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Assessing baloxavir susceptibility of influenza viruses circulating in the United States during the 2016/17 and 2017/18 seasons.

ABSTRACT: The anti-influenza therapeutic baloxavir targets cap-dependent endonuclease activity of polymerase acidic (PA) protein. We monitored baloxavir susceptibility in the United States with next generation sequencing analysis supplemented by phenotypic one-cycle infection assay. Analysis of PA sequences of 6,891 influenza A and B viruses collected during 2016/17 and 2017/18 seasons showed amino acid substitutions: I38L (two A(H1N1)pdm09 viruses), E23G (two A(H1N1)pdm09 viruses) and I38M (one A(H3N2) virus); conferring 4-10-fold reduced susceptibility to baloxavir.

SUBMITTER: Gubareva LV

PROVIDER: S-EPMC6344838 | biostudies-other | 2019 Jan

REPOSITORIES: biostudies-other

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Assessing baloxavir susceptibility of influenza viruses circulating in the United States during the 2016/17 and 2017/18 seasons.

Gubareva Larisa V LV Mishin Vasiliy P VP Patel Mira C MC Chesnokov Anton A Nguyen Ha T HT De La Cruz Juan J Spencer Sarah S Campbell Angela P AP Sinner Mallory M Reid Heather H Garten Rebecca R Katz Jackie M JM Fry Alicia M AM Barnes John J Wentworth David E DE

Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin 20190101 3

The anti-influenza therapeutic baloxavir targets cap-dependent endonuclease activity of polymerase acidic (PA) protein. We monitored baloxavir susceptibility in the United States with next generation sequencing analysis supplemented by phenotypic one-cycle infection assay. Analysis of PA sequences of 6,891 influenza A and B viruses collected during 2016/17 and 2017/18 seasons showed amino acid substitutions: I38L (two A(H1N1)pdm09 viruses), E23G (two A(H1N1)pdm09 viruses) and I38M (one A(H3N2) v ...[more]

PMID: 30670144

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Genetic and antigenic characterisation of influenza A(H3N2) viruses isolated in Yokohama during the 2016/17 and 2017/18 influenza seasons.

Project description:BackgroundInfluenza A(H3N2) virus rapidly evolves to evade human immune responses, resulting in changes in the antigenicity of haemagglutinin (HA). Therefore, continuous genetic and antigenic analyses of A(H3N2) virus are necessary to detect antigenic mutants as quickly as possible.AimWe attempted to phylogenetically and antigenically capture the epidemic trend of A(H3N2) virus infection in Yokohama, Japan during the 2016/17 and 2017/18 influenza seasons.MethodsWe determined the HA sequences of A(H3N2) viruses detected in Yokohama, Japan during the 2016/17 and 2017/18 influenza seasons to identify amino acid substitutions and the loss or gain of potential N-glycosylation sites in HA, both of which potentially affect the antigenicity of HA. We also examined the antigenicity of isolates using ferret antisera obtained from experimentally infected ferrets.ResultsInfluenza A(H3N2) viruses belonging to six clades (clades 3C.2A1, 3C.2A1a, 3C.2A1b, 3C.2A2, 3C.2A3 and 3C.2A4) were detected during the 2016/17 influenza season, whereas viruses belonging to two clades (clades 3C.2A1b and 3C.2A2) dominated during the 2017/18 influenza season. The isolates in clades 3C.2A1a and 3C.2A3 lost one N-linked glycosylation site in HA relative to other clades. Antigenic analysis revealed antigenic differences among clades, especially clade 3C.2A2 and 3C.2A4 viruses, which showed distinct antigenic differences from each other and from other clades in the antigenic map.ConclusionMultiple clades, some of which differed antigenically from others, co-circulated in Yokohama, Japan during the 2016/17 and 2017/18 influenza seasons.

| S-EPMC6373070 | biostudies-literature

Heterogeneity of Circulating Influenza Viruses and Their Impact on Influenza Virus Vaccine Effectiveness During the Influenza Seasons 2016/17 to 2018/19 in Austria.

