To assess the effectiveness of PVIR, samples of biomaterial (blood serum) obtained on the 22–25 day after inoculation of the second component of the vaccine from 202 “Sputnik V”-vaccinated, not preimmunized subjects, lacking antibodies to SARS-CoV-2 before vaccination, were examined. The levels of IgG and IgM antibodies to the surface and nucleocapsid antigens of the SARS-CoV-2 virus were determined using several semi-quantitative and quantitative methods and reagent kits from national and foreign manufacturers. To assess the diagnostic effectiveness of the methods, a comparative analysis of the specificity and sensitivity of all the laboratory methods used and a data correlation for various quantitative methods (using the Spearman correlation coefficient) between antibodies specific to the full-sized trimerized S-protein and the receptor-binding domain (RBD) of the SARS-CoV-2 S-protein were carried out. During the study, it was determined that all the reagent kits used to study IgG antibodies against SARS-CoV-2 S-protein and S-protein RBD showed maximum (100%) specificity in in the majority subjects (from 186 to 202 samples). The relevance of the data (comparative specificity), both for semi-quantitative and quantitative ELISA as well as for both ILA test systems regarding qualitative characteristics (“positive”–”negative”) was also close to the maximum magnitude (98.4–99.4%). A post-vaccination immune response during Sputnik V vaccination analyzing production of specific IgG antibodies was observed in 98.9% of all vaccinated subjects. IgG antibody range was studied to assess related “protective” level. Data are presented that a “protective” level of more than 150 BAU/мл was observed in 59.3–90.5% of the subjects, above 500 BAU/ml — in 22.0–52.4% of the subjects, depending on the method used and the set of reagents. Based on the data obtained, it is concluded that all the methods and kits of reagents used, including domestically manufactured semi-quantitative tests, can be considered adequate to assess effectiveness of the post-vaccination immune response analyzing production of SARS-CoV-2-specific antibodies.

Russian Journal of Infection and Immunity. 2023;13(3):469-480
pages 469-480 views
Molecular genetic characterization of the epstein–Barr Virus: a relationship with the clinical features of pediatric infectious mononucleosis
Popkova M.I., Utkin O.V., Filatova E.N., Bryzgalova D.A., Sakharnov N.A., Soboleva E.A., Nazarova L.V.

Introduction. Infectious mononucleosis (IM) is an high priority viral infection in children. Epstein-Barr virus (EBV) is the main etiological agent of IM. EBV is classified into two main types — EBV-1 and EBV-2. In addition, different variants of the virus are isolated based on individual genes, among which the LMP-1 gene and the oncoprotein it encodes are the most well known. So far, the study of the clinical significance of EBV genetic diversity in EBV-IM in children in Russia has not been conducted. The aim of the study was to evaluate a relationship between EBV LMP-1 molecular genetic variants and clinical and laboratory manifestations of IM in children.

Materials and methods. The material of the study was presented by blood leukocyte and saliva samples of children aged 1–17 years with EBV-IM (n = 69). A total of 132 EBV isolates were studied. For differential detection of EBV-1/EBV-2, we used a previously optimized one-round PCR variant with electrophoretic detection of amplification products in agarose gel. The nucleotide sequences of the C-terminal region of the LMP-1 gene were determined by Sanger sequencing followed by analysis of the obtained sequences using the MEGA X software. Multiple Factor Analysis was used to search for the relationship between LMP-1 variants and clinical and laboratory manifestations of IM (32 signs and 8 groups of signs).

Results. It was established that only one type of virus, EBV-1, was identified in all children. At the same time, the severity of clinical manifestations of EBV-IM in children varied significantly (from 15.5 to 35.5 scores in total). Molecular genetic analysis of the sequences of the LMP-1 C-terminal region in Nizhny Novgorod region EBV isolates demonstrated a significant heterogeneity of the viral population, which was not limited only to their grouping according to known variants. According to the frequency of detection, B95-8 was the dominant variant of LMP-1 (60.6±6.0% of cases), other variants were less common (China 1, NC, Med and China 1+В95-8). It was found that EBV-IM proceeded more easily and with less severity of the intoxication syndrome in cases of infection with a virus having the molecular genetic profile of EBV-1/B95-8, in particular EBV-1/B95-8/E214D. Conversely, EBV-1/Med, as well as EBV-1/Med/L338S, EBV-1/Med/S229T, EBV-1/China 1/L338S and EBV-1/NC/S229T profiles were associated with more severe infection.

