FEATURES OF EPIDEMIC PROCESS OF INFLUENZA A(H1N1)PDM09 AND A(H3N2) IN RUSSIA FROM 2009 TO 2017.

The goal of this work is to compare the key parameters of influenza epidemics of different etiology. Four epidemics of influenza with predominance of influenza A(H1N1)pdm09 and 4 epidemics of influenza A(H3N2) were analyzed using the database of the Federal State Research Institute of Influenza on morbidity, hospitalization, deaths from influenza in 59 cities in the period from 2009 to 2017. The intensity of epidemics involving the influenza A(H1N1)pdm09 decreased from high to medium, while the intensity of epidemics of influenza A(H3N2) increased from low to medium. In the epidemic of influenza A(H1N1)pdm09 in the total population, the incidence of influenza and ARI decreased by a factor of 1.6, while the mortality among patients decreased by a factor of 1.7 in all age groups, except for those over 65 years, for whom the incidence and mortality increased by factors of 1.4 of 2.3, respectively. In the epidemic of A(H3N2), a trend for increasing morbidity and mortality was more pronounced among individuals older than 65 years. Pandemic influenza remains the leading cause of deaths. Among the dead in the epidemic of influenza A(H1N1)pdm09, the proportion of young individuals decreased (including a fourfold decrease of lethality in pregnant women), while the proportion of persons over 65 years increased 7.8 times; in the epidemic of influenza A(H3N2) only 2.5-fold increase was observed. In the epidemic of influenza A(H1N1)pdm09, the proportion of lethality increased among people with cardiovascular diseases and diseases of the internal organs; in the epidemic of influenza A(H3N2), the proportion of lethality increased among people with immunodeficiency, diseases of the internal organs and respiratory system.

[Comparison of the influenza epidemics in Russia caused by the pandemic virus A(H1N1)pdm09 within the period from 2009 to 2013].

Comparative analysis of the three past epidemics with the participation of the pandemic influenza A(H1N1)pdm09 was conducted according to the results of the epidemiological trials of two WHO National influenza centers for the morbidity, hospitalization, and mortality of the influenza in 59 cities of Russia for the period from 2009 to 2013. The first wave of the pandemic of 2009 was the most severe. Compared with this wave, during the next epidemics of 2011 and 2013, the involvement of urban population in the epidemic was reduced, as well as the morbidity in the people 15-64 years old and schoolchildren 7-14 years old. The duration of the epidemic among the adult population, the mortality rate of the total population, and the mortality rates in all age groups were also decreased. Vice versa, the incidence in the children of preschool age and the elderly people and the duration of the epidemic among children (especially preschool children) were increased. The share of patients 65 years and older, children 0-2 years old, and patients with pathology of the cardiovascular systems among the deceased patients increased to 33.6%.

[An influenza pandemic in Russia as a part of a global spread of the influenza A(H1N1)pdm09 in 2009-2011].

The comparison of the first and second waves of the pandemic influenza A(H1N1)pdm09 in the world and Russia was performed on the basis of weekly reports of Regional offices for Europe and on the data of the Federal Center for Influenza on a weekly incidence of influenza and acute respiratory viral infections, hospitalization, and mortality from the influenza in the age groups of population in 49 cities of the Russian Federation. The first wave of the pandemic, which continued in the countries of the world all summer, was of mixed etiology and, in spite of the availability of imported cases, has not caused a steep increase in Russia. The second wave of the pandemic in the countries of the Southern hemisphere was less intense. In the countries of the Northern hemisphere (in autumn 2009), on the contrary, it was more intensive, which was associated with different seasonality of influenza in these hemispheres. In Russia, the second wave (2011) was of a lesser intensity as compared to the first with respect to the duration in the country and in urban areas, the incidence in the entire population, including schoolchildren and adults, the rate of hospitalization and case fatality rate reduction of laboratory-confirmed influenza infection. The duration of the last pandemic of 2009 was the same as in 1957 and 1968, and longer than in 1977. The morbidity was one-half less than in the pandemic of 1957 and 1968, and was approaching the pandemic 1977. At the same time, the incidence in children 3-6 and 7-14 years was higher than in previous pandemics.

