#Virological #Surveillance of #Influenza in the eight #epidemic seasons after the 2009 #pandemic in Emilia-Romagna (Northern #Italy) (Acta Biomed., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Acta Biomed. 2019 Sep 13;90(9-S):35-44. doi: 10.23750/abm.v90i9-S.8722.

Virological Surveillance of Influenza in the eight epidemic seasons after the 2009 pandemic in Emilia-Romagna (Northern Italy).

Affanni P1, Colucci ME, Bracchi MT, Capobianco E, Zoni R, Caruso L, Castrucci MR, Puzelli S, Cantarelli A, Veronesi L.

Author information: 1 Department of Medicine and Surgery, University of Parma, Italy. paola.affanni@unipr.it.

 

Abstract

BACKGROUND AND AIM OF THE WORK:

Influenza virological surveillance is essential for monitoring the evolution of influenza viruses (IVs) as well as for annual updating of the vaccine composition. The aim of this study is to analyse IVs circulation in Emilia-Romagna during the eight epidemic seasons after the 2009 pandemic and to evaluate their match with seasonal vaccine strains.

METHODS:

A total of 7882 respiratory specimens from patients with influenza-like illness (ILI), were collected by regional sentinel practitioners and hospital physicians. Viral investigations were conducted by rRT-PCR assay. Genetic characterization was performed for a spatial-temporal representative number of influenza laboratory-confirmed specimens.

RESULTS:

Influenza-positive samples per season ranged between 28.9% (2013-2014) and 66.8% (2012-2013). Co-circulation of IVs type A and type B was observed in all seasons, although with a different intensity. In all seasons, the highest number of positive samples was recorded in younger patients aged 5-14 years with relative frequencies ranging from 40% in the 2013-2014 season and 78% in the 2012-2013 season. Since the 2009 pandemic, A/H1N1pdm09 IVs circulating were closely related to the vaccine strain A/California/7/2009. Antigenic mismatch between vaccine strain and A/H3N2 IVs was observed in the 2011-2012 and 2014-2015 seasons. During 2015-2016, 2016-2017 and 2017-2018 seasons a complete or nearly complete mismatch between the predominant influenza B lineage of IVs type B circulating and vaccine B lineage occurred.

CONCLUSIONS:

This analysis confirms the importance of the virological surveillance and highlights the need of a continuous monitoring of IVs circulation, to improve the most appropriate vaccination strategies. (www.actabiomedica.it).

PMID: 31517888 DOI: 10.23750/abm.v90i9-S.8722

Keywords: Seasonal Influenza; H1N1pdm09; H3N2; Influenza B; Italy.

——

Advertisements

TMPRSS2 is the major activating #protease of #influenza A virus in primary human #airway cells and influenza B virus in human type II #pneumocytes (J Virol., abstract)

[Source: Journal of Virology, full page: (LINK). Abstract, edited.]

TMPRSS2 is the major activating protease of influenza A virus in primary human airway cells and influenza B virus in human type II pneumocytes

Hannah Limburg, Anne Harbig, Dorothea Bestle, David A. Stein, Hong M. Moulton, Julia Jaeger, Harshavardhan Janga, Kornelia Hardes, Janine Koepke, Leon Schulte,Andreas Rembert Koczulla, Bernd Schmeck, Hans-Dieter Klenk, Eva Böttcher-Friebertshäuser

DOI: 10.1128/JVI.00649-19

 

ABSTRACT

Cleavage of influenza virus hemagglutinin (HA) by host cell proteases is essential for virus infectivity and spread. We previously demonstrated in vitro that the transmembrane protease TMPRSS2 cleaves influenza A and B virus (IAV/IBV) HA possessing a monobasic cleavage site. Subsequent studies revealed that TMPRSS2 is crucial for activation and pathogenesis of H1N1pdm and H7N9 IAV in mice. In contrast, activation of H3N2 IAV and IBV was found to be independent of TMPRSS2 expression and supported by as-yet undetermined protease(s).

