Vol 9, No 3-4 (2019)

REVIEW ARTICLES

General characteristics and clinical significance of Nocardia and Gordonia genera

Lyamin A.V., Zhestkov A.V., Nikitina T.R., Podsevalov V.S., Trofimov A.R., Ismatullin D.D.

Abstract

Over the last years, an increasing attention in modern medical microbiology has been paid to examining Actinomycetaceae, Corynebacteriaceae, Mycobacteriaceae, Nocardiaceae, Gordoniaceae sps. Members of the Mycobacteriaceae family are increasingly examined in research and real-life practice, whereas bacteria belonging to families such as Nocardiaceae and Gordoniaceae remain poorly investigated despite novel methods emerging in practical microbiology that allow to more accurately identify microorganisms. According to the current classification, the genus Nocardia includes over 80 species, most of which rarely result in human disease development. Most often, members of the genus Nocardia cause lesions in bronchopulmonary system, which, however, may also cause development of pathological processes in other anatomical sites. Likewise, members of the genus Gordonia may also trigger infectious lesions in human, which were previously often incorrectly identified as other actinomycetes or mycobacteria. Owing to use of 16S rRNA sequencing, it substantially improved identification of these bacteria. Currently, an increasing number of microorganisms with potential clinical significance has been recorded. In addition, similar to nocardiosis, diverse primary and secondary immunodeficiencies play a primary role in gordonii-associated development of pathological processes. However, an additional risk factor may be represented by pathological conditions associated with ingestion of foreign bodies colonized by such microorganisms. Most often, members the genus Nocardia cause lesions in the bronchopulmonary system able, however, affect other anatomical areas. Half of all cases of pulmonary nocardiosis are accompanied by pathological processes of extrapulmonary localization, whereas as low as 20% of patients manifest with extrapulmonary form of the disease usually occurring when the pathogen spreads hematogenously or via other routes also highlighted by primary pulmonary lesion. Moreover, members of the genus Gordonia may result in similar infectious lesions. Currently, the number of aerobic actinomycetes of potential clinical significance is increasing that may be due to their role in diverse pathological processes of various etiologies, which have been more often reported in scientific publications. Few reports regarding infections caused by the genus Gordonia ara available which may be due to a paucity of microorganisms isolated from clinical material or false identification as mycobacteria or Nocardia. Similar to nocardiosis, diverse immunodeficiencies play a primary role in the development of pathological processes associated with Gordonia. However, an additional risk factor may be linked to pathological conditions associated with the ingestion of foreign bodies colonized by these microorganisms. Available publications allows to underline etiological significance of Gordonia in development of cholecystitis, granulomatous skin lesions, eyelid abscess of other soft tissues, granulomatous mastitis, brain abscess and meningitis, as well as external otitis, bronchitis, endocarditis and mediastinitis. In addition, all these microorganisms can cause bacteremia associated with use of a central venous catheter. Owing to emergence of new detection methods as well as elevated rate of immunocompromised patients, and subsequently increased amount of new cases caused by members of the Nocardiaceae and Gordoniaceae families, an interest they rise will grow progressively.
Russian Journal of Infection and Immunity. 2019;9(3-4):429-436
pages 429-436 views

Yersinia pseudotuberculosis-derived adhesins

Byvalov A.A., Konyshev I.V.

Abstract

Around fifteen surface components referred to adhesins have been identified in Yersinia pseudotuberculosis combining primarily microbiological, molecular and genetic, as well as immunochemical and biophysical methods. Y. pseudotuberculosis-derived adhesins vary in structure and chemical composition but they are mainly presented by protein molecules. Some of them were shown to participate not only in adhesive but in other pathogen-related physiological functions in the host-parasite interplay. Adhesins can mediate bacterial adhesion to eukaryotic cell either directly or via the extracellular matrix components. These adhesion molecules are encoded by chromosomal DNA excepting YadA protein which gene is located in the calcium-dependence plasmid pYV common for pathogenic yersisniae. An optimum temperature for adhesin biosynthesis is located close to the body temperature of warm-blooded animals; however, at low temperature only invasin InvA, full-length smooth lipopolysaccharide and porin OmpF are produced in Y. pseudotuberculosis. Several adhesins (Psa, InvA) can be expressed at low pH (corresponds to intracellular content), thereby defining pathogenic yersiniae as facultative intracellular parasites. Three human Yersinia genus pathogens differ by ability to produce adhesins. Y. pseudotuberculosis adherence to host cells or extracellular matrix components is determined by a cumulative adhesion-based activity, which expression depends on chemical composition and physicochemical environmental conditions. It’s proposed that at the initial stage of infectious process adherence of Y. pseudotuberculosis to intestinal epithelium is mediated by InvA protein and “smooth” LPS form. These adhesins are produced in bacterial cells at low (lower than 30°С) temperature occurring in environment from which a pathogen invades into the host. At later stages of pathogenesis, after penetrating through intestinal epithelium, bacterial cells produce other adhesins, which promote survival and dissemination primarily into the mesenteric lymph nodes and, possibly, liver and spleen. At later stages of pathogenesis, after penetrating through intestinal epithelium, bacterial cells produce other adhesins, which promote survival and dissemination primarily into the mesenteric lymph nodes and, perhaps, liver and spleen. Qualitative and quantitative spectrum of Y. pseudotuberculosis adhesins is determined by environmental parameters (intercellular space, intracellular content within the diverse eukaryotic cells).
Russian Journal of Infection and Immunity. 2019;9(3-4):437-448
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Implementation of the program of measles elimination in the WHO African region

Camara J..., Antipova A.Y., Bichurina M.A., Zarubaev V.V., Magassouba N..., Lavrentieva I.N.

Abstract

The review is devoted to the analysis of the available literature on the elimination of measles. The review focuses on the current measles epidemic situation in the African Region (AFR) and the implementation of the WHO strategic plan for the elimination of measles in AFR by 2020. Measles in the AFR is characterized by a severe course with a high risk of death due to malnutrition, vitamin A deficiency, concomitant bacterial and viral infections, and malaria. In 2015, 105,256 cases of measles were reported in the WHO African Region, most of them among children under 5 years old, 79% of whom were not vaccinated or had unknown vaccine status. Initially, the strategy for implementing the measles elimination program in AFRs was based on a combination of immunization campaigns for children under 14 years of age (coverage of more than 90%) and routine vaccination of at least 90% of children aged 9–15 months. It was recommended to repeat the campaign of mass immunization of children aged 9 months up to 4 years every 3–5 years. The use of this strategy has reduced the number of measles cases by 83–97% during the first year of additional immunization programs. The recommended age of routine measles vaccination in AFRs is 9 months — a strategy to reduce infant mortality, including that due to complications of measles. In 2016, measles vaccination was introduced into the national immunization schedule in all AFR countries, and 24 countries introduced revaccination. Currently, the measles elimination program in a number of AFR countries is based on two-dose immunization (MCV1 and MCV2). The measles prevention program in a number of AFR countries was disrupted due to the Ebola epidemic. There are some common problems in the realization of the program in AFR countries. All AFR countries are committed to the measles elimination program. The review provides information on strategies and successes in overcoming challenges to achieve the goals set for the WHO African Region in the implementation of the programme of measles elimination.
Russian Journal of Infection and Immunity. 2019;9(3-4):449-456
pages 449-456 views

Anti-Helicobacter pylori vaccine: mith or reality?

