Vol 9, No 5-6 (2019)


T cell thymic selection and peripheral homeostatic proliferation in infectious diseases

Kozlov V.A.


There is no doubt that infectious agents and host undergo multilayered yet not fully understood interactions. This is primarily due to at least mechanisms resulting in chronic course of infectious process. Acute infection proceeds in parallel with primary immune response and its typical phases, each of which manifests as certain stage in clinical picture featured with disease onset and subsequent recovery. A whole process of immune response developing against infectious agent occurs in peripheral lymphoid organs and immune tissues. With regard to the role of immune system in infectious process, process, two main outstanding issues still remain unanswered: 1) what are the mechanisms of host death in the case of acute infectious process? 2) what is a “fault” of immune system in it? In its inferiority or in abruptly suppressed functions induced by infectious agent, when it “does not have time” to mount an immune response of sufficient power? So far, no answer is still found yet. The second question concerns mechanisms of converting to chronic course of infectious process. The obtained available in publications evidence about an intimately involved thymus as the central immune organ in infectious process of, the main function of which is to ensure developing central immune tolerance to self-antigens accomplished via T-cell positive and negative selection. It turned out that in case of some examined infections due to pathogens, which entered the thymus, such intimate events such as partial tolerance to pathogens and autoimmune reactivity are altered. Moreover, these processes are further aggravated by homeostatic proliferation, which is also induced by an infectious agent. In both cases, it accounts for decreased magnitude of immune response against a certain pathogen, burdened by emergence of autoimmune reactions.

Russian Journal of Infection and Immunity. 2019;9(5-6):629-638
pages 629-638 views

Current understanding of Bacillus anthracis toxin molecules organization and approaches for blocking their cytotoxic action

Firstova V.V., Shemyakin I.G., Dyatlov I.A.


Here, we review the data on mechanisms inhibiting cytotoxic effect of anthrax toxin on the immune system cells. Various disease forms, immunopathogenesis and contemporary methods for anthrax treatment are discussed. In addition, an anthrax toxin was outlined, whereas structural and functional organization of the protective antigen, lethal and edema factors was detailed. A mechanism for association of a protective antigen and lethal factor, protective antigen and edema factor leading to formation of a lethal toxin and edema toxin, respectively, was described. Participation of protective antigen domains in the process of interaction with surface receptors of imunocompetent cells as well as features of binding a protective antigen with lethal factor and edema factor are discussed. A mechanism of endosomal toxin complex internalization and subsequent transfer of effector molecules to the cytosol are described. Effects of the lethal factor and the edema factor on components of eukaryotic cells as well as cytotoxicity mechanisms are analyzed. The approaches to block anthrax toxin action at various stages of toxicoemia have been analyzed based on previously uncovered sequential signs of cytotoxic activity for Bacillus anthracis toxins. Currently available chimeric and humanized monoclonal antibodies are capable of neutralizing B. anthracis toxins at diverse assembly stages, particularly considering the drugs inhibiting: inter-receptor interaction between protective antigen with eukaryotic cells; furin-like enzymes activating prepore assembly; protective antigen oligomerization; binding of the lethal factor or edema factor to the protective antigen; translocation of the lethal factor or the edema factor into cell cytosol; transport of protective antigen with lethal factor or edema factor from endosomes; enzymatic activity of lethal factor or edematous factor. The anti-toxin agents approved for anthrax prevention and treatment in Russia and worldwide are discussed. The limitations of anti-toxin agents and perspectives for their improvement are also described including inhibition of lethal factor activity, interference with integration of toxin components, blockade of interactions between toxic complexes and immune cell receptors.

Russian Journal of Infection and Immunity. 2019;9(5-6):639-647
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Genetic and phenotypic characteristics of Klebsiella michiganensis isolates

Sivolodskii E.P., Freylikhman O.A.


The aim of the study was to identify an optimal research target for detection of Klebsiella michiganensis isolates, determine their genetic and phenotypic characteristics necessary for identification. Here, we examined 11 Klebsiella oxytoca strains, lacking (atypical, negative) a marker 5-aminosalicylate decarboxylase (detected by the chromogenic reaction by 5-aminosalicylic acid) unique for the genus Klebsiella bacteria. They were selected for genetic analysis subsequent to a phenotypic characterization of K. oxytoca clinical isolates, collected in within 2015–2018 period in medical institutions in St. Petersburg. Two K. oxytoca and two Raoultella ornithinolytica clinical strains displaying typical properties were used as a control. The presence of 5-aminosalicylate decarboxylase was detected by the chromogenic reaction with the “Klebsiella 5-ASK CHROME C” nutrient medium (Pasteur Institute, St. Petersburg). Substrate utilization as the sole carbon source was detected on a solid minimal synthetic medium added with 2 g/L substrate during incubation for 72 hours at 37°C. Biochemical bacteria features were studied by the microvolume method with the “Rapid-Entero” test system (Pasteur Institute, St. Petersburg). Genetic strain characterization was performed by estimating 16S rRNA, gyrA, rpoB by using a routine PCR with primer sequences described before. Two rpoB gene fragments with a total length 834 bp, 16S rRNA gene fragment — 387 bp, and gyrA gene fragment — 441 bp were amplified followed by their sequencing by Singer on an ABI 3130 automatic capillary sequencer (Applied Biosystems, USA) and subsequently determined similarity levels. Amplification pattern for pehX gene PCR fragments was performed by using a method described elsewhere with two primer pairs flanking fragment AD with a 513 bp length and 344 bp CD-long motifs. While examining 11 clinical bacterial strains identified earlier as Klebsiella oxytoca, lacking (atypical, negative) a 5-aminosalicylate decarboxylase (detected by the chromogenic reaction by 5-aminosalicylic acid) unique for the genus Klebsiella, molecular techniques identified 9 K. michiganensis strains and 1 strain highly homologous to Klebsiella kielensis based on the rpoB gene nucleotide sequence, confirming its high informative value. We used the methods for estimating a similarity level for sequenced fragments of 16S rRNA genes (fragment length 387 bp), gyrA gene (fragment length 441 bp), rpoB gene (rpoB-b and rpoB-e with a total fragments length 834 bp), and the analysis of marker amplicon patterns for pehX gene (AD, CD). It was shown that for the 4 K. oxytoca strains, 99–100% similarity to K. michiganensis was identified for all fragments in the sequenced genes. Moreover, similarity of all 9 strains detected with K. michiganensis was revealed only in the rpoB gene, hereby allowing to recommend it as the most informative approach. The pehX gene encoding polygalacturonase was verified by PCR in the majority of K. michiganensis strains, pointing that this approach is not rational for their identification (distinguish with K. oxytoca). The most informative for the phenotypic identification of K. michiganensis are were assays characterized by a common profile for the majority of strains: lack of 5-aminosalicylate decarboxylase, lack of utilized histamine, dulcitol, tricarballylic acid; positive for indole production, as well as D-melezitose and putrescine utilization.

