#Influenza-like illness #outbreaks in #China during 2017-2018 surveillance season (Zhonghua Yu Fang Yi Xue Za Zhi, abstract)

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

Zhonghua Yu Fang Yi Xue Za Zhi. 2019 Oct 6;53(10):982-986. doi: 10.3760/cma.j.issn.0253-9624.2019.10.006.

[Influenza-like illness outbreaks in China during 2017-2018 surveillance season].

[Article in Chinese; Abstract available in Chinese from the publisher]

Liu LJ1, Yang J, Zhu F, Wang LJ, Guo Q, Tang J, Fang QQ, Wang DY, Chen T.

Author information: 1 Chinese National Influenza Center, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Key Laboratory for Medical Virology, National Health, Beijing 102206, China.


Abstract in English, Chinese


To analyze epidemiological characteristics of influenza-like illness outbreaks in mainland China during 2017-2018 surveillance season, and to provide scientific evidence for developing influenza prevention and control strategies.


We collected the data on reported influenza outbreaks in 2017-2018 surveillance season from China Influenza Surveillance Information System and China Public Health Emergency Management Information System and analyzed the data of laboratory-confirmed influenza-like illness outbreaks by descriptive epidemiological methods.


During the surveillance season, a total of 2 398 influenza-like illness outbreaks (with 10 or more incidences in an outbreak) in mainland China were reported, involving 87 084 patients, of which 2 323 were influenza outbreaks, involving 85 531 patients. The reported influenza-like illness outbreaks occurred most frequently from November 2017 to January 2018 in both the southern and northern regions and the highest peaks were in December 2017. During the period 1 850 influenza-like illness outbreaks (77.15%) were reported in the southern region, and 548 influenza-like illness outbreaks (22.85%) were reported in the northern region. The most of the outbreaks occurred in primary, secondary schools and nursery care schools, with a total of 2 210 reports (92.16%). And the majority of the outbreaks involved 10-29 incident cases. The dominant isolated virus strains for the outbreaks were influenza B (1 505 outbreaks, 62.76% of all the outbreaks).


Seasonality of influenza outbreaks were observed in mainland China during 2017-2018 surveillance season and the reported influenza outbreaks were most frequently occurred in autumn-winter season and in southern China. Primary, secondary schools and nursery care schools are high-risk places for outbreaks, and the dominant isolated virus strains for the outbreaks were influenza B.

KEYWORDS: Disease attributes; Influenza, human; Pandemics

PMID: 31607042 DOI: 10.3760/cma.j.issn.0253-9624.2019.10.006

Keywords: Seasonal Influenza; Influenza B; Institutional outbreaks; China.


#Hemagglutinin cleavability, acid-stability and #temperature dependence optimize #influenza B virus for #replication in human #airways (J Virol., abstract)

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

Hemagglutinin cleavability, acid-stability and temperature dependence optimize influenza B virus for replication in human airways

Manon Laporte, Annelies Stevaert, Valerie Raeymaekers, Talitha Boogaerts, Inga Nehlmeier, Winston Chiu, Mohammed Benkheil, Bart Vanaudenaerde, Stefan Pöhlmann, Lieve Naesens

DOI: 10.1128/JVI.01430-19



Influenza A virus (IAV) and influenza B virus (IBV) cause yearly epidemics with significant morbidity and mortality. When zoonotic IAVs enter the human population, the viral hemagglutinin (HA) requires adaptation to achieve sustained virus transmission. In contrast, IBV has been circulating in humans, its only host, for a long period of time. Whether this entailed adaptation of IBV HA to the human airways is unknown. To address this question, we compared two seasonal IAV (A/H1N1 and A/H3N2) and two IBV viruses (B/Victoria and B/Yamagata lineage) with regard to host-dependent activity of HA as the mediator of membrane fusion during viral entry. We first investigated proteolytic activation of HA, by covering all type II transmembrane serine protease (TTSP) and kallikrein enzymes, many of which proved present in human respiratory epithelium. Compared to IAV, the IBV HA0 precursor is cleaved by a broader panel of TTSPs and activated with much higher efficiency. Accordingly, knockdown of a single protease, TMPRSS2, abrogated spread of IAV but not IBV in human respiratory epithelial cells. Second, the HA fusion pH proved similar for IBV and human-adapted IAVs (one exception being HA of 1918 IAV). Third, IBV HA exhibited higher expression at 33°C, a temperature required for membrane fusion by B/Victoria HA. This indicates pronounced adaptation of IBV HA to the mildly acidic pH and cooler temperature of human upper airways. These distinct and intrinsic features of IBV HA are compatible with extensive host-adaptation during prolonged circulation of this respiratory virus in the human population.



