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INTRODUCTION: COVID-19 is characterized by a varied clinical course. The aim of the work was to identify associations of SNPs of hemostatic system genes with COVID-19. MATERIALS AND METHODS: DNA was isolated from patients (n=117) and healthy participants (n=104). All infected patients were divided into 3 groups, depending on disease severity assessment, which was appreciated by NEWS2. Another group consisted of participants, who had asymptomatic infection in the past. Determination of SNPs of the genes FGB (-455 G/A), FII (20210 G/A), FV (1691 G/A), FVII (10976 G/A), FXIIIA1 (103 G/T), ITGA2 (807 C/T), ITGB3 (1565 T/C), SERPINE1 (-675 5G/4G) were performed by PCR using the "Genetics of Hemostasis" kit ("DNA-Technology", Russia). RESULTS: In analyzed SNPs, no significant differences were detected between the group of infected patients and healthy participants. But significant association was revealed in gene SERPINE1 (-675 5G/4G), when patient groups, differing in the disease severity, were analyzed relative to the group of participants with asymptomatic infection (p=0.0381; p=0 .0066; p=0.0009). It was found, that as COVID-19 severity scores increased, the proportion of 5G allele of gene SERPINE1 decreased, and the proportion of the 4G allele increased (p=0.005; p=0.009; p=0.0005). Similar processes were observed for genotypes 5G/5G and 4G/4G. DISCUSSION: The gene SERPINE1 (-675 5G/4G) is associated with the severity of COVID-19. CONCLUSION: For the first time, it was discovered that 5G/5G genotype of gene SERPINE1 (-675 5G/4G) can be a marker of a milder course of COVID-19, and the 4G/4G genotype as a more severe one.
Assuntos
COVID-19 , Hemostáticos , Humanos , Infecções Assintomáticas , COVID-19/epidemiologia , COVID-19/genética , Genótipo , Hemostasia/genética , DNA , Inibidor 1 de Ativador de Plasminogênio/genéticaRESUMO
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.
Assuntos
Epidemias , Monitoramento Epidemiológico , Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Influenza Humana/epidemiologia , Adolescente , Adulto , Feminino , Glicoproteínas de Hemaglutininação de Vírus da Influenza/isolamento & purificação , Humanos , Vírus da Influenza A Subtipo H1N1/isolamento & purificação , Vírus da Influenza A Subtipo H1N1/patogenicidade , Vírus da Influenza A Subtipo H3N2/genética , Vírus da Influenza A Subtipo H3N2/isolamento & purificação , Vírus da Influenza A Subtipo H3N2/patogenicidade , Vírus da Influenza A/genética , Vírus da Influenza A/isolamento & purificação , Vírus da Influenza A/patogenicidade , Vírus da Influenza B/genética , Vírus da Influenza B/isolamento & purificação , Vírus da Influenza B/patogenicidade , Vacinas contra Influenza/uso terapêutico , Influenza Humana/genética , Influenza Humana/prevenção & controle , Influenza Humana/virologia , Masculino , Federação Russa/epidemiologia , Estações do Ano , Adulto JovemRESUMO
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.
RESUMO
Serologic studies occupy a significant place in influenza diagnosis. The article presents an analysis of the developed experimental version of ELISA test-systems for the detection of specific antibodies to the virus influenza A(H1N1)pdm09, and their dynamics at different stages of infection as compared with those of the traditional HAI method. The study included 20 paired samples of serum from patients hospitalized at different stages of the disease with etiology associated with the influenza virus A(H1N1)pdm09. Two groups were formed on the basis of HAI data, which showed the presence or absence of significant growth of specific antibodies to the influenza virus A(H1N1)pdm09. The control group consisted of 20 serum samples from individuals without influenza but with chronic hepatitis C. To examine the virus specific antibody two types of ELISA test systems were used. The first system was intended for the detection of IgM to the influenza virus A(H1N1)pdm09; the second was used for revealing specific IgG. The study showed the accuracy and specificity of detectable IgM and IgG to the virus influenza A(H1N1)pdm09. The dynamics of specific IgG titers in 15 of the 20 pairs of sera was reliable. The increase in titers was more pronounced than in the HAI. IgM against influenza virus could be detected up to 10 days, although reliable dynamics of these antibodies was not detected in paired samples. The test system was specific for the determination of both IgG and IgM antibodies to the influenza virus A(H1N1)pdm09 and significantly more sensitive than HAI. Using this ELISA test system, it is possible to monitor the dynamics of IgG to this virus even in the absence of diagnostic increases in antibody titers in HAI.