Russian Journal of Infection and Immunity. 2019;9(5-6):648-654
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Features 2016–2018 current human influenza A(H3N2) viruses circulating in Russia

Petrova P.A., Konovalova N.I., Vassilieva A.D., Eropkina E.M., Ivanova A.A., Komissarov A.B., Eropkin M.Y., Danilenko D.M.


Influenza A(H3N2) viruses demonstrate the highest level of evolutionary variability compared to other influenza viruses circulating in human population. The strains of this subtype affect a large number of people belonging to highrisk groups: children under three years of age, pregnant women, people over 65 years, medical professionals, and persons with chronic nervous, cardiovascular and respiratory diseases. Influenza A(H3N2) viruses result in high mortality rate in subjects over 65 years causing the most severe course, accompanied by serious complications. Here, we present the data on analyzing antigenic and biological properties of human influenza A(H3N2) viruses which circulated in 2016–2018 epidemic seasons in Russia. The data on the neuraminidase activity (MUNANA test) of recent influenza A(H3N2) viruses isolated on MDCK and MDCK-Siat1 cell cultures are presented to compare with NA sequencing data in order to assess possible influence of the isolation system on NA activity. Due to changes in virus receptor properties, a choice of optimal isolation conditions is of high importance. The WHO recommended cell cultures differing in receptor properties were used. Efficiency of virus isolation on MDCK and MDCK-Siat1 cell lines was also analyzed. It has been established that the efficiency of influenza A(H3N2) virus isolation in MDCK-Siat1 cell culture was 77.3%, whereas in MDCK — 71.3%. It was shown that the majority of isolated strains (68.6% in 2016–2017 and 44.6% in 2017–2018) exhibited a NA-induced erythrocyte agglutination. It was found that current A(H3N2) strains isolated in Russia displayed no significant antigenic differences regardless of cell cultures used; however, adaptive substitutions in neuraminidase may emerge. While studying antigenic properties of influenza A(H3N2) viruses by using the HI assay and the microneutralization assay (cell-ELISA), it was noted that the majority of strains isolated in the 2017–2018 epidemic season was antigenically related and interacted with antiserum against the reference strain A/Singapore/INFIMH-16–0019/2016 (MDCK-Siat1) at a homologous titer. According to the sequencing data, it was established that during the 2017–2018 epidemic season, viruses of subclade 3C.2a2, as well as 3C.2a3 and 3C.2a1b were detected in Russia. Thus, an increasing genetic heterogeneity of A(H3N2) viruses was revealed in Russia.

Russian Journal of Infection and Immunity. 2019;9(5-6):655-664
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Isolation of Mycobacterium avium subsp. paratuberculosis from mouflon in Bulgaria

Savova T., Petrova R., Valcheva V., Bonovska M., Najdenski H.


Mycobacterium avium subsp. paratuberculosis (MAP) is the etiological agent of paratuberculosis (John’s disease) mainly in large and small domestic and wild ruminants, and suspected causative agent in human Crohn’s disease. In Bulgaria, paratuberculosis is still poorly researched in both groups of ruminants. We present results of the first in-depth study of mouflon, grown free in one hunting reserve in the Western region of the country. The aim was to prove the presence of MAP in diagnostic materials from regularly hunted or dead mouflon suspected for paratuberculosis. Small intestine and mesenteric lymph nodes (MLN) from 12 hunted and 4 dead mouflon and 10 faecal samples (Fc) were studied in the period of 2009–2013. Typical for paratuberculosis pathomorphological lesions were observed in four mouflon (of 16 examined). The intestinal wall was thickened, strongly folded and soft, with severe hyperemia. The MLN were enlarged, soft, with marbled appearance. The affected section of the ileum showed hyperplasia of the mucous corion and submucosa with diffuse infiltration of epithelioid cells. Lymphadenopathy with atrophy of T and B lymphocytes areas was observed in the mesenteric lymph nodes. For bacteriological isolation of MAP, the tissue and faecal samples were decontaminated with NALC-NaOH, cultured in Middlebrook 7H9 Broth and on Herrold’s medium. The Ziehl–Neelsen stained smears and isolates were examined microscopically for acid-fast bacteria. Presence of MAP was observed in tissue samples of 4 (25%) mouflon and in 2 (20%) faecal samples. The same samples were confirmed by the IS900 PCR for the presence of specific for MAP fragments with a commercial amplification kit. The cases of paratuberculosis found at different times in the free-living mouflon in our study prove that the disease exists in Bulgaria and highlight the need for more serious control of the disease among wild and domestic ruminants.

Russian Journal of Infection and Immunity. 2019;9(5-6):665-670
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Prevalence of carbapenemase-producing Klebsiella pneumonia in Gomel Region of Belarus and their sensitivity to antibiotics, antibiotic combinations, and decontaminants

Tapalski D.V., Savchenko O.I., Bonda N.A.