Comparison of influenza outbreaks in the Republic of Kazakhstan and Russia induced by 2009 yearly new variant of A(H1N1) influenza virus.

The aim of the work is the comparison of the epidemiology of influenza and acute respiratory virus infections (ARVI) in the Republic of Kazakhstan with the corresponding influenza epidemic in Russia induced by influenza pandemic virus A/California/07/2009 in 2009. Data on influenza and ARVI from the Republic of Kazakhstan and Federal Center of influenza was collected and investigated over the course of several weeks from hospitalized patients with the same diagnosis among all population and in age groups on 16 territories of Kazakhstan and in 49 major cities of Russia. The epidemic in Kazakhstan resembled the Russian epidemic in terms of its abnormally early beginning, expression of monoaetiology, the spread of the epidemic into all territories and start of the epidemics among adult population. High percentage of hospitalized people and lethal outcome were registered in this epidemic. Similarity of epidemic process character in corresponding border-line territories of both countries was found out.

[H1N1V influenza epidemic of 2009 in Russia].

The paper describes dynamics, distribution and morbidity rate during the 2009 A(H1N1)v influenza epidemic in Russia. The epidemic appears to have been especially severe in the cities of the Far-East and Siberian Federal Districts where the average morbidity rate ranged from 6.4% to 19.2% (mean 10.3%) and the epidemic duration from 7.8 to 8 weeks. In less affected Southern and Central Federal Districts A(H1N1)v influenza occurred in 5.7% of the population. Schoolchildren aged 7-4 years showed the highest morbidity rate of 28.8%. The age group of 18-53 years accounted for 79.4% of the total lethality. Viral isolates were genetically stable and exhibited 98.9% hemagglutnin (HA) homology with reference viruses. None of the strains had an amino acid substitution at position 275 of neuraminidase (NA) responsible for resistance to oseltamivir. Towards the end of the epidemic, the viral population displayed a significant rise in the number of strains containing mutations in 4 genes (4 HA, 2 NA, 2 PB2 and 1 PA mutations respectively). 26.7% of the viral isolates obtained in the end of the epidemic had D222G substitution responsible for tropism of viruses to lung tissues. Epidemiologically, the 2009 A(H1NI)v influenza epidemic is described as moderate based on the absence of pathogenicity determinants typical of both A(H1N1) influenza virus of 1918 and A(H5N1) virus. The paper compares the 2009 epidemic with those caused by A/Honkong/68 and A/USSR/ 90/77 viruses. The necessity of classification for the discrimination between A(H1N1) subtype viruses is emphasized.

[Epidemiology of influenza A/California/07/09 (H1N1) in foreign countries in 2009 - 2010 season].

AIM: Study of spread ofa new influenza variant A(H1N1) in the world in 2009. MATERIALS AND METHODS: Analysis of WHO weekly situation reports on influenza epidemic in the countries of the Northern and Southern hemisphere. RESULTS: The first laboratory confirmed cases ofA/California/07/09 (H1N1) were registered in the countries of the Northern hemisphere in 10 days, and in other continents--in 1 month after the increase of morbidity. In the countries of Northern hemisphere 2 increases of A/California/07/09 (H1N1) morbidity were present--spring and autumn, and in the autumn period an increase of population morbidity, rate of hospitalization and number of lethal outcomes was noted. Only in Canada autumn increase of morbidity was not accompanied by an increase in severe influenza cases. In the Southern hemisphere a single but longer increase of morbidity was registered during the summer period. In the South-eastern Asia 2 increases were mostly present with a higher level during the first one. CONCLUSION: A significant increase in morbidity in the autumn periodand its decrease at the same time in the Southern hemisphere are determined by varying seasonality of influenza in the countries of Northern and Southern hemisphere. Spring increase of morbidity was of mixed etiology; and in the autumn period influenza A/ California/07/09 (H1N1) virus dominated in the etiology of diseases.

