[Characteristics of imported cases of Dengue fever and hemorrhagic Dengue fever in 2009-2019].

INTRODUCTION: In Russia, the approved morbidity statistics system is represented by the International Classification of Diseases of the 10th revision (ICD-10). This classification provides two forms of dengue fever (DF): dengue fever (A90) and hemorrhagic dengue (A91). Official statistics on the ratio of forms of DF is not published in open sources and this lack of information about the real ratio of the forms of DF makes it difficult to objectively assess the factors that determine the severity of this disease. THE AIM: compare the clinical and epidemiological features of dengue fever and hemorrhagic dengue fever in patients hospitalized in 2009-2019 to the City Infectious Clinical Hospital No. 1, Moscow. MATERIALS AND METHODS: A retrospective cohort study. We analyzed the patient database and reviewed 391 medical records of patients with diagnosed dengue fever. We compared gender, age characteristics, travel geography including information about previous visits of patients to endemic regions and dengue virus serotype. To determine the primary and re-infection rate, an analysis of IgG for the dengue virus was carried out on days 1-5 of the disease. To compare indicators, 95% confidence intervals for proportions, medians, and interquartile ranges were calculated. The significance of differences between independent samples for assessing qualitative characteristics was carried out using the criteria χ2, the odds ratio. To assess the quantitative characteristics, the Mann-Whitney test was used. Differences were considered statistically significant at p ≤ 0.05. RESULTS: The proportion of patients with dengue fever was 14.9% of all hospitalized with febrile illnesses that developed after international travel. Hemorrhagic dengue fever (DHF) was diagnosed in 15.7% of patients with dengue fever. DHF developed significantly more often in women, as well as in those who had history of repeated visits to endemic regions. However, DHF was also diagnosed in 10.9% of first-time travelers to tropical countries. We did not find significant differences in the rates of DHF development depending on age and dengue virus serotype. In a number of patients who had not previously traveled to endemic regions, IgG to the dengue virus were detected, which may indicate a previous infection with related flaviviruses. CONCLUSION: It has been established that in the regions most visited by Russians, there is a circulation of all serotypes of the dengue virus with an annual change in the predominant serotype.

[Peculiarities of the influenza and ARVI viruses circulation during epidemic season 2019-2020 in some regions of Russia].

INTRODUCTION: The surveillance of influenza viruses in ARVI structure and study of their properties in epidemic season 2019-2020 in Russian Federation are actual for investigations due to tasks of Global Influenza Strategy initiated by WHO in 2019. MATERIAL AND METHODS: The data of epidemiological surveillance on influenza- and ARVI-associated morbidity and hospitalization in different age groups of population were analyzed; virological, genetic and statistical methods were used. RESULTS: Preschool children were involved in epidemic the most. Meanwhile, the highest rate of hospitalization was observed in patients of 18-40 years old. Influenza A(H1N1)pdm09 virus dominated in etiology of ARVI in hospitalized patients and pneumonia. The role of respiratory viruses in severe cases of pneumonia and bronchoalveolar syndrome in children was shown. The differences in spectrum of circulating viruses caused ARVI in different regions of Russia were found. Influenza A(H1N1)pdm09 and B/Victoria-like viruses were the main etiological agents that caused of epidemic; its activity among all ARVI was 7.3 and 8.0%, respectively. The differences in antigenic properties of influenza A(H3N2) and B epidemic strains compared to vaccine viruses were found. The populations of epidemic strains were presented by following dominant genetic groups: 6B1.A5/183P for A(H1N1)pdm09, 3С.2а1b+137F for A(H3N2) and V1A.3 line B/Victoria-like for B viruses. The good profile of epidemic strains susceptibility to anti-neuraminidase inhibitors has been saved. The most of the studied influenza strains had the receptor specificity characteristic of human influenza viruses. CONCLUSIONS: Obtained results identified the peculiarities of viruses caused the influenza and ARVI in epidemic season 2019-2020 in different regions of Russia. These results suggested the important role of influenza A(H1N1) pdm09 in severe cases and pneumonia in adults 18-40 years old. The continuing drift in influenza viruses was found, which, apparently, could not but affect the efficacy of vaccine prophylaxis and was also considered in the recommendations of WHO experts on the composition of influenza vaccines for the countries of the Northern Hemisphere in the 2020-2021 season.