Uspenskiy Y.P., Baryshnikova N.V., Ermolenko E.I., Suvorov A.N., Svarval A.V.

Abstract

Here we review the data on the current studies aimed at developing anti-Helicobacter pylori vaccines. Unfortunately, no vaccines recommended for use in human are available now, despite a more than 30-year history of their development and a great body of evidence on vaccine efficiency in animals. Mechanisms underlying vaccine-related effects in animals and human are poorly determined and expect to be further clarified. Moreover, side effects related to vaccines have not investigated in detail. A long-lasting stay of H. pylori in the gastric lumen restricts potential protective effects of host cellular immunity (an effect is mainly associated with antibodies and antimicrobial peptides), that results in low efficacy of systemic immunization and weak immune response. In addition, further complications in developing natural and artificial (vaccination) immune response may be due to the high pathogen variability and low immunogenicity of related antigens. A choice of antigen is crucial upon generating any vaccine. The data on the main pathogen-derived antigens is of high importance while generating both mono- and multicomponent H. pylori vaccines. A number of various antigens was proposed for immunization against H. pylori, some of which are involved in the pathogenetic mechanisms of Helicobacter pylori infection: VacA, CagA, NapA, BabA, SabA and urease. Such vaccines turned out to be efficient in preventing experimental infection in animals. The use of purified microbial antigens successfully induces protective mechanisms to fight against infection, as demonstrated in animal studies (preventive and therapeutic protocols). Compared to using a single antigen, an association of two or three antigens can trigger stronger immune response. Currently, bacterial urease is considered as the most promising candidate antigen, which has been proved to be a valuable a vaccine antigen in numerous studies with mice, ferrets and primates. It remains unclear which route of administration for Helicobacter pylori vaccine would be superior compared to the remainder. Comparing various routes of vaccine administration demonstrated that that mice immunized intranasally and intrarectally resulted in markedly higher protection against Helicobacter pylori infection compared to oral vaccination. Development of H. pylori vaccine faced substantial obstacles due to the pathophysiological, immunological and technological challenges noted above, still remaining an issue so far. At present, a promising approach in advancing H. pylori vaccines is based on using mucosal adjuvants and generation of recombinant probiotics expressing H. pylori-derived antigens for triggering specific immune response upon vaccination.

Russian Journal of Infection and Immunity. 2019;9(3-4):457-466
pages 457-466 views

Enterovirus infection in the Socialist Republic of Vietnam

Golitsyna L.N., Nguyen T.T., Romanenkova N.I., Luong M.T., Vu L.T., Kanaeva O.I., Bichurina M.A., Novikova N.A.

Abstract

Human enterovirus infections comprise a group of infectious diseases caused by viruses of Enterovirus A-D species (genus Enterovirus, family Picornaviridae). Enterovirus infections can vary in clinical manifestations and severity, from asymptomatic infection to serious multisystem diseases. During evolution, enterovirus strains with increased neurovirulence or atypical pathogenicity may emerge exhibiting an epidemic potential. Recently, outbreaks of enterovirus infection with an increased rate of neurological manifestations, a significant percentage of severe cases and lethal outcomes have been observed worldwide, which were associated with enteroviruses EV-A71, EV-D68 etc. The World Health Organization has included EV-A71 and EV-D68 enterovirus infection together with some other dangerous viral diseases considered for inclusion in the List of Blueprint Priority Diseases. In connection with this, global enterovirus surveillance is important for controlling emergence and spread of epidemic enterovirus variants, prediction of establishing epidemic situation, timely conduction of preventive measures and vaccine development. A growing multi-field cooperation between Russia and Vietnam leads to increased two-way population migration, which actualizes scientific and practical collaboration in surveillance and control of infectious disease spread, including enterovirus infection. Currently, epidemiological surveillance of enterovirus infection in Vietnam is based on monitoring hand, foot and mouth disease (HFMD) rate, laboratory diagnostics of enterovirus infection and identification of enterovirus strains, mainly detected in severe patients. In 2001–2016, 34 non-polio virus types were identified in patients with enterovirus infection, largely represented by viruses EV-A71, CVA6, CVA10, and CVA16. Moreover, the peak incidence of enterovirus infection and related mortality rate were associated with the increased activity of EV-A71 virus. In Vietnam, EVA71 enterovirus of genotypes C1, C4, C5 and B5 circulated at different times. Over the last years, a new pandemic genotype virus CVA6 has been dominating as a causative agent of enterovirus infection in Vietnam as well as the majority of other countries. The data on phylogenetic relation between Vietnamese epidemic EV-A71 and CVA6 strains allowed to find that they underwent multiple betweencountry spreads, whereas their subsequent in-country dissemination resulted in 2011–2012 enterovirus outbreak and sustained high-level HFMD morbidity.

Russian Journal of Infection and Immunity. 2019;9(3-4):467-475
pages 467-475 views

ORIGINAL ARTICLES

Suppression of hepatitis b virus by a combined activity of CRISPR/Cas9 and HBx proteins

Brezgin S.A., Kostyusheva A.P., Simirsky V.N., Volchkova E.V., Chistyakov D.S., Kostyushev D.S., Chulanov V.P.