Conclusion. For the first time, the influence of the genetic diversity of EBV on the clinical manifestations of IM in children was revealed. In the context of the tasks to be solved in this study, it is necessary to conduct a larger-scale and systemic studies in different territories of Russia.

Russian Journal of Infection and Immunity. 2023;13(3):481-496
pages 481-496 views
A relation between specific immune status indicators and activity of “lipid peroxidation — antioxidant defense” system in COVID-19 neonates
Rychkova L.V., Darenskaya M.A., Petrova A.G., Semenova N.V., Moskaleva E.V., Kolesnikov S.I., Vanyarkina A.S., Kolesnikova L.I.

The 2019 coronavirus infection (COVID-19) has not been considered as a solved issue for public health. Pregnant women and newborns are specifically vulnerable to COVID-19 infection compared to older children and healthy young adults. Virtually no data on relation between diverse arms of immunity in patients in neonatal period and coronavirus infection are available. The obtained results can contribute to a better understanding of the pathogenetic mechanisms on reactivity of immune processes in young patients and corresponding formation of approaches for prevention and correction of such disorders. The aim of the study was to determine magnitude of specific altered parameters in immune system and their relation with lipid peroxidation parameters in COVID-19 newborns. Two groups of newborns (mean age 4±3.1 days) were examined: SARS-CoV-2-positive (COVID-19 patients, n = 44) and negative (control group, n = 80) PCR test of nasopharyngeal swab. All newborns were assessed for specific indicators of peripheral blood immune status and lipid peroxidation activity. The concentration of Th1-pro-inflammatory cytokines and Th2-anti-inflammatory interleukins was assessed by enzyme immunoassay method (a panel of monoclonal antibodies). Spectrophotometric, fluorometric and enzyme immunoassay methods to evaluate the lipid peroxidation system were used. According to our data, newborns with COVID-19 vs. healthy newborns had decreased CRP, pro-inflammatory cytokines — TNFα, IL-1β, IL-6, IL-8, and anti-inflammatory factor (IL-4). Change in lipid peroxidation system in children with COVID-was 19 related to higher level of DC, KD and CT, TBARs, increased SOD activity and reduced GPO. Numerous intersystem dependencies in the group of newborns with COVID-19 (CRP — Total AOA, IL-4 — KD and CT, IL-4 — TBARs, IL-4 — Total AOA, IL-4 — SOD, IL-8 — SOD, IFNγ — GSH) were noted. It can be concluded that in newborns with COVID-19, changes in the immune system are nonspecific and are accompanied by an increased intensity of lipid peroxidation reactions against the background of reduced values of pro- and anti-inflammatory cytokines. These results may contribute to a more accurate assessment of intensity and dynamics of emerging neonatal coronavirus infection, which should be an important arm in preventing subsequent complications.

Russian Journal of Infection and Immunity. 2023;13(3):497-505
pages 497-505 views
Comparative characteristics of nasal mucosa microflora in various forms of chronic rhinitis
Smirnova O.V., Goncharova N.S.