Project description:The constantly changing pattern in the dominance of viral strains and their evolving subclades during the seasons substantially influences influenza vaccine effectiveness (IVE). In order to further substantiate the importance of detailed data of genetic virus characterization for IVE estimates during the seasons, we performed influenza virus type and subtype specific IVE estimates. IVE estimates were assessed using a test-negative case-control design, in the context of the intraseasonal changes of the heterogeneous mix of circulating influenza virus strains for three influenza seasons (2016/17 to 2018/19) in Austria. Adjusted overall IVE over the three seasons 2016/17, 2017/18, and 2018/19 were -26, 39, and 63%, respectively. In accordance with the changing pattern of the circulating strains a broad range of overall and subtype specific IVEs was obtained: A(H3N2) specific IVE ranged between -26% for season 2016/17 to 58% in season 2018/19, A(H1N1)pdm09 specific IVE was 25% for the season 2017/18 and 65% for the season 2018/19 and Influenza B specific IVE for season 2017/18 was 45%. The results obtained in our study over the three seasons demonstrate the increasingly complex dynamic of the ever changing genetic pattern of the circulating influenza viruses and their influence on IVE estimates. This emphasizes the importance of detailed genetic virus surveillance for reliable IVE estimates.

| S-EPMC7092378 | biostudies-literature

Effectiveness of influenza vaccine against influenza A in Europe in seasons of different A(H1N1)pdm09 and the same A(H3N2) vaccine components (2016-17 and 2017-18).

Project description:IntroductionInfluenza A(H3N2) viruses predominated in Europe in 2016-17. In 2017-18 A(H3N2) and A(H1N1)pdm09 viruses co-circulated. The A(H3N2) vaccine component was the same in both seasons; while the A(H1N1)pdm09 component changed in 2017-18. In both seasons, vaccine seed A(H3N2) viruses developed adaptations/alterations during propagation in eggs, impacting antigenicity.MethodsWe used the test-negative design in a multicentre primary care case-control study in 12 European countries to measure 2016-17 and 2017-18 influenza vaccine effectiveness (VE) against laboratory-confirmed influenza A(H1N1)pdm09 and A(H3N2) overall and by age group.ResultsDuring the 2017-18 season, the overall VE against influenza A(H1N1)pdm09 was 59% (95% CI: 47-69). Among those aged 0-14, 15-64 and ≥65 years, VE against A(H1N1)pdm09 was 64% (95% CI: 37-79), 50% (95% CI: 28-66) and 66% (95% CI: 42-80), respectively. Overall VE against influenza A(H3N2) was 28% (95% CI: 17-38) in 2016-17 and 13% (95% CI: -15 to 34) in 2017-18. Among 0-14-year-olds VE against A(H3N2) was 28% (95%CI: -10 to 53) and 29% (95% CI: -87 to 73), among 15-64-year-olds 34% (95% CI: 18-46) and 33% (95% CI: -3 to 56) and among those aged ≥65 years 15% (95% CI: -10 to 34) and -9% (95% CI: -74 to 32) in 2016-17 and 2017-18, respectively.ConclusionsOur study suggests the new A(H1N1)pdm09 vaccine component conferred good protection against circulating strains, while VE against A(H3N2) was <35% in 2016-17 and 2017-18. The egg propagation derived antigenic mismatch of the vaccine seed virus with circulating strains may have contributed to this low effectiveness. A(H3N2) seed viruses for vaccines in subsequent seasons may be subject to the same adaptations; in years with lower than expected VE, recommendations of preventive measures other than vaccination should be given in a timely manner.

| S-EPMC6807025 | biostudies-literature

Viral Shedding in Recipients of Live Attenuated Influenza Vaccine in the 2016-2017 and 2017-2018 Influenza Seasons in the United Kingdom.

Project description:BackgroundThe (H1N1)pdm09 live attenuated influenza vaccine (LAIV) strain was changed for the 2017-2018 influenza season to improve viral fitness, following poor protection against (H1N1)pdm09 viruses in 2015-2016. We conducted LAIV virus shedding studies to assess the effect of this change.MethodsChildren aged 2-18 years were recruited to receive LAIV in the 2016-2017 (n = 641) and 2017-2018 (n = 362) influenza seasons. Viruses from nasal swabs taken 1, 3, and 6 days postvaccination were quantified by reverse-transcription polymerase chain reaction and area under the curve titers were determined. Presence and quantity of shedding were compared between strains and seasons with adjustment for age and prior LAIV (n = 436), inactivated seasonal vaccine (n = 100), or (H1N1)pdm09 vaccine (n = 166) receipt.Results(H1N1)pdm09 detection (positivity) in 2016-2017 and 2017-2018 (11.2% and 3.9%, respectively) was lower than that of H3N2 (19.7% and 18.7%, respectively) and B/Victoria (28.9% and 33.9%, respectively). (H1N1)pdm09 positivity was higher in 2016-2017 than 2017-2018 (P = .005), but within shedding-positive participants, the (H1N1)pdm09 titer increased in 2017-2018 (P = .02). H3N2 and influenza B titers were similar between seasons. Positivity declined with age, and prior vaccination reduced the likelihood of shedding influenza B but not (H1N1)pdm09.ConclusionsThe (H1N1)pdm09 titer increased in 2017-2018, indicating more efficient virus replication in shedding-positive children than the 2016-2017 strain, although overall positivity was reduced. Age and vaccination history require consideration when correlating virus shedding and protection.Clinical trials registrationNCT02143882, NCT02866942, and NCT03104790.

