The World Health Organization (WHO) searches influenza virus circulation in community and in natural biocenosis, studies virus strains and their properties, develops diagnostic methods and preventive measures since 1940 th worldwide because of epidemic actuality and high pandemic potential of the influenza virus. The Federal Influenza Center (including Federal Research Institute of Influenza, Saint-Petersburg, and the Center of Virus Ecology, D.I.Ivanovskiy Virology Institute, Honorary Academician N.F.Gamaleya Federal Research Center of Epidemiology and Microbiology, Federal Research Center for Epidemiology and Microbiology, Moscow) performs similar work in Russia in close cooperation with WHO within the framework of the International Programme of Influenza Monitoring. A(H1N1)pdm09 influenza virus dominated in the Northern Hemisphere in the 2015 – 2016 epidemic season. Morbidity growth was noted from the end of January, 2016, to the beginning of March, 2016. The peak morbidity at the 5th week of the year exceeded the epidemic threshold (132 cases per 10,000 of population) and morbidity in the 2014 – 2015 season significantly and approached to the peak morbidity of the 2009 – 2010 epidemic season. The epidemic growth in Russian Federation was provided by three influenza viruses: A(H1N1)pdm09, В and A (H3N2). A(H1N1)pdm09 virus caused 18% of all acute respiratory diseases and accounted for 84% of circulating influenza viruses. Flu was diagnosed in patients of different age with maximal frequency in 3- to 6-year old children. Peak admission number was registered at 5 and 6 weeks (3,538 and 4,109 cases, respectively); this number exceeded the similar parameter of the 2009 – 2010 season. Patients of 15 to 64 years old were admitted more often including those with acute respiratory infection. Two hundred and thirty nine deaths were registered to the 5 th of April, 2016, according to data from the Federal Influenza Center and the Center of Virus Ecology. The diagnosis of A(H1N1)pdm09 flu was confirmed in 97.9% of deaths. Molecular analysis of isolated strains of A(H1N1)pdm09 influenza virus revealed amino acid substitutions in receptor binding site and SA site of hemagglutinin and in genes coding intrinsic proteins PA, NP, M1, and NS1. Influenza virus strains resistive to anti-neuraminidase drugs were encountered in #< 1% in the Northern Hemisphere countries. No strains studied were sensitive to adamantine derivates.

The results of study of the specific features of influenza virus circulation in 2013-2014 in 10 cities of Russia were presented. The results were obtained in basic laboratories of the Center for Ecology and Epidemiology of Influenza, D.I. Ivanovsky Institute of Virology, FSBI «N.F. Gamaleya FRCE M» Ministry of Health of the Russian Federation. The increasing rate of the ARD morbidity was detected during week 9 with further decrease in the morbidity rate till threshold levels reached during week 13. Children 0-2 years old and 3-6 years old were the most involved age group, while the highest rate of hospitalization was found in the age group of 15-64 years old (66%). The influenza A(H1N1)pdm09 and A(H3N2) viruses were the cause of the epidemic, but their activity differed over regions of Russia. The results of study of the antigenic and genetic properties of influenza strains showed for the most of them a close relation to the vaccine strains. Certain heterogeneity of circulating strains and their drift variants was found as well. All the tested strains were sensitive to the oseltamivir and zanamivir, while preserving resistance to the rimantadine. The ratio of the AR D viruses was comparable with the last epidemic seasons.

The peculiarities of the influenza viruses circulation in 2012-2013 are discussed. The results were obtained in 10 cities of Russia, where basic laboratories of the Influenza Ecology and Epidemics Center of on the basis of Ivanovsky Institute of Virology, Ministry of Health of the Russian Federation, are situated. The increasing rate of the ARD morbidity caused by influenza viruses was observed in January-March 2013. The highest indices of the morbidity were detected during 6-7 weeks with the following decreasing rate till threshold levels to week 14. The influenza A (H1N1) pdm09, A (H3N2), and B viruses were the cause of the epidemic, but their activity differed over areas of Russia. The results of study of the antigenic and genetic properties of the influenza strains demonstrated closed relatives with respect to vaccine strains. In addition, some heterogeneity of the circulating strains and their drift variants were found as well. All tested strains were sensitive to oseltamivir (excluding one A (H1N1) pdm09 strain), zanamivir, arbidol, and remained resistant to rimantadine. The ratio of the ARD viruses was comparable with the last epidemic seasons.

The results of analysis of the peculiarities of the epidemic 2011-2012 development in the areas of 10 cities of Russia obtained by basic laboratories of IEES on the base of D.I. Ivanovsky Research Institute of Virology, Ministry of Public Health and Social Development of Russia, are presented. The increasing ARD morbidity caused by the influenza viruses was detected rather late--in February-March 2012. The highest indices of the morbidity were detected during weeks 10-13 followed by decreasing to threshold levels by week 27. Children 0-2 and 3-6 years old were involved the most, meantime the high rate of hospitalization was found for 15-64 years old aged group (25%). Influenza A(H3N2) and B viruses were the cause of the epidemic. The results of studies of the antigenic and genetic properties of the influenza strains showed most of them to be close relatives to the vaccine strains. Some heterogeneity of circulating strains and their drift variants were found as well. All tested strains were sensitive to arbidol, oseltamivir and zanamivir, and saved resistance to rimantadine. The ratio of ARD viruses was comparable with the last epidemic seasons.

