[PRINCIPLES OF MONITORING OF ADVERSE EVENTS AFTER VACCINATION IN RUSSIAN FEDERATION AND THE WORLD].

Difference in terminology accepted in our and foreign countries for designating disease of post-vaccination period is shown. Analysis ofthe existing regulating documents in Russian Federa- tion regarding registration of adverse events in post-vaccination period and system of registration accepted in many countries of the world and recommended by WHO is presented. In Russian Federation in accordance with the documents ofthe Federal Service of Surveillance for Protection of Consumers Rights and Human Welfare only certain conditions (post-vaccinal complications) are subject to registration. In accordance with WHO recommendations. all adverse events taking place 1 month after the vaccination must be registered. Summarization of these data allows to detect interconnection between these conditions and vaccination or prove the lack thereof.

[ASSESSMENT OF ATTITUDES TOWARDS IMMUNIZATION IN DIFFERENT GROUPS OF POPULATION OF THE RUSSIAN FEDERATION].

AIM: The study the attitude of population towards the necessity of vaccination. MATERIALS AND METHODS: The survey about the attitude towards vaccination among different groups of population was held. In total there were 1209 respondents: 1031 students of medical, humanitarian and tech- nical universities and 178 parents of children under 2. RESULTS: The most positive attitude towards vaccination was shown by medical students (77%) and parents (71%) and only 33% and, 37% of humanitarian and technical students correspondently realize the significance of vaccination. It is worth noting that large number of people could not define their attitude to vaccination. The ma- jority of respondents notices the lack of knowledge about vaccination wherein less than 50% of respondents get the information from doctors. The rest gets it from different sources mostly from the Internet. About 80% of respondents would prefer to get answers to their questions about vaccination in the Internet. CONCLUSION: The adherence of population of Russia to vaccination has a rather low level. The main reason for it is the lack of knowledge and availability oftrue information about vaccination. It is necessary to use diverse sources of information to provide the population with true facts about vaccination, its significance and safety via mass media and the Internet as well.

[COMPARATIVE CHARACTERISTICS OF EPIDEMIC SEASONS OF INFLUENZA 2015-2016AND 2009 -2010].

AIM: Analyze epidemiologic and- clinical features of influenza epidemic seasons 2009 - 2010 and 2015 - 2016. Materials and methods Forms of federal state statistic observation No.4 , 2, 5, and 6; information from the official web-site of the Research Institute of Influenza of the Ministry of Health of Russian Federation; materials of various conferences and congresses on problems of influenza; information-analytical certificates of the Ministry of Health .of Russian Federation. RESULTS: Epidemic morbidity increases in the season 2009 - 2010. and 2015 - 2016 started at various time and had different duration. Children younger than 14 years of age predominated in the structure of patients in the 2009 - 2010 epidemic season, the main mass of patients were presented by individuals aged 45 - 59 years in the 2015 - 2016 season. The number of lethal outcomes with laboratory confirmed influenza diagnosis in 2009 - 2010 was 687-cases, and in 2015 - 2016 - 663 cases. Almost all the deceased from influenza were not vaccinated against this infection. Cardiovascular system diseases were noted in 484 individuals of the total number of deceased. Most of the deceased were late to seek medical aid. CONCLUSION: Influenza epidemic season 2015 - 2016 differs from 2009 - 2010 season by dynamics of morbidity development and a lower amount of severe forms of the disease and lethal outcomes. This may be-due to an increase of population immunity against pandemic strain A(H1N1)pdm09 via pro-epidemizing in the recent years as well as an increase of influenza vaccination coverage.

[PAPILLOMAVIRUS INFECTION: PRINCIPLE CHARACTERISTICS, CLINICAL MANIFESTATIONS, VACCINE PROPHYLAXIS].

Papillomaviruses are a large and diverse group of viruses. It includes approximately 200 fully described types that have been detected in humans. Human papilloma viruses (HPV) are etiologic agents during various, benign and malignant lesions of mucous membrane and skin epithelium. Very importantly, persistent HPV infection of certain types is a leading cause of carcinoma of uterine cervix, penis, vulva; vagina, anal canal and fauces (including tongue base and tonsils). HPV infection prophylaxis is the best means to control HPV-conditioned diseases, and vaccination, as had been demonstrated, --the most effective method of its prophylaxis. In this paper principle characteristics and clinical manifestations of papillomavirus infection, as well as effectiveness of vaccination against HPV are examined.

