scholarly journals Sensitivity of influenza viruses to specific drugs in Russia during 2017−2020. The rare finds and perspective antivirals

2020 ◽  
Vol 25 (2) ◽  
pp. 65-77
Author(s):  
Natalia V. Breslav ◽  
Kirill G. Krasnoslobotsev ◽  
Evgeniya A. Mukasheva ◽  
Elena S. Kirillova ◽  
Alexandra G. Rosatkevich ◽  
...  

BACKGROUND: The article presents the results of studying the effectiveness of anti-influenza drugs in Russia in the period 20172020. The sensitivity of circulating strains of influenza viruses A(H1N1)pdm09, A(H3N2) and B to neuraminidase inhibitors oseltamivir, zanamivir and rimantadine was determined. The analysis of scientific articles by both domestic and foreign researchers on new promising chemotherapy drugs for influenza viruses was carried out. AIMS: study of the sensitivity of influenza viruses circulating strains to specific anti-influenza drugs in the framework of monitoring in the period 20172020. MATERIALS AND METHODS: The study was conducted within the framework of epidemiological surveillance of the influenza viruses circulation using the collection of the influenza etiology and epidemiology laboratory with the following criteria for selecting strains isolated from pregnant women, patients with complicated flu infection and severe acute respiratory infection (SARI), lethal outcomes, as well as patients undergoing treatment with specific drugs. Virological, immunological, and molecular genetic methods were used in the study, and following drugs substances were used: oseltamivir carboxylate, zanamivir, and rimantadine. RESULTS: For the period 20172020, the sensitivity of 541 influenza A and B viruses epidemic strains to anti-influenza drugs was studied. Most of the studied strains remained sensitive to neuraminidase inhibitors. The exceptions were: in 2017/2018 5 strains of the influenza A(H1N1)pdm09 virus resistant to oseltamivir and 2 strains of the influenza B virus, one with reduced sensitivity to oseltamivir, the second to zanamivir; in 2019/2020 influenza A(H1N1)pdm09 virus strain with reduced sensitivity to both drugs. In the 2018/2019 season, an influenza A/Moscow/246/2018 A(H1N1)pdm09 strain was found to be sensitive to rimantadine. CONCLUSIONS: The main and most common genetic markers of influenza viruses resistance to specific drugs are: for oseltamivir substitution H274Y in the influenza A(H1N1)pdm09 virus NA; for rimantadine substitution S31N in the influenza A(H1N1)pdm09 and A(H3N2) viruses M2 protein. Taking into account the low frequency of strains with reduced sensitivity to drugs with antineuraminidase activity, can confidently approve that they remain the drugs of choice for the treatment and prevention of influenza infection.

2020 ◽  
pp. 26-28
Author(s):  
I. A. Malchikov ◽  
A. V. Slobodenyuk ◽  
I. V. Vyalykh ◽  
A. Yu. Markaran ◽  
Yu. V. Grigorieva ◽  
...  

Donor blood serum was tested to detect antibodies against circulating influenza viruses. The titer of specific antibodies was determined in the hemagglutination inhibition test (RTGA) against influenza viruses A/California/07/09(H1N1) pdm09, A/HongKong/4801/14(H3N2) and B/Brisben/46/15. In the pre-epidemic period 2018–2019, the immune layer of people with conditionally protective titers of antiviral antibodies was detected in terms of the lowest to A(H3N2) virus (50.0 %), the highest to influenza B (85.4 %). In the post-epidemic season of 2018–2019, the immune layer to influenza A(H1N1) pdm09 virus did not change significantly, which could indicate the preservation of the activity of this virus in the adult population; an increase in the immune layer of individuals with protective titers of antibodies to influenza A(H3N2) – 67.4 % and a decrease in influenza B virus – 49.2 %. A comparison of the results of laboratory data carried out in the pre- and post-epidemic seasons revealed significant differences in the number of people with average antibody titers against influenza A(H3N2) and B viruses (p < 0.05).


PLoS ONE ◽  
2021 ◽  
Vol 16 (11) ◽  
pp. e0258798
Author(s):  
Victor Daniel Miron ◽  
Leontina Bănică ◽  
Oana Săndulescu ◽  
Simona Paraschiv ◽  
Marius Surleac ◽  
...  

