#Paradoxical clade- and age-specific #vaccine #effectiveness during the 2018/19 #influenza A #H3N2 #epidemic in #Canada: potential imprint-regulated effect of vaccine (I-REV) (Euro Surveill., abstract)

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

Paradoxical clade- and age-specific vaccine effectiveness during the 2018/19 influenza A(H3N2) epidemic in Canada: potential imprint-regulated effect of vaccine (I-REV)

Danuta M Skowronski 1,2, Suzana Sabaiduc 1, Siobhan Leir 1, Caren Rose 1,2, Macy Zou 1, Michelle Murti 3,4, James A Dickinson 5, Romy Olsha 3, Jonathan B Gubbay 3,4, Matthew A Croxen 6,7, Hugues Charest 8, Nathalie Bastien 9, Yan Li 9, Agatha Jassem 1,2, Mel Krajden 1,2, Gaston De Serres 8,10,11

Affiliations: 1 British Columbia Centre for Disease Control, Vancouver, Canada; 2 University of British Columbia, Vancouver, Canada; 3 Public Health Ontario, Toronto, Canada; 4 University of Toronto, Toronto, Canada; 5 University of Calgary, Calgary, Canada; 6 Alberta Precision Laboratories, Edmonton, Alberta; 7 University of Alberta, Edmonton, Canada; 8 Institut National de Santé Publique du Québec, Québec, Canada; 9 National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Canada; 10 Laval University, Quebec, Canada11 Centre Hospitalier Universitaire de Québec, Québec, Canada

Correspondence:  Danuta M Skowronski

Citation style for this article: Skowronski Danuta M, Sabaiduc Suzana, Leir Siobhan, Rose Caren, Zou Macy, Murti Michelle, Dickinson James A, Olsha Romy, Gubbay Jonathan B, Croxen Matthew A, Charest Hugues, Bastien Nathalie, Li Yan, Jassem Agatha, Krajden Mel, De Serres Gaston. Paradoxical clade- and age-specific vaccine effectiveness during the 2018/19 influenza A(H3N2) epidemic in Canada: potential imprint-regulated effect of vaccine (I-REV). Euro Surveill. 2019;24(46):pii=1900585. https://doi.org/10.2807/1560-7917.ES.2019.24.46.1900585

Received: 19 Sep 2019;   Accepted: 04 Nov 2019




The Canadian Sentinel Practitioner Surveillance Network reports vaccine effectiveness (VE) for the 2018/19 influenza A(H3N2) epidemic.


To explain a paradoxical signal of increased clade 3C.3a risk among 35–54-year-old vaccinees, we hypothesise childhood immunological imprinting and a cohort effect following the 1968 influenza A(H3N2) pandemic.


We assessed VE by test-negative design for influenza A(H3N2) overall and for co-circulating clades 3C.2a1b and 3C.3a. VE variation by age in 2018/19 was compared with amino acid variation in the haemagglutinin glycoprotein by year since 1968.


Influenza A(H3N2) VE was 17% (95% CI: −13 to 39) overall: 27% (95% CI: −7 to 50) for 3C.2a1b and −32% (95% CI: −119 to 21) for 3C.3a. Among 20–64-year-olds, VE was −7% (95% CI: −56 to 26): 6% (95% CI: −49 to 41) for 3C.2a1b and −96% (95% CI: −277 to −2) for 3C.3a. Clade 3C.3a VE showed a pronounced negative dip among 35–54-year-olds in whom the odds of medically attended illness were > 4-fold increased for vaccinated vs unvaccinated participants (p < 0.005). This age group was primed in childhood to influenza A(H3N2) viruses that for two decades following the 1968 pandemic bore a serine at haemagglutinin position 159, in common with contemporary 3C.3a viruses but mismatched to 3C.2a vaccine strains instead bearing tyrosine.


Imprinting by the first childhood influenza infection is known to confer long-lasting immunity focused toward priming epitopes. Our findings suggest vaccine mismatch may negatively interact with imprinted immunity. The immunological mechanisms for imprint-regulated effect of vaccine (I-REV) warrant investigation.

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

Keywords: Seasonal Influenza; Vaccines; H3N2; Origin Antigenic Sin; Canada.


#Adult #influenza A (#H3N2) with reduced susceptibility to #baloxavir or #peramivir cured after switching anti-influenza agents (IDCases, abstract)

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

IDCases. 2019 Oct 1;18:e00650. doi: 10.1016/j.idcr.2019.e00650. eCollection 2019.

Adult influenza A (H3N2) with reduced susceptibility to baloxavir or peramivir cured after switching anti-influenza agents.

Seki M1, Sakai-Tagawa Y2, Yasuhara A2, Watanabe Y3.

Author information: 1 Division of Infectious Diseases and Infection Control, Tohoku Medical and Pharmaceutical University Hospital, Sendai, Japan. 2 Department of Virology, Institute of Medical Science, University of Tokyo, Tokyo, Japan. 3 Laboratory for Clinical Microbiology, Tohoku Medical and Pharmaceutical University Hospital, Sendai, Japan.