Here, we investigated the role of TMPRSS2 in proteolytic activation of IAV and IBV in three human airway cell culture systems: primary human bronchial epithelial cells (HBEC), primary type II alveolar epithelial cells (AECII) and Calu-3 cells. Knockdown of TMPRSS2 expression was performed using a previously described antisense peptide-conjugated phosphorodiamidate morpholino oligomer, T-ex5, that interferes with splicing of TMPRSS2 pre-mRNA, resulting in the expression of enzymatically inactive TMPRSS2. T-ex5 treatment produced efficient knockdown of active TMPRSS2 in all three airway cell culture models and prevented proteolytic activation and multiplication of H7N9 IAV in Calu-3 cells and H1N1pdm, H7N9 and H3N2 IAV in HBEC and AECII. T-ex5 treatment also inhibited activation and spread of IBV in AECII, but did not affect IBV activation in HBEC and Calu-3 cells.

This study identifies TMPRSS2 as the major HA-activating protease of IAV in human airway cells and IBV in type II pneumocytes and as a potential target for the development of novel drugs to treat influenza infections.

 

Importance

Influenza A and B viruses (IAV/IBV) cause significant morbidity and mortality during seasonal outbreaks. Cleavage of the viral surface glycoprotein hemagglutinin (HA) by host proteases is a prerequisite for membrane fusion and essential for virus infectivity. Inhibition of relevant proteases provides a promising therapeutic approach that may avoid the development of drug resistance. HA of most influenza viruses is cleaved at a monobasic cleavage site and a number of proteases have been shown to cleave HA in vitro. This study demonstrates that the transmembrane protease TMPRSS2 is the major HA-activating protease of IAV in primary human bronchial cells and of both IAV and IBV in primary human type II pneumocytes. It further reveals that human and murine airway cells can differ in their HA-cleaving protease repertoire. Our data will help drive the development of potent and selective protease inhibitors as novel drugs for influenza treatment.

Copyright © 2019 American Society for Microbiology. All Rights Reserved.

Keywords: Influenza A; Influenza B; H1N1pdm09; H3N2; H7N9; Viral pathogenesis.

——

End of season #influenza #vaccine #effectiveness in #adults and #children in the #UK in 2017/18 (Euro Surveill., abstract)

[Source: Eurosurveillance, full page: (LINK). Abstract, edited.]

End of season influenza vaccine effectiveness in adults and children in the United Kingdom in 2017/18

Richard Pebody 1, Abdelmajid Djennad 1, Joanna Ellis 1, Nick Andrews 1, Diogo F P Marques 2, Simon Cottrell 3,Arlene J Reynolds 2, Rory Gunson 4, Monica Galiano 1, Katja Hoschler 1, Angie Lackenby 1, Chris Robertson 5, Mark O’Doherty 6,Mary Sinnathamby 1, Nikolaos Panagiotopoulos 1, Ivelina Yonova 7,8, Rebecca Webb 7, Catherine Moore 3, Matthew Donati 1, Muhammad Sartaj 6,Samantha J Shepherd 4, Jim McMenamin 2, Simon de Lusignan 7,8, Maria Zambon 1

Affiliations: 1 Public Health England, United Kingdom; 2 Health Protection Scotland, Glasgow, United Kingdom; 3 Public Health Wales, Cardiff, United Kingdom; 4 West of Scotland Specialist Virology Centre, Glasgow, United Kingdom; 5 University of Strathclyde, Glasgow, United Kingdom; 6 Public Health Agency Northern Ireland, Belfast, United Kingdom; 7 University of Surrey, Guildford, United Kingdom; 8 Royal College of General Practitioners, London, United Kingdom