| S-EPMC7286380 | biostudies-literature

Inactivated influenza vaccine effectiveness among department of defense beneficiaries aged 6 months-17 years, 2016-2017 through 2019-2020 influenza seasons.

Project description:A test-negative case-control study was conducted to assess inactivated influenza vaccine effectiveness (VE) in children aged 6 months-17 years. The database was developed from the US Department of Defense Global Respiratory Pathogen Surveillance Program over four consecutive influenza seasons from 2016 to 2020. A total of 9,385 children including 4,063 medically attended, laboratory-confirmed influenza-positive cases were identified for VE analysis. A generalized linear mixed model with logit link and binomial distribution was used to estimate the VE. The adjusted VE for children was 42% [95% confidence interval (CI): 37-47%] overall, including 55% (95% CI: 47-61%) for influenza A(H1N1)pdm09, 37% (95% CI: 28-45%) for influenza A(H3N2), and 49% (95% CI: 41-55%) for influenza B. The analysis by age groups indicated that the adjusted VE in children aged 6 months-4 years was higher against influenza A(H1N1)pdm09 and influenza B, and comparable against influenza A(H3N2), compared to those in children aged 5-17 years. Further age-stratified analysis showed that the VE against any types of influenza was low and non-significant for children aged 6-11 months (33%; 95% CI:-2-56%), but it was high (54%; 95% CI: 34-67%) in children aged 12-23 months, and then declined linearly with increasing age. In conclusion, the inactivated influenza vaccination was moderately effective against influenza infection, based on the analysis from a large number of children aged 6 months-17 years over multiple influenza seasons.

| S-EPMC8397503 | biostudies-literature

Global update on the susceptibility of human influenza viruses to neuraminidase inhibitors and status of novel antivirals, 2016-2017.

Project description:A total of 13672 viruses, collected by World Health Organization recognised National Influenza Centres between May 2016 and May 2017, were assessed for neuraminidase inhibitor susceptibility by four WHO Collaborating Centres for Reference and Research on Influenza and one WHO Collaborating Centre for the Surveillance Epidemiology and Control of Influenza. The 50% inhibitory concentration (IC50) was determined for oseltamivir and zanamivir for all viruses, and for peramivir and laninamivir in a subset (n?=?8457). Of the viruses tested, 94% were obtained from the Western Pacific, Americas and European WHO regions, while limited viruses were available from the Eastern Mediterranean, African and South East Asian regions. Reduced inhibition (RI) by one or more neuraminidase inhibitor was exhibited by 0.2% of viruses tested (n?=?32). The frequency of viruses with RI has remained low since this global analysis began (2015/16: 0.8%, 2014/15: 0.5%; 2013/14: 1.9%; 2012/13: 0.6%) but 2016/17 has the lowest frequency observed to date. Analysis of 13581 neuraminidase sequences retrieved from public databases, of which 5243 sequences were from viruses not included in the phenotypic analyses, identified 58 further viruses (29 without phenotypic analyses) with amino acid substitutions associated with RI by at least one neuraminidase inhibitor. Bringing the total proportion to 0.5% (90/18915). This 2016/17 analysis demonstrates that neuraminidase inhibitors remain suitable for treatment and prophylaxis of influenza virus infections, but continued monitoring is important. An expansion of surveillance testing is paramount since several novel influenza antivirals are in late stage clinical trials with some resistance already having been identified.

| S-EPMC6094047 | biostudies-other

Characteristics of hospitalizations with an influenza diagnosis, France, 2012-2013 to 2016-2017 influenza seasons.