Abstract

Chronic hepatitis B is a severe liver disease associated with persistent infection with hepatitis B virus. According to recent estimations, 250 million people in the world are chronically infected, including 3 million chronically infected people in Russia. Antiviral therapeutics (nucleos(t)ide analogues and PEGylated interferon) suppress viral transcription and replication, but do not eliminate the virus from infected cells. The key reason for HBV persistency is a stable form of the viral genome (covalently closed circular DNA, cccDNA) that exists as a minichromosome protected from novel cccDNA-targeting therapeutics. Novel therapeutic approaches aimed at elimination or inactivation of cccDNA are urgently needed. CRISPR/Cas9 systems induce double strand breaks in target sites of DNA sequences. Experiments with CRISPR/Cas9 demonstrated high antiviral activity and efficient cleavage of cccDNA, but a small part of cccDNA pool remains intact. One of the main reasons of incomplete cccDNA elimination might be the structural organization of cccDNA, which persists in a heterochromatinized, very compacted form and is not be accessible to CRISPR/Cas9 systems. Viral protein HBx unwinds cccDNA and regulates cccDNA epigenetically by recruiting transcription-remodeling factors. In this work, we analyzed effects of CRISPR/Cas9 in combination with an HBxencoding plasmid or plasmids encoding mutant forms of HBx (HBxMut, which does not interact with pro-apoptotic factors Bcl-2 и Bcl-xL, and HBxNesm is localized exclusively in the nucleus and does not generate reactive oxygen species and double strand breaks in the genome). We showed that HBx improves CRISPR/Cas9 efficiency, decreasing pregenomic RNA transcription level over 98%. Moreover, we analyzed optimal ratios of plasmids encoding CRISPR/ Cas9 and HBx proteins for better antiviral efficacy. Furthermore, we discovered that HBx proteins do not have an effect on proliferation and viability of the transfected cells. In conclusion, CRISPR/Cas9 with HBx proteins exhibit high antiviral effect.
Russian Journal of Infection and Immunity. 2019;9(3-4):476-484
pages 476-484 views

Features of immune response against influenza infection in animals vaccinated with recombinant cross-protective vaccine

Tsybalova L.M., Stepanova L.A., Korotkov A.V., Shuklina M.A., Zaitseva M.V., Grishchenko V.I., Kotlyarov R.Y.

Abstract

Generating cross-reactive vaccines aimed at targeting all human influenza A virus subtypes is among high priority tasks in contemporary vaccinology. Such vaccines will be primarily demanded during pre-pandemic period as well as used to prime some population cohorts prior to vaccination with standard vaccines containing area-relevant epidemic virus. Unlike routine approach universal vaccines do not induce a sterilizing immunity, but significantly ameliorate overt infection and probable complications. Our study was aimed at evaluating characteristics of immune response in experimental animals primed with a candidate universal vaccine challenged with sublethal influenza A virus infection. Mice were immunized intranasally with the recombinant protein FlgH2-2-4M2e containing conservative peptides derived from two influenza A virus proteins: M2 protein ectodomain and 76–130 amino acid sequence from the second hemagglutinin (HA2) subunit genetically linked to bacterial flagellin protein, which is a ligand for Toll-like receptor 5 (TLR5). Control mice received saline. Two weeks after immunization, mice from both groups were infected with a sublethal dose of A/Aichi/2/68 AN3N2 influenza virus strain. Level of immunoglobulins G and A in the blood sera and bronchoalveolar lavages (BAL) were determined two weeks after immunization and 1 month post infection. Percentage of lung CD4+ T and CD4+ Tem (CD44+CD62L–) cells secreting cytokines TNFα, IFNγ, IL-2 was determined. Immunized vs. control mice responded to sublethal infection with the influenza virus by insignificant weight loss and more pronounced production of vaccine peptide-specific (M2e and aa76–130 HA2) and pan-influenza A/Aichi/2/68 virus IgG and A in the blood sera and BAL. After challenge the number of CD4+ T cells secreting cytokines TNFα and/or IL-2 in immunized mice significantly exceeded counterpart T cells in unimmunized animals that was true for both CD4+T and CD4+ Tem cells. Memory CD4+ T cells were previously shown to play a key role in the prime-boost event and heterosubtypic immune response. Thus, we were able to demonstrate a priming effect for recombinant cross-protective vaccine used in our experiment.
Russian Journal of Infection and Immunity. 2019;9(3-4):485-494
pages 485-494 views

Detecting specific memory t and b cells in volunteers annually revaccinated with live anthrax vaccine

Firstova V.V., Kartseva A.S., Silkina M.V., Marin M.A., Muntian I.O., Ryabko A.K., Shemyakin I.G.

Abstract

Currently, live anthrax vaccine has been used for vaccine prophylaxis in Russia and neighbor countries for seve ral decades, but precise mechanism of post-vaccination protection mechanism remains unclear. Here, we provide data on examining serum antibody level against protective antigen (PA) and lethal factor (LF) in repeatedly vaccinated volun teers at early stage (5–8 days) and 1 month after the performing pre-scheduled annual revaccination. Amount of peripheral blood antigen-specific memory T cells after previous vaccinations was analyzed. It was showed that frequency of CD3+CD45RO+CD62L– memory effector T cells was increased in the majority of volunteers on day 5-8 day after performing pre-scheduled annual revaccination that peaked at day 7 by elevating it by 2-fold compared with the control group. Percentage of anthrax-specific central memory T cells did not increase at early stage after vaccination, whereas amount of activated CD3+CD45RO+CD62L+HLA-DR+ subset within this memory T cell population was increased. Likewise, percentage of activated CD3+CD45RO+CD62L–HLA-DR+ effector memory T cell subset was also increased. Moreover, serum anti-PA IgG were detected on day 5–8 day after pre-scheduled annual revaccination in half of volunteers, whereas anti-LF IgG were found only in a single volunteer. Rapidly elevated amount of serum anthrax-specific IgG antibodies evidences about sustained memory B cell response in peripheral blood samples in volunteers after pre-scheduled annual revaccination. However, percentage of CD19+CD27+ memory B cells was not significantly elevated at early stage after revaccination that tended to increase. Both helper and cytotoxic T cell subsets were activated on day 5–8 after revaccination revealed by upregulated expression of CD69 and/or CD25 markers, with the latter predominantly found on helper T cells, thereby accounting for their high proliferative activity, whereas the former — on cytotoxic T cell subsets. Detection of anti-PA IgG antibodies correlates with protection against anthrax, which was confirmed in animal models. Unfortunately, the level of serum anti-PA IgG antibodies rapidly declines after vaccination. Ability of memory B cells to rapidly trigger production of anthrax-specific antibodies in response to revaccination suggests that anti-anthrax immunity may be evaluated by measuring frequency of peripheral blood anthrax-specific memory B and T cells.
Russian Journal of Infection and Immunity. 2019;9(3-4):495-503
pages 495-503 views

Intestinal microbiota composition and peripheral blood Th cell subsets in patients with multiple sclerosis

Abdurasulova I.N., Tarasova E.A., Kudryavtsev I.V., Negoreeva I.G., Ilves A.G., Serebriakova M.K., Ermolenko E.I., Ivashkova E.V., Matsulevich A.V., Tatarinov A.E., Stoliarov I.D., Klimenko V.M., Suvorov A.N.