[Epidemiology of influenza A/California/07/09 (H1N1) in population of 49 cities in Russia in 2009 - 2010].

AIM: Comparison of influenza A(H1N1) epidemic in Russia caused by pandemic virus A/ California/07/09 (H1N1) in 2009 with previous epidemics of influenza A of this subtype. MATERIALS AND METHODS: Analysis of A/California/07/09 (H1N1) epidemic was carried out in 49 cities--bases of Federal center of influenza. Parameters of this epidemic by duration, influenza and acute respiratory viral illness morbidity, hospitalization and mortality rates from laboratory confirmed influenza in the population in general and in age groups (0 - 2 years, 3 - 6 years, 7 - 14 years, 15 - 64 years, 65 years and older) were studied. RESULTS: A/California/07/09 (H1N1) epidemic differed from the seasonal epidemics by unusually early onset, monoetiology, wide coverage of the population of cities, longer duration and higher morbidity in the population from 7 to 64 years of age, higher rate of hospitalizations and number of lethal outcomes in the population from 15 to 64 years of age. Lower morbidity, rate of hospitalizations and number of lethal outcomes was notable in individuals older than 65 years, that is an indication of the presence of an anamnestic immunity. CONCLUSION: Comparative analysis of A/ California/07/09 (H1N1) epidemic with 3 previous influenza pandemics in Russia has shown, that during this epidemic population morbidity was 2 times lower than during 1957 and 1968 pandemics, and the rate approached that of the 1977 pandemic. This epidemic differed from previous pandemics by a delay of city-megapolis and preschool aged children involvement, early onset and lower intensity of peak; lower relative rate of morbidity among adult population and higher--among school children; higher multiplicity of excessive morbidity of children compared with morbidity of people older than 15 years.

[Analysis of pandemic influenza in Russia as a part of the global process based on data of an influenza monitoring reference center].

AIM: Characterization of features of influenza pandemic development in Russia in relation to global process. MATERIALS AND METHODS: Pandemic monitoring was performed by using results of integrative analysis of laboratory diagnostic and population morbidity data from 49 supporting bases of Federal center of influenza from various cities in Russian Federation. Isolation of influenza virus was carried out in MDCK cells and chicken embryos under BSL-3 conditions. Reference virus A/California/07/09 obtained from CDC (Atlanta, USA) and antisera against this strain contained in WHO kit were used for antigenic analysis; rat antisera, new monoclonal antibodies against pandemic influenza virus developed by Research institute of influenza were also used. RESULTS: Based on PCR monitoring during epidemic peak, rate of pandemic influenza identification reached 45-49% of examined patients. About 53% of lethal cases of respiratory infections were caused by pandemic influenza virus, while predominately young people died from pneumonia and acute respiratory distress syndrome. Russian isolates generally were antigenically and genetically similar to the parent pandemic strain--influenza virusA/California/07/09, but contained S203T substitution in hemagglutinin. A number of strains contained D222G mutation that is responsible for the expansion of substrate specificity, as well as strain specific substitutions in hemagglutinin and neuraminidase molecules. The investigated isolates were resistant to remantadin, but sensitive to oseltamivir. CONCLUSION: Due to the formation of population immunity after the end of the first pandemic wave new drift variants of the virus capable of overcoming this formed immunity should be expected that apparently will require the correction of vaccine composition for the 2011 - 2012 season.

[Etiology of influenza according to the data of serological diagnostics in hospital patients in St. Petersburg at the period of 1968 - 2000].