Two main mechanisms contribute to the continuous evolution of influenza viruses: accumulation of mutations in the hemagglutinin and neuraminidase genes (antigenic drift) and genetic re-assortments (antigenic shift). Epidemiological surveillance is important in identifying new genetic variants of influenza viruses with potentially increased pathogenicity and transmissibility. In order to characterize the 2019/20 influenza epidemic in Romania, 1042 respiratory samples were collected from consecutive patients hospitalized with acute respiratory infections in the National Institute for Infectious Diseases “Prof. Dr. Matei Balș”, Bucharest Romania and tested for influenza A virus, influenza B virus and respiratory syncytial virus (RSV) by real-time PCR. Out of them, 516 cases were positive for influenza, with relatively equal distribution of influenza A and B. Two patients had influenza A and B co-infection and 8 patients had influenza-RSV co-infection. The most severe cases, requiring supplemental oxygen administration or intensive care, and the most deaths were reported in patients aged 65 years and over. Subtyping showed the predominance of A(H3N2) compared to A(H1N1)pdm09 pdm09 (60.4% and 39.6% of all subtyped influenza A isolates, respectively), and the circulation of Victoria B lineage only. Influenza B started to circulate first (week 47/2019), with influenza A appearing slightly later (week 50/2019), followed by continued co-circulation of A and B viruses throughout the season. Sixty-eight samples, selected to cover the entire influenza season and all circulating viral types, were analysed by next generation sequencing (NGS). All A(H1N1)pdm09 sequences identified during this season in Romania were clustered in the 6b1.A clade (sub-clades: 6b1.A.183P -5a and 6b1.A.187A). For most A(H1N1)pdm09 sequences, the dominant epitope was Sb (pepitope = 0.25), reducing the vaccine efficacy by approximately 60%. According to phylogenetic analysis, influenza A(H3N2) strains circulating in this season belonged predominantly to clade 3C.3A, with only few sequences in clade 3C.2A1b. These 3C.2A1b sequences, two of which belonged to vaccinated patients, harbored mutations in antigenic sites leading to potential reduction of vaccine efficacy. Phylogenetic analysis of influenza B, lineage Victoria, sequences showed that the circulating strains belonged to clade V1A3. As compared to the other viral types, fewer mutations were observed in B/Victoria strains, with limited impact on vaccine efficiency based on estimations.


Author(s):  
Marianne Wedde ◽  
Djin-Ye Oh ◽  
Silke Buda ◽  
Andrea Thürmer ◽  
Sandra Kaiser ◽  
...  

Background Influenza A(H1N1)pdm09 virus entered the human population in 2009 and evolved within this population for more than ten years. Despite genetic evolution no remarkable changes in the antigenic reactive pattern of these viruses were observed so far. Methods Primary respiratory samples of the German influenza virological sentinel were investigated by qPCR. Influenza virus-positive samples were characterized genetically and antigenetically. Results In December 2019, a antigenic drift variant characterized by an N156K substitution in the hemagglutinin of influenza A(H1N1)pdm09 virus emerged in Germany, which exhibited a reactivity to ferret antiserum that was an average 6 log2 lower than the vaccine virus A/Brisbane/02/2018 and the other A(H1N1)pdm09 viruses circulating in the influenza season 2019-2020. These viruses accounted for 20% of all A(H1N1)pdm09 viruses characterized in the German influenza sentinel. Patients infected with these viruses had a shorter median time period of medical consultation after onset of symptoms and were more frequently treated with neuraminidase inhibitors in comparison to patients infected with other A(H1N1)pdm09 viruses. Conclusions This parallel circulation of two antigenic variants of A(H1N1)pdm09 viruses which differ remarkably in their antigenic reactive pattern contributes to a greater variability in circulating influenza viruses and challenges vaccination.


2021 ◽  
Vol 11 (4) ◽  
pp. 723-736
Author(s):  
O. G. Kurskaya ◽  
A. V. Anoshina ◽  
N. V. Leonova ◽  
O. A. Simkina ◽  
T. V. Komissarova ◽  
...  

Influenza and other acute respiratory viral infections lead to a substantial incidence of severe cases and hospitalizations and so remain a global health problem. Within the frame of the Global Influenza Hospital Surveillance Network (GIHSN), we assessed the contribution of influenza and other respiratory viruses to severe cases of influenzalike diseases in patients hospitalized to the Novosibirsk infectious hospitals in the years 2018–2019. We analyzed 484 nasopharyngeal swabs collected from patients admitted to the hospitals with acute respiratory infections (ARI) using real-time polymerase chain reaction commercial kits. We confirmed viral etiology of ARI in 69.8% cases. Influenza viruses were detected in 47.1% cases, wherein concomitant circulation of influenza A(H1N1)pdm09 and A(H3N2) viruses was observed in 20.7% and 26% of patients, respectively, whereas influenza B virus was detected only in one sample. All analyzed influenza A viruses were antigenically similar to vaccine strains. Genetically, the Novosibirsk strains were closely related to influenza A viruses distributed in Russia and worldwide. Influenza A(H1N1)pdm09 virus was detected in all patients aged 0 to 14 years and required intensive care. Other respiratory viruses were detected in 36.4% of children and 5.8% of adults, and 8.3% of children had viral coinfection, whereas no cases of coinfection were detected in adults. The most common viruses in children were metapneumovirus — 12.8%, rhinovirus — 9.3% and respiratory syncytial virus — 8.0%. In adults, metapneumovirus, adenovirus, parainfluenza virus and rhinovirus were detected with a detection rate no exceeding 2%. In this study, we found no differences in the detection rate of the influenza virus due to concomitant chronic diseases, pregnancy, or smoking habits. At the same time, the detection rate of other respiratory viruses in non-smokers vs. smokers was significantly lower than in smokers and former smokers (26.15%, 66.67% and 62.50%, respectively). In addition, the level of detection of respiratory viruses in children with vs. without chronic pathology was significantly higher (55.3% and 38.7%, respectively). Thus, our and similar studies are important for monitoring and control of the infection.