Here, we characterized in public health organizations prevalence of carbapenemase-producing Klebsiella pneumoniae, sensitivity to antimicrobial agents (AMAs), combined antimicrobial agents, and decontaminants. For this, there were selected 58 clinical isolates of K. pneumoniae resistant to carbapenems and/or polymyxins and examined within the microbiological monitoring program. Genes encoding KPC, OXA-48, VIM, IMP, NDM carbapenemases were detected by real-time multiplex PCR. Sensitivity to antimicrobial agents was determined by an automated method on a microbiological VITEK-2 Compact analyzer (bioMérieux, France) and by serial broth microdilution method. Sensitivity to 11 dual antimicrobial agent combinations was determined by a modified method of multiple combination bactericidal antibiotic testing. As a part of combinations, AMAs at pharmacokinetic/pharmacodynamics (PK/PD) threshold concentrations (meropenem — 8 μg/ml, amikacin — 16 μg/ml, levofloxacin — 1 μg/ml, tigecycline — 0.5 μg/ml, phosphomycin — 32 μg/ml, colistin — 2 μg/ml) were tested. Susceptibility to 7 combined decontaminants of different composition was determined by the suspension method. Carbapenemase genes were detected in 22 K. pneumoniae clinical isolates, of which 19 isolates contained a blaOXA-48 gene and 3 isolates — gene blaNDM. Carbapenemase producing K. pneumoniae were identified in 10 Gomel public health organizations and five regional centers of the Gomel region. The majority of such strains were isolated from patients in ICU (63.6%) and surgical departments (27.3%). Tigecycline (100% of the sensitive isolates, МIC50 — 1 μg/ml, MIC90 — 1 μg/ml) and colistin (86.4% of the sensitive isolates, МIC50 — 0.5 μg/ml, MIC90 — 4 μg/ml) exhibited the highest activity against carbapenemase-producing K. pneumoniae, whereas aminopenicillins, cephalosporins, aztreonam, aminoglycosides, fluoroquinolones, chloramphenicol (no sensitive isolates) had exhibited the lowest efficacy. Bactericidal activity of all antibiotic combinations containing colistin was shown against 86.4–95.5% of K. pneumoniae isolates. At least 3 distinct combinations of antimicrobial agents with bactericidal activity were efficient against 21 K. pneumoniae isolates (95.5%). Only 1 bactericidal combination (meropenem–amikacin) was unveiled for one isolate (producer of NDM MBL with MIC of colistin 32 μg/ml). Geksadekon, duacid, oksidez, hlorocid and diajsid exerted a bactericidal effect at 1/4 work dose against all isolates. Duacid, oksidez, hlorocid and diajsid showed bactericidal effect at 1/16 work dose against 95.5–100% isolates. Thus, several decontaminant groups (oxidizing agents, chlorine-containing preparations) were characterized by bactericidal activity against multidrug-resistant and extremely drug-resistant of K. pneumoniae even at 4–16 times lower than recommended concentration.

Russian Journal of Infection and Immunity. 2019;9(5-6):671-679
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IgA-protease activity coupled to cellular enzymes of different Streptococcus pneumonia serotypes isolated in pediatric bacteria carriers

Zaripova A.Z., Tyurin Y.A., Bayazitova L.T., Tyupkina O.F., Isaeva G.S.


Streptococcus pneumoniae are significant causative agents of severe and life-threatening acute pneumonia, meningitis, as well as otitis and sinusitis both in children and elderly. As many as 1.2 million pediatric lethal outcomes due to pneumonia and infections of the central nervous system (meningitis) caused by S. pneumoniae, are recorded worldwide annually, a large proportion of which occur in developing countries. Metal-dependent IgA1 proteases derived from pathogenic bacteria comprise an important group of bacterial enzymes cleaving human immunoglobulin A1 (IgA1) at the hinge region, thereby interfering with fully-executed host antibacterial immunity.

Objective. To study activity of IgA1proteinases and their class profile (Na2-EDTA and PMSF-inhibited) in various pneumococcal serotypes isolated from nasopharyngeal carrier children.

Materials and methods. There were examined 585 children attending preschool facilities residing in Kazan (n = 331) and rural areas (n = 254). Microbiological, molecular genetics and immunochemical methods were used to identify, serotyping composition and protease activity of Streptococcus pneumoniae isolates. Data statistical processing was carried out by using software Graph Pad Prism version 5.0.

Results. Prevalence of S. pneumonie in pediatric carriers aged 1.5–3 years was 35.1%, 3–5 years — 23.4%, 5–7 years — 19.6%, and over 7 years — 21.9%. Vaccine serotypes 14, 19F, 23F as a part of current pneumococcal vaccines (Prevenar, Pneumavax-23) comprised as high as 55.8%. However, in 19% of cases were positive for non-vaccine S. pneumoniae strains. Non-typeable strains were detected in 5.8% isolates. IgA-proteinase activity was detected in cell lysates of 45 (86.5%) S. pneumoniae strains isolated from pediatric carriers. Cell lysates of S. pneumoniae strains showing no proteolytic properties, were assigned to serotypes 12F, Sg18. Thus, studies on development of alternative vaccines containing immunogenic proteins, adhesins or other virulence factors common to capsulated and non-typeable (encapsulated) pneumococcal strains hold promise. All the aforementioned accounts for a need for microbiological monitoring of S. pneumoniae carriage and search for new diagnostic approaches for etiological interpretation of S. pneumoniae-associated diseases.

Russian Journal of Infection and Immunity. 2019;9(5-6):680-686
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Characteristics of immune response in patients with acute chronic maxillary sinusitis associated with intra-cellular bacterial infections

Parilova O.V., Kapustina T.A., Markina A.N., Belova E.V.


Currently, chronic inflammatory pathology of paranasal sinuses mostly affecting maxillary antrum is one of the pressing issues for health care. Over the last two decades, a great etiological importance in inducing inflammation in paranasal sinuses was referred to bacterial intracellular infections caused by Mycoplasma and Chlamydia. In particular, Chlamydia, whose life cycle is closely linked to residence inside host cells defines them as pathogenic obligate intracellular gram-negative bacteria, whereas Mycoplasma is a membrane-associated microorganism able to self-replication and long persistence on host cellular membranes. Increased incidence of chronic pathology in paranasal sinuses associated with intracellular infection is shaped by a range of circumstances, primarily increased prevalence of immunocompromised subjects, worsened social and ecological conditions, uncontrolled and unjustified administration of available of antimicrobials and anti-septic agents, hormone preparations altering community of extracellular microbe populations (microbiocenoses), inhabiting natural biotope in the upper respiratory tract mucosa. These factors contribute to the lowering colony resistance, entrance and propagation of Chlamydia and Mycoplasma as a monoor mixed infection. Upon that, mixed variants of Chlamydia-Mycoplasma infection are characterized by development of more severe sinusitis accompanied with diverse complications in the lower respiratory tract, digestive tract, urinary and nerve system. There were examined 189 subjects for assessing epidemiologic characteristics and features of systemic and mucosal immune responses in patients with exacerbated chronic maxillary sinusitis associated with intracellular bacterial infection. Presence of intracellular bacterial infection was confirmed by laboratory tests: direct immune fluorescent analysis and PCR. It was found that high prevalence of Сhlamydia trachomatis, Chlamydophila pneumoniae and Mycoplasma pneumoniae in patients with exacerbated chronic inflammatory pathology of paranasal sinuses. Comparing laboratory test data for patients with identified intracellular bacterial pathogens vs. those with negative results revealed a common trend in pathologic immune-related changes that fits to typical host anti-infection response manifested by inflammatory process. Besides, we described features of immune reactivity in patients with verified Chlamydia infection including more pronounced unbalance in Т cell immunity as well as evelated parameters of humoral immunity in patients with verified Chlamydia and Mycoplasma infection.

Russian Journal of Infection and Immunity. 2019;9(5-6):687-694
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Cellular immune response in convalescents from Ixodes tick-borne borreliosis

Zaporozhets T.S., Sokotun S.A., Simakova A.I., Persiyanova E.V.