The specific features of the etiology of influenza in children and adults at the period of the simultaneous circulation of two subtypes of influenza virus A, according to the results in the hemagglutination-inhibition reaction in 261,490 influenza and ARD patients hospitalized in St. Petersburg in the course of 32 years, were analyzed. The results of serological diagnostics was shown to correspond to the data of the identification of influenza viruses in Russia and all over the world. At the period of epidemics diseases caused by the main infective agents of the epidemics were detected in 11.0% - 51.0% of cases and by concomitant infective agents, in 0.6% - 12.4% of cases. After the reappearance of influenza virus A(H1N1) in circulation higher frequency of mixed forms of infection and the presence of competition between the subtypes of influenza virus A was noted. In young children a decrease in differences in the proportion of influenza cases, caused by the main and concomitant infective agents, as well as between the detection of influenza in epidemic and in summer periods, was registered.

[Genetic predisposition to latent influenza A virus in children with blood type B(III) as a possible cause of new epidemiologic strains in the countries of South-Eastern Asia]. / Geneticheskaia predraspolozhennost detei s gruppoi krovi B(III) k latentnomu nositelstvu virusov grippa A - vozmozhnaia prichina vozniknoveniia novykh épidemicheskikh shtammov v stranakh Iugo- Vostochnoi Azii.

Regular clinical and epidemiological surveys of two groups of healthy 14-16-year-old boys were carried out for 3 years from September 1989 to May 1992 to investigate the latent circulation of influenza A viruses in the human population. Once or twice a quarter clinical materials were laboratorily studied to detect virus antigens, virus-specific NA-sequences and to determine changes in humoral immunity. The latent circulation of influenza A viruses might be identified in 10-20% of cases long before (2-4 months) the onset of epidemic development. The incidence of epidemic isolations was found to reach 33-36%, gradually decreasing from 29 to 9 or 3.5% in the postepidemic period. The long-term persistence (for 5 months) of virus antigens was reported among healthy children who had chiefly blood group B(III). The new hypothesis that the genetic predisposition of children with blood group B(III) to latent persistence of influenza A viruses may be a possible cause of the emergence of new epidemic strains in the South-East Asian countries has been forwarded.

[Long-term carriers of genomic structures of the influenza virus in the blood leukocytes of children with congenital pathology of central nervous system]. / Dlitelnoe nositelstvo genomnykh struktur virusa grippa v leikotsitakh krovi detei s vrozhdennoi patologiei tsentralnoi nervnoi sistemy.

Children with central nervous abnormality were followed up for a long time (180 days). The clinical samples (nasal swabs, blood samples) were investigated for influenza virus antigens or RNA detection by virologic and molecular biological techniques. No viral isolate was found throughout the follow-up. The use of the polymerase chain reaction made it possible to reveal the long-term persistence (for 180 days) of NS- and genes of influenza A (H1N1) viruses in the leukocytes and of HA-gene in the nasal swabs. No NS-gene was found in the nasal swabs. The polymerase chain reaction appears to be more effective for the diagnosis of persistent influenza infection that the conventional techniques--immunofluorescence and enzyme-linked immunosorbent assay (ELISA).

[Assessment of potential epidemiologic danger of sources of respiratory syncytial infection by biological properties of the pathogen]. / Otsenka potentsial'noi épidemiologicheskoi opasnosti istochnikov respiratorno-sintsitial'noi infektsii po biologicheskim svoistvam vozbuditelia.

Biological properties of 188 strains of respiratory syncytial (RS) virus isolated from 93 institutionalized children during 4 years of observations were correlated with the form and stage of the infectious process, frequency of ARD, and blood group of the children for the evaluation of the epidemiological hazard of sources of RS infection. The degree of virulence of a strain was evaluated by its yields in human embryo lung culture and sensitivity to antibodies (avidity). In clinically manifest forms of RS infection more virulent strains were isolated than in inapparent infections and transitory asymptomatic virus-carrier state. Among the strains derived from children with frequent ARD, highly and moderately virulent strains were prevalent (in 72.7% high and moderate yields in cell culture, and 94.2% low avidity to antibodies) whereas children with rare ARD yielded mainly low virulent strains (70% none or low yields, and 62.5%--highly sensitive to antibodies). The RS virus strains isolated from children with A (II) blood group were found to be less sensitive to antibodies.

