[Monitoring of influenza and other respiratory diseases causative agents in children, hospitalized with community-acquired pneumonia in 2012-2013 epidemic season].

AIM: Study the circulation of respiratory viruses in children with community-acquired pneumonia (CAP) during the period from October 2012 to May 2013. MATERIALS AND METHODS: 136 children with CAP aged from 3 months to 16 years with ARI symptoms at the disease debut were studied. RNA/DNA of influenza A, B, parainfluenza (PI); adeno-, rhino-, RS-viruses, corona-, metapneumo- (MPV) and bocaviruses were detected in nasopharynx smears by PCR with hybridization-fluorescent detection in real time. Antibodies against influenza viruses A/H1N1/pdm09 California/07/09, epidemic reference strains of influenza viruses A/H1N1/Brisbane/59/07, A/ H3N2/Victoria/361/201 1, B/Wisconsin/1/10, against PI viruses type 1, 2, 3 were determined in paired sera by HAI. RESULTS: In February-March 2013 the number of children protected by antibodies against influenza decreased, and circulation of influenza viruses A/H3N2 and A/H1N1/ pdm09 was detected. Rhinoviruses and PI viruses were determined throughout the epidemic season, bocavirus and adenoviruses--during the autumn-winter period, RS-virus and MPV--during winter-spring. Coronaviruses were not detected. The peak of virus detection was established in February when the threshold of influenza and ARI morbidity was exceeded. The main pathogens of children of the first 3 years of life are rhinoviruses, RS-virus, PI viruses and bocavirus. RS-virus infection at the debut of CAP in children younger than 3 years in 55.5% of cases is associated with the development of broncho-obstructive syndrome. Bocavirus infection in 50% of cases progresses with laryngo-tracheitis and bronchiolitis. CONCLUSION: The fraction of viruses in etiologic structure ofARI in children varies depending on immune layer, season and age of children. Etiology of viral infection at the debut of CAP could only be proven using specialized laboratory studies.

[Molecular-epidemiological monitoring of enterovirus circulation in the Far East and Zabaikalye].

6 year molecular-biological monitoring of enteroviruses in the Far East and Zabaikalye was carried out. Nucleotide sequence of 125 strains was determined from 2006 to 2011. Molecular analysis was carried out in VP1 virus genome region. Phylogenetic interactions for ECHO-6, ECHO-30, ECHO-11, Coxsackie B-5 (CB-5), Coxsackie B-1 (CB-1) and Coxsackie A-9 (CA-9) were analyzed. Highly dynamic epidemiology was shown to be inherent for ECHO-6 and ECHO-30 viruses and is characterized by genetic heterogeneity and consequent change of virus variants. On the contrary a relative stability of circulating genotypes is intrinsic for CB-1, CB-5 and ECHO-11 enteroviruses. The results of molecular-biological studies indicate frequent introduction of new enterovirus variants from countries of Europe and Asia.

[Correlation between the receptor specificity of pandemic influenza A (H1N1)pdm09 virus strains isolated in 2009-2011 and the structure of the receptor-binding site and the probability of fatal primary viral pneumonia].

The receptor specificity (RS) of pandemic influenza A(H1N1) pdm09 virus strains deposited into the State Collection of Viruses of the Russian Federation, D. I. Ivanovsky Research Institute of Virology, Ministry of Health and Social Development of Russia, in the 2009-2010 and 2010-2011 epidemic seasons to a panel of 9 sialoglycopolymers (SGP). The strains were divided into 3 groups according to the W(3/6) index proposed by the authors, which was equal to the amount of reactivities to unbranched alpha2-3-SGP to that of reactivities to unbranched alphal-6-SGP: W(3/6) < or = 1.0; 1.0 < W(3/6) < or = 1.5. The W(3/6) < or = 1.5 group showed a predominance of a2-3-RS, attended by the high incidence of fatal primary viral pneumonias (FPVP) (60.0%) and amino acid replacements in the HA1 receptor-binding site (RBS) (80.0%): D222{G, N} and Q223R. The 1.0 < W(3/6) < or = 1.5 group was characterized by mixed alpha2-3/alpha2-6-RS with the incidence of FPVP (29.7%) and amino acid replacements in the HA1 RBS (40.5%) (D222{G, N, V} and Q223), respectively. In the W(3/6) < or = 1.0 group, alpha2-6-RS was prevalent, FPVPs were absent and amino acid replacements in HA1 RBS (D222{G, E}) were seen only in 6.0% of cases. The number of strains with increased specificity to alpha2-3-sialosides increased in the 2010-2011 epidemic season as compared to the previous season. With their further spread among the population, there may be a rise in cases of severe primary viral pneumonias with possible fatal outcomes, which can be, however, accompanied by a decrease in the capacity of mutants to air-dropwise transmission.