Correspondence:  Richard Pebody

Citation style for this article: Pebody Richard, Djennad Abdelmajid, Ellis Joanna, Andrews Nick, Marques Diogo F P, Cottrell Simon, Reynolds Arlene J, Gunson Rory,Galiano Monica, Hoschler Katja, Lackenby Angie, Robertson Chris, O’Doherty Mark, Sinnathamby Mary, Panagiotopoulos Nikolaos, Yonova Ivelina, Webb Rebecca,Moore Catherine, Donati Matthew, Sartaj Muhammad, Shepherd Samantha J, McMenamin Jim, de Lusignan Simon, Zambon Maria. End of season influenza vaccine effectiveness in adults and children in the United Kingdom in 2017/18. Euro Surveill. 2019;24(31):pii=1800488. https://doi.org/10.2807/1560-7917.ES.2019.24.31.1800488

Received: 31 Aug 2018;   Accepted: 11 Jun 2019

 

Abstract

Background

In the United Kingdom (UK), in recent influenza seasons, children are offered a quadrivalent live attenuated influenza vaccine (LAIV4), and eligible adults mainly trivalent inactivated vaccine (TIV).

Aim

To estimate the UK end-of-season 2017/18 adjusted vaccine effectiveness (aVE) and the seroprevalence in England of antibodies against influenza viruses cultured in eggs or tissue.

Methods

This observational study employed the test-negative case–control approach to estimate aVE in primary care. The population-based seroprevalence survey used residual age-stratified samples.

Results

Influenza viruses A(H3N2) (particularly subgroup 3C.2a2) and B (mainly B/Yamagata/16/88-lineage, similar to the quadrivalent vaccine B-virus component but mismatched to TIV) dominated. All-age aVE was 15% (95% confidence interval (CI): −6.3 to 32) against all influenza; −16.4% (95% CI: −59.3 to 14.9) against A(H3N2); 24.7% (95% CI: 1.1 to 42.7) against B and 66.3% (95% CI: 33.4 to 82.9) against A(H1N1)pdm09. For 2–17 year olds, LAIV4 aVE was 26.9% (95% CI: −32.6 to 59.7) against all influenza; −75.5% (95% CI: −289.6 to 21) against A(H3N2); 60.8% (95% CI: 8.2 to 83.3) against B and 90.3% (95% CI: 16.4 to 98.9) against A(H1N1)pdm09. For ≥ 18 year olds, TIV aVE against influenza B was 1.9% (95% CI: −63.6 to 41.2). The 2017 seroprevalence of antibody recognising tissue-grown A(H3N2) virus was significantly lower than that recognising egg-grown virus in all groups except 15–24 year olds.

Conclusions

Overall aVE was low driven by no effectiveness against A(H3N2) possibly related to vaccine virus egg-adaption and a new A(H3N2) subgroup emergence. The TIV was not effective against influenza B. LAIV4 against influenza B and A(H1N1)pdm09 was effective.

©  This work is licensed under a Creative Commons Attribution 4.0 International License.

Keywords: Seasonal Influenza; H1N1pdm09; H3N2; Influenza B; Vaccines, UK.

——

#Influenza #vaccine #effectiveness against laboratory-confirmed influenza in hospitalised adults aged 60 years or older, Valencia Region, #Spain, 2017/18 influenza season (Euro Surveill., abstract)

[Source: Eurosurveillance, full page: (LINK). Abstract, edited.]

Influenza vaccine effectiveness against laboratory-confirmed influenza in hospitalised adults aged 60 years or older, Valencia Region, Spain, 2017/18 influenza season

Ainara Mira-Iglesias 1, F Xavier López-Labrador 1,2, Víctor Baselga-Moreno 1, Miguel Tortajada-Girbés 3, Juan Mollar-Maseres 4,Mario Carballido-Fernández 5,6, Germán Schwarz-Chavarri 7, Joan Puig-Barberà 1,8, Javier Díez-Domingo 1,on behalf of the Valencia Hospital Network for the Study of Influenza and Respiratory Viruses Disease 9

