In recent years, a critical mass of information has accumulated, which has made it possible to equate platelets to the cells of innate immunity, which ensures the initiation of inflammation and the reactions of innate immunity. In the presented review platelets were examined from the point of view of antibacterial immune reactions. Mechanisms that allow platelets to recognize bacteria and their soluble products as characteristic of immune cells (via TLR2, TLR4, TLR7 and TLR9, FcγRIIa and receptors for complement components), as well as the mechanisms involved in the hemostasis process (GPIb, GPIIb-IIIa). The consequence of the recognition of bacteria is the activation of platelets, the initiation of hemocoagulation and the innate immune response. The ability of platelets to phagocyte bacteriae and stop their growth due to the pronounced microbicidal potential (thrombocidins or microbicidal proteins of platelets and human β-defensins hBD-1, -2 and-3), which these anucleate cells possess, is shown. Discussed that bacteria actively oppose antimicrobial reactions, including using various toxins. Several groups of bacterial toxins have been isolated that activate platelets, destroying the electrochemical gradient of the plasma membrane through membrane perforation. A number of toxins cause the activation of platelets and cells of the immune system, acting as superantigens. In the antibacterial immunity, platelets attract neutrophils, monocytes and activate the complement system. In this case, platelets act together with these cells and proteins, promoting the full disclosure of the microbicidal potential of phagocytes and complement. This is especially important for bacterial infections, which monocytes / macrophages or only platelets cannot control, but, combining, they create the necessary conditions for the clearance of pathogenic bacteria from circulation.

Article is devoted to studying of the submitted epidemiological, clinical, tool, laboratory data on pathology of cardiovascular system at various viral infections. The review is based on results of domestic and foreign researches. At viral infections damage of heart and his carrying-out system perhaps as during the sharp period of a disease, and the period of a convalescence or at the chronic course of virus process. The greatest cardiothrogenism is possessed by enteroviruses, which affect the myocardium in 5–15% of cases. Much attention is paid to herpesviruses, widespread, persistently persistent in the body, as one of the reasons for the development of dilated cardiomyopathy, coronary vasculitis, early atherosclerosis, cardiac rhythm disturbance. Other infections that may affect the cardiovascular system include influenza viruses, adenovirus, poliovirus, Epstein-Barr virus, cytomegalovirus, human immunodeficiency virus, hepatitis, mumps, rubella, herpes simplex, varicella, arbovirus, respiratory-syntial virus, yellow fever virus et al. Complications from cardiovascular system can come to light at various age.

The review presents current data on the role of viral hepatitis B in on-cohematological patients. Possible ways of infection, prophylaxis of infection and activation of hepatitis B in this category of patients are considered. Specific features of the course of hepatitis B in various clinical situations are described: against the background of other viral infections and in the conduct of specific anti-leukemia therapy. The need to identify occult (occult) hepatitis in donors and patients with hemoblastosis is emphasized and methods for its detection are considered.

Objective: to study inflammatory response in patients with drug-resistant Mycobacterium tuberculosis. Materials and methods. 56 patients were examined. The first group consisted of (n=38) patients with extensively drug-resistant pathogen (23 men and 15 women) from 17,0 to 63,0 years old, the second group (n=18) – patients with multi-drug resistant pathogen (12 men and 6 women) from 16,0 to 69,0 years old. Reference group – 30 practically healthy donors. Were examined: level of ceruloplasmin, haptoglobin, α1acid glycoprotein, activity of α1-proteasome inhibitor, α2macroglobulin, activity of adenosine deaminase and elastase. Statistical data processing was performed using Statistica 7.0. Results. In both groups average level of haptoglobin exceeded the upper limit of normal range 2,5 times; grade depended on clinical form of tuberculosis. Level of α1-acid glycoprotein in both groups was increased on average 1,5 times (p<0.01). Low activity of α2-macroglobulin and normal values of α1-proteasome inhibitor were observed in both groups. Activity of elastase in both groups was within the limits of normal ranges. Elevated values of ceruloplasmin were observed in 39% and 50% correspondently in both groups. Level of ceruloplasmin above X+σ was detected more frequently in patients with fibro-cavernous tuberculosis than with infiltrative (76,0% vs. 10.0 percent, p=0,001, respectively), in patients with polycavernosive process compared to patients with presence of single cavities (p=0,003) and with cavities of destruction more than 4,0 cm (100,0%, p=0,0004). Increase of adenosine desaminase was observed only in patients with extensive drug-resistant pathogen (p=0,038). Conclusion. In both groups the most expressed changes were observed in levels of haptoglobin, α1-acid glycoprotein and α2-macroglobulin. Activity of adenosine desaminase may reflect tension of immune response with extensive drug resistance of the pathogen and probably suggests an adequate response of the organism to ongoing chemotherapy in patients with multidrug-resistant mycobacteria.