[A possible association of fatal pneumonia with mutations of pandemic influenza A/H1N1 sw1 virus in the receptor-binding site of the HA1 subunit].

The paper gives the results of sequence analysis of 150 positive samples in real-time RT-PCR, including 47 autopsy materials from patients (including 10 pregnant women), who died from fatal pneumonia mainly in November-December 2009, in whom the lifetime etiological diagnosis had not been made and hence no early etiotropic therapy performed. 70% of the primary materials from the deceased patients were found to have pandemic influenza A(H1N1) v mutants in the lung tissue with D222G (15%), D222N (15%), D222E (2%) substitutions, as well as a mixture of mutants (38%). Nasopharyngeal lavages from 3 Chukotka deceased patients exhibited only consensus (nonmutant) D222 virus variants; there was a mixture of consensus and mutant virus variants in the trachea and a mixture of mutant ones in the lung. Preliminary data from the study of the interaction of the hemagglutinin of two strains having D222G and D222N mutations with 9 oligosaccharides imitating the variants of cell receptors for influenza A virus suggest that there is a double receptor specificity for alpha2'-3' and alpha2'-6'-sialosides with a preponderance of alpha2'-3'-specificity. Further spread of the mutants that have acquired a high virulence and preserved their capacity for the respiratory route of human infection may lead to the situation similar to that seen in the 1918-1919 pandemic. Another scenario for evolution of the virus is to preserve its receptor specificity for alpha2'-3'-sialosides and high virulence with losses of alpha2'-6' specificity and capacity for aerosol transmission, by damping the pandemic.

[Molecular epidemiology of ECHO 6 virus, the causative agent of the 2006 outbreak of serous meningitis in Khabarovsk].

A total of 3194 cases of enterovirus meningitis were notified in the Russian Federation in 2005, of them there were 1434 cases in the Khabarovsk Territory. Enteroviruses were isolated from 1020 out of the virologically studied 1362 patients from the Khabarovsk Territory. Viruses E6 and E30 were isolated in 80 and 14.7% of cases, respectively. E1, E3, E7, E33, Coxsackie virus B1, B4, B5, and A10 were sporadically detected. The E6 strains isolated in Komsomolsk-on-Amur were identical while E6 strains isolated in Khabarovsk belonged to two different genotypes and greatly differed from those isolated in Konsomolsk-on-Amur. The virus E30 strains isolated in Khabarovsk and Komsomolsk-on-Amur had a 1% difference in VP1 genome nucleotide sequence and belonged to E30 subtype that circulated in Russia and Kazakhstan in 2004-2005.

[Epidemiologic and etiologic characteristic of enterovirus infections in Khabarovsk region].

Results of epidemiologic, virologic, and serologic studies of enterovirus infections in Khabarovsk region from 1975 to 2006 were analyzed. Patterns of epidemic process of these infections were established: periodic change of dominating type of pathogen in the population; onset of the large epidemic peaks of incidence during emergence of circulation of new for the given area serotypes of enteroviruses; possibility of realization of several routes of virus transmission. Role of water factor in the progress of the epidemic process was revealed. Etiology of the large epidemic rise of aseptic meningitis incidence in Khabarovsk region in 2006 was established--the leading pathogens were ECHO viruses serotypes E6 and E30.

Molecular epidemiology of enteroviruses causing uveitis and multisystem hemorrhagic disease of infants.