Abstract

At present, the role of intestinal microbiota in diverse diseases of the central nervous system, including of multiple sclerosis (MS) has been extensively investigated. Self-reactive CD4+ Th1 and Th17 cells specific to myelin-derived antigens play a key role in the MS pathogenesis. Taking into consideration pathogenetic features related to MS development, we examined a relation between intestinal microbiocenosis and abundance of various peripheral blood helper T (Th) cell subsets in MS patients. Objective of the study: to assess prevalence of individual members of the intestinal microbiota in MS patients and analyze a relation with peripheral blood Th cell subsets. Prevalence of symbiotic and opportunistic microbial species was estimated by bacteriological method and real time PCR in 112 MS patients (72 females, 40 males) of varying severity and duration. Th cell subsets (Th1, Th2, Th17, Th1/Th17, Th17/Th22, DP Th17) were analyzed by using multi-color flow cytometry based on Th cell subset-specific surface expression of chemokine receptors. A relationship between individual intestinal microbiota species and severity, duration and rate of MS progression, as well as with the phenotype of immune cells was assessed. It was found that the most significant correlation between percentage of peripheral blood Th cell subsets was observed with prevalence of Lactobacillus spp., Enterococcus spp. and Enterobacter spp. Moreover, prevalence of Enterococcus spp. Th cell composition influenced synergistically or antagonistically together with Enterobacter spp. or Lactobacillus spp., respectively. It is suggested that direct and indirect impact of intestinal microbiota composition on human immune system might contribute to developing novel strategies for treating MS.

Russian Journal of Infection and Immunity. 2019;9(3-4):504-522
pages 504-522 views

Non-invasive laboratory markers assessing efficacy of Helicobacter pylori eradication therapy

Drygina L.B., Ellenidi V.N., Bardysheva N.A., Bogoslovskiy M.M.

Abstract

Effective eradication of Helicobacter pylori infection is an important means to reduce the risk of precancerous changes in the gastric mucosa and prevention of gastric cancer. A search for non-invasive diagnostic tools for Helicobacter pylori infection, evaluation of the effectiveness of eradication remains of high importance.

The aim of the study was to assess an informative value of detecting pepsinogen I and II as well as serum antibodies to Helicobacter pylori while assessing an efficacy of treated chronic Helicobacter gastritis and identifying preneoplastic changes in the stomach mucosa. There enrolled 113 male patients with chronic gastritis aged 41 to 76, average age- (56.7±0.7) years. Examination of patients was carried out at admission to the clinic, as well as at 2 and 12 months after administering a standard eradication therapy. It was found that Helicobacter pylori infection was detected in 101 (89.4%) patients. Groups of patients with effective eradication therapy were noted. A time-dependent level of antibodies to Helicobacter pylori, as well as measured concentration of pepsinogen I and II after the onset of eradication treatment were determined. Which were analyzed in connection with the results of histology examination of gastric mucosa biopsy specimens and expression of oncoproteins Ki-67, Bcl-2, c-erbB-2, p16 in the gastric mucosa depending on efficacy of eradication therapy. It is shown that effective eradication therapy was characterized by significantly decreased serum level of IgG antibodies to Helicobacter pylori 2 months after the onset of treatment. Moreover, a significantly decreased pepsinogen II and serum IgG antibodies to Helicobacter pylori during eradication therapy were accompanied by a significant decrease in Ki-67 expression in the gastric epithelium. Decreased concentration of pepsinogen II within the first year after Helicobacter pylori eradication therapy was due to a greater decrease in activity of inflammatory changes in the gastric mucosa than to dynamic changes in gastric atrophy and metaplasia. An inverse relation between the serum level of pepsinogen I and atrophy as well as intestinal metaplasia within the gastric mucosa were found.

Russian Journal of Infection and Immunity. 2019;9(3-4):523-530
pages 523-530 views

Tuberculosis outcomes related to the Mycobacterium tuberculosis genotype

Pasechnik O.A., Vyazovaya A.A., Dymova M.A., Blokh A.I., Stasenko V.L., Tatarintseva M.P., Mokrousov I.V.

Abstract

Mycobacterium tuberculosis strains of different phylogenetic lineages and genetic families differ in biological properties that determine, to some extent, epidemiological features and clinical manifestation in tuberculosis (TB) patients.

The aim of the study was to assess the risk of an adverse outcome of the disease in TB patients caused by various M. tuberculosis genotypes.

Materials and methods. A total of 425 patients with respiratory TB were enrolled in this study. They were registered at phthisiatric facilities in the Omsk region from March 2015 to June 2017 period and included: males — 73.1%, mean age 39.9 years, females — 26.9%, mean age 42.0 years. M. tuberculosis culture and drug susceptibility testing and DNA extraction were performed in accordance with standard methods. Strains were assigned to the M. tuberculosis Beijing genotype and its epidemiologically relevant clusters B0/W148 and 94-32 by PCR based detection of specific markers. Non-Beijing strains were subjected to spoligotyping.

Results. We found that 66.5% isolates belonged to the Beijing genotype, 12.8% — to LAM, 10.1% — to T, and 4.7% — to the Ural genotype. Multi-drug resistance (MDR) to anti-TB drugs was observed in 195 M. tuberculosis strains (45.9%). Moreover, Beijing genotype was more often isolated from patients with MDR-TB infection (PR = 2.09 (95% CI 1.6–2.74) and TB infection associated with HIV infection (PR = 1.14 (95% CI 1.01–1.31). Lethal outcome was double higher in patients infected with Beijing vs. non-Beijing strains, 28.6% vs. 14.0% (PR = 2.03; 95% CI 1.3–3.17). The risk factors were identified as follows: young age 18–44 years (RR = 1.7; 95% CI 1.18–2.7), co-morbidity with HIV (RR = 5.0; 95% CI 3.39–7.45), multiple (RR = 1.7; 95% CI 1.14–2.55) and extensive drug resistance (RR = 2.57; 95% CI 1.35–4.92), and association with the Beijing genotype (RR = 2.0, 95% CI 1.3–3.17).

Conclusion. M. tuberculosis spread in the Omsk region is characterised by significant prevalence of the Beijing genotype, associated with multiple and extensive drug resistance. A significant association of adverse clinical outcomes and various factors, including association with the Beijing genotype, requires development of new approaches in the fight against tuberculosis.