We describe two adults with A/H3N2 influenza with (patient 1), and without (patient 2) polymerase acidic (PA) subunit I38 T substitution during the same season. Patient 1 had a reduced clinical response to baloxavir, a cap-dependent endonuclease inhibitor (CEI), but was cured by peramivir, a neuraminidase inhibitor. Baloxavir was clinically effective for patient 2, for whom peramivir had been ineffective. Susceptibility to baloxavir can be decreased by a PA unit mutation, but response to treatment can be increased by switching and/or combination with a neuraminidase inhibitor, even though CEI are clinically effective against influenza in adults.

© 2019 The Authors.

KEYWORDS: Baloxavir; Peramivir; Polymerase; Polymerase acidic subunit; Viral infection

PMID: 31692637 PMCID: PMC6804930 DOI: 10.1016/j.idcr.2019.e00650

Keywords: Seasonal Influenza; Antivirals; Drugs Resistance; H3N2; Japan; Baloxavir; Peramivir.


Spread of antigenically drifted #influenza A(#H3N2) viruses and #vaccine #effectiveness in the #USA during the 2018-2019 season (J Infect Dis., abstract)

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

Spread of antigenically drifted influenza A(H3N2) viruses and vaccine effectiveness in the United States during the 2018-2019 season

Brendan Flannery, Rebecca J Garten Kondor, Jessie R Chung, Manjusha Gaglani, Michael Reis, Richard K Zimmerman, Mary Patricia Nowalk, Michael L Jackson, Lisa A Jackson, Arnold S Monto, Emily T Martin, Edward A Belongia, Huong Q McLean, Sara S Kim, Lenee Blanton, Krista Kniss, Alicia P Budd, Lynnette Brammer, Thomas J Stark, John R Barnes, David E Wentworth, Alicia M Fry, Manish Patel

The Journal of Infectious Diseases, jiz543, https://doi.org/10.1093/infdis/jiz543

Published: 30 October 2019




Increased illness due to antigenically drifted A(H3N2) clade 3C.3a influenza viruses prompted concerns about vaccine effectiveness and vaccine strain selection. We used U.S. virologic surveillance and Influenza Vaccine Effectiveness (VE) Network data to evaluate consequences of this clade.


Distribution of influenza viruses was described using virologic surveillance data. The VE Network enrolled ambulatory patients aged ≥6 months with acute respiratory illness at five sites. Respiratory specimens were tested by RT-PCR for influenza and sequenced. Using a test-negative design, we estimated VE comparing odds of influenza among vaccinated versus unvaccinated participants.


During the 2018-2019 influenza season, A(H3N2) clade 3C.3a viruses caused an increasing proportion of influenza cases. Among 2,763 VE Network case patients, 1,325 (48%) were infected with A(H1N1)pdm09 and 1,350 (49%) with A(H3N2); clade 3C.3a accounted for 977 (93%) of 1,054 sequenced A(H3N2) viruses. VE was 44% (95% confidence interval [CI], 37 to 51%) against A(H1N1)pdm09 and 9% (95% CI, -4 to 20%) against A(H3N2); effectiveness was 5% (95% CI, -10 to 19%) against A(H3N2) clade 3C.3a viruses.


Predominance of A(H3N2) clade 3C.3a viruses during the latter part of the 2018-2019 season was associated with decreased vaccine effectiveness, supporting the A(H3N2) vaccine component update for 2019-2020 northern hemisphere influenza vaccines.

Topic: influenza – influenza vaccines – orthomyxoviridae – respiratory tract infections – reverse transcriptase polymerase chain reaction – vaccination – vaccines – influenzavirus a – viruses – surveillance, medical – influenza a virus, h1n1 subtype – influenza a virus, h3n2 subtype – swine influenza – swine-origin influenza virus

Issue Section: Major Article

This content is only available as a PDF.

Published by Oxford University Press for the Infectious Diseases Society of America 2019.

his work is written by (a) US Government employee(s) and is in the public domain in the US.

Keywords: Seasonal Influenza; H3N2; Vaccines; USA.


Locally Acquired #Human #Infection with #Swine-Origin #Influenza A(#H3N2) Variant Virus, #Australia, 2018 (Emerg Infect Dis., abstract)

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

Volume 26, Number 1—January 2020 / Dispatch

Locally Acquired Human Infection with Swine-Origin Influenza A(H3N2) Variant Virus, Australia, 2018

Yi-Mo Deng  , Frank Y.K. Wong, Natalie Spirason, Matthew Kaye, Rebecca Beazley, Miguel Grau, Songhua Shan, Vittoria Stevens, Kanta Subbarao, Sheena Sullivan, Ian G. Barr, and Vijaykrishna Dhanasekaran