Aim is to assess repeatedly cytogenetic effects of co- or monoinfection caused by Lyme borreliosis and tick-borne encephalitis during the acute and convalescent periods of the disease depending on variants of glutathione-S-transferase (GSTM1 or GSTT1) genes in the patient’s genotype. Material and methods: The study included 186 patients and 166 healthy (control) residents of the north of the Tomsk and Tyumen regions, who were examined by clinical, laboratory and cytogenetic methods (micronucleus analysis). Among the 186 examined patients, Lyme borreliosis was diagnosed in 65 individuals, tick-borne encephalitis was in 59 patients, and coinfection was found in 62 individuals. The material for the study (smears of buccal cells) 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. Results: significant increase in the frequency of micronucleated buccal cells in patients with coinfection, as compared with the groups of control and patients with monoinfection. The significantly increased frequency of micronucleated cells was associated with the mutant inactive alleles of the GSTM1(0/0) and GSTT1(0/0) genes. If the patients were carriers of the mutant allele of the GSTM1(0/0) gene, the cytogenetic instability could persist for half a year. It was found that chronic arthritis in the Lyme borreliosis patients was associated with a long persistence of an increased frequency of micronucleated cells. Conclusion: Significant differences in the frequency and the lasting of persistence of micronucleated cells between groups of patients with coinfection and monoinfections were found. The most significant increase in those parameters was detected in the coinfected patients in whose genotype contained non-active forms of the GSTM1(0/0) and GSTT1(0/0) genes.

The influenza virus is the most unique in the level of variability of antigenic and biological properties. Because of constant mutations into genes coding surface viral proteins, in modern vaccines it is necessary to replace 1–2 virus components annually. Traditional influenza vaccines are the strain – specific and have limited efficiency in prevention of new strains of influenza viruses. In this regard, creation of influenza vaccines based on conserved determinants of viral proteins with broad spectrum protection and the short period of production is one of priority tasks which decision will lead to real control of an influenza infection. A current trend in the design of universal flu vaccines is the construction of recombinant proteins based the combination of conserved viral proteins or peptides. The goals of this study: to develop the candidate recombinant flu vaccine based on the two conserved influenza proteins (М2 and НА); to investigate immune response; and to measure the protection activity in an animal model. Results: In this study we investigated the humoral and T-cell response in mice after intranasal immunization with recombinant proteins (Flg-4M2ehs and Flg-HA2-2-4M2ehs). Both proteins induce a robust M2e-specific humoral and CD4+ T-cell response in mice lung. The recombinant protein with two target antigens (M2e and HA2) induces virusspecific CD4+ and CD8+ T-cell response and full protection (100% survival) of mice from lethal challenge human and avian influenza viruses A (A/H3N2, A/H2N2, A/H5N1). In mice immunized with Flg-4M2ehs, the survival after lethal challenge was 60–75%. Conclusion: Our results show an essential role of a conserved fragment of the HA2 in the formation of protective T-cell response and protection of mice from lethal challenge with influenza viruses A of various subtypes. The prospects of the development of vaccine formulation based on two conserved antigenic determinants of influenza virus A are shown.