[UNIVERSALITY OF CHANGES IN EPIDEMIC PROCESS MANIFESTATIONS OF ANTHROPONOSIS INFECTIONS IN RECENT DECADES].

AIM: Detection of main regularities of anthroponosis infections with various degrees of manageability and factors that determine them in contemporary social-demographic conditions. MATERIALS AND METHODS: A comparative retrospective epidemiologic analysis of morbidity of the population with viral hepatitis A, Sonnei and Flexneri shigellae, rotavirus infection, pertussis, diphtheria, varicella, rubella, pneumococcal infection and possible risk factors by 47 European countries and territories of Russian Federation was carried out, the maximum depth of search was 89 years. RESULTS: Common epidemiologic regularities were shown to be characteristic for anthroponosis infection regardless of the degree of their manageability, that are manifested by the presence of large and small cycles in the multi-year dynamics of morbidity changes of age-related morbidity structure and its pronounced territorial non-uniformity. Intensity of epidemic process of anthroponosis infections and features of its manifestation were established to be determined largely by demographic conditions, size of the child population, including those attending child preschool establishments, number of child preschool establishments and the degree of their admission. A decrease of morbidity with many child infections took place against the background of reduction of the child population in the age structure. CONCLUSION: Universality of changes in the manifestations of epidemiologic process of anthroponosis infections is largely determined by features of the demographic situation.

[Frequency of diseases caused by group A streptococci among invasive infections of soft tissues and characteristics of the causative agent].

AIM: Determine frequency of diseases caused by group A streptococci (GAS) among invasive infections of soft tissues; identify emm-types of the isolated streptococci, determine the presence of bacteriophage integrases and toxin genes in their genomes. MATERIALS AND METHODS: 4750 case histories of patients with soft tissue infections of the purulent-surgical department of the 23rd City Clinical Hospital.of Moscow "Medsantrud" in 2008 - 2011 were analyzed. 46 strains of GAS isolated from patients with invasive streptococcus infection (ISI) were studied. GAS identification was carried out by latex-agglutination method. GAS emm-type was determined by molecular-genetic methods, as well as the presence of bacteriophage integrases int2, int3, int4, int5, int6, int7, int49, bacteriophage toxins speA, speI, sla, speC/J, speL, speH, speC, ssa and speB gene present on the chromosomal DNA. RESULTS: 132 cases (2.8%) were attributed to invasive infections. In 46 cases of invasive infections (35%) GAS were isolated. 22 different emm-types of invasive GAS strains were detected. Only speB gene among all the toxin genes (as well as the expression of the gene--SpeB toxin) was detected in all the strains, whereas sla and speI genes were not detected in any of the strains. Genes of the other toxins (ssa, speL, speC, speA, speH, speC/J) occurred in a number of strains. Genes of phage integrases were detected among all the strains however in varying combinations (from 1 to 4 genes). CONCLUSION: Invasive infections caused by GAS are more frequently spread than had been previously assumed and a high degree of genetic heterogeneity of invasive GAS strains was detected.

[Invasive streptococcal (group A) infection of soft tissues in a Moscow surgical hospital].

AIM: To study features and risk factors of soft tissue's invasive streptococcal infection in surgical unit's patients: a) emm-types of the most often recovered streptococcus; b) human immune response for streptococcal antigens (streptolysin-O and the group A carbohydrate antigen); c) main patient's conditions that complicate the course of soft tissue's streptococcal infection. PATIENTS AND METHODS: 101 surgical unit's patients with soft tissue's infection, which group A streptococcal (GAS) nature, were examined. Emm-types were determined by comparison ofemm gene sequenced part with data of CDC Streptococcus Laboratory. ASO and specific anti-group-carbohydrate IgM were measured with photometry and ELISA4 accordingly. Patient's personal data were analyzed by standard statistical programs. RESULTS: Among 34 emm-types of all streptococcal isolates emm28 and emm64 were registered only in invasive infection. Emm-types 1, 49, 60, 66, 77, 84, 88 were most often. Among 23 sera from invasive GAS-infection's patients, 15(65%) were ASO-negative, 6 (26%) were ASO-low-positive, and 2 (8%) were positive, but negative for the anti-group-A-carbohydrate IgM. CONCLUSION: Lower levels of the humoral immune response as well as risk factors such as trauma, alcoholism, diabetes, chronic venous insufficiency contributed to development of severe forms of GAS-infection. The main streptococcal emm-types for soft tissue's invasive GAS infection in one of Moscow surgical unit's patients in 2008-2011 were registered.