Russian Journal of Infection and Immunity. 2019;9(3-4):531-538
pages 531-538 views

The phenotype of NK-cells in the dynamics of the post-operative period in patients with peritonitis in depending on the outcome of the disease

Savchenko A.A., Borisov A.G., Kudryavcev I.V., Belenjuk V.D.

Abstract

Our study was aimed at investigating dynamic phenotype pattern of peripheral blood NK cells in patients with widespread purulent peritonitis (WPP) during postoperative period depending on disease outcome. A total of 48 patients aged 30–63 with acute surgical diseases and abdominal injuries complicated by WPP were examined. Blood sampling was performed before surgery (preoperative period) as well as on day 7, 14 and 21 during postoperative period. 40 apparently healthy age-matched subjects were included in control group. Peripheral blood NK cell phenotyping was performed by using flow cytometry with directly immunofluorescently tagged antibodies. Mean fluorescence intensity was measured to estimate expression levels of NK cell surface receptors was measured. It was found that in patients with a favorable WPP outcome during preoperative period the percentage of mature NK cells was decreased that was restored by the end of the postoperative period (21 days post-surgery) due to elevated mature, cytotoxic and cytokine-producing NK cell subsets. In addition, percentage of CD11b-positive NK cell subsets was increased upon favorable outcome by the end of postoperative period as well as frequency of CD57-positive NK cells relative to the preoperative period. However, frequency of mature NK cells with unfavorable WPP outcome vs. control vs. favorable outcome was decreased during preoperative and entire postoperative period. Moreover, amount of cytotoxic NK cells was elevated during examination period upon unfavorable WPP outcome. Further, percentage of mature CD11b-positive NK cells in this patient cohort was decreased during preoperative period and post-surgery. Percentage of CD57-positive NK cells was decreased during entire postoperative period in patients with unfavorable vs. favorable outcome vs. control group. At the same time, patients with unfavorable outcome of this infectious-inflammatory disease were shown to display upregulated expression of CD28 and CD57 markers on NK cells. such features identified in phenotype of peripheral blood NK cells in patients with unfavorable WPP outcome reflect abnormal mechanisms in NK cell maturation and migration, which, in turn, determines disturbance in events regulating acute inflammatory reaction in WPP. 

Russian Journal of Infection and Immunity. 2019;9(3-4):539-548
pages 539-548 views

Assessing efficiency of synthetic peptide-containing spray in combination therapy of chronic generalized periodontitis

Sarkisian N.G., Kataeva N.N., Tuzankina I.A., Melikyan S.G., Zurochka V.A., Zurochka A.V.

Abstract

Antibacterial drugs are routinely used in therapy of periodontal diseases. However, increasing incidence of antibiotics resistance necessitates development of novel therapeutic approaches for oral diseases. Currently, newly designed antibacterial agents based on natural, semi-synthetic and synthetic peptides is the most promising approach in dentistry. Among them is a product containing synthetic peptide (ZP2) replicating active site of granulocyte-macrophage colonystimulating factor (GM-CSF) as the main active ingredient in Atsegram-spray (manufactured by Academic Innovation Research Center, Chelyabinsk). Our study was aimed at assessing efficacy of a combination therapy of inflammatory periodontal diseases by introducing Atsegram-spray as well as examining potential relationship between peptide ZP2-related biological properties, physicochemical properties of the spray and mechanism of antibacterial and immunotropic action for substantiating its application on oral mucosa. During the first stage experiments, it was found that the peptide ZP2 was able to trigger lymphocyte blast transformation in vitro indicating that it might influence cell proliferation and exhibit marked immunotropic activity. Next, we assessed potential effects of the peptide ZP2 on biofilm formation mediated by staphylococcal clinical isolates. It was shown that peptide ZP2 inhibited biofilm formation in 75.0±9.0% of S. aureus and 50.0±15.1% of S. epidermidis strains, with mean inhibition index of biofilm formation reaching 25.1±3.8 and 50.4±6.0%, respectively. However, peptide ZP2 in 8.3–25.0% of staphylococcal clinical isolates was found to stimulate/lack effect on biofilm formation by 14.9–48.5 and 16.7–25.0% cultures, respectively. Thus, the synthetic peptide ZP2 exerts divergent, but mainly inhibitory effects on biofilm formation with staphylococcal clinical strains, which are characterized by inter- and intraspecific (strain) variability. Use of a synthetic peptide-based spray in antibacterial therapy of mild chronic generalized periodontitis (main group) one month after the onset was found to improve oral hygiene by 28.5% as well as decrease PMA index and gum bleeding index by 82.8 and 100%, respectively. In contrast, such parameters in patients receiving basic therapy (comparison group) were lower on average by 2-fold. While analyzing physicochemical properties of the spray such as pH, buffer capacity and solution osmotic pressure, it was found that they were related to the antibacterial mechanism of drug activity and efficacy in treatment of inflammatory periodontal diseases. Thus, assessing peptide ZP2-related biological properties and physicochemical parameters of the spray allows to evaluate their role in mechanism of previously unknown antibacterial and immunotropic activity. These findings confirm feasibility and efficacy of using Atsegram-spray in dentistry as an alternative means to antimicrobial agents, such as antibacterial drugs.
Russian Journal of Infection and Immunity. 2019;9(3-4):549-558
pages 549-558 views

Comprehensive assessment of specific antibodies on infectious activity of tick-borne encephalitis virus

Leonova G.N., Majstrovskaya O.S., Lubova V.A., Sanina N.B.

Abstract

Vaccines for prophylactic immunization provide the most reliable and effective protection against the vast majority of infectious diseases. Tick-borne encephalitis (TBE) represents a high-priority medical issue at the territory of the Eurasian continent. Of great importance is assessing a role of distinct antibody titers especially low titers, observed quite often in vaccinated individuals, sometimes posing obstacles in determining a threshold of seropositivity as well as the level of specific protection against TBE virus. We aimed at obtaining data to assess antiviral activity of virus-specific antibodies with distinct titer levels based on the in vitro, ex vivo and in vivo experimental studies with a highly virulent Far-Eastern strain of tick-borne encephalitis virus. The in vitro, ex vivo and in vivo comprehensive experimental studies with a highly virulent Far-Eastern strain of tick-borne encephalitis virus (TBEV) were conducted and the dynamics of antiviral activity of virus-specific antibodies at variable titers (1:100–1:3200) was measured (timeframe ranged within 1–96 hours p.i.) to provide a rationale for evaluating the antiviral immune response. It was found that the in vitro experiments demonstrated that the IgG at 1:100 titer exerted a weak anti-TBEV neutralizing effect at all time-points examined. The IgG 1:400 titer caused a 2 log PFU/mL decline in TBEV Dal strain yield at 72 h post-infection, whereas at 1:3200 titer it completely suppressed TBEV replication throughout the observation period. The ex vivo experiments with blood serum obtained from vaccinated subjects demonstrating a range of TBEV antibody titers (sera from vaccinated individuals with varying anti-TBEV antibody titers) and in vivo (outinbred white mice) experiments revealed a delayed virus elimination for antibody titers at 1:100 and 1:200 as well as rapid virus elimination (1–2 days p.i.) for antibody titers greater than 1:400. Thus, antibody titer at 1:400 may be considered as the universal anti-TBEV protection threshold. In order to properly conclude regarding the revaccination schedule it is advised to start with testing blood serum for durability of anti-TBEV immune response. Subjects with TBEV antibody titers at 1:100 and 1:200 should be strongly recommended to undergo a mandatory revaccination. Such an approach is believed to be the most effective way toward enhancing efficacy of vaccine-mediated protection against TBE.
Russian Journal of Infection and Immunity. 2019;9(3-4):559-567
pages 559-567 views