Influenza is one of the most outspread infections not seldom leading to lethal outcomes. Immediate death causes are analyzed rarely. Material and methods. We provided clinic-pathological correlations in 23 cases with lethal outcomes in 1999, 15 – in 2009, 31 in 2016 and 10 in 2017. Results. It was shown that in 2009 and 2017 most frequent lethal outcomes were related to bacterial superinfection in elderly people with severe background pathology. In 2009 and 2016 the leading role played respiratory distress syndrome predominantly in people of middle age, frequently with obesity. Conclusions: by circulation of different strains of influenza A virus the disease has substantial peculiarities. Lethal outcomes may be related: 1) severe respiratory insufficiency due to respiratory distress syndrome; 2) generalized viral infection; 3) secondary bacterial pneumonia; 4) aggravation of severe somatic diseases. Many aspects of pathogenesis need complex.study.

Aim. Study of efficacy and safety of ribavirin in combination to pegylated interferon α-2a (PegIFN- α-2a) within combined mode of treatment of patients with chronic hepatitis C (CHC) including patients with compensated cirrhosis and and HIV coinfection were conducted. Material and methods. Two open prospective multicenter, non-comparative clinical trials ML16709 NCT00922779 and ML27851 «Standart» (NCT01609049) were conducted. 6661 and 1496 patients with CHC were included accordingly. All were administrated combined therapy: ribavirin and PegIFN- α-2a. Patients with HCV genotype 1 received prescribing treatment for at least 12 but not more than 48 weeks, patients with HCV genotypes 2 and 3 – for at least 12 but not more than 24 weeks. The efficacy analysis included determining the frequency of achieving a rapid virologic response (BVO), an early virologic response (RVO), a virologic response at the end of therapy, and a sustained virologic response (SVR). The safety endpoints were assessed on data of all adverse events (AEs), serious adverse events (SNP), and clinical laboratory findings. Results. At 24 weeks SVR frequency was 43.4% in the subgroup of patients with HCV genotype 1 in the ML16709 study and 72,0% in the ML27851 study; 58,9% and 89,3% in the subgroup of patients with HCV genotypes 2 and 3 accordingly. In the ML27851 study proportion of patients with BVO was 46,8% in patients with HCV genotype 1 and 86,0% in patients with a different HCV genotype. RVO frequency was 37,4% in the subgroup of patients with HCV genotype 1 in the ML16709 study and 90,1% in the ML27851 study; 79,7% and 97,4% in a subgroup of patients with HCV genotypes 2 and 3 accordingly. The proportion of patients with virologic response at the end of therapy was 44,6% in the ML16709 study and 86.7% in the ML27851 study; in a subgroup of patients with genotypes 2 and 3, 73.8% and 97.6%, accordingly. In the ML16709 study 5887 AEs were registered, including 5812 (99%) of non-serious AEs and 75 serious AEs. In the ML27851 study 2557 non-serious AEs occurred in 822 (54.95%) patients. 49 serious AEs were registered in 39 patients (2.6%). Conclusion. The results of studies ML16709 and ML27851 confirm the efficacy and safety of treatment with ribavirin plus peginterferon alfa-2a in patients with chronic hepatitis C. The registered AEs profile is representative of pegylated interferons and ribavirin combination.

Aim: to study the level of antibodies to strains of the influenza virus in trivalent vaccine, in pregnant women vaccinated in different trimester of the gestation. Materials and methods: according to CPMP criteria the level of postvaccinal antibodies to the strain of influenza A and B virus was determined by the hemagglutination inhibition reaction in sera of 48 women vaccinated in the second and third trimester of gestation. Results: in 1 month after vaccination against influenza in pregnant women the level of the seroprotection, seroconversion and the factor of the seroconversion increased in accordance with CPMP requirements. In six months after the birth, the protective titer of antibodies to different strains was registered in 30,4–70,2% of women wich was vaccinated in second trimester and 52,4–66,7% in the third trimester of gestation. Conclusion: the level of the postvaccination antibodies to influenza virus (except for the strain A / H3N2 / in vaccinated in the second trimester) in pregnant women met the criteria for CPMP irrespective of the trimester of gestation.