Vaccines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1094
Author(s):  
Hyder Mir ◽  
Inaamul Haq ◽  
Parvaiz A. Koul

Influenza vaccine uptake in India is poor, and scant data exist regarding the effectiveness of influenza vaccine against hospitalization. Methods: From October 2019 to March 2020, vaccination status of 1219 patients (males n = 571, aged 5–107 years; median, 50 years) hospitalized with severe acute respiratory illness (SARI) was assessed. The patients were tested for influenza viruses and their subtypes by RT PCR. Sequencing of the HA gene was performed. Vaccine effectiveness (VE) against influenza subtypes was estimated by the test negative design. Results: A total of 336 (27.5%) patients were influenza-positive, with influenza B/Victoria accounting for 49.7% (n = 167), followed by influenza A/H1N1 (47.6%; n = 155) and influenza A/H3N2 (4.4%; n = 15). About 6.8% and 8.6% of the influenza-positive and influenza-negative patients, respectively, had been vaccinated. Adjusted VE for any influenza strain was 13% (95% CI −42 to 47), which for influenza B was 0%. HA sequencing revealed that influenza B samples mainly belonged to subclade V1A.3/133R with deletion of residues 163–165, as against the 2-aa deletion in influenza B/Colorado/06/2017 strain, contained in the vaccine. VE for influenza A/H1N1 was 55%. Conclusions: Poor VE due to a genetic mismatch between the circulating strain and the vaccine strain calls for efforts to reduce the mismatch.


2020 ◽  
Vol 18 (6) ◽  
pp. 15-25
Author(s):  
L. S. Karpova ◽  
M. Yu. Pelikh ◽  
N. M. Popovtseva ◽  
T. P Stolyarova ◽  
K. M. Volik

Relevance. Influenza is characterized by global distribution and the difference in its seasonality in countries with temperate and tropical climates. The importance of studying antigenic variation of influenza viruses due to the fact that changes in the antigenic structure is an evolutionary mechanism of adaptation of the virus to ensure its survival and cause annual epidemics.Aims. The Aim of this study was to identify the peculiarities of the geographical spread of influenza (seasonal), etiology and the rate of antigenic variability of influenza viruses A and B.Materials and methods. Based on data from WHO Reference research centers, information was collected on circulating influenza virus strains from 1975 A(H3N2), 1977 A(H1N1)pdm09 and type B of the Yamagata and Victoria lines from 1987 to 2019, as well as data on the number of all identified influenza viruses and individual strains circulating in the Northern and Southern hemispheres from 2008 to 2018.Results and discussion. Analysis of the global spread of influenza, its etiology and antigenic variability of viruses, according to WHO, showed that the influenza A(H1N1)pdm09 virus was the main causative agent of epidemics and regional outbreaks in seasons of high influenza activity in all countries except the United States and Canada, where influenza A(H3N2) and B viruses dominated in countries with severe seasonality, the change of season led to a change in the etiology of influenza, and in tropical countries, the A(H1N1)pdm09 virus more often remained dominant in all seasons of the year.Conclusions. The pronounced seasonality of influenza in Northern countries and its absence in tropical countries, where regional outbreaks prevailed in all seasons of the year, were confirmed. Low antigenic variability of influenza A(H1N1)pdm09 strains was confirmed, and the highest – A(H3N2). Among influenza B strains in the Victoria line had less antigenic variability, because the duration of its circulation before the appearance of a new drift variant was longer than that of the Yamagata line. The tendency to increase the total duration of circulation of influenza viruses B/Victoria, A(H1N1)pdm09 and B/Yamagata due to increased circulation before the emergence of new drift variants is shown.