Ixodes tick-borne borreliosis is a natural focal transmissive infectious multi-system disease featured with complex pathogenesis, which multiple aspects remain unclarified. The persistence stage during this infection associated with prolonged Borrelia presence in metastatic foci and repeated multiple dissemination is most complicated for clinical practice. It is assumed that the chronic process can be caused by an inadequate immune response associated with activated autoimmune mechanisms leading to emergence of permanent irreversible (degenerative and atrophic) changes in affected organs. Patients who experienced tick-borne borreliosis need dynamic observation for assessing disease prognosis providing a maintenance therapy. The purpose of the study was to evaluate an opportunity of using cellular immunity indices for predicting disease transition to a chronic course.

Materials and methods. The study was carried out at the Medical Association of the Far East Branch of the Russian Academy of Sciences. Case report form data, serum and blood plasma samples collected from 22 patients aged 29–83 years old were examined. Immunological examination data from patients with ixodes tick-borne borreliosis (12–18 months after the onset of acute period) were analyzed. Specific IgM and IgG against Borrelia burgdorferi were determined by using the OMNICS diagnostic test system (St. Petersburg). Lymphocyte immunophenotyping was performed on BD FACSCalibur flow cytometer (Becton Dickinson, USA) by using doublelabeled monoclonal antibodies (Beckman Coulter, France).

Results. A variability of activated peripheral blood lymphocytes was found in patients with tick-borne borreliosis evidencing about individual immune response. An imbalanced cellular immune response recorded in seronegative convalescents from tick-borne borreliosis, may be an indirect finding of ongoing Borrelia infection. Finding of specific serum IgG and IgM antibodies in convalescents at late stage coupled to impaired immune system is a warning sign presuming a risk to developing autoimmune reactions. Detection of specific IgM antibodies at late timepoint combined with increased immune cytotoxic potential may be referred to a marker of possible disease transition to chronic course.

Russian Journal of Infection and Immunity. 2019;9(5-6):695-702
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Diagnostic significance of intrathecally synthesized immunoglobulins against neurotropic viruses (MRZ-reaction) in diagnosis of multiple sclerosis

Moshnikova A.N., Maksimchuk V.K., Lapin S.V., Nazarov V.D., Surkova E.A., Novikov S.A., Makshakov G.S., Krutetskaya I.Y., Krasnov V.S., Kushnir Y.B., Neofidov N.A., Totolian N.A., Skoromets A.A., Evdoshenko E.P., Totolian A.A.


Multiple sclerosis is chronic demyelinating disease of the central nervous system with autoimmune inflammation and accretive neurodegeneration. One of the characteristics of autoimmune inflammation in multiple sclerosis is a polyspecific intrathecal humoral immune response against neurotropic viruses (Measles, Rubella and varicella Zoster) called MRZ-reaction. This immune response is based on polyclonal activation of mature B lymphocytes in the central nervous system and intrathecal synthesis of antibodies to anamnestic antigens unrelated to viral replication in the central nervous system as well as serum antibody release. Immunoglobulins produced against neurotropic viruses are an integral part of the oligoclonal antibody pool in the cerebrospinal fluid. Because immunoglobulins can penetrate the blood brain barrier, not only serum and cerebrospinal fluid specific antibody indices are calculated, but also blood-brain barrier antibody permeability (Qalbumin, QIgG) are taken into account to assess their intrathecal synthesis. The aim of the study was to assess the informative value of the intrathecal antibodies against neurotropic viruses (MRZ-reaction) in multiple sclerosis. There were enrolled 60 patients divided into 2 groups: group 1 — 35 patients diagnosed with multiple sclerosis, group 2 — 25 patients with inflammatory and non-inflammatory disоrders of the central nervous system. Paired cerebrospinal fluid and serum samples were collected from all patients to measure level of oligoclonal IgG, immunoglobulin free kappa and lambda light chains, IgG index and specific antibodies indices, followed by assessing magnitude of MRZ-reaction. We found that the MRZ-reaction was the most specific test to diagnose multiple sclerosis. Intrathecally produced antibodies against neurotropic viruses were detected in 3 of 35 multiple sclerosis patients with lacking oligoclonal IgG antibodies. In addition, a relationship between MRZ-reaction and degree of EDSS disability was found in MS patients: peak EDSS score was reported in patients with intrathecally synthesized antibodies against 3 viral agents, whereas the minimum EDSS score — among MRZ-negative patients. Thus, assessing MRZ-reaction seems rational for confirming MS diagnosis in case of other negative laboratory tests (oligoclonal immunoglobulins and free kappa/lambda light chains in cerebrospinal fluid) allowing to improves diagnostic accuracy and evaluation of MS severity.

Russian Journal of Infection and Immunity. 2019;9(5-6):703-712
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Dynamics in IgM and IgG antibodies against a polysaccharide capsule-containing complex of various S. pneumonia and H. influenza type b serotypes in children with chronic lung and bronchial inflammatory diseases after vaccination with “Pneumo-23” and “Act-HIB”

Korovkina E.S., Krakovskaya A.V., Kostinov M.P., Kozlov V.K., Jastrebova N.E., Magarshak O.O., Polishchuk V.B.


A lead place among pathogens resulting in pediatric chronic bronchopulmonary diseases is held by S. pneumoniae and Haemophilus influenzae. Vaccination against pneumococcal and hemophilic infections is approved and recommended for patients with chronic pathologies, but no clear recommendations for combined use of Pneumo-23 and Act-HIB vaccines in children with congenital pulmonary malformations and bronchial asthma were proposed.

Materials and methods. There were enrolled 92 children aged 0–17 years old with chronic bronchopulmonary diseases; 55 healthy children, and 57 unvaccinated children with chronic broncho-pulmonary pathology were included into control group. Mono- and combination vaccination by Pneumo-23 and/or Act-HIB was performed in remission period. IgM and IgG level against H. influenzae antigens, H. influenzae type b, to S. pneumoniae (serotypes 3, 6B, 9N, 23F) vaccine-specific polysaccharide as well as polysaccharide complex antigens were measured by using ELISA developed by us. Statistical processing was carried out by methods of descriptive, parametric and nonparametric statistics by using Statistica 5.0 software.