For purpose of clinical and morphological characterization of typhoid fever with fatal outcome was perform analysis of medical documentation as well as postmortem studies of internal tissues in 36men aged 21 to 34 years with severe body weight loss and in the conditions of combat stress in period from 1983 to 1985. The results of the study find a number of clinical and pathomorphological features of typhoid fever in patients with body weight deficiency that were in extreme conditions. Focal changes of the central nervous system were detected. The defeat of the respiratory system was characterized from the first days of the disease by bronchitis, and in the subsequent development of pneumonia, plevritis and empyema of the pleura. Majority of patients had symptoms of cardiovascular and renal failure. In died in the first week of the disease and in 2/3 parts – in a later period were combined with the symptoms of infectious-toxic encephalopathy and severe acute respiratory failure. All died had postmortem dystrophic changes of cardiomyocytes, and in patients had fatal outcome in 2–5 weeks – also focal or diffuse myocarditis. In a third of the patients who died, the disease was complicated by intestinal perforations. In a number of cases, peritonitis was a consequence of necrosis of mesenteric lymph nodes. In all patients with a fatal outcome, hemorrhagic (thrombohemorrhagic) syndrome was diagnosed. A significant proportion of patients posthumously detected signs of sepsis and other complications, many of which could be the cause of death.

Тhe aim: to analyze reasons of late diagnostics and course specifics of tuberculosis meningitis (TBM) in children in Saint Petersburg, Russia.

Materials and methods: Data was obtained from the Russian official statistics on the frequency of childhood tuberculosis meningitis in 2000-2016. We also analyzed the frequency, the course and the diagnostic specifics of tuberculosis meningitis in children in 2005–2016 in Saint Petersburg.

Results and discussion: In the Russian Federation the number of children diagnosed with tuberculosis meningitis per year was reduced from 51 in 2000 to 13 in 2016. In Saint Petersburg over the period of 2005 to 2016 there were seven registered cases of childhood tuberculosis meningitis. Unfortunately only three children out of seven in Saint Petersburg tuberculosis meningitis cases survived. The main factors associated with tuberculosis meningitis in children were young age, children three years old and younger (5 out of 7 children), the presence of a TB patient in the family (6 out of 7 children), lack of BCG vaccination (5 out of 7 children), and poor socio-economic situation (5 out of 7 children). Three out of seven children developed tuberculosis meningitis after becoming HIV positive. The following methods of tuberculosis meningitis diagnostics exist in Russia: Diaskintest, PCR, and Bactec culture tests for Mycobacterium tuberculosis. QuantiFERON-TB Gold and T-SPOT.TB are available but too expensive for most patients. However, a low prevalence of tuberculosis meningitis cases resulted in insufficient attention to TBM, late diagnostics and fatal cases. Three clinical cases were analyzed.

Conclusion: To improve tuberculosis meningitis treatment outcomes it is necessary to raise awareness of TB infection among treatment providers, especially when evaluating high risk children population. It is critical to determine presence of latent Mycobacterium tuberculosis, use all etiological diagnostic methods, including PCR and Bactec, when analyzing cerebrospinal fluid and other specimen, and initiate anti-TB treatment immediately when tuberculosis meningitis is suspected. 