[Significance of the heterogeneity of respiratory syncytial viral populations in the development of the epidemic process]. / Znachenie geterogennosti respiratorno-sintsitial'nykh virusnykh populiatsii v razvitii épidemicheskogo protsessa.

The manifestations of the epidemic process in respiratory syncytial (RS) virus infection induced by the strains of the infective agent, differing in their capacity for reproduction at 39 degrees and 37 degrees C and in their sensitivity to antibodies, were compared. The observation of children in a group (about 80 children simultaneously) with the systematic serological and virological examination of sick and healthy children was the main method in this investigation. The circulation of RS viruses with greater capacity for reproduction at 39 degrees and 37 degrees C and lesser sensitivity to antibodies, i.e. viruses with greater virulence, was accompanied by the increased intensity of manifestations of the epidemic process. An increase in the heterogeneity of RS virus populations isolated at the same period of observation was accompanied by the intensification of the epidemic process, which was manifested by increased morbidity rate and a higher level of contamination in children, an increase in the incidence of outbreaks and in the frequency of RS virus reinfection.

Dynamics of some genetic marker changes of respiratory-syncytial virus strains circulating among nursery-school children.

Respiratory-syncytial (RS) virus strains circulating during several years appeared polymorphic in respect of two genetic markers: the regression coefficient of infectious activity (RCIA39) characterizing the isolates by their reproduction in tissue cultures at supraoptimal temperature (39 degrees C) and the regression coefficient of neutralization indices (RCNI) characterizing the degree of sensitivity of the strains to antibodies. High-yield RS viruses were more often isolated from children frequently afflicted by the disease, moderate-yield viruses from moderately sick children, while low-yield or none-yield (at 39 degrees C) strains were isolated from rarely afflicted children. On the other hand, RS strains of low reactivity with prototype antibodies were mainly found in often or moderately sick children and the high-reactive ones in rarely sick children. The variability of the RS virus population was continuous, which is consistent with the uninterrupted course of the epidemic process in the nursery-school community. A change of the RCIA39 marker was observed in nearly 50% of strains already after 1 1/2 to 2 months, but most frequently within 5-6 months from the end of disease. The changes of growth intensity at 39 degrees C followed the pattern: high----moderate----low----none, however, in the next epidemic season these properties showed reversion in an opposite direction.

Natural variability of respiratory-syncytial viruses, their interference and reproduction characteristics.

Over a 5-year observation period in a children-institution community, the severity of respiratory-syncytial (RS) virus infection varied within a broad range depending on biological properties of the circulating virus population. The type of virus population was characterized by a complex of biological features, namely, the extent of their reproduction and interference in tissue cultures of different origin at optimal incubation temperature. The dynamics of genetic alterations in respect to these properties within 1976-1980 was established. Moreover, the seasonal variability of the strains with respect to these properties has been determined.

[Antigenic anachronism of the influenza A(H2N2) viruses in Leningrad in 1980. I. The epidemiological and serological characteristics of the influenzal infection caused by A/Leningrad/80 (H2N2) viruses]. / Antigennyi anakhronizm virusov grippa A(H2N2) v Leningrade v 1980 g. Soobshchenie I. Epidemiologicheskaia i serologicheskaia kharakteristika grippoznoi infektsii, vyzvannoi virusami A/Leningrad/80 (H2N2).