Results. Vaccination with Pneumo 23 was accompanied by IgG production against serotypes 3, 6, 9N, 23F-derived polysaccharide. A markedly increased anti-serotype 3 and 23F antibody level was observed 6 months after vaccination. Moreover, a significant increase in anti-polysaccharide 23F and anti-vaccine-derived polysaccharide IgM levels was found 1 month after the onset. In addition, anti-serotype 6B and 9N IgM antibodies were maintained 18 months after vaccination at high level, whereas it was significantly elevated against serotypes 3, 23F. Assessing an effectiveness of vaccine prophylaxis against Hemophilus type b infection, it was shown that a significantly increased anti-vaccine-derived polysaccharide IgM level was found 1, 6, 18 months after Act-HIB vaccination. In addition, IgG to the anti-H. influenzae type b polysaccharide tended to rise 1 month after the vaccination.

Summary. Children with chronic bronchopulmonary diseases vaccinated by Pneumo-23 and Act-HIB demonstrated activated adaptive immunity manifested by increased vaccine-derived antigen-specific IgM and IgG antibodies.

Russian Journal of Infection and Immunity. 2019;9(5-6):713-722
pages 713-722 views

Apoptosis- and survival-related gene mRNA profile in peripheral blood leukocytes in children with acute EBV infectious mononucleosis

Sakharnov N.A., Utkin O.V., Filatova E.N., Knyazev D.I., Presnyakova N.B.


Acute EBV-associated mononucleosis develops mainly in children and in patients with functionally impaired immune system. Consequently, it may result in developing secondary immunodeficiency, neoplasms as well as diverse alterations in cell-mediated immune reaction. Despite extensively examining molecular mechanisms of EBV infection, it is also necessary seek for new molecular and genetic factors underlying pathogenesis of EBV-mediated mononucleosis and EBV-associated malignant cell transformation is necessary, which might be used in clinical practice to monitor clinical score as well as predictive parameters for EBV-associated complications such as immunocompromised conditions and neoplasms. Here, we proposed to use our splicing sensitive DNA microarrays to perform a comprehensive semi-quantitative mRNA expression analysis for major apoptosis- and survival-related signaling components in peripheral blood leukocytes collected from children with acute EBV infectious mononucleosis as well as during recovery period. Using such DNA microchips allowed to assess both total (denoted by Σ) and separate transcript expression resulting from alternative splicing. It was shown that the balance of mRNA levels in acute phase of EBV-infectious mononucleosis was shifted towards upregulated expression of anti-apoptotic factors and components of of NF-κB-linked pro-survival signaling able to profoundly augment apoptosis resistance. Moreover, some EBV-associated changes (BIM/BCL2L11-Σ, PUMA/ BBC3-NM_001127241, BID-Σ, CASP3-Σ, NFKB1-Σ, RELA-Σ) were in agreement with the data published before. In addition, we also found previously unknown changes in level of EBV-associated coding and noncoding transcripts (DCR1/ TNFRSF10C-NM_003841, DR5/TNFRSF10B-NR_027140, CASP6 beta/CASP6-NM_032992, CASP7-NM_033338). Analyzing their properties allowed to suggest that they play an important role in the pathogenesis of EBV-associated mononucleosis. However, at asymptomatic recovery stage, level of some mRNA expression was kept altered compared to healthy volunteers (DCR2/TNFRSF10D-NM_003840, CASP8-Σ, CASP3-Σ, BIM/BCL2L11-Σ, BCL2-NM_000633, MCL1-Σ, BCL-W/BCL2L2-Σ, BCL-XL/BCL2L1-NM_138578, BIRC2-NM_001166, XIAP-NM_001167, TRAF2-NM_021138, MAP3K14-Σ, NFKB1-Σ), which may point at postponed EBV-associated molecular consequences. On one hand, such changes may be due to long-lasting anti-EBV immune response, whereas, on the other hand, they might be influenced by EBV-associated factors facilitating virus persistence. Overall, we identified the molecular features predisposing to chronic course of EBV-infection. The data obtained further expand our understanding about the molecular pathogenetic mechanisms for EBV infectious mononucleosis.

Russian Journal of Infection and Immunity. 2019;9(5-6):723-734
pages 723-734 views

Parameters of mineral metabolism and bone density in young males with Helicobacter pylori-associated chronic gastritis

Drygina L.B., Dorofeytchik-Drygina N.A.


Here we present the current data on the chronic gastritis prevalence in young people. An issue regarding involvement of Helicobacter pylori infection in formation of low bone density is discussed. Examining the features of bone tissue metabolism in infection-associated chronic gastritis to optimize diagnostic algorithm was shown to be of high significance. In the study there were enrolled 200 employees working at the EMERCOM of Russia, who suffered from the acid-dependent gastric diseases and risk factors for reducing bone mineral density. Depending on the bone mineral density parameters, examining functional activity of the gastric mucosa, verification of the H. pylori infection, examining parameters of mineral metabolism, vitamin D level, parathyroid hormone, bone tissue remodeling markers was performed. It was shown that atrophic changes in the gastric mucosa the played a lead role in developing low bone mineral density.

Russian Journal of Infection and Immunity. 2019;9(5-6):735-742
pages 735-742 views

A screening for serum markers of arbovirus infections in healthy blood donors from the Volgograd Region

Negodenkoa A.О., Luchinin D.N., Konovalov P.S., Pavlyukova O.A., Skrynnikova E.A., Prilepskaya D.R., Molchanova E.V., Barkova I.A., Viktorov D.V., Toporkov A.V.


Volgograd region is considered to be endemic West Nile fever (WNF) area due to the established circulation of the West Nile virus (WNV) therein. Some previous independent studies examining samples collected on the territory of the Volgograd region revealed markers related to the California serogroup (CSG), Sindbis and Ukuniemi viruses. WNF, CSG, Sindbis and Ukuniemi fever mainly being asymptomatic posing thereby a threat of virus spread due to transfusiological manipulations along with vector-borne transmission are manifested by diverse clinical signs. The study was aimed at detection of antibodies specific to West Nile, tick-borne encephalitis, California serogroup (Tyaginya, Inko), Sidbis, and Ukuniemi viruses in blood donors from the Volgograd region. For this, 404 blood sera samples collected from blood donors residing in the Volgograd as well as the Volgograd region were examined by ELISA. It was found that percentage of blood serum samples positive for arbovirus-specific antibodies was 18.32%. Among the, 67 out of 404 (16.58%) samples contained anti-WNV antibodies, 3 out of 279 (1.08%) samples — to tick-borne encephalitis virus, 1 out of 92 (1.09%) — to California serogroup fever and Ukuniemi viruses, and 2 out of 92 (2.17%) — to Sindbis fever virus. Importantly, the peak number of IgG and IgM WNV-positive samples was found among residents of Volgograd (29 out of 110, 26%) and Oktyabrsky district (7 out of 25, 28%). In addition, anti-Sindbis, Ukuniemi and CSG virus antibodies were detected in blood serum samples from blood donors residing in the Kalachevsky region and the city of Volgograd. Analyzing age-related distribution and percentage of seropositive subjects in each age group showed as follows: the lowest percentage (14.5%) was positive for anti-WNV, Sindbis, Ukuniemi and CSG virus antibodies in blood donors aged 32–41 years, whereas the peak percentage (25%) — in the subjects aged 52–61 years. Thus, virus specific antibodies detected in healthy individuals in the aforementioned region evidence about potential recovery after asymptomatic infections. In this regard, further research is required to determine a role of the such arboviruses in the structure of regional infectious diseases. The data obtained suggest a need to continue serological arbovirus monitoring in the Volgograd region.