Dysbiosis of the nasal mucosa contributes to the development of secondary immune disorders, maladjustment and contributes to the development of pathological processes, regardless of the phenotype of chronic rhinitis. The aim of our work was to comparatively assess microbial species and quantitative composition as well as frequency of its occurrence in patients with various forms of chronic rhinitis. We present the results of a laboratory examination of patients with chronic rhinitis (79 subjects aged 18 to 70 years), including 20 patients with chronic allergic,20 with chronic vasomotor,18 with chronic atrophic,21 with chronic infectious rhinitis. The control group consisted of 40 apparently healthy donors. All patients underwent nasal mucosa bacteriological examination. Statistical analysis of the obtained results was carried out using the Statistica for Windows 8.0 software package (StatSoft Inc., USA,2008). Nonparametric Kruskal–Wallis, Mann–Whitney, and Wilcoxon tests were used to assess differences in groups. The critical level of statistical significance in testing scientific hypotheses was considered equal to p < 0.05. In the control group, microorganisms of the genera Staphylococcus, Streptococcus, Neisseria, Acinetobacter, Klebsiella, Proteus are detected in the microflora of the nasal mucosa, which do not cause pathological changes. An interesting fact is the detection of Proteus mirabilis and Acinetobacter baumannii in healthy volunteers in the absence of clinical manifestations of infection, which proves the possibility of coexistence with opportunistic flora while maintaining the immune system functionining. In chronic allergic rhinitis, microorganisms of the genera Staphylococcus, Streptococcus, Neisseria, Enterobacter, Сorynebacterium are detected. In chronic vasomotor rhinitis, representatives of the genera Staphylococcus, Streptococcus, Neisseria, Klebsiella are detected. In chronic atrophic rhinitis, representatives of the genera Staphylococcus, Streptococcus, Neisseria, Acinetobacter are detected, with a predominance of Klebsiella bacteria. In chronic infectious rhinitis, representatives of the genera Staphylococcus, Streptococcus, Neisseria, Acinetobacter, Escherichia, Enterobacter, Corynebacterium, Pseudomonas, Proteus, Candida are detected. The absence and/or decrease in the number of representatives of the normoflora was found identifying pathogenic and opportunistic bacteria. With inflammation in the mucous membrane of the nasal cavity, regardless of its etiology, there is a change in the microflora quantitative and species composition. The most pronounced dysbiosis of the nasal mucosa microflora was found in chronic infectious rhinitis.

Russian Journal of Infection and Immunity. 2023;13(3):506-516
pages 506-516 views
Microbiological evaluation of probiotic therapy in patients with pulmonary tuberculosis
Otdushkina L.Y., Zakharova Y.V., Kholodov A.A., Pyanzova T.V.

Patients with pulmonary tuberculosis and multiple pathogen resistance (MDR) develop persistent disorders of the intestinal microbiome during prolonged multicomponent chemotherapy requiring correction. However, there is limited data on the use of bacterial drugs in patients with tuberculosis followed by assessing their effectiveness. The aim of the study was to evaluate changes in the intestinal microbiome after a course of probiotics along with anti-tuberculosis chemotherapy in patients with MDR tuberculosis.

Materials and methods. The design — a prospective small-cohort study (n = 30). Patients with pulmonary tuberculosis received anti-tuberculosis drugs according to the IV or V regimen, the median of the doses taken was 34.5 (30; 57.5); gastrointestinal syndrome was recorded in all study subjects. Probiotic therapy was applied by using a preparation containing Bifidobacterium bifidum and B. animalis and Lactobacillus casei, L. plantarum, L. delbrueckii subsp.bulgaricus, L. acidophilus. The course of therapy comprised 21 days,1 capsule twice a day. Before and 7 days after probiotics therapy, studies on composition of the intestinal microbiota were carried out, the frequency of virulence factors Enterococcus spp., Staphylococcus spp., Candida spp. was examined; fatty acid composition and activity of enterococcal organic acid production were studied.

Results. After a course of probiotics, a significant increase in lactobacillus titers was recorded from 5.2 (4.0; 6.0) to 6.1 (6.0; 8.0) lg CFU/g (p = 0.05). The frequency of mucosal colonization by Candida fungi and lactose-negative Escherichia decreased by 2-fold (p = 0.001) and 3-fold (p = 0.05), respectively. The frequency of detected virulent strains significantly decreased: hemolysin-producing staphylococci — by 9 times (p = 0.009), enterococci with gelatinase activity — by 6 times. E. faecalis membrane oleic acid level significantly increased (C9-C18:1) (p = 0.03). In E. faecium, cis-7-palmitoleic acid (C7-C16:1) and oleic (C9-C18:1) fatty acid level increased by 2-fold (p = 0.05), and for linoleic acid (C18:2) — by 4 time (p = 0.04) accompanied by elevated acid formation by 1.5 times.

