Effect of early #oseltamivir #treatment on #mortality in critically ill patients with different types of #influenza: a multi-season cohort study (Clin Infect Dis., abstract)

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

Clin Infect Dis. 2019 Feb 7. doi: 10.1093/cid/ciz101. [Epub ahead of print]

Effect of early oseltamivir treatment on mortality in critically ill patients with different types of influenza: a multi-season cohort study.

Lytras T1, Mouratidou E1,2, Andreopoulou A1, Bonovas S3,4, Tsiodras S1,5.

Author information: 1 Hellenic Centre for Disease Control and Prevention, Athens, Greece. 2 European Programme for Intervention Epidemiology Training (EPIET), European Centre for Disease Prevention and Control (ECDC), Stockholm, Sweden. 3 Department of Biomedical Sciences, Humanitas University, Milan, Italy. 4 Humanitas Clinical and Research Center, Milan, Italy. 5 4th Department of Internal Medicine, Attikon University Hospital, University of Athens Medical School, Athens, Greece.




The available evidence on whether neuraminidase inhibitors reduce mortality in patients with influenza is inconclusive, and focuses solely on influenza A/H1N1pdm09. We assessed whether early oseltamivir treatment (≤48 hours from symptom onset) decreases mortality compared to late treatment in a large cohort of critically ill patients with influenza of all types.


The study included all adults with laboratory-confirmed influenza hospitalized in intensive care units (ICU) in Greece over eight seasons (2010-2011 to 2017-2018) and treated with oseltamivir. The association of early oseltamivir with mortality was assessed with log-binomial models, and a competing risks analysis estimating cause-specific and subdistribution hazards for death and discharge. Effect estimates were stratified by influenza type and adjusted for multiple covariates.


1330 patients were studied, of whom 622 (46.8%) died in the ICU. Among patients with influenza A/H3N2, early treatment was associated with significantly lower mortality (Relative Risk 0.69, 95% CrI 0.49-0.94; subdistribution Hazard Ratio 0.58, 95% CrI 0.37-0.88). This effect was purely due to an increased cause-specific hazard for discharge, while the cause-specific hazard for death was not increased. Among survivors, the median length of ICU stay was shorter with early treatment by 1.8 days (95% CrI 0.5-3.5). No effect on mortality was observed for A/H1N1 and influenza B patients.


Severely ill patients with suspected influenza should be promptly treated with oseltamivir, particularly when A/H3N2 is circulating. The efficacy of oseltamivir should not be assumed to be equal against all types of influenza.

PMID: 30753349 DOI: 10.1093/cid/ciz101

Keywords: Seasonal Influenza; H1N1pdm09; H3N2; Antivirals; Oseltamivir.



#Influenza #Infection in #Humans Induces Broadly Cross-Reactive and Protective #Neuraminidase-Reactive #Antibodies (Cell, abstract)

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

Cell. 2018 Apr 5;173(2):417-429.e10. doi: 10.1016/j.cell.2018.03.030.

Influenza Infection in Humans Induces Broadly Cross-Reactive and Protective Neuraminidase-Reactive Antibodies.

Chen YQ1, Wohlbold TJ2, Zheng NY1, Huang M1, Huang Y1, Neu KE3, Lee J4, Wan H5, Rojas KT1, Kirkpatrick E2, Henry C1, Palm AE1, Stamper CT3, Lan LY3, Topham DJ6, Treanor J7, Wrammert J8, Ahmed R8, Eichelberger MC5, Georgiou G4, Krammer F9, Wilson PC10.

Author information: 1 Department of Medicine, Section of Rheumatology, the Knapp Center for Lupus and Immunology, University of Chicago, Chicago, IL 60637, USA. 2 Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. 3 The Committee on Immunology, University of Chicago, Chicago, IL 60637, USA. 4 Department of Chemical Engineering, University of Texas at Austin, Austin, TX 78731, USA. 5 Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20993, USA. 6 Center for Vaccine Biology & Immunology, Department of Microbiology & Immunology, University of Rochester Medical Center, Rochester, NY 14642, USA. 7 Division of Infectious Disease, Department of Medicine, University of Rochester Medical Center, Rochester, NY 14642, USA. 8 Emory Vaccine Center, Department of Pediatrics, Division of Infectious Disease, Emory University School of Medicine, Atlanta, GA 30322, USA. 9 Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. Electronic address: florian.krammer@mssm.edu. 10 Department of Medicine, Section of Rheumatology, the Knapp Center for Lupus and Immunology, University of Chicago, Chicago, IL 60637, USA. Electronic address: wilsonp@uchicago.edu.



Antibodies to the hemagglutinin (HA) and neuraminidase (NA) glycoproteins are the major mediators of protection against influenza virus infection. Here, we report that current influenza vaccines poorly display key NA epitopes and rarely induce NA-reactive B cells. Conversely, influenza virus infection induces NA-reactive B cells at a frequency that approaches (H1N1) or exceeds (H3N2) that of HA-reactive B cells. NA-reactive antibodies display broad binding activity spanning the entire history of influenza A virus circulation in humans, including the original pandemic strains of both H1N1 and H3N2 subtypes. The antibodies robustly inhibit the enzymatic activity of NA, including oseltamivir-resistant variants, and provide robust prophylactic protection, including against avian H5N1 viruses, in vivo. When used therapeutically, NA-reactive antibodies protected mice from lethal influenza virus challenge even 48 hr post infection. These findings strongly suggest that influenza vaccines should be optimized to improve targeting of NA for durable and broad protection against divergent influenza strains.