Assessing efficiency of epidemiological security system for the medical organization

Stepanova T.F., Bakshtanovskaya I.V., Rebeshchenko A.P., Mazurkevich V.V.

Abstract

Healthcare workers comprise a high-risk cohort of developing diverse infections caused by opportunistic and pathogenic microbes. Among medical workers of the Russian Federation the first rank place in occupational diseases is held by tuberculosis of respiratory organs accounting for more than half of all registered occupational diseases. Moreover, its high incidence is particularly noted among forensic specialists and medical workers in anti-tuberculosis institutions. The organization of epidemiological surveillance and tuberculosis prevention medical workers so far remains unsolved both scientifically and practically. On one hand, high TB incidence in pattern of clinical TB forms may be due to higher percentage of patients suffering from common, advanced and complicated forms of drug-resistant Mycobacterium tuberculosis infection as well as rise of socially significant co-infections (HIV+tuberculosis) among the population. Specialists from the Regional Bureau of Forensic Medicine were examined during 2009–2018 time period by using molecular genetic approaches to analyze 4948 wash samples (2009–2013 — 3649 samples; 2014–2018 — 1299 swabs) collected from various environmental objects, medical overalls and hands of medical specialists while performing professional duties in autopsy rooms, laboratories as well as facilities housekeeping department. It was demonstrated that M. tuberculosis DNA was detected in 353 and 81 swabs in 2009–2013 and 2014–2018 time period. Based on intensity of contacting with pathogenic biological agents, production technologies applied in the Regional Bureau of Forensic Medicine were divided into two groups. M. tuberculosis contamination in diverse facilities or any item as well as a contamination risk for medical worker hands and medical overalls were evaluated in accordance with professional duties assigned to individual specialists, followed by calculating significant differences in groups exami ned. It was found that some facilities and environmental items most exposed to a high-risk M. tuberculosis contamination were identified, which are involved in pathogen spreading from autopsy rooms outside to the remainder of facilities. It allowed for autho rities to improve performance of activities ensuring epidemiological security for attending specia lists that not only resulted in significantly decreased incidence of M. tuberculosis DNA detection, but also lowered TB incidence rate among them from 292.4 down to 280.9 cases and 46.3 per 10 thousand workers during 2007–2009 and 2017–2018 time period, respectively.
Russian Journal of Infection and Immunity. 2019;9(3-4):568-576
pages 568-576 views

SHORT COMMUNICATIONS

Chronic hepatitis b associated without/with a delta agent in Kyrgyzstan (epidemiological situation, clinical features)

Nogoibaeva K.A., Tobokalova S.T., Bekenova D.S., Nazarbaeva J.N.

Abstract

Objective. To compare epidemiological, clinical and laboratory characteristics of chronic hepatitis B (ChHB) associated with/without delta agent (ChHB+DV) study.

Materials and methods. The Kyrgyzstan State Reporting Form No. 12 covering 2010–2017 period was examined. For this, 133 and 130 case histories of ChHB and ChHB+DV patients, respectively, were analyzed. The data were statiastically processed by using Microsoft Office Excel software.

Results and discussion. Over the 2010–2017 period, prevalence of the “HBV Carrier” (60.4 ) was higher by 20-fold than that one for ChHB [3.8 , 95% CI (2.4–4.0)] and CVHD [3.4 , 95% CI (2.2–3.4)], as the vast majority of patients were not thoroughly examined after detecting HBsAg, and the HBV Carrier was empirically diagnosed at the primary health care units. As a result, routine case definitions for such conditions were revised and an improved system of epidemiological surveillance of viral hepatitis was developed, according to the 2016 WHO recommendations approved by the Ministry of Health of the Kyrgyz Republic (Order No. 524, dated of July 20, 2018). Asthenia was observed in ~60% of patients in both groups, whereas arthralgia — in ~5–10% of patients, more often in those comorbid with ChHB+DV, and myalgia — in as low as ~3% of cases. Impaired central nervous system functions manifested as headache and restless sleep were evenly recorded in about 10–15% of patients, without significant difference between groups. In contrast, dominating dyspeptic manifestations such as poor appetite (72±3.9% vs. 20.6±3.5%, p < 0,05), nausea (23.8±3.7% vs. 7.3±2.3%, p < 0,05), vomiting (12.3±2.6% vs. 3.3±1.5%, p < 0,05) and flatulence (27±3.9% and 13±2.9%, p < 0,05) were revealed in ChHB+DV patients. Pain in the right hypochondrium was noted in 52–56% of patients, insignificantly differed between patient groups. Incidence of yellowness of the sclera and skin layers as well as skin itching were recorded by 2–3 and 8 times, respectively, more frequently in ChHB+DV patients. A more profound cytolysis and signs of altered bilirubin metabolism were also more common in HBV patients comorbid with the delta agent. Thus, a more severe ChHB+DV course requires that all patients with primary HBsAg detection were mandatorily examined for anti-HDV antibodies to ensure early diagnostics and timely organization of the secondary and tertiary preventive measures in the Kyrgyzstan. 

Russian Journal of Infection and Immunity. 2019;9(3-4):577-582
pages 577-582 views

SIR+A mathematical model for evaluating and predicting 2016–2017 ARVI-influenza incidence by using on the Moscow territory

Kontarov N.A., Arkharova G.V., Grishunina Y.B., Grishunina S.A., Yuminova N.V.