The paper gives the results of monitoring the circulation of influenza viruses in the 2010-2011 season, that covers the second year of circulation of pandemic A(H1N1)v virus strains, and their interaction with seasonal A (H3N2) and B strains. Unlike the previous season, the beginning of an increase in morbidity was recorded in January 2011; its peak in the most of contiguous areas was noted at 5-7 weeks of 2011, with its further decline to threshold levels at week 11 of 2011. Preschool and school children were most involved in the epidemic process. Three influenza virus strains (A(H1N1)v, A(H3N2), and B) were found to circulate. Differences were found in the level of participation of the isolated strains in individual areas of the Russian Federation. Detailed typing of the isolated strains determined the compliance of the vast majority of them with vaccine viruses. The pandemic influenza A(H1N1)v virus strains retained their susceptibility to oseltamivir and were resistant to rimantadine. The participation of non-influenza acute respiratory viral infection pathogens was estimated as follows: 11.9% for parainfluenza viruses, 5.9% for adenoviruses, and 3.5% for PC viruses, and 0.7% for pneumonia Mycoplasma, which was comparable with the previous epidemic seasons.

The paper gives the results of monitoring the circulation of influenza viruses in the 2010-2011 season, that covers the second year of circulation of pandemic A(H1N1)v virus strains, and their interaction with seasonal A (H3N2) and B strains. Unlike the previous season, the beginning of an increase in morbidity was recorded in January 2011; its peak in the most of contiguous areas was noted at 5-7 weeks of 2011, with its further decline to threshold levels at week 11 of 2011. Preschool and school children were most involved in the epidemic process. Three influenza virus strains (A(H1N1)v, A(H3N2), and B) were found to circulate. Differences were found in the level of participation of the isolated strains in individual areas of the Russian Federation. Detailed typing of the isolated strains determined the compliance of the vast majority of them with vaccine viruses. The pandemic influenza A(H1N1)v virus strains retained their susceptibility to oseltamivir and were resistant to rimantadine. The participation of non-influenza acute respiratory viral infection pathogens was estimated as follows: 11.9% for parainfluenza viruses, 5.9% for adenoviruses, and 3.5% for PC viruses, and 0.7% for pneumonia Mycoplasma, which was comparable with the previous epidemic seasons.

The data on monitoring influenza viruses in Russia are presented based on the research underway at Ivanovsky Research Institute of Virology since 1959. The Institute's priority in isolation and identification of influenza viruses during epidemics and 2009 pandemic is confirmed. Results of assessment of influenza vaccines and etiotropic preparations, development and introduction of new methods for diagnostics of influenza are discussed.

The paper presents the results of the investigations of the development of a influenza A(H1N1)v pandemic, conducted by the D. I. Ivanovsky Research Institute of Virology, Russian Academy of Medical Sciences, and collaborating laboratories in the European part of Russia, in the Urals, Siberia, and in the Far East. In the prepandemic period (April 27 - June 11, 2009) its first diagnosis was established on May 21, 2009; the first strain was isolated on May 24, 2009; the data on complete genome sequencing were sent to the GenBank; the sensitivity of the strain to commercial antiviral commercial agents was studied. In the early pandemic period (June 11 - August 15), 73 patients who had come from 14 countries of Europe, America, and Asia were identified; 19 virus strains (partially or completely sequenced) were isolated. The pandemic period (August 15 - December 1) was marked by absolute dominance of pandemic influenza virus virtually in the absence of seasonal influenza; the first death caused by pandemic influenza was detected in late August; 3053 subjects were infected with the pandemic strain, as shown by polymerase chain reaction diagnosis; 202 strains were identified.

The antineuraminidase activity of 5 inactivated split and subunit influenza vaccines (IIV) was studied in individuals aged above 65 years. Postvaccinal antibody titers were determined in the lectin test. All the vaccines were shown to have a high antigenicity, by providing high titers of neuraminidase antibodies in most vaccinated persons: The mean geometric titers (MGT) to influenza viruses A(H1N1) and A(H3N2), and B were 7.4-8.0, 8.5-9.2, and 6.8-8.5 log2, respectively. Neuraminidases showed a higher activity in Vaxigrip-vaccinated persons in terms of both the rate of MGT increases and seroconversion that was 78-84%. The parameters of the anti-neuraminidase (anti-NA) and anti-hemagglutinating (anti-HA) activities of IIV are summarized in the paper. There was a high coincidence of the results of both tests. At the same time it was shown that the postvaccinal humoral immune response might be directed only to one of the surface influenza virus proteins. The highest rate of seroconversions as to the surface antigens of all three influenza viruses was observed in Vaxigrip-vaccinated persons. The paper presents the results of comparison of the levels of MGT of antibodies to both viral surface proteins for all vaccinated with IIV, for those vaccinated who were infected during an epidemic season and a place group. The findings confirmed the value of higher titers of postvaccinal antibodies against influenza infection and illness.