We studied molecular epidemiology of highly virulent echovirus 11 and 19 strains that were isolated during five outbreaks of enterovirus uveitis (EU) in Siberia in 1980-1989, and three outbreaks of multisystem hemorrhagic disease of infants (MHD) in 1988-1991. Three genome regions, 5'NTR, VP1-2A junction, and a fragment of 3D polymerase, were analyzed. Phylogenetic grouping in the VP1-2A region correlated with serotyping results. All studied EV11 and EV19 strains, including the prototype EV11 and EV19, formed a major phylogenetic group in VP1-2A region. Within that group, several EV11 isolates from EU and MHD outbreaks formed a distinct cluster in VP1-2A and 5' NTR genome regions, designated EV11/B. All strains of this cluster possessed high virulence for monkeys compared with the prototype echoviruses. Subgrouping within this cluster correlated with year of virus isolation, not with the disease the viruses caused in infants (EU or MHD).

[Etiology, clinical manifestations, and epidemiology in community-acquired respiratory infection in children in the Khabarovsk region]. / Etiologicheskaia kharakteristika, klinika i épidemiologiia gruppovogo zabolevaniia respiratornoi infektsiei u detei Khabarovskogo kraia.

Clinico-epidemiological analysis and etiological verification of the outbreak of respiratory infection among school children in a rural district of the Khabarovsk territory, registered in spring 1997, were made. According to clinical signs, one-third of the patients had whooping cough, while the rest of the children exhibited the signs of respiratory infection with the symptoms of longering bronchitis. A half of the children had not been vaccinated against whooping cough, as they had been given injections of adsorbed DT vaccine with reduced antigen content. Etiologically, the diagnosis of whooping cough was confirmed in 57% of the patients with 47.4% of them having Bordetella pertussis monoinfection and 52.6% having mixed infection, mainly in combination with chlamydiosis. Whooping cough took an abnormal course under these circumstances. Treatment with erythromycin produced a good effect.

[The importance of virological studies in uveitis]. / Znachenie virusologicheskikh issledovanii pri uveitakh.

The paper describes results of the analysis of 853 case histories of patients with uveitis and those of virologic examinations (viruses of respiratory group) in 47 patients with severe uveitis predisposed to chronic recurrent course and resistant to used therapy. As a result of virologic studies, adenovirus from the conjunctiva of one patient was obtained; immunofluorescent studies were positive in 11 patients (virus of grip B in 2, of paragrippe in 1, adenovirus in 4, RS virus in 3, mixed virus infection in 1 patient). Positive serologic reactions were observed in 22 patients (virus of grip A in 7, of grip B in 2, of paragrippe in 1, RS virus in 1, mixed virus infection in 11 persons). The results obtained speak about necessity of virological studies in patients with severe uveitis. It is advisable to combine immunofluorescence and serologic examinations of patients.

[Formation and protective functions of antibodies to neuraminidase of the influenza A virus]. / Formirovanie i zashchitnye funktsii antitel k neiraminidaze virusa grippa A.

The features of production and protective properties of antineuraminidase antibodies in subjects of various ages with influenza infection caused by currently important influenza A virus strains of H1N1 and H3N2 serosubtypes were studied. In children, antineuraminidase antibodies were found to accumulate less intensively than in adults and in infants under 1 year they were detected extremely rarely. In young infants, their titres after the disease decreased more rapidly than antihemagglutinin titres. As compared with adults, in younger children these antibodies have a higher protective role in modifying the severity of influenza infection. A direct correlation between the age of the children and the levels of antineuraminidase antibodies demonstrable in them was established. Within the same period of time, ratio of antihemagglutinins and antineuraminidase antibodies was shown to differ significantly in the population of different regions of the country. The results of trials in volunteers of 10 strains as candidates for a live influenza type A vaccine (H3N2) indicate considerable variability of the immunogenic potency of hemagglutinin and neuraminidase of these strains.

[Characteristics of the epidemic process in enterovirus infections in relation to the study of a serous meningitis outbreak]. / O nekotorykh zakonomernostiakh épidemicheskogo protsessa énterovirusnykh infektsii v sviazi s izucheniem vspyshki seroznogo meningita.