Genetic diversity of group A rotaviruses in Moscow in 2018-2019.

Here, we present the results of a study in which 639 samples obtained between October 2018 and April 2019 from patients with symptoms of acute gastroenteritis were tested for the presence of a rotavirus infection. The antigen of group A rotavirus was detected in 160 samples (25% of those tested). To study the genetic diversity of group A rotavirus, RNA was isolated from the samples, and polymerase chain reaction combined with reverse transcription (RT-PCR) with primers specific for the VP4, VP6, and VP7 genes of group A rotaviruses was performed. At least one fragment of the group A rotavirus genome was found in 101 samples (15.8%). These fragments were sequenced, and their G and P genotypes-as well as their combinations-were determined. The predominant G genotypes were G9 (35.8% of all genotyped samples) and G4 (28.4%), but the rare G12 genotype was also found (3.0%). The dominant P genotype was P[8]. The spectrum of certain G/P combinations of genotypes included seven variants. The most common variants were G9P[8] (37.2%) and G4P[8] (30.2%).

DRIFT OF INFLUENA A(H3N2) VIRUS: BIOLOGICAL, ANTIGENIC AND GENETIC PROPERTIES IN EPIDEMIC SEASON 2016-2017 IN RUSSIA AND COUNTRIES OF THE NOTHERN HEMYSPHERE.

The article presents the features of the influenza virus circulation for the period from October 2016 to May 2017 in some territories of Russia collaborating with the D.I. Ivanovsky Institute of Virology, Federal State Budgetary Institution "N.F. Gamaleya Federal Research Centre for Epidemiology and Microbiology", Ministry of Health of the Russian Federation. One of the 2016-2017 season's peculiarities in Russia and countries of the Northern hemisphere was the earlier start of an increase in ARD morbidity with peak indexes reached towards the end of December 2016 - January 2017. First, influenza A(H3N2) virus was predominant; then, it was followed by influenza B virus activity observed until the end of the season. The indexes of morbidity were higher than in the previous season, while the rates of hospitalization and mortality were lower, lethal cases being detected in persons 65 years old and older. Epidemic strains of influenza A(H3N2) virus belonged to 3c.2a genetic group, reference strain A/Hong Hong/4408/2014, and its subgroup 3c.2a1, reference A/Bolzano/7/2016, that are antigenically similar. Strains of influenza B virus were antigenically similar to the B/Brisbane/60/2008 vaccine virus. Strains were sensitive to oseltamivir and zanamivir. The share participation of non-influenza ARI viruses was similar to preliminary epidemic seasons. WHO has issued recommendations for influenza virus vaccines composition for 2017-2018 for the Northern hemisphere.

[Enterovirus infections and meningitis in children].

OBJECTIVE: To compare clinical characteristics in children with enterovirus infections (EVI) and meningitis with detailed characteristics of the changes in the content of cerebrospinal fluid (CSF) confirmed in the laboratory. MATERIAL AND METHODS: The results of examinations of 97 children, aged from 2.5 to 15 years, 3 adolescents and 1 adult female patient with EVI were analyzed. Enterovirus RNA isolation and detection in feces and CSF was performed using PCR. RESULTS AND CONCLUSION: Enterovirus RNA in CSF was detected in 44 children, including 3 patients with cytosis (5-7-19 cells in 3 mm3). The frequency and severity of symptoms in 42 patients with EVI and meningitis, 14 children with EVI without meningitis and 8 patients with ICD-10 «Meningitis unspecified¼ are presented. The initial CSF pleocytosis in 1-3 day (4-5 day for two-wave course) in EVI and meningitis was <100 in 4, from 100 to 1000 in 33, >1000 (max 3036) cells in 3 mm3 in 5 patients, including 15 with the predominance of neutrophils (from 77 to 97% in cytosis 114-2300 cells in 3 mm(3)). In the peripheral blood, leukocytosis 10.9-13.8×10(9)/л was noted in 12 children and leukocytosis 14.4-18.7×10(9)/л with the «left shift¼ in 7. Most of the children (n=37) with EVI and meningitis were discharged from the hospital within 10-17 days. The authors suggest the importance of including the variety of clinical presentations of EVI in the additional item «B10 Enterovirus infections¼ in upcoming ICD-11.