Influenza epidemics are caused by influenza A (IAV) and influenza B (IBV) viruses. IBV causes substantial disease, however it is far less studied than IAV. While IAV originates from animal reservoirs, IBV circulates in humans only. Virus spread requires that the viral hemagglutinin (HA) is active and sufficiently stable in human airways. We here resolve how these mechanisms differ between IBV and IAV. Whereas human IAVs rely on one particular protease for HA activation, this is not the case for IBV. Superior activation of IBV by several proteases should enhance shedding of infectious particles. IBV HA exhibits acid-stability and a preference for 33°C, indicating pronounced adaptation to the human upper airways, where the pH is mildly acidic and a cooler temperature exists. These adaptive features are rationalized by the long existence of IBV in humans, and may have broader relevance for understanding the biology and evolution of respiratory viruses.

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

Keywords: Seasonal Influenza; Influenza B.


Viral #Kinetics and #Resistance Development in #Children Treated with #Neuraminidase #Inhibitors: The Influenza Resistance Information Study (IRIS) (Clin Infect Dis., abstract)

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

Clin Infect Dis. 2019 Sep 27. pii: ciz939. doi: 10.1093/cid/ciz939. [Epub ahead of print]

Viral Kinetics and Resistance Development in Children Treated with Neuraminidase Inhibitors: The Influenza Resistance Information Study (IRIS).

Roosenhoff R1, Reed V2, Kenwright A3, Schutten M4, Boucher CA1, Monto A5, Clinch B3, Kumar D6, Whitley R7, Nguyen-Van-Tam JS8, Osterhaus ADME9,10, Fouchier RAM1, Fraaij PLA1,11.

Author information: 1 Department of Viroscience, Erasmus Medical Center, Rotterdam, The Netherlands. 2 Micron Research Ltd, Ely, UK. 3 Roche Products Ltd, Welwyn Garden City, UK. 4 Clinical Virology and Diagnostics, Alkmaar, The Netherlands. 5 Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI, USA. 6 University Health Network, Toronto, ON, Canada. 7 Department of Pediatrics, Microbiology, Medicine and Neurosurgery, The University of Alabama at Birmingham, Birmingham, AL, USA. 8 School of Medicine, Division of Epidemiology and Public Health, University of Nottingham, Nottingham, UK. 9 Research Institute for Infectious Diseases and Zoonosis, University of Veterinary Medicine, Hannover, Germany. 10 Artemis One Health Foundation, Utrecht, The Netherlands. 11 Department of Pediatrics, Subdivision Infectious Diseases and Immunology, Erasmus Medical Center – Sophia, Rotterdam, The Netherlands.




The effect of age, baseline viral load, vaccination status, antiviral therapy and emergence of drug resistance on viral shedding in children infected with influenza A or B virus was studied.


Samples from children (aged ≤13 years) enrolled during the 7 years of the prospective Influenza Resistance Information Study (IRIS; NCT00884117) were analyzed by polymerase chain reaction to determine the influenza virus(sub-)type, viral load and resistance mutations. Disease severity was assessed; clinical symptoms were recorded. The association of age with viral load and viral clearance was examined by determining the area under the curve for viral RNA shedding using logistic regression and Kaplan-Meier analyses.


A total of 2131 children infected with influenza (683 A/H1N1pdm09; 825 A/H3N2; 623 influenza B) were investigated. Age did not affect the mean baseline viral load. Children aged 1>5 years, infected with A/H1N1pdm09, A/H3N2 or influenza B virus had prolonged viral RNA shedding (±1-2 days) compared with older children (aged >5 years) and up to 1.2-fold higher total viral burden. Besides older age (odds ratio [OR] 1.08; confidence interval [CI]: 1.05-1.12), prior vaccination status (OR 1.72; CI: 1.22-2.43) and antiviral treatment (OR 1.74; CI: 1.43-2.12) increased the rate of viral clearance. Resistance mutations were detected in 49 children infected with influenza A virus (34 A/H1N1pdm09; 15 A/H3N2) treated with oseltamivir, most of whom were aged <5 years (n = 39).


Children aged 1>5 years had a higher total viral burden with prolonged virus shedding and had an increased risk of acquiring resistance mutations following antiviral treatment.

© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.

KEYWORDS: Influenza; Influenza Resistance Information Study; pediatrics; resistance mutations; viral load

PMID: 31560055 DOI: 10.1093/cid/ciz939

Keywords: Seasonal Influenza; H1N1pdm09; H3N2; Antivirals; Drugs Resistance; Oseltamivir; Pediatrics.


#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.




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.


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.


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.


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.


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



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.



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




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).


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.


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.


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.


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




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.


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.


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.


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%).


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.