[Clinical epidemiology: theory and practice].

The paper gives the definition, goal, and objectives of clinical epidemiology. The latter is shown to be an epidemiology section that makes it possible to elaborate evidence-based standards for diagnosis, treatment, and prevention and to select a respective algorithm of actions for each specific clinical case. Randomized controlled trials are the gold standard for obtaining evidence. Scales are proposed to evaluate the efficacy of preventive and therapeutic agents: the levels of evidence for their efficacy and the level of strength of its evidence. The authors propose to set up clinical epidemiology centers, one of whose goals should be to introduce a unified system to evaluate the efficacy of preventive and therapeutic agents, by using the principles of evidence-based medicine and the methods of clinical epidemiology.

[Peculiarities of clinical and laboratory characteristics of the activity of streptococcal infection in the patients presenting with tonsillar pathology].

The objective of the present study was to characterize peculiar clinical and laboratory features of trivial tonsillitis for the substantiation of the necessity of prescription of antibacterial therapy. A total of 386 patients presenting with various forms of trivial tonsillitis were available for the determination of anti-streptococcal antibody (ASLO, anti-DN-ase B, ASPH) levels. The results of the measurement were compared based on the Centor scale generally used to estimate the necessity of prescribing antibacterial therapy for the treatment of sore throat. It is concluded that laboratory studies of characteristics of S. Рyogenes activity are needed in all the patients presenting with tonsillitis in order to elucidate the etiological factors responsible for pharyngalgia and the necessity of prescription of antibacterial therapy for the prevention of pyogenic systemic complications of streptococcal infection.

[Scientific, practical and educational aspects of clinical epidemiology].

This article defines clinical epidemiology and describes its goal and objectives. The author claims that clinical epidemiology is a section of epidemiology which underlies the development of evidence-based standards for diagnostics, treatment and prevention and helps to select the appropriate algorithm for each clinical case. The study provides a comprehensive overview of the relationship between clinical epidemiology and evidence-based medicine. Epidemiological research is shown to be methodological basis of clinical epidemiology and evidence-based medicine with randomized controlled trials being the "gold standard" for obtaining reliable data. The key stages in the history of clinical epidemiology are discussed and further development of clinical epidemiology and the integration of courses on clinical epidemiology in education is outlined for progress in medical research and health care practice.

[Role of infectious agents in the emergence of malignant tumors].

According to the data of the International Agency for Research on Cancer (IARC), at least 6 virus species (HPV, EBV, HHV-8/KSHV, HTLV-1, HBV, HCV), 4 helminthes species (Schistosoma haematobium and japonicum, Opisthorchis viverrini, Clonorchis sinensis) and I bacterium species (Helicobacter pylori) have been proved to be capable of causing the development of cancer. The analysis of the data available shows that Merkel cell polyomavirus (MCV), herpes simplex virus (HSV), John Cunningham polyomavirus (JCV), monkey virus 40 (SV40), cytomegalovirus (CMV), xenotropic murine leukemia virus (XMRV), Helicobacter bilis and hepaticus, Campylobacter jejuni, Fusobacterium varium, enteropathogenic Escherichia coli, enterotoxigenic Bacteroides fragilis, Bacteroides vulgatus, Prevotella spp., Streptococcus bovis and anginosus, Treponema denticola, Salmonella typhi, paratyphi and typhimurium, Borrelia burgdorferi, Bartonella spp., Mycobacterium tuberculosis, Chlamydia pneumoniae, trachomatis and psittaci, Neisseria gonorrhoeae, Propionibacterium acnes, Tropheryma whippelii, Schistosoma mansoni, Opistorchis felineus, Strongyloides stercoralis, Taenia solium, Candida spp., Paracoccidioides brasiliensis, Histoplasma capsulatum and Trichomonas vaginalis can also be potential etiological agents of cancer. Apparently, detection of new associations between infectious agents and risk of the development of cancer will facilitate progress in elaboration of prophylaxis measures, early diagnostic methods and, probably, methods of treatment of malignant tumors.