Affiliations: 1 Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO-Public Health), Valencia, Spain; 2 Consorcio de Investigación Biomédica de Epidemiología y Salud Pública (CIBERESP), Instituto de Salud Carlos III, Madrid, Spain; 3 Hospital Doctor Peset, Valencia, Spain; 4 Hospital Universitario y Politécnico La Fe, Valencia, Spain; 5 Hospital General Universitario de Castellón, Castellón, Spain; 6 Universidad CEU Cardenal Herrera, Castellón, Spain; 7 Hospital General de Alicante, Alicante, Spain; 8 Centro de Salud Pública de Castellón, Castellón, Spain; 9 The Network members are acknowledged at the end of the article

Correspondence:  Javier Díez-Domingo

Citation style for this article: Mira-Iglesias Ainara, López-Labrador F Xavier, Baselga-Moreno Víctor, Tortajada-Girbés Miguel, Mollar-Maseres Juan,Carballido-Fernández Mario, Schwarz-Chavarri Germán, Puig-Barberà Joan, Díez-Domingo Javier,on behalf of the Valencia Hospital Network for the Study of Influenza and Respiratory Viruses Disease. Influenza vaccine effectiveness against laboratory-confirmed influenza in hospitalised adults aged 60 years or older, Valencia Region, Spain, 2017/18 influenza season. Euro Surveill. 2019;24(31):pii=1800461. https://doi.org/10.2807/1560-7917.ES.2019.24.31.1800461

Received: 21 Aug 2018;   Accepted: 05 Mar 2019

 

Abstract

Introduction

Influenza immunisation is recommended for elderly people each season. The influenza vaccine effectiveness (IVE) varies annually due to influenza viruses evolving and the vaccine composition.

Aim

To estimate, in inpatients ≥ 60 years old, the 2017/18 trivalent IVE, overall, by vaccine type and by strain. The impact of vaccination in any of the two previous seasons (2016/17 and 2015/16) on current (2017/18) IVE was also explored.

Methods

This was a multicentre prospective observational study within the Valencia Hospital Surveillance Network for the Study of Influenza and Respiratory Viruses Disease (VAHNSI, Spain). The test-negative design was applied taking laboratory-confirmed influenza as outcome and vaccination status as main exposure. Information about potential confounders was obtained from clinical registries and/or by interviewing patients; vaccine information was only ascertained by registries.

Results

Overall, 2017/18 IVE was 9.9% (95% CI: −15.5 to 29.6%), and specifically, 48.3% (95% CI: 13.5% to 69.1%), −29.9% (95% CI: −79.1% to 5.8%) and 25.7% (95% CI: −8.8% to 49.3%) against A(H1N1)pdm09, A(H3N2) and B/Yamagata lineage, respectively. For the adjuvanted and non-adjuvanted vaccines, overall IVE was 10.0% (95% CI: −24.4% to 34.9%) and 7.8% (95% CI: −23.1% to 31.0%) respectively. Prior vaccination significantly protected against influenza B/Yamagata lineage (IVE: 50.2%; 95% CI: 2.3% to 74.6%) in patients not vaccinated in the current season. For those repeatedly vaccinated against influenza A(H1N1)pdm09, IVE was 46.4% (95% CI: 6.8% to 69.2%).

Conclusion

Our data revealed low vaccine effectiveness against influenza in hospitalised patients ≥60 years old in 2017/18. Prior vaccination protected against influenza A(H1N1)pdm09 and B/Yamagata-lineage.

©  This work is licensed under a Creative Commons Attribution 4.0 International License.

Keywords: Seasonal Influenza; H1N1pdm09; H3N2; Influenza B; Vaccines; Spain.

——

The Val430Ile #neuraminidase (NA) #substitution, identified in #influenza B virus isolates, impacts the catalytic 116Arg residue causing reduced susceptibility to NA #inhibitors (Antiviral Res., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Antiviral Res. 2019 Jul 16:104561. doi: 10.1016/j.antiviral.2019.104561. [Epub ahead of print]

The Val430Ile neuraminidase (NA) substitution, identified in influenza B virus isolates, impacts the catalytic 116Arg residue causing reduced susceptibility to NA inhibitors.