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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.
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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.
Assuntos
Vírus da Influenza A Subtipo H1N1 , Vírus da Influenza A Subtipo H3N2 , Influenza Humana/epidemiologia , Adolescente , Adulto , Algoritmos , Criança , Pré-Escolar , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Influenza Humana/diagnóstico , Influenza Humana/tratamento farmacológico , Moscou , Gravidez , Federação Russa/epidemiologia , Estações do Ano , Adulto JovemRESUMO
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.
Assuntos
Antivirais/uso terapêutico , Vírus da Influenza A Subtipo H1N1/patogenicidade , Vírus da Influenza A Subtipo H3N2/patogenicidade , Vírus da Influenza B/patogenicidade , Influenza Humana/epidemiologia , Adolescente , Adulto , Criança , Pré-Escolar , Monitoramento Epidemiológico , Feminino , Hospitais/estatística & dados numéricos , Humanos , Lactente , Recém-Nascido , Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos , Vírus da Influenza A Subtipo H1N1/isolamento & purificação , Vírus da Influenza A Subtipo H3N2/efeitos dos fármacos , Vírus da Influenza A Subtipo H3N2/isolamento & purificação , Vírus da Influenza B/efeitos dos fármacos , Vírus da Influenza B/isolamento & purificação , Influenza Humana/complicações , Influenza Humana/tratamento farmacológico , Masculino , Moscou/epidemiologia , Gravidez , Federação Russa/epidemiologia , Estações do Ano , Fatores de Tempo , Adulto JovemRESUMO
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.
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Epidemias , Vírus da Influenza A Subtipo H1N1/patogenicidade , Influenza Humana/epidemiologia , Antivirais/uso terapêutico , Europa (Continente)/epidemiologia , Humanos , Influenza Humana/tratamento farmacológico , Influenza Humana/patologia , Influenza Humana/virologia , Federação Russa/epidemiologiaRESUMO
The goal of this work was to compare the efficiency of the influenza A and B viruses Isolated during 2010-2011 epidemic season. The clinical samples were taken in the test tubes with the transport medium on the.basis of the medium EMEM and commercial test tubes Sigma-Virocult (M40 Compliant, Sigma Virocult) and Virocult (M40 Compliant, Virocult). The results of this work demonstrated higher efficiency of influenza A and B viruses isolation from nasopharyngeal swabs of the patients taken in the test tubes Sigma-Virocult (M40 Compliant, Sigma Virocult) and Virocult (M40 Compliant, Virocult) with the transport medium as compared with the efficiency of influenza strains isolation from nasopharyngeal swabs taken in test tubes with the medium EMEM with respect to all estimated indicators: efficiency of isolation, a passage of isolation and the titer of isolates. The possibility of the long-term storage of a clinical material at room temperature and at 4 degrees C was confirmed, without resorting to freezing, which is significant in the absence of the necessary equipment.