Russian Journal of Infection and Immunity. 2019;9(5-6):743-749
pages 743-749 views

Biological microchip for assessing tetracycline-resistance in Neisseria gonorrhoeae clinical isolates in Russian Federation

Dementieva E.I., Shaskolskiy B.L., Leinsoo A.T., Gryadunov D.A., Petrova N.P., Chestkov A.V., Kubanov A.A., Deryabin D.G.


A total of 399 Neisseria gonorrhoeae clinical isolates collected in different regions of the Russian Federation in 20152017 were analyzed for tetracycline susceptibility and genetic markers of resistance. Drug susceptibility testing was performed by serial dilution method in agar and minimum inhibitory concentration (MIC) was measured according to the Russian “Guidelines for microbial susceptibility testing for antibacterial agents No. 4.2.1890-04”. Tetracycline resistance determinants were studied by using hydrogel microarray with immobilized oligonucleotide probes able to identify a series of chromosomal mutations and detect plasmid tetM gene. Different resistance determinants were found in 193 isolates (48.4%). Mutation in codon 57 in the rpsJ gene (41.2%) was most common that decreases tetracycline affinity to ribosome 30S subunit, mainly due to Val57Met substitution both as a point mutation as well as in combination with others. Mutations in the rpsJ gene were found in strains with the intermediate tetracycline susceptibility. Mutations in the porB gene (lower tetracycline influx) held the se cond place in prevalence pattern (23.1%); the Gly120Lys substitution usually led to emergence of tetracycline resistance either as a point mutation or in combination with other substitutions. Substitutions of Gly120 for other residues (Asp, Asn, and Thr) and Ala121 for Asp, Asn, and Gly had much less effect on resistance level. The –35 delA deletion in the promoter region of mtrR gene (increased expression of MtrC-MtrD-MtrE efflux pump) was observed in 11.3% strains. The tetM gene was found in 27 strains including 17 American and 10 Dutch type tetM determinants. Evolutionary tree was constructed for the tetM genes with the estimation of their homology with similar genes in genera Streptococcus, Enterococcus and Mycoplasma. Mutations in chromosomal genes resulted in increase of tetracycline MIC up to 2–4 mg/L; 4 mg/L MIC was observed in case of simultaneous presence of several mutations. Strains bearing tetM gene-containing plasmid showed extremely high resistance level: MIC ≥ 8 mg/L (64 mg/L for the two samples). Thus, long-lasting withdrawal of tetracycline use for treatment of gonococcal infections in Russia (since 2003) resulted in decreased percentage of resistant strains (including strains with intermediate susceptibility) from 75% down to 45.4%. However, currently tetracycline resistance in Russia remains elevated that is explained by the presence of different resistance determinants in the half of isolates under study.

Russian Journal of Infection and Immunity. 2019;9(5-6):750-762
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Microneutralization reaction compared to hemagglutination inhibition assay to evaluate immunogenicity of influenza vaccines and influenza diagnostics

Krivitskaya V.Z., Kuznecova E.V., Majorova V.G., Kadyrova R.A., Lvov N.I., Go A.A., Sominina A.A.


The aim of this study was to compare the results of the hemagglutination inhibition test (HI-test) and microneutralization reaction in detection of antibodies to influenza A(H1N1), A(H1N1)pdm09, and A(H3N2) viruses in human sera, as well optimize microneutralization reaction conditions. The proposed variant of microneutralization reaction is based on detecting decreased influenza virus reproduction in infected MDCK cells in the presence of virus-specific serum antibodies. Virus reproduction was evaluated by enzyme-linked immunosorbent assay in 96-well cell culture plates using type-specific anti-influenza A viruse NP-protein monoclonal antibodies. In parallel, in microneutralization reaction and HI-test paired sera collected from 205 volunteers inoculated with inactivated seasonal influenza vaccines were analyzed, as well as from 117 adult patients with laboratory-confirmed influenza. The rationale for treatment of human serum with receptor-destroying enzyme (RDE) was proved not only for HI-test, but also for microneutralization reaction. Compared to HI-assay, the microneutralization reaction displayed higher sensitivity. According to microneutralization data, seroconversion rates and increase in antibody titer against influenza A viruses in both vaccinated and infected persons were superior to HI-test data by 1.4–2.5-fold. Moreover, higher sensitivity of this method was of great importance for the diagnostics of disease caused by new pathogens. The efficacy of influenza A(H1N1)pdm09 serodiagnostics in PCRpositive patients was 1.5 times higher based on microneutralization reaction vs. HI-assay data. According to the data from early studies, it is commonly believed that 1/40 titer of flu-specific antibodies detected by HI-test is set as protective. However, a consensus on protective level for virus-specific antibodies in neutralization reaction has not been established yet. It was found that serum antibody levels detected by the proposed version of microneutralization reaction were significantly higher than those in HI-assay. In the post vaccination sera collected from vaccinated volunteers, average titers of virus neutralizing antibodies corresponding to 1/40 in HI-test were 1/195, 1/203, and 1/ 426–1/430 for influenza A(H1N1), A(H1N1)pdm09 and A(H3N2), respectively, whereas in influenza patients they were 1/285, 1/215 and 1/488, respectively. Thus, it was suggested to consider a threshold value for “conditionally protective” level of neutralizing antibodies in adult vaccinated volunteers or infected patients, an average titer 1/160 for A(H1N1) and A(H1N1)pdm09 viruses, as well as 1/320 — for A(H3N2) virus, which agree with data published elsewhere.

Russian Journal of Infection and Immunity. 2019;9(5-6):763-772
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Next-generation sequencing of drug resistant Mycobacterium tuberculosis clinical isolates in low-incidence countries

Sodja E., Toplak N., Koren S., Kovač M., Truden S., Žolni-Dovč M.