Abstract

Influenza is a major challenge to global healthcare due to its high transmissivity and ability to cause major epidemics. Influenza epidemics and pandemics are associated with changes in the society structure that contribute to the spread of new viral strains in certain environmental and social settings. Currently, influenza is one of the most common global diseases that results in annual epidemics or even pandemics, often leading to lethal outcome. Influenza viruses are uniquely prone to variability via point mutations, recombination and gene reassortment accompanied with changes in their biological properties considered as the main cause of uncontrolled infection spread. Hence, examining cohorts of predisposed individuals by using probability models provides not only additional information about viral outbreaks, but also allows monitoring dynamics of viral epidemics in controlled areas. Understanding influenza epidemiology is crucial for restructuring healthcare resources. Public healthcare service mainly relies on influenza vaccination. However, there are vulnerable cohorts such as elderly and immunocompromised individuals, which usually contain no protective antiinfluenza virus antibody level. Despite advances in the developing vaccines and chemotherapy, large-scale influenza epidemics still continue to emerge. Upon that, no reliable methods for disease prognosis based on rate of ongoing epidemic situation are currently available. Monitoring and predicting emerging epidemics is complicated due to discrepancy between dynamics of influenza epidemics that might be evaluated by using surveillance data as well as platform for tracking influenza incidence rate. However, it may be profoundly exacerbated by mutations found in the influenza virus genome by altering genuine morbidity dynamics. Use of probabilistic models for assessing parameters of stochastic epidemics would contribute to more accurately predicted changes in morbidity rate. Here, an SIR+A probabilistic model considering a relationship between infected, susceptible and protected individuals as well as the aggressiveness of external risks for predicting changes in influenza morbidity rate that allowed to evaluate and predict the 2016 ARVI influenza incidence rate in Moscow area. Moreover, introducing an intensity of infection parameter allows to conduct a reliable analysis of incidence rate and predict its changes.
Russian Journal of Infection and Immunity. 2019;9(3-4):583-588
pages 583-588 views

Detecting a psoriatic antigen analogous to infectious prion proteins

Sinitsyn B.F.

Abstract

Until now, psoriatic antigen as a specific antigen derived from some infectious agent potentially related to origin of psoriasis has not been identified, thereby strongly arguing against infectious theory of psoriasis. However, the lack of specific psoriasis-associated antigens may be theoretically accounted for by an idea that psoriatic antigen could be analogous to infectious prion proteins (PrPSc analogue). It might be identical to some epidermal protein in psoriasis-free subjects that might differ antigenically from related normal protein by resistance to digestive enzymes similarly to PrPSc. Since PrPSc cytopathogenic effect is associated with its location within cell structures of affected body tissue, by analogy with PrPSc we aimed at identifying a potential carrier of psoriatic antigen by examining peptic hydrolysates of psoriatic squamous elements. Psoriatic squamous elements and epidermal stratum corneum were collected from heel area of healthy subjects with a metal grater for further examination. Squamous elements were homogenized in isotonic saline followed by centrifugation to separate them from soluble components. Homogenates of squamous elements structures and their homogenate supernatants underwent peptic hydrolysis reaction. Antigens and their identity were analysed by Ouchterlony immunoprecipitation in agar with antiserum obtained after immunizing rabbits with homogenate of the psoriatic squamous element structures, before and after hydrolysis, using peptic hydrolysates of squamous element structures and relevant supernatants. It was found that two antigens were precipitated in peptic hydrolysates of homogenates of psoriatic squamous cell structures, underlying acidin-pepsin resistance of antigen carriers. However, compared to the remainder of antigens precipitated in examined substrates only one out of two antigens might be considered as a psoriatic antigen being some PrPSc analogue that was identical to one of supernatant antigens derived from epidermal stratum corneum homogenates collected from healthy subjects. Similar to PrPSc, it differed from antigenically related normal protein by acidin-pepsin resistance. Albeit confirming available reports revealing no psoriasis-associated pathogen-specific antigens, this, nonetheless, might not be sufficient for rejecting infectious theory of psoriasis, as psoriatic antigen exhibits some properties similar to those of PrPSc.
Russian Journal of Infection and Immunity. 2019;9(3-4):589-594
pages 589-594 views

Assessing survival rate of HPV-positive and HPV-negative cervical cancer patients

Ibragimova M.K., Tsyganov M.M., Churuksaeva O.N., Kolomiets L.A., Litviakov N.V.

Abstract

Currently, studies highlighting features of emergence, development, clinical score and prognosis for patients with HPV-negative cervical cancer are scarce. However, the data regarding high recurrence rate and mortality in patients with HPV-negative head and neck cancer are demonstrated. Here, cervical canal and exocervical scraping samples collected from 116 patients with primary cervical cancer, I–IV stages, aged 24 to 79 years, were examined with real-time PCR assay for assessing prevalence of 12 high oncogenic risk human papillomavirus (HPV) strains, genotyping and viral load. It was found that 84 (72.4%) and 32 cervical cancer patients (27.6%) were positive and negative, respectively, for high oncogenic risk (HR) HPV strains. Based on these data, patients were further subdivided into two groups: HPV-positive and HPVnegative patient group. Genotyping HPV-positive samples revealed that HPV genotype 16 was found in 67.8% of cases that agrees with data published worldwide. In addition, relapse-free and overall survival (HPV-positive and HPV-negative patients) rate were also evaluated in both groups. It was demonstrated that survival rate was significantly decreased in HPVnegative cervical cancer patients additionally characterized by less favorable prognosis. Moreover, length of relapse-free survival as well as overall survival for HPV-positive vs. HPV-negative patients was 102 vs. 68 months as well as 52 vs. 83 months, respectively. On the other hand, it was demonstrated that recurrence rate, clinical score and progression of cervical cancer directly depend on cancer spread observed at primary medical examination. Of note, the majority of primary cervical cancer relapses are diagnosed within the first 2 years after completing treatment. In addition, an increasing relapse rate has been documented in cervical cancer patients at advanced stages. Upon that, biological cancer behavior remains poorly predictable even in patients at similar disease stage. Therefore, it is essential that HPV as an important prognostic factor would be taken into account for choosing proper therapeutic strategy for treatment of patients with cervical cancer.
Russian Journal of Infection and Immunity. 2019;9(3-4):595-599
pages 595-599 views

Monitoring of cytogenetic instability by micronuclei assay of both immunocompetent and non-immunocompetent cells in tick-borne encephalitis patients depending on variants of glutathione-S-transferase genes in the genotype

Ilyinskikh N.N., Ilyinskikh E.N., Zamyatina E.V., Lee S.V.