The etiological investigation of an epidemic outbreak of aseptic meningitis occuring in 1978 in Khabarovsk was performed. The leading etiological agent was found to be ECHO-4 virus. Some of the cases were associated with ECHO-20 and Coxsackie B1 viruses. Investigation of the herd immunity to these viruses in the urban population showed that before the outbreak the immune portion to ECHO-4 and ECHO-20 viruses was low, particularly in children and youngsters. This might be due to the fact that active circulation of these viruses and outbreaks of diseases associated with them had occurred 13--15 years before. The immune portion to enteroviruses in different towns of the Far East was shown to be uneven. The results of investigations of the epidemic outbreak and herd immunity permit to consider it to be a typical manifestation of the cyclic circulation of enteroviruses in the territory and in time.

[Etiologic and immunologic characteristics of the influenza A1 epidemic in the Khabarovsk region in November--December 1977]. / Etiologicheskaia i immunologicheskaia kharakteristika épidemii grippa A1 v Khabarovskom krae v noiabre--dekabre 1977 g.

The etiology of an influenza outbreak which had occurred in Khabarovsk since 14 November, 1977 was elucidated. The largest number of cases was recorded among children and adolescents (under 22 years of age). Virological studies during the epidemic yielded 90 strains of influenza virus which were found to be antigenically quite close to A1 virus (HINI) which had circulated in this country in 1947-1956. Influenza viruses could be isolated from subjects under 22. Serological tests (H1, CFT) with paired sera from influenza patients and determinations of IgM showed A1 virus (HINI) to circulate more intensively among subjects under 22 years. A correlation between the presence of humoral immunity in subject over 22 and low incidence of influenza in these population are groups was observed.

[Antigenic relationships of strains of the epidemic virus H1N1 isolated in November-December 1977 in the USSR to inluenza viruses of human and animal origin]. / Antigennye sviazi shtammov épidemicheskogo virusa H1N1, vydelennykh v noiabre--dekabre 1977 g. v SSSR s virusami grippa chelovecheskogo i zhivotnogo proiskhozhdeniia.

The results of the study on the antigentic properties of influenza viruses causing an epidemic outbreak in November, 1977, in the USSR established their relationship with human influenza viruses H1N1 to the homologous titer, with H0N1 to 1/16 titer and the virus isolated from whales in the Pacific ocean (H0-H1Nav2) to 1/8 titer. The epidemic strains have been shown to possess neuraminidase of human influenza virus type 1.

Return of epidemic A1 (H1N1) influenza virus.

Limited outbreaks of influenza were reported in the far east of the U.S.S.R. early in November, 1977, and a week or two later in cities in Siberia and the European parts of the U.S.S.R. The majority of influenza-virus isolates belonged to the H1N1 subtype of influenza-A virus, though strains of the current H3N2 subtype were also isolated. A moderate epidemic of H1N1 influenza spread throughout the country in the middle of December. Mainly children over 5 years and young adults were infected.

Comparison of influenza viruses isolated from man and from whales.

Four isolates of influenza virus strains from Moscow and Habarovsk that caused outbreaks of influenza in November and December 1977 in several cities of the USSR were studied and their haemagglutinins and neuraminidases were compared with those of other human and animal influenza viruses including A/whale/Pacific Ocean/76. In H1 tests these isolates, designated A/USSR/77, reacted with immune serum against A/FM/1/47 (H1N1) to the homologous titre, and with antiserum against A/whale/PO/19/76 virus to 1/8 of the homologous titre. In neuraminidase inhibition tests all A/USSR/77 isolates showed the presence of human N1 type neuraminidase, more closely related to A/sw/New Jersey/76 (Hsw1N1) than to A/FM/1/47 (H1N1) virus. The haemagglutinin of A/whale/Pacific Ocean/19/76 virus occupies an intermediate position between H0 and H1, but its neuraminidase is close to Nav2. The virus from whales multiplies better at low (28 degrees C) and at high (40 degrees C) temperatures than do the viruses of human origin that were tested.