[The 2015-2016 epidemic season in Russia and the world: Circulation of influenza viruses, trends in incidence, clinical aspects, and treatment algorithm]. / Épidemicheskii sezon 2015-2016 gg. v Rossii i mire: osobennosti tsirkuliatsii virusov grippa, dinamika zabolevaemosti, klinicheskie aspekty i algoritm lecheniia.

In the 2015-2016 epidemic season, there were dominant influenza A(H1N1)pdm09 strains (over 90%) among the circulating influenza viruses in most countries of the Northern Hemisphere and in Russia. A study of the antigenic properties of influenza A(H1N1)pdm09 strains revealed no differences in those of vaccine virus. Sequencing showed that there were amino acid substitutions in hemagglutinin (receptor binding and Sa sites) and in the genes encoding internal proteins (PA, NP, M1, and NS1). The rise in the incidence in the Russian Federation, which was etiologically associated with influenza viruses, was registered in January-February 2016 with its maximum being observed at 4-5 weeks of 2016. Within the framework of the epidemiological surveillance of circulating influenza viruses in the Russian Federation, which was conducted by the WHO European Office, the D.I. Ivanovsky Institute of Virology, Honorary Academician N.F. Gamaleya Federal Research Centre for Epidemiology and Microbiology, Ministry of Health of Russia, and the Research Institute of Influenza, Ministry of Health of Russia, monitored at the Infectious Diseases Hospital One (IDH-1), Moscow Healthcare Department. Among 1491 examinees, influenza was verified in 104 (21.3%) adults, 208 (42.5%) pregnant women, and 177 (36.2%) children. Influenza A(H1N1)pdm09 was more often diagnosed in the age group of 15-40 years (63.7%); the proportion of influenza patients aged over 50 years increased (22.1%). Most adult patients had moderate influenza; pneumonia complicated the disease in 27.4%. Influenza in the pregnant women was complicated by pneumonia in 4.8% of cases. Influenza was more frequently diagnosed in infants and preschool children aged 0 to 3 years (42.9%), 4 to 6 years (41.2%), and older (15.9%), namely: 7-9 years (10%) and 10-12 years (5.9%). Influenza in the children was complicated by acute tonsillitis (19.4%) and varying degrees of laryngeal stenosis (12.4%). Bronchial obstructive syndrome developed in 2.5%, the rate of pneumonia was 6.2%. Antiviral therapy (AVT) in the early stages of the disease reduces the risk of its severity, the frequency of secondary complications, and the duration and degree of clinical symptoms of influenza. AVT with oseltamivir, zanamivir, imidazolyl ethanamide pentandioic acid (ingavirin), and interferon-a2b (viferon) has been performed in the patients hospitalized at Moscow IDH-1 in the 2015-2016 epidemic season.

Virological, epidemiological, clinic, and molecular genetic features of the influenza epidemic in 2015-2016: prevailing of the influenza A(H1N1)09 pdm virus in Russia and countries of the Northern hemisphere.