Abstract

Aim of this study was to study the dynamics of the frequency of cytokinesis-blocked T-lymphocytes with micronuclei in peripheral blood and the frequency of buccal micronucleated epithelium cells for a period of half a year in patients with acute tick-borne encephalitis, depending on burden of active and inactive variants of glutathione-S-transferase genes (GSTM1 and GSTT1) in the patient's genotype. We carried out micronucleus assay in immunocompetent and non-immunocompetent cells in 54 patients with acute tick-borne encephalitis and 35 healthy persons (control) residing in the Tomsk and Tyumen regions. To analyze the frequency of cytokinesis-blocked micronucleated T-lymphocytes was used venous peripheral blood as material for phytohemagglutinin-stimulated cultures, and to study the frequency of buccal micronucleated cells, samples of the buccal mucous membrane epithelial cells were obtained. To carried out both techniques of micronucleus assay, cytological preparations were prepared, which were stained using the Giemsa or Felgen methods. The material for the study was obtained repeatedly during admission of patients to treatment, and also after 1 week, 1, 3 and 6 months.  Polymerase chain reaction was used to analyze the alleles of the GSTM1 and GSTT1 genes. As a result of this analysis was found a significant increase in the frequency of micronucleated cells in tick-borne encephalitis patients compared with the control group. In addition, the frequency of cytokinesis-blocked micronucleated T-lymphocytes was increased significantly higher than the one of micronucleated buccal cells. The most significant and prolonged increase in the frequency of micronucleated cells was associated with the mutant inactive variants of the genes GSTM1 (0/0) and GSTT1 (0/0). In the patients with burden the inactive forms of these genes, the cytogenetic instability of the cytokinesis-blocked blood T-lymphocytes could persist for up to six months. In case of buccal cells, the frequency of micronucleated cells was close to the one in the control group as early as 1-3 months after a course of treatment. Conclusion. It was found that the most increased and prolonged frequency of cytogenetically instable cells persisted in cytokinesis-blocked T-lymphocytes of peripheral blood of patients with tick-borne encephalitis who were carriers of the genotype with inactive variants of  both GSTM1 (0/0) and GSTT1 (0/0 ) glutathione-S-transferase genes.

Russian Journal of Infection and Immunity. 2019;9(3-4):600-606
pages 600-606 views

Humoral and cellular immunity to measles and rubella virus antigens in healthy subjects

Smerdova M.A., Toptygina A.P., Andreev Y.Y., Sennikova S.V., Zetkin A.Y., Klykova T.G., Belyakov S.I.

Abstract

An issue of eradicating measles and rubella virus-induced infections currently remains unresolved, despite existing effective methods for specific prophylaxis and WHO’s commitment to a mass vaccination policy. While improving epidemic situation, analysis of new challenges, such as measles incidence in adults, especially in adults vaccinated in childhood, is of particular interest. The aim of the study was to analyze serum measles and rubella virus-specific IgG antibodies in young healthy people and estimate antigen-specific cellular immune response in seronegative subjects. There were examined 100 healthy adults aged 18–30 years old. Level of serum specific IgG was measured by ELISA (Vector-Best, Russia). Antigen-specific cellular immune response was assessed by magnitude of surface CD107a expression on CD8hi T cells challenged by measles and rubella virus-derived antigens. It was found that average level of antibodies against rubella virus comprised 175.5 IU/ml, 49% of which recovered after rubella, 46% were vaccinated, whereas 5% subjects contained no virus-specific antibodies. In addition, mean level of anti-measles virus antibodies was below protective magnitude, among which 1% subjects recovered after measles, 31% displayed post-vaccination immunity, 55% subjects were seronegative, and 13% had equivocal levels of specific antibodies. Thus, 68% subjects were unprotected against measles virus based on the level of serum virus-specific antibodies. Moreover, 40 out of 68 subjects were vaccinated against measles in childhood. Additional screening adult subjects for intensity of measles and rubella virus-specific cellular immunity demonstrated that 57.37% of them contained peripheral blood CD8 T cells against measles virus and 59.01% — against rubella virus. Further analysis allowed to identify 4 subgroups displaying: 1) high level of virus-specific antibodies and T cells; 2) neither antibodies nor specific T-cells reaching as low as 20% of baseline group; 3) high antibody level combined with low amount of specific T cells; and 4) low antibody level combined with high level of specific T cells. thus, it may be assumed that cellular and humoral immune arms are maintained independently and being active for a long term after vaccination. Preserving a specific T-cell immunity seems to provide protection against infection, thereby accounting for the lack of measles manifestation in all seronegative subjects. 

Russian Journal of Infection and Immunity. 2019;9(3-4):607-611
pages 607-611 views

Dynamics of proinflammatory cytokine serum levels in patients with acute inflammatory diseases of pelvic organs in the early stages of conservative treatment

Burova N.A., Soltys P.A., Zharkin N.A., Selikhova M.S., Sviridova N.I., Belan E.B.

Abstract

Dynamics of serum proinflammatory cytokines such as interleukins (IL)-1, -2 and -6, tumor necrosis factor alpha (TNFα) was examined in patients of reproductive age suffering from acute inflammatory diseases of the pelvic organs. Our study was carried out with female patients at hospital admission prior to therapy applied with conventional methods of treatment and improved treatment by using vaginal low-frequency laser in a constant continuous magnetic field. The data obtained were compared with serum cytokine level from 20 healthy female volunteers of reproductive age consulted on better contraception methods. It was found that cytokine profile of in patients with acute inflammatory processes in pelvic organs was characterized by a high level of proinflammatory cytokines. It was shown that patients receiving conventional treatment contained decreased level of serum IL-1, IL-2, IL-6 and TNFα displaying slight dynamics, which did not reach it in control group. This may contribute to ongoing inflammatory process, despite the positive clinical dynamics. In turn, imbalance of immune responses leads to a persistently impaired fertility in women and need to perform subsequent comprehensive rehabilitation measures. Moreover, patients applied with intravaginal low-frequency laser radiation in a constant magnetic field were found to contain serum TNFα < 100 pg/ml observed in 59.7% of cases, IL-6 level was lower than 20 pg/ml (prevalent in control group) found in 54.2% of cases. Serum IL-2 level was decreased by 3.5-fold compared to baseline, whereas for IL-1β it was higher than 100 pg/ml in as few as 23.6% patients. Such temporal pattern of inflammatory markers with rapid significant decrease of serum proinflammatory cytokines in patients with preformed pathogenic factors can reduce probability of connective tissue formation and activate their own repair as well as regenerative events. The results obtained allow to wider use combined physical interventional factors for therapy of patients with acute inflammatory diseases of the pelvic organs.
Russian Journal of Infection and Immunity. 2019;9(3-4):612-616
pages 612-616 views

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