Conclusion. A single course of probiotic therapy in patients with pulmonary tuberculosis leads to qualitative microbiome changes, which are characterized by decreased levels of conditionally pathogenic microorganisms with virulent properties and altered composition of the enterococcal cell membrane accompanied by their increased biochemical activity.

Russian Journal of Infection and Immunity. 2023;13(3):517-525
pages 517-525 views
Characteristics of acute diarrhea in adult cases with Campylobacter spp. positive fecal samples
Kozhukhova E.A., Andreeva N.V., Dmitrieva M.I., Nikilaenko S.L.

Recently, cases caused by Campylobacter spp. in Russia similar to other countries tended to clearly rise, partly due to the widely implemented biomolecular PCR-based laboratory analysis that substantially facilitated Campylobacter spp. detection in patient’s samples. The problem of being infected by Campylobacter spp. is so far worth studying because of campilbacteriosis signs in a form of a variety of clinical patterns including local and general forms, possible trigger role in forming the consequent chronic digestive tract pathology as well as general systemic pathology. Development of colitis or heamocolitis as the pattern part of acute diarrhea caused by Campylobacter spp. is usually considered as associated with the disease burden. So far as adult patients have acute diarrhea with positive Campylobacter spp. samples it might be of interest to compare and analyze their clinical and laboratory data to find some possible associations as particular features of different disease patterns. Objective — to analyze clinical features and laboratory data of hospitalized AD adult cases with feces samples positive for Campylobacter spp. When carrying out the retrospective cohort study the analyzed were clinical and laboratory data of 111 hospitalized adult patients suffering from moderate acute diarrhea with clinical samples (feces) positive for Campylobacter spp. To verify acute infectious diarrhea all patients went through complex specific laboratory examination that included PCR — based methods (feces) with use of “Amplisense® AD screen-FL” in addition to routine standard culture (feces), serologic (specific antibody detection) and ELISA laboratory methods. The analysis results have shown that more than 1/2 part of patients developed colitis syndrome with blood in feces in practically every forth case. In patients (predominantly males) without chronic digestive tract problems relative risks to develop colitis and haemocolitis are respectively 1.6 and 2.6 times higher given they are hospitalized on day 4 after the onset and later versus those hospitalized earlier.

Russian Journal of Infection and Immunity. 2023;13(3):526-534
pages 526-534 views
Tick-borne infections in the south of Russia: modern epidemiological situation, new approach to create “forecasting” and “explaining” morbidity models (in astrakhan rickettsiosis fever and crimean-congo hemorrhagic fever)
Prislegina D.A., Maletskaya O.V., Dubyanskiy V.M., Taran T.V., Platonov A.E.

The article presents a description of the current tick-borne infection epidemiological situation in the south of Russia from the years 2013 to 2022, proposes a new approach to develop “forecasting” models for morbidity dynamics of Astrakhan rickettsial fever (ARF) and Crimean hemorrhagic fever (СCHF) in the Astrakhan region and presents data assessing 2022 “explaining” models for the Stavropol Territory and Astrakhan Region. Materials and methods. A comprehensive research was performed using epidemiological analysis and non-parametric statistical methods. The data assessing tick-borne infections epidemic process manifestations were retrieved from ARF and CCHF morbidity databases (developed as a project) and documents of infectious disease focus epidemiological examination provided by the departments of Rospotrebnadzor in the subjects of the Southern and North Caucasian Federal Districts. Morbidity models were developed using the Bayes’ theorem and Wald’s sequential statistical analysis, with a preliminary calculation of indicators informativeness by the Kullback method. The values of climatic factors from the database of the Center for Collective Use “IKI-monitoring” of the Space Research Institute of the Russian Academy of Sciences were used. Results. The results of the study indicate persistence of serious epidemiological situation regarding rickettsiosis of the tick-borne spotted fever group, Q fever, tick-borne borreliosis and CCHF in the south of Russia. Almost all tick-borne infections nosological forms in children under 14 years (including young children and infants) were widely involved in the epidemic process, which belong to patients at risk for a complicated disease course due to complicated diagnostics and treatment. The annual registration of tick-borne infections cases in the resort areas, with the subsequent occurrence of imported cases in other, including non-endemic regions poses a serious problem. The proposed “forecasting” models allow to predict the CСHF and ARF morbidity for each administrative district of the Astrakhan region with up to 91.7% accuracy. The “explaining” models CСHF accuracy for the Stavropol Territory and Astrakhan Region, when tested in 2022, was 88.5 and 83.3%, respectively, for ARF — 91.7%. Conclusions. The further continuation of “forecasting” and “explaining” models verification for planning preventive measures and propose similar steps for tick-borne borreliosis and Q fever to epidemiological tick-borne infections to stabilize situation in the south of Russia.