The dynamics of immunological characteristics after the administration of polycomponent vaccine B[symbol: see text]-4 to elderly persons, constituting a risk group with respect to acute respiratory diseases and exacerbations of chronic inflammatory diseases of respiratory organs, was studied. The nasal-oral administration of the vaccine induced immunological shifts in the systems of local and systemic immunity. The content of the populations of lymphocytes with markers CD3, CD4, CD16, CD20 was found to have positive dynamics. Considerable shifts in the system of local immunity were registered: the content of sIgA and IgA in the saliva greatly increased; in addition, an increase in the titers of antibodies to Staphylococcus aureus, Klebsiella pneumoniae and Escherichia coli was observed in persons with initially low titers.

To improve the vaccinal prophylaxis of influenza, the comparative study of live trivalent influenza allantoic vaccine, dried, for adults, produced by the Irkutsk Enterprise for Immunological Preparations (Russia), and inactivated trivalent influenza split vaccine, obtained from Wyeth-Ayerst Company (USA), as well as schedules of their combined use for the vaccination of elderly persons, was carried out. The examination of 600 subjects revealed that the vaccines were well tolerated; the combined use of these two vaccines, as well as the use of the inactivated influenza vaccine (IIV) alone, ensured high immunogenic activity (60.0-80.0% of seroconversions). The live influenza vaccine (LIV) stimulated the production of specific antibodies only in 19.0-35.0% of the vaccinees; most of these vaccinees exhibited positive reaction only to one of the vaccine strains. Following the injection of LIV, the level of postvaccinal immunity was retained for at least 6 months. In the vaccinees receiving both vaccines the tendency towards a decrease in mean geometric titer values was less pronounced (0.2-0.4 log2) than in those receiving only IIV (0.5-0.7 log2). At the period of the rise of influenza morbidity, the contamination rate in the vaccinees with the positive postvaccinal dynamics of antibodies was low (26.0%). The indices of effectiveness were 3.8 for combined vaccination, 3.5 for IIV and 2.6 for LIV. The schedule of vaccination with IIV with the possible revaccination LIV 3-4 weeks later was recommended.

The antiviral drug arbidole reduces influenza and acute respiratory diseases (ARD) in children by 1.5-2 times when given in a dose of 0.1-0.2 g 2-3 or 5 times a week, by making influenza and ARD milder and decreasing their duration by 1.4-2.8 days. Unified regimens for prophylactic use of arbidole in influenza and ARD in children and adults are proposed.

Six-year immunologic surveillance of schoolchildren vaccinated according to different schedules in the town of Novgorod demonstrated the efficacy of overall vaccinations of children and young people with live anti-influenza vaccines in autumn and winter for 2 years. Then an interval of 3 years is to be made, followed by another 2-year revaccination cycle, provided the same serologic subtypes of influenza A and B are still circulating.

Children aged 3 to 14 were immunized with live recombinant influenza A vaccine; about 120,000 children were followed up for 6 months. Analysis of the morbidity (excepting ARVI and influenza) of the immunized and control groups permitted a conclusion about the safety of the preparation. The protective index of vaccine efficacy during influenza epidemic caused by A/Taiwan/1/86(H1N1) virus was 1.3 to 1.42. Live recombinant influenza vaccine is recommended for public health to be used for protection of children aged 3 to 14 from influenza.

Studies of influenza virus type A and B strains isolated during the epidemics of 1990 and 1991 in Novgorod from sick children previously vaccinated with influenza vaccines demonstrated no influence of postvaccination immunity on the antigenic properties of the isolates from patients with different vaccination history. Under conditions of the concurrent circulation of viruses with previously known and new antigenic structures the difference in the immune response consisted in its greater stimulation of this response to new influenza virus strains.

This study was carried out to compare reactogenicity, immunogenicity, and efficacy of live attenuated and inactivated influenza vaccines prepared from influenza A/Philippines/2/82-like virus strains. Schoolchildren of a boarding school of Moscow were randomly divided into three groups: (1) vaccinated with a live attenuated vaccine, (2) vaccinated with inactivated influenza vaccine, and (3) given placebo. Both vaccines were well tolerated by the children, with practically no severe general or local reactions. The inactivated vaccine was found to be superior to the live one in its capacity to stimulate humoral immunity studied by HI, EIA, and microneutralization tests. In 69.7% of the children given the inactivated vaccine, seroconversion to the vaccine strain was detected by two or three methods of antibody titration used. Only 35.4% seroconversions were demonstrated in children immunized with the live influenza vaccine. Enzyme immunoassay was found to be a more sensitive but less specific method for antibody titration as compared with HI test whereas microneutralization proved to be more specific but less sensitive for titration of antibodies to influenza A (H3N2) viruses.