Drug resistant tuberculosis (TB), especially multidrug (MDR) and extensively drug-resistant (XDR) TB, is still a serious problem in global TB control. Slovenia and North Macedonia are low-incidence countries with TB incidence rates of 5.4 and 10.4 in 2017, respectively. In both countries, the percentage of drug resistant TB is very low with sporadic cases of MDR-TB. However, global burden of drug-resistant TB continues to increase imposing huge impact on public health systems and strongly stimulating the detection of gene variants related with drug resistance in TB. Next-generation sequencing (NGS) can provide comprehensive analysis of gene variants linked to drug resistance in Mycobacterium tuberculosis. Therefore, the aim of our study was to examine the feasibility of a full-length gene analysis for the drug resistance related genes (inhA, katG, rpoB, embB) using Ion Torrent technology and to compare the NGS results with those obtained from conventional phenotypic drug susceptibility testing (DST) in TB isolates. Between 1996 and 2017, we retrospectively selected 56 TB strains from our National mycobacterial culture collection. Of those, 33 TB isolates from Slovenian patients were isolated from various clinical samples and subjected to phenotypic DST testing in Laboratory for Mycobacteria (University Clinic Golnik, Slovenia). The remaining 23 TB isolates were isolated from Macedonian patients and sent to our laboratory for assistance in phenotypic DST testing. TB strains included were either mono-, poly- or multidrug resistant. For control purposes, we also randomly selected five TB strains susceptible to first-line anti-TB drugs. High concordance between genetic (Ion Torrent technology) and standard phenotypic DST testing for isoniazid, rifampicin and ethambutol was observed, with percent of agreement of 77%, 93.4% and 93.3%, sensitivities of 68.2%, 100% and 100%, and specificities of 100%, 80% and 88.2%, respectively. In conclusion, the genotypic DST using Ion Torrent semiconductor NGS successfully predicted drug resistance with significant shortening of time needed to obtain the resistance profiles from several weeks to just a few days.

Russian Journal of Infection and Immunity. 2019;9(5-6):773-778
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Surveying children and adult vaccination program against diphtheria, tetanus, measles and viral hepatitis B in the Russian Federation

Galina N.P., Mindlina A.Y., Polibin R.V.


Over the last years, incidence of vaccine-preventable infections tended to increase both in Russia and multiple European countries due to diverse reasons, including loss of alertness in medical workers to ensure proper quality of immunization. Currently, vaccination is considered to be the most efficient means for preventing infectious diseases. However, vaccination efficacy is directly related to population coverage and proper timeframe for its application.

Materials and methods. Diphtheria, tetanus, measles and hepatitis B vaccination coverage and timeframe were analyzed for population of Russia, Moscow as well as the three pediatric and adult out-patient hospitals.

Results. It was found that compared to adults, pediatric subjects were vaccinated better. However, in case of 95% or higher coverage against all infections, shortcomings in vaccination timeframe were uncovered. In 2017, despite pediatric subjects should be vaccinated against diphtheria and tetanus at the age of 3-to-6 months, coverage was as low as 46.9% in Russia, 48.7% in Moscow that ranged in some polyclinics from 21.8% in 2012 down to 1.7% in 2017. Moreover, this situation was even more unfavorable in case of revaccination program. In particular, it was found that at the age of 18 months only 50, 54, and 49–55% underwent revaccination in the Russia, Moscow 54%, and some out-patient hospitals, whereas at the age of 7–14 years in Russia there were revaccinated up to 97% population. Likewise, at the age of 6 months there were covered with vaccination against hepatitis B as few as 49% population in Russia and Moscow, whereas more than 90% coverage was achieved only at the age of 1 year. Immunization coverage reaching more than 85% of adult population against hepatitis B is superior to diphtheria and tetanus. Immunization coverage against measles in Russia at all age groups was over 90% population. Thus, it is necessary to optimize activities on adhering to vaccination timeframe, as decline in quality of vaccination inevitably leads to elevated incidence rate of vaccine-preventable infections. This and vaccination coverage might be adjusted by introducing a Preventive Vaccination Surveillance and Reporting Automated System in the Russian Federation.

Russian Journal of Infection and Immunity. 2019;9(5-6):779-786
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Analysis of medical and social factors affecting the formation and course of co-infection HIV, tuberculosis and viral hepatitis

Azovtseva O.V., Panteleev A.M., Кarpov А.V., Arkhipov G.S., Veber V.R., Belyakov N.A., Arkhipova E.I.


Currently, HIV infection is characterized by emergence of its severe and comorbid forms. Mid-1990 HIV epidemics was expanded due to injection drug users who brought viral hepatitis C to the cohort. Along with developing immunosuppression, opportunistic and AIDS-defining diseases, including tuberculosis emerged. Various combinations of coinfections (HIV infection+tuberculosis±viral hepatitis) affect clinical manifestations and clinical score, reduce the therapeutic efficacy and worsen disease prognosis.

Objective: to study an impact medical and social factors on course of TB-co-infection associated with immunosuppression related to HIV infection and viral hepatitis.

Materials and methods. Comorbid cases (HIV infection, tuberculosis and chronic hepatitis) dominated by verified TB-infection (n = 137) were analyzed.

Results. It was shown that socially maladapted young people with previous experience of intravenous drug and alcohol abuse dominated among subjects with co-infections, half of which were held in penal institutions. More-over, the mean CD4 lymphocyte level in generalized tuberculosis was significantly lower than in patients with significantly reaching 164±21.5 cells. In addition, lung-specific lesions were observed in 73.4% of patients with generalized tuberculosis that developed by initial targeting of the lymphoid system followed by affecting other organs, mainly the central nervous system, urinary system and abdominal organs. Introduction of antiretroviral drugs to anti-TB therapy reduced mortality rate by 8 times. Viral hepatitis was the most common concomitant disease found in co-infected patients, with dominating viral hepatitis C both as a mono-infection (86.8%) as well as in combination with viral hepatitis B (9.43%). In addition, co-morbid viral hepatitis resulted in progression of TB infection affected due to intra-thoracic lymph nodes being involved in tuberculosis process as well as development of opportunistic diseases due to a markedly decreased CD4 cell count. Analysis of potentially aggravating risk factors for developing hepatotoxicity (viral hepatitis, combined treatment with anti-TB and anti-retroviral drugs) did not reveal their any additional negative impact on hepatic functions. Thus, use of a combination therapy with anti-TB and anti-retroviral drugs in co-infected patients was shown to be safe and not accompanied by a high rate of hepatotoxic reactions.

Russian Journal of Infection and Immunity. 2019;9(5-6):787-799
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Importance of Epstein–Barr virus infection in pathogenesis of proliferative complications in children with endogenous uveitis

Petrovskaya M.S., Krichevskaya G.I., Denisova E.V., Katargina L.A., Kulikova I.G.