Interferon-free therapy for genotype 1 hepatitis C is highly effective at any severity of liver fibrosis. The purpose of work was to assess cost-effectiveness and the budget impact of paritaprevir/ombitasvir/dasabuvir/ ritonavir (PTV/OBV/DSV/r) ± ribavirin therapy depending on time treatment initiation at different stages of liver fibrosis. Materials and methods. The cost-effectiveness analysis was performed from the payer perspective using a Markov model with a lifetime and 10-year time horizon for male patients at the age of 45 years. The budget impact analysis was performed with the horizon of 10 years. In base case the analysis of PTV/OBV/DSV/r costs was carried out on the basis of estimated price of registration including VAT and the average wholesaler extra charge taking into account population of the Russian Federation. During cost-effectiveness assessment life expectancy and costs have been discounted for 3,5% a year. The budget impact analysis was performed without discounting. Results. In the analysis with a lifetime horizon the costeffectiveness of PTV/OBV/DSV/RTV + ribavirin for patients with genotype 1a is 66,71–392,02 thousand rubles/QALY. For HCV genotype 1b therapy with PTV/OBV/DSV/RTV can dominate over lack of antiviral therapy (i.e. to lead to cost saving at increase in life expectancy) (at F2) or to be up to 204,22 thousand rubles/QALY (at F0). The cost-effectiveness of PTV/OBV/DSV/RTV ± ribavirin at the 10-year horizon for HCV patients with genotype 1a varies within 575,68-1424,15 thousand rubles/QALY, and for HCV patients with genotype 1b – within 350,05–871,46 thousand rubles/QALY. The budget impact of PTV/OBV/DSV/RTV ± ribavirin decreases in some cases at earlier purpose of antiviral therapy. So, PTV/OBV/DSV/RTV + ribavirin therapy for patients with HCV with fibrosis 3 stage (genotype 1a), decreases budget impact by 27,5% in comparison with its prescription only after development of the compensated cirrhosis. Conclusions. PTV/OBV/DSV/RTV ± ribavirin therapy of HCV (genotype 1) may be considered as economically highly effective therapy for patients with any severity of liver fibrosis

The aim of the study was to conduct clinical testing of the rapid diagnostic test system «Streptatest» (Dectra Pharm, France) and to evaluate its performance in accordance with its purpose in solving the functional problems of express diagnostics of Group A streptococci. In the work the evaluation of the performance characteristics of the test systems «Streptatest» with an assessment of the feasibility and acceptability of its use in the interests of practical public health have been studied. Materials and methods: Clinical approbation was carried out by examining 200 military personnel contracted for outpatient admission to a medical service with suspected acute tonsillitis for the carriage of Group A beta-hemolytic streptococcus using this test system. The following results were obtained during the study. Of 200 examined patients, the number of people with a positive test was 31 (15,5%), negative – 169 (84,5%), which corresponds to the literature data on the prevalence of acute tonsillitis caused by GAS. Before the application of «Streptatest» antibiotic therapy was prescribed in 80-90% of cases, after the start of the use of the test system, the number of antibiotic prescriptions was reduced to 16%, which led to a reduction in the costs of treatment of acute tonsillitis. Test system «Streptatest» is a highly effective and sufficiently reliable medical device, the ease of using test strips and a simple evaluation of the results of the study are its advantages. The indication for the application of the rapid diagnostic test system is the request for medical care of a patient with clinical signs of acute tonsillitis, tonsillopharyngitis, pharyngitis. The social significance lies in obtaining a reliable result with the simplicity and ease of working with the test system. Conclusions. Estimating the prevalence of streptococcal group A infections in organized groups, providing rapid differential diagnosis, primarily of tonsillitis and viral streptococcal etiology, allows timely and adequate appointment of the necessary treatment, reduce the risk of complications and reduce the severity of the disease, reduce the economic costs of medical care .

Acute respiratory viral infections remain the most common group of diseases causing significant social and economic damage to society. Objective: to study the epidemiological characteristics of respiratory disease influenza and other etiology in the modern period in the Republic of Karelia – one of the most disadvantaged of this group of diseases regions of the country.

Materials and methods: On the basis of statistical data and publications is analysed and compared with the performance of the country a long-term dynamics and of etiological structure of acute respiratory viral infections over the years 1980–2016, seasonality of morbidity in separate age and social groups of the population in the years 2013–2016, etiological structure allocated from sore viruses. On the basis of outpatient clinic investigated the clinical characteristics of acute respiratory viral infections in adult outpatients during the period of seasonal rise of morbidity.

Results: it was found a marked reduction in the incidence of flu, partly due to clinical underdiagnosis of the infection, its rejuvenation, the prevalence of mild forms of influenza in adults; the increase in the incidence of infections influenza is not the etiology, mainly due to rhinovirus infection, forming a pronounced autumn rises, the lack of differences between the incidence of viral respiratory infections «organized» and «disorganized» children.