Russian Journal of Infection and Immunity. 2023;13(3):535-548
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Assessment of protein s and c level and its relationship with health-related factors in people living with hiv: a cross-sectional study
Rezaei E., Jamali E., Foroozanfar Z., Ataei F., Beheshti S., Joulaei H.

Introduction. Not only does Human Immunodeficiency Virus (HIV) threaten the complications associated with immunodeficiency, but also does it cause a set of chronic conditions that may lead to serious problems in these patients. Hypercoagulable state and other hematologic manifestations are reported as leading factors in various clinical problems like deep vein thrombosis in People Living with HIV (PLHIV). The present study aimed to investigate whether there is any correlation between proteins S and C levels (the thrombophilic conditions in HIV seropositive cases) and hematological factors, biochemical markers, CD4 count, HIV viral load, anti-retroviral therapy, Hepatitis C (HCV) and hepatitis B (HBV) confection, drug use, infectious diseases, and demographic characteristics.

Materials and methods. Protein S and C levels in 100 PLHIV were measured. Coagulation tests, CD4 count, HIV viral load, biochemical and hematological factors, and infectious tests were measured in these cases to assess any possible correlation between these factors and the patients’ proteins S and C levels.

Results. Protein S, and C deficiency among PLHIV 8% and 10%, respectively. Red blood cell, hemoglobin, hematocrit, fasting blood sugar, and albumin were directly related to protein S, and the patients with positive VDRL significantly had a lower level of protein S. The patients receiving anti-retroviral therapy and those with positive VDRL had a higher level of protein C. CD4 count, prothrombin time, and cholesterol had also a direct correlation with protein C level.

Conclusion. According to our results and the reduction of protein S, protein C, and the other factors affecting the lifestyle of PLHIV, there is an urge to pay special attention to thromboembolic disease. Moreover, there is a more possibility of hemostatic imbalances and coagulation disorders in them.

Russian Journal of Infection and Immunity. 2023;13(3):549-558
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Post-COVID-19 complications in kidney transplant recipients
Shafiekhani M., Abolghasemi S., Asgharpour M., Zare Z., Negahban H., Akbari R., Nikoupour H., Roozbeh J., Oliaie F., Yahyapour Y., Geraili Z., Barari M., Ebrahimpour S., Baziboroun M.

Background. Although most people recover from acute COVID-19 within a few weeks, some have long-lasting clinical problems. The prevalence of these prolonged complications in kidney transplant (KT) recipients has not been determined.

Materials and methods. Six months following of 148 patients with post-COVID-19 syndrome admitted to three centers in Iran (Tehran, Shiraz and Babol) that underwent KT were included in this study. Also, one-hundred COVID-19 patients without KT were included as the control group. The demographic data, medications, and disease course were recorded. The baseline and demographic characteristics were analyzed using the Chi-square test. Moreover, student’s t-test were utilized to compare case and control groups.