Abed Y1, Fage C2, Checkmahomed L2, Begin G3, Carbonneau J2, Lague P3, Boivin G4.

Author information: 1 Research Center in Infectious Diseases of the CHU of Québec and Laval University, Québec City, Québec, Canada. Electronic address: yacine.abed@crchul.ulaval.ca. 2 Research Center in Infectious Diseases of the CHU of Québec and Laval University, Québec City, Québec, Canada. 3 Proteo and IBIS, Department of Biochemistry, Microbiology and Bioinformatics, Faculty of Science and Engineering, Laval University, Québec City, QC, Canada. 4 Research Center in Infectious Diseases of the CHU of Québec and Laval University, Québec City, Québec, Canada. Electronic address: guy.boivin@crchul.ulaval.ca.

 

Abstract

As part of a 2015-2018 clinical trial of peramivir treatment for acute influenza infections in the elderly, an influenza B/Yamagata/16/1988-like isolate harbouring a Val430Ile neuraminidase (NA) substitution was recovered from a single patient. This substitution was detected in respiratory samples collected before and during peramivir treatment. In NA inhibition assays, oseltamivir, zanamivir and peramivir IC50s of the Val430Ile isolate were 4-, 15- and 16-fold higher compared to a wild-type (WT) strain. In reverse genetics experiments, the Ile430Val reversion restored the drug susceptible phenotype. The Val430Ile mutant and the WT strain had comparable replication kinetics in ST6GalI-MDCK cells and the NA mutation was stable after four passages in that cell line. Molecular dynamics simulations suggested that Val430Ile impacts the NA binding through a mechanism involving the catalytic Arg116 residue. The potential of some NA mutations not part of the active site to alter the susceptibility to NA inhibitors highlights the need to develop novel antiviral strategies against influenza B infections.

Copyright © 2019. Published by Elsevier B.V.

KEYWORDS: Influenza B; Mutation; Neuraminidase; Peramivir; Resistance; Val430Ile

PMID: 31323237 DOI: 10.1016/j.antiviral.2019.104561

Keywords: Seasonal Influenza; Influenza B; Antivirals; Drugs Resistance; Oseltamivir; Zanamivir; Peramivir.

——

Susceptibility of #Influenza A, B, C, and D Viruses to #Baloxavir (Emerg Infect Dis., abstract)

[Source: US Centers for Disease Control and Prevention (CDC), Emerging Infectious Diseases Journal, full page: (LINK). Abstract, edited.]

Volume 25, Number 10—October 2019 / Dispatch

Susceptibility of Influenza A, B, C, and D Viruses to Baloxavir

Vasiliy P. Mishin, Mira C. Patel, Anton Chesnokov, Juan De La Cruz, Ha T. Nguyen, Lori Lollis, Erin Hodges, Yunho Jang, John Barnes, Timothy Uyeki, Charles T. Davis, David E. Wentworth, and Larisa V. Gubareva

Author affiliations: Centers for Disease Control and Prevention, Atlanta, Georgia, USA (V.P. Mishin, M.C. Patel, A. Chesnokov, J. De La Cruz, H.T. Nguyen, L. Lollis, E. Hodges, Y. Jang, J. Barnes, T. Uyeki, C.T. Davis, D.E. Wentworth, L.V. Gubareva); Battelle Memorial Institute, Atlanta (M.C. Patel, J. De La Cruz, H.T. Nguyen, L. Lollis)

 

Abstract

Baloxavir showed broad-spectrum in vitro replication inhibition of 4 types of influenza viruses (90% effective concentration range 1.2–98.3 nmol/L); susceptibility pattern was influenza A ˃ B ˃ C ˃ D. This drug also inhibited influenza A viruses of avian and swine origin, including viruses that have pandemic potential and those resistant to neuraminidase inhibitors.