2018 ◽  
Vol 3 (2) ◽  
pp. 1-2
Author(s):  
Bishnu Prasad Upadhyay

Influenza virus type A and B are responsible for seasonal epidemics as well as pandemics in human. Influenza A viruses are further divided into two major groups namely, low pathogenic seasonal influenza (A/H1N1, A/H1N1 pdm09, A/H3N2) and highly pathogenic influenza virus (H5N1, H5N6, H7N9) on the basis of two surface antigens: hemagglutinin (HA) and neuraminidase (NA). Mutations, including substitutions, deletions, and insertions, are one of the most important mechanisms for producing new variant of influenza viruses. During the last 30 years; more than 50 viral threat has been evolved in South-East Asian countriesof them influenza is one of the major emerging and re-emerging infectious diseases of global concern. Similar to tropical and sub-tropical countries of Southeast Asia; circulation of A/H1N1 pdm09, A/H3N2 and influenza B has been circulating throughout the year with the peak during July-November in Nepal. However; the rate of infection transmission reach peak during the post-rain and winter season of Nepal.


Folia Medica ◽  
2015 ◽  
Vol 57 (2) ◽  
pp. 104-110 ◽  
Author(s):  
Golubinka Bosevska ◽  
Nikola Panovski ◽  
Elizabeta Janceska ◽  
Vladimir Mikik ◽  
Irena Kondova Topuzovska ◽  
...  

AbstractEarly diagnosis and treatment of patients with influenza is the reason why physicians need rapid high-sensitivity influenza diagnostic tests that require no complex lab equipment and can be performed and interpreted within 15 min. The Aim of this study was to compare the rapid Directigen Flu A+B test with real time PCR for detection of influenza viruses in the Republic of Macedonia. MATERIALS AND METHODS: One-hundred-eight respiratory samples (combined nose and throat swabs) were routinely collected for detection of influenza virus during influenza seasons. Forty-one patients were pediatric cases and 59 were adult. Their mean age was 23 years. The patients were allocated into 6 age groups: 0 - 4 yrs, 5 - 9 yrs, 10 - 14 yrs, 15 - 19 yrs, 20-64 yrs and > 65 yrs. Each sample was tested with Directigen Flu A+B and CDC real time PCR kit for detection and typisation/subtypisation of influenza according to the lab diagnostic protocol. RESULTS: Directigen Flu A+B identified influenza A virus in 20 (18.5%) samples and influenza B virus in two 2 (1.9%) samples. The high specificity (100%) and PPV of Directigen Flu A+B we found in our study shows that the positive results do not need to be confirmed. The overall sensitivity of Directigen Flu A+B is 35.1% for influenza A virus and 33.0% for influenza B virus. The sensitivity for influenza A is higher among children hospitalized (45.0%) and outpatients (40.0%) versus adults. CONCLUSION: Directigen Flu A+B has relatively low sensitivity for detection of influenza viruses in combined nose and throat swabs. Negative results must be confirmed.


1978 ◽  
Vol 80 (1) ◽  
pp. 13-19 ◽  
Author(s):  
N. Masurel ◽  
J. I. de Bruijne ◽  
H. A. Beuningh ◽  
H. J. A. Schouten

SUMMARYHaemagglutination inhibition (HI) antibodies against the influenza viruses A/Hong Kong/8/68 (H3N2) and B/Nederland/77/66 were determined in 420 paired sera from mothers and newborns (umbilical cord sera), sampled in 1970–1.A higher concentration of antibodies against influenza A virus was found more frequently in neonatal than in maternal sera. By contrast, low titres against influenza B virus were more frequently observed in neonatal than in maternal sera. Maternal age, duration of pregnancy, and birth-weight did not affect the results of the tests.It is suggested that the titre of the newborn against an epidemic influenza virus can be predicted from that of the mother. Furthermore, the maternal titre may be an indication of the susceptibility of the newborn infant to influenza infections.


2014 ◽  
Vol 66 (1) ◽  
pp. 43-50 ◽  
Author(s):  
J. Radovanov ◽  
V. Milosevic ◽  
I. Hrnjakovic ◽  
V. Petrovic ◽  
M. Ristic ◽  
...  

At present, two influenza A viruses, H1N1pdm09 and H3N2, along with influenza B virus co-circulate in the human population, causing endemic and seasonal epidemic acute febrile respiratory infections, sometimes with life-threatening complications. Detection of influenza viruses in nasopharyngeal swab samples was done by real-time RT-PCR. There were 60.2% (53/88) positive samples in 2010/11, 63.4% (52/82) in 2011/12, and 49.9% (184/369) in 2012/13. Among the positive patients, influenza A viruses were predominant during the first two seasons, while influenza B type was more active during 2012/13. Subtyping of influenza A positive samples revealed the presence of A (H1N1)pdm09 in 2010/11, A (H3N2) in 2011/12, while in 2012/13, both subtypes were detected. The highest seroprevalence against influenza A was in the age-group 30-64, and against influenza B in adults aged 30-64 and >65.


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