Results. The total number of patients was 248, of which 148 were in the case groups. Hospitalization associated with COVID-19 was for all patients; besides, there were 18 patients in control and 24 case groups admitted to an intensive care unit (ICU). The most commonly reported symptom was fever. Multivariate analysis identified the history of chronic kidney disease, hypertension, cerebral vascular accident, and diabetes mellites as predictors for developing post-COVID clinical complications.

Conclusion. Evidence shows the high commonness of post-COVID-19 syndrome among kidney transplant patients after COVID-19, and the most common symptoms were fever, chills, and myalgia. So, all patients recovered from acute COVID-19 should undergo long-term monitoring to evaluate and treat possible complications.

Russian Journal of Infection and Immunity. 2023;13(3):559-566
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Fungal allergy as a risk factor for developing rosacea
Barilo A.A., Smirnova S.V.

The pathogenesis of rosacea is not fully understood. In this disease, the release of inflammatory molecules and overgrowth of skin-colonizing microorganisms, including fungal microbiota, are noted. The study of the frequency of occurrence and the nature of the spectrum of sensitization to fungal allergens in patients with rosacea is of particular interest and accounts for relevance of the study. Purpose of the study: to analyze the frequency of occurrence and the nature of the spectrum of sensitization to fungal allergens in patients with rosacea.

Materials and methods. The study included patients with rosacea aged 18 to 60 years (group 1, n = 31). All patients underwent a specific allergic examination: collected allergic history, skin prick testing using the following allergens: nutritional yeast, Candida albicans, Alternaria alternate, Aspergillus fumigatus, Cladosporium herbarum, Penicillium notatum (Allergopharma, Germany). Concentration of total immunoglobulin E (IgE) and eosinophilic cationic protein in blood serum was measured in indirect immunofluorescence analysis with Thermo Scientific Multiskan FC semi-automatic analyzer. Statistica 8.0 software package was used for statistical analysis.

Results. Analysis of the features of the spectrum of sensitization to fungal allergens in the group of patients with rosacea showed that the most significant allergens are Cladosporium herbarum (74.2% of patients) and Candida albicans (58.1%). Sensitization to nutritional yeast and Penicillium notatum was detected in almost half of the patients. The concentration of total immunoglobulin E in blood serum in the group of patients with rosacea was 79.4 IU/ml [23.4; 105.1], in the control group — 45.1 IU/ml [23.4; 144.0]. The concentration of eosinophilic cationic protein in blood serum in the group of patients with rosacea was significantly higher compared to the control group: 50.3 ng/ml [43.0; 62.0] and 7.9 ng/ml [4.6; 27.1], respectively. After skin prick testing with fungal allergens, patients with rosacea were prescribed an individual elimination diet with the exclusion of causally significant allergens for a period of 1 month. In 61.2% (n = 19) of cases in patients with rosacea, a positive elimination effect was noted: a significant decrease in the severity of erythema, papules and pustules in the face.

Conclusion. Thus, the study revealed a high incidence of fungal allergy and established the features of the spectrum of sensitization to fungal allergens in patients with rosacea. The most significant fungal allergens in rosacea are fungi of the genus Cladosporium herbarum, Candida albicans, Penicillium notatum as well as nutritional yeast.

Russian Journal of Infection and Immunity. 2023;13(3):567-572
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Adhesiveness of the specific phages to yersiniae cells assessed by optical trapping
Konyshev I.V., Dudina L.G., Morozova N.A., Byvalov A.A.

In recent years, there has been increasing interest in using bacteriophages in the complex therapy of some infectious diseases. Objectively, it is related to the spread of antibiotic resistance and a small number of side effects triggered by phages applied locally and parenterally. Yersiniae are no exception to this rule, but their interaction with virions has not been studied thoroughly. In three types of lytic Yersiniae bacteriophages are used for diagnostic purposes, which differ in specificity, virulence, and morphological features. We evaluated the interaction force between phages and bacteriae by optical trapping.