Author affiliations: World Health Organization Collaborating Centre for Reference and Research on Influenza, Melbourne, Victoria, Australia (Y.M. Deng, N. Spirason, M. Kaye, K. Subbarao, S. Sullivan, I.G. Barr, V. Dhanasekaran); CSIRO Australian Animal Health Laboratory, Geelong, Victoria, Australia (F.Y.K. Wong, S. Shan, V. Stevens); South Australian Department of Health and Wellbeing, Adelaide, South Australia, Australia (R. Beazley); Monash University, Melbourne (M. Grau, V. Dhanasekaran); University of Melbourne, Melbourne (S. Sullivan, I.G. Barr)



In 2018, a 15-year-old female adolescent in Australia was infected with swine influenza A(H3N2) variant virus. The virus contained hemagglutinin and neuraminidase genes derived from 1990s-like human seasonal viruses and internal protein genes from influenza A(H1N1)pdm09 virus, highlighting the potential risk that swine influenza A virus poses to human health in Australia.

Keywords: Swine Influenza; Influenza A; Seasonal Influenza; Reassortant strain; H3N2; H1N1pdm09; Human; Australia.


Seasonal #Influenza and #Avian Influenza A(#H5N1) Virus #Surveillance among Inpatients and Outpatients, East #Jakarta, #Indonesia, 2011–2014 (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 11—November 2019 / Research

Seasonal Influenza and Avian Influenza A(H5N1) Virus Surveillance among Inpatients and Outpatients, East Jakarta, Indonesia, 2011–2014

Kathryn E. Lafond1  , Catharina Y. Praptiningsih1, Amalya Mangiri, Misriyah Syarif, Romadona Triada, Ester Mulyadi, Chita Septiawati, Vivi Setiawaty, Gina Samaan, Aaron D. Storms, Timothy M. Uyeki, and A. Danielle Iuliano

Author affiliations: University of Tampere, Tampere, Finland (K.E. Lafond); US Centers for Disease Control and Prevention, Atlanta, Georgia, USA (K.E. Lafond, A.D. Storms, T.M. Uyeki, A.D. Iuliano); US Centers for Disease Control and Prevention, Jakarta, Indonesia (C.Y. Praptiningsih, A. Mangiri, E. Mulyadi); Ministry of Health, Jakarta (M. Syarif, R. Triada, C. Septiawati, V. Setiawaty); Australian National University, Canberra, Capital Territory, Australia (G. Samaan)



During October 2011–September 2014, we screened respiratory specimens for seasonal and avian influenza A(H5N1) virus infections among outpatients with influenza-like illness and inpatients with severe acute respiratory infection (SARI) in East Jakarta, an Indonesia district with high incidence of H5N1 virus infection among poultry. In total, 31% (1,875/6,008) of influenza-like illness case-patients and 15% (571/3,811) of SARI case-patients tested positive for influenza virus. Influenza A(H1N1)pdm09, influenza A(H3N2), and influenza B virus infections were detected in all 3 years, and the epidemic season extended from November through May. Although 28% (2,810/10,135) of case-patients reported exposure to poultry, only 1 SARI case-patient with an H5N1 virus infection was detected. Therefore, targeted screening among case-patients with high-risk poultry exposures (e.g., a recent visit to a live bird market or close proximity to sick or dead poultry) may be a more efficient routine surveillance strategy for H5N1 virus in these types of settings.

Keywords: Seasonal Influenza; Avian Influenza; H1N1pdm09; H3N2; H5N1; SARI; Indonesia.


#Adaptation of #H3N2 #canine #influenza virus to #feline cell culture

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

PLoS One. 2019 Oct 10;14(10):e0223507. doi: 10.1371/journal.pone.0223507. eCollection 2019.

Adaptation of H3N2 canine influenza virus to feline cell culture.

Kamiki H1, Matsugo H1, Ishida H1, Kobayashi-Kitamura T1, Sekine W1, Takenaka-Uema A1, Murakami S1, Horimoto T1.

Author information: 1 Department of Veterinary Microbiology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.



H3N2 canine influenza viruses are prevalent in Asian and North American countries. During circulation of the viruses in dogs, these viruses are occasionally transmitted to cats. If this canine virus causes an epidemic in cats too, sporadic infections may occur in humans because of the close contact between these companion animals and humans, possibly triggering an emergence of mutant viruses with a pandemic potential. In this study, we aimed to gain an insight into the mutations responsible for inter-species transmission of H3N2 virus from dogs to cats. We found that feline CRFK cell-adapted viruses acquired several mutations in multiple genome segments. Among them, HA1-K299R, HA2-T107I, NA-L35R, and M2-W41C mutations individually increased virus growth in CRFK cells. With a combination of these mutations, virus growth further increased not only in CRFK cells but also in other feline fcwf-4 cells. Both HA1-K299R and HA2-T107I mutations increased thermal resistance of the viruses. In addition, HA2-T107I increased the pH requirement for membrane fusion. These findings suggest that the mutations, especially the two HA mutations, identified in this study, might be responsible for adaptation of H3N2 canine influenza viruses in cats.

PMID: 31600274 DOI: 10.1371/journal.pone.0223507

Keywords: Canine Avian Influenza; H3N2; Cats; Dogs.


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.