Project description:BackgroundEstimating the global burden of influenza hospitalizations is required to allocate resources and assess interventions that aim to prevent severe influenza. In France, the current routine influenza surveillance system does not fully measure the burden of severe influenza cases. The objective was to describe the characteristics and severity of influenza hospitalizations by age-group and by season between 2012 and 2017.MethodsAll hospitalizations with a diagnosis of influenza in metropolitan France between July 2012 and June 2017 were extracted from the French national hospital discharge database (PMSI). For each season, the total number of influenza hospitalizations, admissions to intensive care units (ICU), proportion of deaths, lengths of stay, and distribution in diagnosis-related groups were described by age-group.ResultsOver the five seasons, 91 255 hospitalizations with a diagnosis of influenza were identified. The average influenza hospitalization rate varied from 13/100 000 in 2013-2014 to 46/100 000 in 2016-2017. A high rate was observed in elderlies during the 2014-2015 and 2016-2017 seasons, dominated by A(H3N2) virus. The youngest were impacted in 2015-2016, dominated by B/Victoria virus. The proportion of influenza hospitalizations with ICU admission was 10%, and was higher in age-group 40-79 years. The proportion of deaths and length of stay increased with age.ConclusionsThe description of influenza hospitalizations recorded in the PMSI give key information on the burden of severe influenza in France. Analyses of these data annually is valuable in order to document the severity of influenza hospitalizations by age-group and according to the circulating influenza viruses.

| S-EPMC7182605 | biostudies-literature

Influenza Vaccine Effectiveness in the United States During the 2016-2017 Season.

Project description:BACKGROUND:In recent influenza seasons, the effectiveness of inactivated influenza vaccines against circulating A(H3N2) virus has been lower than against A(H1N1)pdm09 and B viruses, even when circulating viruses remained antigenically similar to vaccine components. METHODS:During the 2016-2017 influenza season, vaccine effectiveness (VE) across age groups and vaccine types was examined among outpatients with acute respiratory illness at 5 US sites using a test-negative design that compared the odds of vaccination among reverse transcription polymerase chain reaction-confirmed influenza positives and negatives. RESULTS:Among 7083 enrollees, 1342 (19%) tested positive for influenza A(H3N2), 648 (9%) were positive for influenza B (including B/Yamagata, n = 577), and 5040 (71%) were influenza negative. Vaccine effectiveness was 40% (95% confidence interval [CI], 32% to 46%) against any influenza virus, 33% (95% CI, 23% to 41%) against influenza A(H3N2) viruses, and 53% (95% CI, 43% to 61%) against influenza B viruses. CONCLUSIONS:The 2016-2017 influenza vaccines provided moderate protection against any influenza among outpatients but were less protective against influenza A(H3N2) viruses than B viruses. Approaches to improving effectiveness against A(H3N2) viruses are needed.

| S-EPMC6522684 | biostudies-other

Transmissibility of influenza during the 21st-century epidemics, Spain, influenza seasons 2001/02 to 2017/18.

Project description:BackgroundUnderstanding influenza seasonality is necessary for determining policies for influenza control.AimWe characterised transmissibility during seasonal influenza epidemics, including one influenza pandemic, in Spain during the 21th century by using the moving epidemic method (MEM) to calculate intensity levels and estimate differences across seasons and age groups.MethodsWe applied the MEM to Spanish Influenza Sentinel Surveillance System data from influenza seasons 2001/02 to 2017/18. A modified version of Goldstein's proxy was used as an epidemiological-virological parameter. We calculated the average starting week and peak, the length of the epidemic period and the length from the starting week to the peak of the epidemic, by age group and according to seasonal virus circulation.ResultsIndividuals under 15 years of age presented higher transmissibility, especially in the 2009 influenza A(H1N1) pandemic. Seasons with dominance/co-dominance of influenza A(H3N2) virus presented high intensities in older adults. The 2004/05 influenza season showed the highest influenza-intensity level for all age groups. In 12 seasons, the epidemic started between week 50 and week 3. Epidemics started earlier in individuals under 15 years of age (-1.8 weeks; 95% confidence interval (CI):-2.8 to -0.7) than in those over?64 years when influenza B virus circulated as dominant/co-dominant. The average time from start to peak was 4.3 weeks (95% CI: 3.6-5.0) and the average epidemic length was 8.7 weeks (95% CI: 7.9-9.6).ConclusionsThese findings provide evidence for intensity differences across seasons and age groups, and can be used guide public health actions to diminish influenza-related morbidity and mortality.

| S-EPMC7268270 | biostudies-literature

Ehrlichia muris in Ixodes cookei Ticks, Northeastern United States, 2016-2017.

Project description:Ehrlichia muris is an agent of human ehrlichiosis. To determine its geographic spread in the United States, during 2016-2017, we tested 8,760 ticks from 45 states. A distinct clade of E. muris found in 3 Ixodes cookei ticks from the northeastern United States suggests transmission by these ticks in this region.

| S-EPMC6004831 | biostudies-literature

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