Materials and methods. Live Yersinia pseudotuberculosis and Y. pestis cells with different LPS structure and preparations of three bacteriophages — Pokrovskaya’s phage, d’Herelle’s phage (also named as the pseudotuberculosis phage) and the phage L-413C were used. The Pokrovskaya’s phage is well studied and widely used in diagnostics, but the mechanism of its adsorption on Y. pestis and Y. pseudotuberculosis cells is not well-understood. The phage L-413C lyses plague bacteria, while d’Herrel’s phage can lyse both pathogens. Virions were linked to the surface of aminated glass. Optically trapped microbial cells were approached to the glass surface and then retracted in the opposite direction. The amplitude of the leap was recalculated into force through calibration coefficients. The primary data were processed in the program “R”; statistical analysis was performed using “Matlab 7.0” and “Statistica 12”

Results and discussion. The analysis of histograms revealed the presence of a specific component in the «Y. pseudotuberculosis–d’Herrell’s phage» (Fmean = 7.46±3.52 pN) system, as well as in all pairs involving plague microbe. In the latter case, the interaction forces were comparable: 8.64±3.83 pN for d’Herelle’s phage,11.03±4.22 pN for Pokrovskaya’s phage, and 10.42±4.79 pN for phage L-413C. The average detachment force from the substrate treated with bovine serum albumin (BSA) was comparable for both cell types. Our results convincingly prove an opportunity for using the optical trapping to estimate interaction force in other «bacterium–phage» systems.

Russian Journal of Infection and Immunity. 2023;13(3):573-578
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TLR3 and TLR7 prognostic role in early pediatric rotavirus infection
Gorbunov S.G., Mazankova L.N., Os'kin A.N.

Introduction. Rotavirus infection is an urgent problem for pediatric infectology. The disease does not always proceed smoothly, it is assumed that TLR3 and TLR7 play an important role in its prognosis. The initial number of cells expressing such receptors in early children can probably be considered a predictor of unfavorable course and outcomes of rotavirus infection.

Materials and methods. Infants with rotavirus infection were divided into groups depending on the initial count of TLR3- and TLR7-expressing immunocompetent cells. All patients were examined using general clinical methods. Rotavirus infection was diagnosed by molecular genetic (RNA detected by PCR) and immunochromatographic (determination of antigen) method. Parameters of cellular immunity were assessed by flow cytometry. Statistical data processing was carried out using the Statistica 8.0 program for independent samples using the nonparametric Mann–Whitney criterion and the Pearson criterion c2.

Results. It was found that in patients with an initially small vs. high count of TLR3-expressing cells, the symptoms of exicosis were observed significantly longer, which determined a significantly longer infusion rehydration therapy. In patients with an initially small count of TLR7-expressing cells, no significant differences were observed during disease course. However, only this group similar to infants with a small count of TLR3-expressing cells were treated with antibiotics due to concomitant bacterial infections. Only convalescents with small count of simultaneously TLR3- and TLR7-expressing cells had repeated episodes of ARI and allergic diseases in catamnesis, whereas infants with extremely low count of TLR3-expressing cells developed additionally an unfavorable outcome such as reactive pancreatopathy.

Conclusion. The initially low count of TLR3- and TLR7-expressing immunocompetent cells leads to a more severe course of rotavirus infection in infants requiring adjusted therapy by introducing antibacterial drugs and in some cases also contributes to arising adverse outcomes and consequences in 6–12 month catamnesis.

Russian Journal of Infection and Immunity. 2023;13(3):579-585
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Antibiotics hypersensitivity reactions during COVID-19 pandemic
Kalikyan Z.G.