Endogenous uveitis (EU) in children is a multifactorial sight-threatening disease that reduces patient’s quality of life. Proliferative syndrome (PS) coupled to developing adhesions, opacity of vitreous body, epiretinal and preretinal membranes is one of the most serious EU complications, with yet-unknown pathogenesis. Among the numerous trigger factors, a role for infections, particularly human herpes group-driven, is proposed. The goal of the study was to assess a potential role of Herpes simplex viruses type 1 (HSV-1), Herpes simplex viruses type 2 (HSV-2), Epstein–Barr virus (EBV) and Cytomegalovirus (CMV) played in the PS pathogenesis in children with endogenous uveitis. 112 patients aged 3–17 years (mean age 10 years) with (93 patients)/without PS (19 children) were examined. IgM and IgG antibodies (markers of chronic and active infection) against HSV-1/2, EBV and CMV were detected by ELISA. A significantly increased PS rate in infected vs. uninfected children was revealed solely for EBV infection (p = 0.03), but not for HSV-1/2 (p > 0.05) or CMV-positive patients (p > 0.05). However, PS emergence in EBV-negative patients also suggests that some factors might contribute to proliferation in intraocular inflammation. In addition, level of serum IL-8 and IL-6 were assessed by multiplex analysis in 28 children. It was found that IL-8 was detected in all patients, with great individual fluctuations (5.6–2743 pg/ml). Enhanced systemic IL-8 level tended to rise in patients with more prominent proliferation and serological markers of EBV reactivation. However, serum IL-6 was detected by about 2-fold less often reaching up to 55% cases (variation of individual indices 1.3–35.5 pg/ml). A correlation between PS severity, EBV infection activity and systemic IL-6 level was not observed. Further studies evaluating a role of EBV infection in PS pathogenesis pediatric endogenous uveitis are necessary, as it may underlie a rationale for including antiherpetic drugs into a combination therapy.

Russian Journal of Infection and Immunity. 2019;9(5-6):800-804
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State of rat colon microbiocenosis in chronic restraint stress treated with Selank

Mukhina A.Y., Medvedeva O.A., Svishcheva M.V., Shevchenko A.V., Efremova N.N., Bobyntsev I.I., Kalutsky P.V., Andreeva L.A., Myasoedov N.F.


It is currently accepted that stress significantly affects composition of microbiocenosis due to changes in permeability of intestinal barrier and pro-inflammatory effects. This, in turn, changes behavioral reactions, anxiety and stress response. In this regard, it seems promising to use regulatory peptide-based neurotropic drugs including Selank to correct stress-induced dysbiosis. Our study was aimed at assessing state of rat colon microbiocenosis in modelled chronic restraint stress and treated with Selankby using 65 Wistar male rats divided into five groups (per 13 rats in each): group 1 — rats injected with saline; group 2 — injected with saline and induced chronic restraint stress; group 3–5 — administered with Selank at dose of 80 μg/kg, 250 μg/kg and 750 μg/kg body weight, respectively, and induced chronic restraint stress. Quantitative and qualitative study of animal colon microbiota was carried out according to the method by L.I. Kafarskaja and V.M. Korshunov. Identification of microorganisms was carried out by using a Maldi Biotyper Microflex mass spectrometer (Bruker, United States). Microbial species-specific composition was presented as lg CFU/g mass of examined sample. For each identified microbial genus, the relative mean and frequency of occurrence were calculated. Statistical significance of differences in mean values was determined by using Student’s t-test. Chronic restraint stress in the experiment did not result in affecting dominant microbiota species in rat colon nor reduce their frequency, however, it significantly influenced examined parameters for commensal microbiota disturbing pattern of pathogenic bacterial strains. Use of Selank led to the reversing changes in composition of colonic microbiocenosis caused by stress model. Moreover, magnitude of parameters examined in experiment after applying Selank at dose of 750 μg/kg reached those in non-stressed animals. Thus, effects related to Selank administration may presumably be mediated due to both central and peripheral effects including immunotropic and anti-inflammatory activities which contributed to restoring colon microbiocenosis composition in stress model.

Russian Journal of Infection and Immunity. 2019;9(5-6):805-810
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Abundance of Ixodes persulcatus ticks in Komi Republic as a function of an air temperature

Tronin A.A., Tokarevich N.K., Gnativ B.R.


The sharp rising incidence of tick-borne encephalitis (TBE) in Komi Republic at the North-east of European Russia was recorded last decades. Tick-bite incidence also was grown. Rapid rise of TBE incidence growth and Ixodidae ticks depends on a number of factors, and the impact of climate change being one of them. Ixodes persulcatus ticks is considered as a main vector of TBE in Komi. Our objective is to estimate the influence of air temperature change on the tickbite incidence and Ixodes persulcatus population in Komi. Komi Republic is located near the Polar circle where the northern frontier of Ixodes persulcatus ticks situated and we expected the growth of tick’s population. The number of Komi inhabitants seeking medical care after tick bites in 1992–2014 was considered. Gridded monthly air temperature data with grid size 0.5 degree were recalculated to temperature referred to Komi administrative units. The time series of annual number of tick victims from 1992 till 2014 and model air temperature from 1948 till 2016 for all Komi administrative units were compiled. We analyzed the data on tick-bite incidence in Komi administrative units in relation to changes in local annual average air temperature within the study area. The linear dependence of the tick-bite incidence on air temperature was established when of the tick-bite incidence is represented in logarithm form. The tick population depends not only on temperature but humidity, landcover and hosts. Described areas of Komi belong to humid climate, where precipitations exceed evaporation. Most of the Komi territory is covered by taiga with underwood, grass and bush. Hosts of the first and the major levels are represented by birds and rodents. The dependence of tick-bite incidence and temperature looks like “Malthus’s law”, but the development of population depends on temperature not on time. The exponential growth in the nearest future will ceased and the population will proceed to stable phase. Ticks population in Komi Republic is moving to the North and the air temperature determines the dynamics of population.

Russian Journal of Infection and Immunity. 2019;9(5-6):811-816
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For the Anniversary of Professor Aleksandr A. Smorodincev


Russian Journal of Infection and Immunity. 2019;9(5-6):817-818
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Instructions to Authors


Russian Journal of Infection and Immunity. 2019;9(5-6):819-821
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Author index


Russian Journal of Infection and Immunity. 2019;9(5-6):822
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Subject index


Russian Journal of Infection and Immunity. 2019;9(5-6):822
pages 822 views

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