In April-May 1980 a number of unrelated outbreaks of influenza-like diseases were registered in Leningrad in an infant home (50 out of 68 children under observation, aged 3 months to 2 years, were affected) and among the pupils of a boarding school (13 out of 50 adolescents under observation, aged 15-17 years, were affected). 5 strains of influenza A virus were isolated from 3 sick children and 1 clinically healthy child. A similar virus was isolated from a sick adolescent in a boarding school, as well as from a female patient aged 24 years at a domiciliary focus of infection (a sporadic case). In the subsequent laboratory investigation all these 7 strains were identified as viruses A/H2N2. Isolated cases of seroconversion to hemagglutinin H2 were definitely registered in 6 patients during February--May 1980. In 3 cases, including the 24-year old female patient with an acute respiratory disease, seroconversion to hemagglutinin H2 was observed in combination with the release of influenza viruses A/H2N2 from these patients. 2 influenza virus strains with this antigenic characteristic were isolated from a young female patient at an interval of 3 days. Among the patients admitted to the clinics of the Research Institute of Influenza in Leningrad on account of acute respiratory diseases isolated cases of diagnostically significant seroconversion to hemagglutinin H2 constituted 3.5% among children and 4.5% among adults. The study of the level of antihemagglutinins in the population revealed that in 1980 persons aged 18-50 years showed a high level of antihemagglutinins.(ABSTRACT TRUNCATED AT 250 WORDS)

Some regularities in variations of respiratory syncytial virus strains during their epidemiological circulation.

Among respiratory syncytial (RS) viruses circulating in the territory of U.S.S.R., strain variations were observed based on the differences in activity of virus reproduction in human embryo kidney cell cultures at 39 degrees C and in virus sensitivity to antibodies. Mathematical expression of the correlation between these two genetic markers made it possible to classify the new isolates of RS virus into three groups differing in their virulence, namely high, mild and low virulent strains. Populations of RS virus strains varied depending on the epidemic season: during the first period (1976-1977) predominated the high virulent (52-78%) while during the second period (1977-1978) the mild virulent (55-65%) strains. The third period (1978-1979) was characterized by the circulation of a mixture of mild and low virulent strains. In summer low virulent virus strains prevailed (56-89%).

Antigenic and biological criteria of differentiation of the newly isolated strains of respiratory syncytial virus.

Respiratory syncytial (RS) virus strains isolated in different years varied by their antigenic and biological properties. The lowest degree of relatedness was found between the "street" virus and the prototype Long strain; the highest occured among the isolates from a given isolation period. Based on the mean indices of efficiency of the virus reproduction in human embryo lung (HEL) cells at 37 degrees C and 39 degrees C as well as on the degree of virus sensitivity to reference antibodies, the isolates from various years could be divided into three groups, namely high, mild and low virulent strains. The incidence of RS virus infections in children depended on the strain characteristic of virus population circulating in a community of children during the long-term observation period of 1976-1979. Cyclic variation was found in isolation rates of RS viruses; the duration of each cycle in different years ranged from 21 to 41 days. The variability of isolation cycles and the frequency of RS virus reinfections were closely related to the biological characteristics of circulating virus strains.

[Epidemiological analysis of the influenza virus A carrier state in healthy children]. / Epidemiologicheskii analiz nositel'stva virusa grippa A u zdorovykh detei.

Clinical and laboratory examinations in two permanently observed children's institutions were carried out in 1968--1978. Altogether, 241 children were examined virologically 759 times, of them 181 children were found to be truly healthy. In the epidemic period the latter yielded virus in 3.7%, in the interepidemic period in 1%. Unlike asymptomatic infection, transitory virus carrier state was not accompanied by antibody production, and in a number of such cases subsequently led to an overt clinical disease.

[Role of genetic factors in the epidemic process in respiratory viral infections]. / Rol' geneticheskikh faktorov v épidemicheskom protsesse pri respiratornykh virusnykh infektsiiakh.

Observations carried out during 1973-1979 indicate that persons, who are frequently ill, determine the incidence of influenza and acute respiratory diseases among various groups of adult population at all epidemic periods. In constantly observed groups of different ages such persons were the source of 60-85% of the outbreaks of acute respiratory diseases. The correlation between genotypic blood markers (the ABO and HLA systems) and susceptibility to respiratory viruses has been established.