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Antígenos Virais/imunologia , Epidemias , Vírus da Influenza A/imunologia , Vírus da Influenza B/imunologia , Influenza Humana/diagnóstico , Nasofaringe/virologia , Kit de Reagentes para Diagnóstico/normas , Antígenos Virais/isolamento & purificação , Testes de Inibição da Hemaglutinação , Humanos , Vírus da Influenza A/isolamento & purificação , Vírus da Influenza B/isolamento & purificação , Influenza Humana/epidemiologia , Influenza Humana/imunologia , Influenza Humana/virologia , Tipagem Molecular , Federação Russa/epidemiologia , Estações do AnoRESUMO
The emergent 2009 A(H1N1) pandemic brought into acute focus the problem of choosing the most effective anti-influenza drugs for successive influenza infection spreading control. Oseltamivir and zanamivir, influenza virus neuraminidase inhibitors (NAIs), were recommended by the WHO experts for the treatment and prevention of influenza, including that caused by pandemic strains. A major concern regarding the use of specific antiviral compounds is the emergence of the drug-resistant strains. Oseltamivir carboxylate and zanamivir IC50 values were equal to 0.3-5.2 microM for the most of A(H1N1)pdm09 pandemic strains and 1.6-8.6 microM for the strains of influenza B virus in cell-based ELISA assay (2009-2010 season). All the studied strains of influenza A(H1N1 ) pdm09 (151) and B (22) viruses were sensitive to NAIs (2009-2011 seasons). For the first time in Russia oseltamivir-resistant A(H1N1) pdm09 influenza virus was isolated from the patient on the 5th day of a treatment course of this drug.
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Farmacorresistência Viral , Inibidores Enzimáticos/administração & dosagem , Vírus da Influenza A Subtipo H1N1 , Neuraminidase , Oseltamivir/administração & dosagem , Pandemias , Animais , Linhagem Celular , Cães , Farmacorresistência Viral/efeitos dos fármacos , Farmacorresistência Viral/genética , Feminino , Humanos , Vírus da Influenza A Subtipo H1N1/enzimologia , Vírus da Influenza A Subtipo H1N1/genética , Influenza Humana/enzimologia , Influenza Humana/epidemiologia , Influenza Humana/genética , Masculino , Neuraminidase/antagonistas & inibidores , Neuraminidase/genética , Estudos Retrospectivos , Federação RussaRESUMO
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.
Assuntos
Vírus da Influenza A Subtipo H3N2 , Vírus da Influenza B , Influenza Humana , Adolescente , Adulto , Fatores Etários , Antígenos Virais/genética , Antígenos Virais/imunologia , Antivirais/administração & dosagem , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Vírus da Influenza A Subtipo H3N2/genética , Vírus da Influenza A Subtipo H3N2/imunologia , Vírus da Influenza B/genética , Vírus da Influenza B/imunologia , Vacinas contra Influenza/administração & dosagem , Vacinas contra Influenza/genética , Vacinas contra Influenza/imunologia , Influenza Humana/tratamento farmacológico , Influenza Humana/epidemiologia , Influenza Humana/genética , Influenza Humana/imunologia , Masculino , Pessoa de Meia-Idade , Filogenia , Federação Russa/epidemiologia , Fatores de TempoRESUMO
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.
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Infecções por Adenoviridae/epidemiologia , Influenza Humana/epidemiologia , Pandemias , Infecções por Respirovirus/epidemiologia , Academias e Institutos , Adenoviridae/efeitos dos fármacos , Adenoviridae/fisiologia , Infecções por Adenoviridae/tratamento farmacológico , Infecções por Adenoviridae/virologia , Adolescente , Adulto , Antivirais/administração & dosagem , Antivirais/uso terapêutico , Criança , Pré-Escolar , Coinfecção , Farmacorresistência Viral , Humanos , Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos , Vírus da Influenza A Subtipo H1N1/fisiologia , Vírus da Influenza A Subtipo H3N2/efeitos dos fármacos , Vírus da Influenza A Subtipo H3N2/fisiologia , Vírus da Influenza B , Influenza Humana/tratamento farmacológico , Influenza Humana/virologia , Oseltamivir/administração & dosagem , Oseltamivir/uso terapêutico , Respirovirus/efeitos dos fármacos , Respirovirus/fisiologia , Infecções por Respirovirus/tratamento farmacológico , Infecções por Respirovirus/virologia , Rimantadina/administração & dosagem , Rimantadina/uso terapêutico , Federação Russa/epidemiologia , Estações do AnoRESUMO
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.