[Humoral immune response in patients with angina and soft tissue infections of group a streptococci etiology].

AIM: Evaluate informativity of simultaneous determination of antibodies (AB) against extracellular (AB against streptolysin-O-ASL-O) and cellular (IgM against A-polysaccharide - A-PSC) antigens in patients with angina and soft tissue infections caused by serogroup A streptococci (SGA) and identify features of humoral immune response to SGA infection according to infectious process localization. MATERIALS AND METHODS. 2 groups of patients with bacteriologically confirmed SGA infection (50 cases of angina - group 1 and 51 case of soft tissue infection - group 2) were examined for the presence of ASL-O by using Architect ci8200 analyzer (Abbott, USA) and IgM against SGA A-PSC by EIA. RESULTS. In group 1, 23 (46%) individuals were recognized as positive by ASL-O level, and in group 2 - 20 (39%; p>0.05); conditionally significant exceeding of normal values (more than 1.5 times) was detected in 25% of patients of each group. Increased level of antibodies against SGA A-PSC was detected in 43 (86%) patients of group 1, and in 30 (59%) of patients of group 2 (p<0.05). In group 1 exceeding of normal values of anti-A-PSC IgM was noted mostly by 1.5 +/- 0.5 times (74%). In group 2 in 43% of patients the level of anti-A-PSC IgM was above normal more than 2 times and in most cases in uncomplicated variants of disease course. In 45% of patients with severe form of soft tissue infection this parameter did not exceed normal values (p<0.05). CONCLUSION. In acute period of disease with simultaneous determination of ASL-O and IgM against A-PSC sensitivity of serologic diagnostics of SGA etiology angina and SGA infection of soft tissues was established to reach 92% and 72%, respectively, and humoral immune response to cellular AG in each form of SGA has its features.

[Development of Streptococcus pyogenes cells inactivation for turbidimetric determination of bacteriolytic activity of phage-associated enzyme].

AIM: Development a method of treatment of Streptococcus pyogenes bacteria that does not disrupt the integrity of surface structure of cell and provides optimal reproducibility of enzyme preparation activity test results. MATERIALS AND METHODS: Museum cultures of S. pyogenes M29 and S. pyogenes T1 were used, as well as standard strain S.pyogenes T5 (ATCC) and 3 phage-associated lysine PlyC preparations (enzybiotics): 2 isolated from phage C1, third--recombinant enzyme obtained by cloning phage C1 DNA. 3 methods of S. pyogenes cells treatment were used: inactivation by chloroform, antibiotics and heating. RESULTS: Treatment of S. pyogenes cells by rifampicin and gentamicin allows simultaneous turbidimetric determination of enzyme preparations activity and streptococci lysis effectiveness with a good reproducibility of test results. Comparison of kinetic curves of streptococci lysis killed by heating with curves of live culture lysis showed that heat treatment of cells results in a decrease oflysis depth and a reduction of enzyme activity. Pattern and effectiveness of lysis of cells incubated with chloroform approached curve of live streptococci lysis, however this method did not exclude lysis of part of cells and required presence of equipment for work with chemical substances. CONCLUSION. S. pyogenes test culture inactivation method by 2-step treatment of culture with antibiotics that does not disrupt the integrity of surface structure of cells and provides optimal reproducibility of enzyme preparation activity test results was developed.

[Terminologic aspects of infections associated with administration of medical aid].

Evolution of key terms used in epidemiology of nosocomial infections is discussed. A modern point of view on terminology and comparison of Russian terms with foreign analogues are presented.

[Infectious diseases in the age of globalization].

The study was aimed to analyse effect of major globalization-related factors on clinical and epidemiological manifestations of infectious diseases. It is shown that they modify the nature of epidemic process influencing its constituent components and significantly accelerate development of infections. All the four major components of globalization, viz. economic, environmental, political, and demographic, are interrelated and influence not only the prevalence of diseases but also the possibility of their prevention. The global character of the threat dictates the necessity of combined approach to its management based on the norms and principles of international law regulating provision of medical services, human rights, environmental protection, trade, and other human activities. Epidemiological safety depends on political will of individual states, financial support of global and national infrastructures for monitoring all factors of the epidemiological process.