This work describes the specific features of the influenza virus circulating in the period from October 2015 to March 2016 in 10 cities of Russia, the basic laboratories of CEEI at the D.I. Ivanovsky Institute of Virology "Federal Research Centre of Epidemilogy and Microbiology named after the honorary academician N.F. Gamaleya" of the Ministry of Health of the Russian Federation. The increase in the morbidity caused by influenza viruses was detected in January-February 2016. The duration of the morbidity peak was 4-5 weeks. The most vulnerable group included children at the age from 3 to 6; a high rate of hospitalization was also detected among people at the age of 15-64 (65%). In clinic symptoms there were middle and severe forms with high frequency of hospitalization as compared with the season of 2009-2010, but much higher in comparison with the season of 2014-2015. Some of the hospitalized patients had virus pneumonias, half of which were bilateral. Among these patients, 10% were children; 30%, adults. The mortality in the intensive care unit of the hospital was 46%. Almost all lethal cases were among unvaccinated patients in the case of late hospitalization and without early antiviral therapy. The predominance of the influenza A(H1N1)09pdm virus both in the Russian Federation and the major part of the countries in the Northern hemisphere was noted. The results of the study of the antigenic properties of influenza strains of A(H1N1)pdm09 virus did not reveal any differences with respect to the vaccine virus. The sequencing data showed the amino acid substitutions in hemagglutinin (receptor binding and Sa sites) and in genes encoding internal proteins (PA, NP, M1, NS1). Strains were sensitive to oseltamivir and zanamivir and maintained resistance to rimantadine. The participation of non-influenza ARI viruses was comparable to that in preliminary epidemic seasons.

[The 2013-2014 epidemic season. Hospital monitoring and antiviral therapy for influenza ].

AIM: To characterize the 2013-2014 epidemic season from the results of detection of influenza infection in patients; to provide the molecular genetic characteristics of the strains isolated from deceased patients. SUBJECTS AND METHODS: The investigators examined 1203 patients (387 children, 509 people older than 16 years of age, 307 pregnant women) admitted to Moscow Clinical Infectious Diseases Hospital One with the clinical signs of acute respiratory viral diseases. Nasal lavage and autopsy specimens were used to isolate viral strains, then to sequence genomic fragments, and to determine receptor specificity. RESULTS: Out of the 1203 examinees, 284 (23.6%) were influenza-positive: 221 (77.8%), 24 (8.5%), and 39 (13.7%) patients had influenza A(H3N2), influenza A(H1N1)pdm09, and influenza B, respectively. Influenza was notified in 42,7% of the pregnant women. There was a preponderance of its moderate form; its severe form developed in single cases having comorbidities. One fatal outcome was registered. The intake of antiviral medications in the first 48 hours of the disease could prevent complications. The investigators revealed mutations in the strain isolated from the bronchoalveolar lavage fluid of a patient with severe pneumonia complicated by acute respiratory distress syndrome. CONCLUSION: There is evidence that there are mutant A(H1N1)pdm09 viruses that have high pneumotropicity. The high risk of their circulation in the population and the risk of severe influenza forms involving the lower respiratory tract remain. Early antiviral therapy in the first 36-48 hours diminishes the clinical manifestations of influenza and reduces the risk of developing complications.

[Isolation of the Chikungunya virus in Moscow from the Indonesian visitor (September, 2013)].

The results of the virological identification of the Chikungunya fever case in Moscow (September, 2013) in an Indonesian visitor are presented. The clinic, electron microscopy, and molecular genetic data are discussed. The Ghikungunya virus (CHIKV) strain CHIKVILEIV-Moscow/1/2013 belonging to the Asian genotype (ID GenBank KF872195) was deposited into the Russian State Collection of viruses (GKV 1239; 18.11.2013).

[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.

[Pandemic influenza in Russia: specific features of clinical course and the absence of early etiotropic therapy as a risk factor of severe forms of the disease].