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Amidas/uso terapêutico , Antivirais/uso terapêutico , Ácidos Dicarboxílicos/uso terapêutico , Imidazóis/uso terapêutico , Vírus da Influenza A Subtipo H1N1/isolamento & purificação , Influenza Humana/tratamento farmacológico , Oseltamivir/uso terapêutico , Pandemias , Adolescente , Adulto , Amidas/administração & dosagem , Antivirais/administração & dosagem , Caproatos , Ácidos Dicarboxílicos/administração & dosagem , Esquema de Medicação , Feminino , Humanos , Imidazóis/administração & dosagem , Influenza Humana/epidemiologia , Influenza Humana/virologia , Masculino , Pessoa de Meia-Idade , Oseltamivir/administração & dosagem , Fatores de Risco , Federação Russa/epidemiologia , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
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.
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Vírus da Influenza A Subtipo H1N1 , Influenza Humana/tratamento farmacológico , Influenza Humana/fisiopatologia , Oseltamivir , Pneumonia Viral/tratamento farmacológico , Tropismo Viral/genética , Zanamivir , Antivirais/administração & dosagem , Antivirais/efeitos adversos , Doenças Transmissíveis Emergentes/virologia , Farmacorresistência Viral , Diagnóstico Precoce , Hemaglutinação por Vírus/genética , Humanos , Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos , Vírus da Influenza A Subtipo H1N1/patogenicidade , Vírus da Influenza A Subtipo H1N1/fisiologia , Vacinas contra Influenza/uso terapêutico , Influenza Humana/epidemiologia , Influenza Humana/virologia , Oseltamivir/administração & dosagem , Oseltamivir/efeitos adversos , Pandemias/prevenção & controle , Pneumonia Viral/epidemiologia , Pneumonia Viral/fisiopatologia , Pneumonia Viral/virologia , Prognóstico , Índice de Gravidade de Doença , Interferência Viral , Zanamivir/administração & dosagem , Zanamivir/efeitos adversosRESUMO
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.
Assuntos
Surtos de Doenças , Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Vírus da Influenza A Subtipo H1N1/genética , Influenza Humana/epidemiologia , Influenza Humana/virologia , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , Complicações Infecciosas na Gravidez/epidemiologia , Complicações Infecciosas na Gravidez/virologia , Subunidades Proteicas/genética , Sítios de Ligação/genética , Feminino , Glicoproteínas de Hemaglutininação de Vírus da Influenza/metabolismo , Humanos , Vírus da Influenza A Subtipo H1N1/patogenicidade , Influenza Humana/mortalidade , Pulmão/virologia , Masculino , Pneumonia Viral/mortalidade , Reação em Cadeia da Polimerase , Gravidez , Complicações Infecciosas na Gravidez/mortalidade , Subunidades Proteicas/metabolismo , Receptores Virais/metabolismo , Federação Russa/epidemiologia , Análise de Sequência de Proteína , VirulênciaRESUMO
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.
Assuntos
Surtos de Doenças , Vírus da Influenza A Subtipo H1N1 , Influenza Humana/epidemiologia , Animais , Antivirais/farmacologia , Linhagem Celular , Embrião de Galinha , Cães , Genoma Viral/genética , Humanos , Vírus da Influenza A Subtipo H1N1/classificação , Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos , Vírus da Influenza A Subtipo H1N1/genética , Vírus da Influenza A Subtipo H1N1/isolamento & purificação , Influenza Humana/mortalidade , Influenza Humana/virologia , Federação Russa/epidemiologia , Análise de Sequência de ProteínaRESUMO
Oseltamivir (Tamiflu) is recommended by WHO experts as a drug to treat and prevent of influenza and to create stocks if its new pandemic variant occurs. The susceptibility of influenza viruses to oseltamivir was studied by polymerase chain reaction-based techniques detecting specific mutations in the neuraminidase gene. The increase in the number of oseltamivir-resistant influenza viruses, isolated from the Russian Federation, with type 1 neuraminidase H274Y mutation from 49% (2007-20008) to 92% (2008-2009) did not depend on the frequency of oseltamivir use. Full correlation of the results obtained by various techniques allows them to be used to monitor the susceptibility of influenza viruses to oseltamivir.