During the COVID-19 pandemic, there have emerged publications about various skin manifestations mainly caused by the related coronavirus, also including some case reports on dermal drug-related adverse reactions. In Armenia, the doctors in COVID-19 hospitals periodically consulted with allergists-immunologists regarding allergic conditions that many patients already suffered on admission or manifested after it. We present the series of three most interesting drug-induced cases with various skin manifestations in patients with COVID-19 pneumonia who requited antibiotic therapy. The causative significance of antibiotics was assessed according to Naranjo’s algorithm. In the first case (a 58-year-old female patient), a diagnosis of maculopapular exanthem was made based on the clinical picture. Although the coronavirus per se can result in similar manifestations, previous history of allergic reaction to ampicillin led to the conclusion that ceftriaxone (both are beta-lactam antibiotics) was the most probable cause. The second case (a 53-year-old male patient), clinically manifested as vasculitis, caused some difficulties because this is quite often skin manifestations related to SARS-CoV-2, and is rarely induced by medications. Taking into account the history of reaction to beta-lactam antibiotic, as well as the fact that the patient took amoxicillin without a prescription before hospitalization and with overt skin lesions at that time, amoxicillin was assessed as a possible cause. In the third case (a 64-years-old female patient), diagnosed with a bullous drug-induced skin eruption, despite isolated cases of such lesions can be manifestations of SARS-CoV-2 infection, moxitec (fluoroquinolone antibiotic) was assessed as the most probable cause, especially taking into account herpes in history. According to current recommendations, an issue of drug tests was discussed with all three patients to confirm the causative significance of indicated drugs and/or to select an alternative drug, if necessary. In this regard, the subjects were included in the database of patients with severe drug hypersensitivity reactions by their informed consent.

Russian Journal of Infection and Immunity. 2023;13(3):586-590
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Method for identification of acinetobacter baumannii bv. tryptophandestruens and its subbiovars A and B
Sivolodskii E.P., Kraeva L.A., Melnikova E.V., Gorelova G.V.

The aim of the study was to increase diagnostic sensitivity for identification of A. baumannii bv. tryptophandestruens bacteria and assess prevalence of this biovar and its subbiovars among A. baumannii clinical isolates. There were examined 210 primary strains of A. baumannii isolated in 2021–2022 at Bacteriological Laboratory of the Military Medical Academy named after S.M. Kirov, of which 42 strains were A. baumannii bv. tryptophandestruens. Tryptophandestruens biovar bacteria were identified by chromogenic biotransformation of sodium benzoate on a dense nutrient medium (g/l): peptone enzymatic 5.0; NaCl 5.0; FeCl3 6H2O (10% aqueous solution) 0.1–1 ml; bromothymol blue (1.6% aqueous solution) 3 ml; agar 15.0; NaOH (4% solution) 2.6–3 ml; distilled water 1 l; all components were dissolved by heating and added with sodium benzoate (CAS 532-32-1) 1.0–2.0; adjusted pH 7.2±0.2; sterilized at 121°С, poured into Petri dishes. Bacteria of subbiovars A and B of biovar tryptophandestruens were identified by chromogenic biotransformation of L-tryptophan using the same nutrient medium supplemented with L-tryptophan (1.0–2.0 g/l) instead of sodium benzoate. Both nutrient media were used simultaneously. The A. baumannii cultures studied were seeded with a loop on the media sectors in the form of a plaque, incubated aerobically at 37°С for 18–24 hours, and analyzed final data as follows: the presence of a dark brown color zone of the nutrient medium around bacterial lawn on sodium benzoate- and L-tryptophan-containing medium indicated detection of subbiovar A of the tryptophandestruens biovar; in case of dark brown zone on sodium benzoate- but not L-tryptophan-containing medium around bacterial lawn identified biovar tryptophandestruens subbiovar B. The study revealed for the first time the chromogenic biotransformation of sodium benzoate (benzoic acid) and its importance as a marker for the biovar tryptophandestruens A. baumannii. Two subbiovars A and B of the tryptophandestruens biovar were found. A method was developed to identify the biovar tryptophandestruens A. baumannii and its subbiovars A and B by chromogenic biotransformation of sodium benzoate and L-tryptophan, which enhances diagnostic sensitivity by detecting the subbiovar B. The frequency of tryptophandestruens biovar distribution among primary clinical isolates of A. baumannii in 2021–2022 was determined: out of 210 strains of A. baumannii were 42 (20.0±3.5%) strains of bv. tryptophandestruens including subbiovar A — 27 (12.9±2.3%), subbiovar B — 15 (7.1±1.7%).

Russian Journal of Infection and Immunity. 2023;13(3):591-596
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