[Demographic structure and dynamics of morbidity due to anthroponosis infections].

A fall in the incidence of both preventable and non-preventable or partly preventable infections with different modes of transmission has recently been documented in Russia and worldwide; it parallels marked changes in the demographic structure of the population. Simulation based on parasite-host mathematical models confirmed that demographic structure is a key factor responsible for the incidence of anthroponosis infections producing long-standing or lifelong immunity. It was shown that differences in the frequency of these diseases between countries may be due to different age structure of their populations. The lowered incidence of preventable and non-preventable infections in Russia appears to be associated with changes in the country's demographics. We have developed prognosis of further dynamics of anthroponosis diseases that predicts reversal of the mean morbidity rate toward that recorded in the 1980s and the shift of its higher values to senior age-groups.

[Mechanism of development of epidemic process of group A streptococcal infection in children collectives].

AIM: To study the characteristics of group A streptococcal infection epidemic process in children aged 12 - 14 years arrived to summer camp "Orlenok" (Tuapse) from different regions of Russia. MATERIALS AND METHODS: Epidemiological (retrospective analysis of incidence of acute respiratory infections, tonsillitis, and scarlet fever), microbiological (isolation and identification of group A streptococci [GAS]), and molecular biological (pulse-electrophoresis, analysis of spe and emm genes) methods were used for the study. Objects of the study were GAS strains isolated from patients and carriers. RESULTS: Performed genotyping showed that cases of GAS infection in newly formed children collectives were caused by 2 - 3 epidemically important clones, which were genotypically heterogenous. CONCLUSION: Performed molecular biologic studies demonstrated polyclonal structure of GAS that determines the features of development of epidemic process.

[Strategy and tactics of epidemiologic surveillance for streptococcal infection].

State-of-the-art views on concept and main routes of epidemiologic surveillance for group A streptococcal infection. Thorough characteristics of surveillance subsystems: information-analytic, diagnostic and managerial. Importance of microbiological monitoring, which includes determination of species composition of group A streptococci as well as study of their biological and genetic characteristics, susceptibility to antibiotics and disinfectants, is underlined. Appropriateness of using pulse-electrophoresis, sequencing of erythrogenic toxins' genes and emm-typing of the pathogen was substantiated. This allows to identify identical (epidemic) as well as related and non-related clusters of studied cultures and widens the capabilities to study features of development of infection's epidemic process. Management decisions implemented through the system of preventive and antiepidemic measures, which are regulated by sanitary rules and methodic guidelines.

[Epidemiological surveillance and policy of specific prophylaxis of invasive pneumococcal infections in Russia].

Literature data on contemporary state of specific prophylaxis of invasive pneumococcal infections in Russia and abroad are summarized in the review. Main advantages and disadvantages of existing polysaccharide and conjugated vaccines are discussed. Main routes for epidemiologic surveillance for invasive pneumococcal infections which will promote improvement of analytic, diagnostic and management activities of specialists from Federal Service on Surveillance for Protection of Consumers Rights and Human Welfare are proposed. Recommendations on assessment of invasive pneumococcal disease burden as well as on policy of its prevention are provided.

[Detection rate of markers of mono- and mixed hemotransmissive viral infections in patients of emergency care hospital].

AIM: The objective of this study was to assess dynamics of prevalence of hemotransmissive viral infections (HTVI) markers as mono- or mixed infections in patients admitted to Sklifosovsky Research Institute of Emergency Medicine. MATERIALS AND METHODS: Two hundred thirty-five thousands and seventy patients admitted to the Institute during 1998 - 2007 were screened for the presence of laboratory markers of HTVI (antibodies to HIV, HBsAg, and anti-HCV). RESULTS: The long-term screening revealed 27,942 (11.9%) persons positive for laboratory markers, of which 3,099 (11.1%) were positive for >1 marker. It was established that HIV infection as well as viral hepatitis B and C have different level of similarity and ability to coexist. HIV infection was more frequently detected in association with other infections, whereas hepatitis B and C--as monoinfections. CONCLUSION: Attempt to consider the mutual influence of HTVI on their prevalence from the view of modern concept of microorganisms' ecology was made. Computation of Jaccard similarity coefficient showed that HIV and HCV have the greatest abilities for coexistence, whereas HIV and HBV--the smallest.