AIM: To assess efficacy and safety of ingavirin in the treatment of the flu caused by pandemic virus of flu A (H1N1) sw1 in hospitalized patients compared with oseltamivir. MATERIAL AND METHODS: A population-based comparative multicenter trial included 194 patients with verified diagnosis of the flu aged 18-60 years with marked clinical symptoms, body temperature over 38 degrees C and duration of the disease 48 hours maximum. The patients were randomized into 2 groups: group 1 (n=152) received ingavirin (90 mg once a day), group 2 received oseltamivir (n=42) in a dose 150 mg twice a day. Duration of the course was 5 days. RESULTS: Ingavirin and oseltamivir normalized body temperature within treatment hours 24-36 if therapy was initiated in the first disease hours 27.0 +/- 10.0 and 31.9 +/- 10.4. Mean duration of the fever for ingavirin was 35.1 +/- 14.5 hours, for oseltamivir--26.3 +/- 13.0 hours (p < 0.817). The antiviral medicines significantly reduced duration of intoxication (head ache, weakness), catarrhal symptoms (cough, tracheitis, rhinitis), rate of complication vs. patients untreated with antivirus drugs (n=30). CONCLUSION: The results of the treatment show safety and efficacy of ingavirin in uncomplicated flu caused by pandemic virus of flu A (H1N1) sw1 in inpatients. Early etiotropic therapy is a basic treatment policy able to reduce the number of severe complications and lethality.

[Emergence of tick-borne spotted fever group rickettsiosis in Moscow].

AIM: Analysis of clinical cases of tick-borne spotted fever (TSF) group rickettsiosis in 2005 - 2010. MATERIALS AND METHODS: General clinical, biochemical and serological parameters were determined in 10 tick-borne spotted fever group rickettsiosis patients who had visited various geographical regions of the World. RESULTS: TSF group rickettsiosis diagnostic criteria, optimal serological diagnostics timing were determined. Possible diagnostic errors, features of serological diagnostics and antibacterial therapy of this nosologic form are discussed. CONCLUSION: Indication for TSF examination are primarily epidemiologic including tick attachment indication and clinical data. Serological studies are positive only in 3 - 4 weeks after the onset of the infection and thus can not be used for early diagnostics.

[Etiotropic therapy of influenza: lessons from the last pandemic].

Analysis of the experience gained during the last pandemic of 'swine' influenza A (H1N1) sw1 is presented with reference to clinical studies and etiotropic therapy. The mechanism of development of severe pneumonia as a result of mutations at the binding site of hemagglutinin receptor enhancing a2'-3'-sialoside specificity and pneumotropism of the virus is described. The data on the efficiency of Ingavirin, a new Russian antiviral for the treatment of influenza, are reported.

[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.

[Spread of new pandemic influenza A(H1N1)v virus in Russia].

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 24 May, 2009 isolation of the first A/IIV-Moscow/01/2009 (H1N1)swl strain similar to swine A(H1N1) influenza virus from the first Moscow case detected on May 21, 2009, and its deposit in the state collection of viruses (SCV No. 2452 dated May 24, 2009)].

The paper presents the results of the first isolation of the new influenza virus in Moscow and the Russian Federation, which was similar to the swine A/IIV-Moscow/01/2009(H1N1)swl strain isolated on May 24, 2009 from a Russian arrived in Moscow from the USA on May 19, 2009. The antigenic, biological, and molecular genetic properties of this virus were studied. The virus was isolated on MDCK and chick embryos, the hemagglutination titers being 1:8-1:16 AE; the infectious titers being 6.51g of the tissue cytopathogenic infective dose (TCID50) and 7.01g of the common infective dose (CID50). The virus was sensitive to arbidol, ribavirin, oseltamivir, and resistant to rimantadine. The complete virus genome was sequenced; the data were accepted to the Gen Bank on May 28, 2009 under GQ219584-GQ219590 and GQ202724. The significant gene substitution of neuraminidase Asp for Gly in position 451, which has been undetectable in any other strain published in the Gen Bank by the present time is unique only to A/IIV-Moscow/01/2009 (H1N1)swl. The virus has been deposited in the State Collection of Viruses, D. I. Ivanovsky Institute of Virology, Russian Academy of Medical Sciences, under No. 2452 dated May 24, 2009.