Keywords: Antivirals; Drugs Resistance; Oseltamivir; Favipiravir; Baloxavir; Influenza A; Influenza B; Influenza C; Influenza D; H1N1pdm09; H3N2; H7N9.

——

#Update: #Influenza #Activity in the #USA During the 2018–19 Season and Composition of the 2019–20 Influenza #Vaccine (MMWR Morb Mortal Wkly Rep., abstract)

[Source: US Centers for Disease Control and Prevention (CDC), MMWR Morbidity and Mortality Weekly Report, full page: (LINK). Abstract, edited.]

Update: Influenza Activity in the United States During the 2018–19 Season and Composition of the 2019–20 Influenza Vaccine

Weekly / June 21, 2019 / 68(24);544–551

Xiyan Xu, MD1; Lenee Blanton, MPH1; Anwar Isa Abd Elal1; Noreen Alabi, MPH1; John Barnes, PhD1; Matthew Biggerstaff, ScD1; Lynnette Brammer, MPH1; Alicia P. Budd, MPH1; Erin Burns, MA1; Charisse N. Cummings, MPH1; Shikha Garg, MD1; Rebecca Kondor, PhD1; Larisa Gubareva, PhD1; Krista Kniss, MPH1; Sankan Nyanseor, MPH1; Alissa O’Halloran, MSPH1; Melissa Rolfes, PhD1; Wendy Sessions, MPH1; Vivien G. Dugan, PhD1; Alicia M. Fry, MD1; David E. Wentworth, PhD1; James Stevens, PhD1; Daniel Jernigan, MD1

Corresponding author: Xiyan Xu, XXu@cdc.gov, 404-639-1657.

{1} Influenza Division, National Center for Immunization and Respiratory Diseases, CDC.

All authors have completed and submitted the ICMJE form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

Suggested citation for this article: Xu X, Blanton L, Elal AI, et al. Update: Influenza Activity in the United States During the 2018–19 Season and Composition of the 2019–20 Influenza Vaccine. MMWR Morb Mortal Wkly Rep 2019;68:544–551. DOI: http://dx.doi.org/10.15585/mmwr.mm6824a3

 

Summary

  • What is already known about this topic?
    • CDC collects, compiles, and analyzes data on influenza activity and viruses in the United States.
  • What is added by this report?
    • The 2018–19 influenza season was a moderate severity season with two waves of influenza A activity of similar magnitude during the season: A(H1N1)pdm09 predominated from October 2018 to mid-February 2019, and A(H3N2) activity increased from mid-February through mid-May.
  • What are the implications for public health practice?
    • Receiving a seasonal influenza vaccine each year remains the best way to protect against seasonal influenza and its potentially severe consequences.
    • Testing for seasonal influenza viruses and monitoring for emergence of antigenic drift variant viruses should continue year-round.

 

Abstract

Influenza activity* in the United States during the 2018–19 season (September 30, 2018–May 18, 2019) was of moderate severity (1). Nationally, influenza-like illness (ILI)† activity began increasing in November, peaked during mid-February, and returned to below baseline in mid-April; the season lasted 21 weeks,§ making it the longest season in 10 years. Illness attributed to influenza A viruses predominated, with very little influenza B activity. Two waves of influenza A were notable during this extended season: influenza A(H1N1)pdm09 viruses from October 2018 to mid-February 2019 and influenza A(H3N2) viruses from February through May 2019. Compared with the 2017–18 influenza season, rates of hospitalization this season were lower for adults, but were similar for children. Although influenza activity is currently below surveillance baselines, testing for seasonal influenza viruses and monitoring for novel influenza A virus infections should continue year-round. Receiving a seasonal influenza vaccine each year remains the best way to protect against seasonal influenza and its potentially severe consequences.

Keywords: Seasonal Influenza; USA; Vaccines; Antivirals; Oseltamivir; Zanamivir; Baloxavir marboxil.

——