Assuntos
Antivirais/farmacologia , Farmacorresistência Viral/genética , Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos , Vírus da Influenza A Subtipo H1N1/genética , Influenza Humana/epidemiologia , Oseltamivir/farmacologia , Genes Virais/genética , Humanos , Influenza Humana/tratamento farmacológico , Influenza Humana/virologia , Testes de Sensibilidade Microbiana , Mutação , Neuraminidase/genética , Polimorfismo de Fragmento de Restrição , Federação Russa/epidemiologia , Proteínas Virais/genéticaRESUMO
The paper presents the results of the first Russian experience in evaluating the sensitivity of the epidemic and pandemic influenza virus strains, circulating in the period 2009-2010, to the anti-neuraminidase drug zanamivir. A complex of studies, including enzyme immunoassay, fluorometric assay and partial sequence of the neuraminidases (NA1 and NA2) from influenza A virus strain, was applied. The findings Indicate that all the test strains, including those resistant to oseltamivir, were susceptible to zanamivir. The latter is recommended by the WHO for the prevention and treatment of influenza in pregnant women.
Assuntos
Antivirais/farmacologia , Surtos de Doenças , Farmacorresistência Viral , Vírus da Influenza A/efeitos dos fármacos , Vírus da Influenza B/efeitos dos fármacos , Influenza Humana/epidemiologia , Zanamivir/farmacologia , Animais , Linhagem Celular , Cães , Humanos , Vírus da Influenza A/enzimologia , Vírus da Influenza B/enzimologia , Influenza Humana/tratamento farmacológico , Influenza Humana/virologia , Testes de Sensibilidade Microbiana , Neuraminidase/antagonistas & inibidores , Oseltamivir/farmacologia , Federação Russa/epidemiologia , Proteínas Virais/antagonistas & inibidoresRESUMO
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.
Assuntos
Vírus da Influenza A Subtipo H1N1/isolamento & purificação , Influenza Humana/epidemiologia , Influenza Humana/virologia , Substituição de Aminoácidos , Animais , Antivirais/farmacologia , Linhagem Celular , Embrião de Galinha , Farmacorresistência Viral , Genoma Viral , Humanos , Indóis/farmacologia , Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos , Vírus da Influenza A Subtipo H1N1/genética , Testes de Sensibilidade Microbiana , Dados de Sequência Molecular , Moscou/epidemiologia , Neuraminidase/genética , Oseltamivir/farmacologia , Ribavirina/farmacologia , Rimantadina/farmacologia , Viagem , Proteínas Virais/genéticaRESUMO
The paper presents the results of studying the spectrum of influenza A and B viruses to rimantadine, arbidol, and oseltamivir and describes the methods used for these purposes for epidemiological surveillance. Different sensitivities to rimantadine were found among influenza A viruses. During the 2007-2008 season, the vast majority of influenza A(H3N2) virus strains were resistant to rimantadine (77%) while all influenza A(H1N1) virus strains preserved their resistance to this drug. The fact that the epidemic influenza A(H1N1) virus strains that carry the mutation responsible for resistance to the neuraminidase inhibitor oseltamivir (Tamiflu) circulated in the Russian Federation was first established. At the same time all the study influenza A(H1N1) virus strains preserved their susceptibility to rimantadine. The sensitivity of the epidemic strains to arbidol has been confirmed.