Conclusions: in the modern period the epidemic process of acute respiratory viral infections has gained some new features, important from the point of view of the organization of preventive and curative interventions.

Globally, infection caused by herpes simplex virus type 2 (HSV-2) is one of the most prevalent sexually transmitted infections and the most frequent cause of the genital ulcer diseases. The information about HSV-2 epidemiology in Russia is insufficient. Aim of the study: to define the prevalence of HSV-2 among general adult population in Northwest Russia (Arkhangelsk).

Material and methods. The study was a part of a large Norwegian-Russian project and has a population-based cross-sectional design. The agency on social researches recruited residents of Arkhangelsk using a quota sampling method. The ELISA method was used to test the blood samples on Ig G g2; kits of Vector Best (Novosibirsk, Russia) were used.

Results. Altogether, 1243 participants provided the blood samples and fulfilled the questionnaire. Men represented 44% (543 persons) and women – 56 (700 persons), the mean age was 27,6±5,6 and 27,0±5,7 years respectively. Seroprevalence of HSV-2 in the sample was 18,8% (95% CI 16,8– 21,1), seroprevalence among women was in 2 times higher compared with men (24,0%, 95% CI 20,1–27,3 and 12,2%, 95% CI 9,7–15,2 respectively; p<0,001). The percentage of positive results increased with age in both men and women.

Conclusion. According to our data seroprevalence of HSV-2 among young adults in Arkhangelsk was comparable with seroprevalence in some European countries with high figures and with USA. High prevalence of HSV-2 among females in reproductive age shows the potential of this infection in vertical transmission.

With the aim of improving the system of epidemiological surveillance and monitoring of the most significant and socially determined co-infections, carried out the epidemiological analysis of viral hepatitis B and C, tuberculosis and HIV infection who were registered in the Clinical infectious hospital named. S. P. Botkin in the beginning of this century (17-year period). Examined 707 patients. The comparison carried out between the three groups of patients co-infected identified in 1998–2001 year (period I, 128 patients), 2008– 2011 year (period II, 334 patients) and in 2013–2014 (period III, 245 patients). The proportion of patients with acute viral hepatitis in the first period was 24.2%, and the second and third periods, their share declined to 0,6% and 0,4%. Among the chronic viral hepatitis in the first and second periods were dominated by chronic viral hepatitis C (of 28,1 and 39,8%), and in the third period came to dominate the hepatitis caused by combination viruses B and C (58,8 per cent). Symptoms of liver damage and the activity of enzymes in patients co-infected testified to the increase in the number of cases of cirrhosis of this body and served morphological studies, the prevalence of liver cirrhosis increased more than 4 times, from 8,6% (first period) to 26,9% (period III). Changes of tuberculosis, showed a significant increase in the share of common forms of tuberculosis, including disseminated tuberculosis of the lungs from 19,5% to 57,6% (3 times), and lymph system, including tuberculosis of lymphatic nodes of the chest from 3,1% (period I) to 27,8% (period II). The main changes in patients with co-infection was associated with HIV, whose share increased from 10,0% of (period I) to 91,8% (period III). The mortality of patients co-infected increased from 11,7 to 34,7% (3 times).

Researches of parenteral viral hepatitis prevalence in Republic of Sakha (Yakutia) showed high frequency of hepatitis B and C infection markers. High level of HBsAg carriage among indigenous nationalities representatives living in isolated ethnic group had been revealed (12,9%). HBsAg and anti-HBc detection frequencies is 12,9% and 76,0% respectively in comparison with 5,8% and 14,6% among newcomer population (p<0,001). In spreading of HBV-infection leading role belong to natural ways which prevalence in majority of age groups. This fact causes necessity of prevention measures correction. Among newcomer population, we can note high level of HCV infection. Results of parenteral viral hepatitis epidemiological distinguishes evaluation among indigenous nationalities in Southern Yakutia shows to necessity of medical care system improvement and special medical programs. To reason that measures we have to perform complex screening researches to parenteral viral hepatitis infection markers.