Copyright © 2018 Elsevier Inc. All rights reserved.

KEYWORDS: B cell; human immunology; humoral immune response; influenza; monoclonal antibody; neuraminidase; therapeutics; vaccine; virus infection

PMID: 29625056 PMCID: PMC5890936 [Available on 2019-04-05] DOI:
10.1016/j.cell.2018.03.030 [Indexed for MEDLINE]

Keywords: Seasonal Influenza; Avian Influenza; Immunology; Animal models.


#Human-Origin #Influenza A(#H3N2) #Reassortant Viruses in #Swine, Southeast #Mexico (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 4—April 2019 / Research

Human-Origin Influenza A(H3N2) Reassortant Viruses in Swine, Southeast Mexico

Martha I. Nelson  , Carine Souza, Nídia S. Trovão, Andres Diaz, Ignacio Mena, Albert Rovira, Amy L. Vincent, Montserrat Torremorell, Douglas Marthaler1, and Marie R. Culhane

Author affiliations: National Institutes of Health, Bethesda, Maryland, USA (M.I. Nelson, N.S. Trovão); National Animal Disease Center, Ames, Iowa, USA (C. Souza, A.L. Vincent); Icahn School of Medicine at Mount Sinai, New York, New York, USA (N.S. Trovão, I. Mena); University of Minnesota, Saint Paul, Minnesota, USA (A. Diaz, A. Rovira, M. Torremorell, D. Marthaler, M.R. Culhane)



The genetic diversity of influenza A viruses circulating in swine in Mexico complicates control efforts in animals and presents a threat to humans, as shown by influenza A(H1N1)pdm09 virus. To describe evolution of swine influenza A viruses in Mexico and evaluate strains for vaccine development, we sequenced the genomes of 59 viruses and performed antigenic cartography on strains from 5 regions. We found that genetic and antigenic diversity were particularly high in southeast Mexico because of repeated introductions of viruses from humans and swine in other regions in Mexico. We identified novel reassortant H3N2 viruses with genome segments derived from 2 different viruses that were independently introduced from humans into swine: pandemic H1N1 viruses and seasonal H3N2 viruses. The Mexico swine viruses are antigenically distinct from US swine lineages. Protection against these viruses is unlikely to be afforded by US virus vaccines and would require development of new vaccines specifically targeting these diverse strains.

Keywords: Seasonal Influenza; Swine Influenza; Reassortant Strain; Pigs; Human; H1N1pdm09; H3N2; Mexico.


Effects of #sequential #influenza A #H1N1pdm09 #vaccination on #antibody waning (J Infect Dis., abstract)

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

Effects of sequential influenza A(H1N1)pdm09 vaccination on antibody waning

Jon Zelner, Joshua G Petrie, Rob Trangucci, Emily T Martin, Arnold S Monto

The Journal of Infectious Diseases, jiz055, https://doi.org/10.1093/infdis/jiz055

Published: 04 February 2019




Antibody waning following influenza vaccination has been repeatedly evaluated, but waning has rarely been studied in the context of longitudinal vaccination history.


We developed a Bayesian hierarchical model to assess the effects of sequential influenza A(H1N1)pdm09 vaccination on hemagglutination-inhibition antibody boosting and waning in a longitudinal cohort of older children and adults from 2011 to 2016, a period during which the A(H1N1)pdm09 vaccine strain did not change.


Antibody measurements from 2,057 serum specimens longitudinally collected from 388 individuals were included. Average post-vaccination antibody titers were similar across successive vaccinations, but the rate of antibody waning increased with each vaccination. The antibody half-life was estimated to decrease from 32 (95% credible interval [CI]: 22, 61) months following first vaccination to 9 (95% CI: 7, 15) months following a seventh vaccination.


Although the rate of antibody waning increased with successive vaccination, the estimated antibody half-life was longer than a typical influenza season even among the most highly vaccinated. This supports current recommendations for vaccination at the earliest opportunity. Patterns of boosting and waning might be different with the influenza A(H3N2) subtype which evolves more rapidly and has been most associated with reduced effectiveness following repeat vaccination.

Influenza, Influenza Vaccine, Antibody, Waning, Hemagglutinin, Longitudinal Cohort

Topic: influenza – influenza vaccines – vaccination – antibodies – influenzavirus a – influenza a virus, h1n1 subtype – swine influenza – swine-origin influenza virus

Issue Section:  Major Article

This content is only available as a PDF.

© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

Keywords: Seasonal Influenza; H1N1pdm09; Vaccines.


Characterization of Host and #Bacterial Contributions to #Lung Barrier #Dysfunction Following Co-infection with #H1N1pdm09 #Influenza and #MRSA (Viruses, abstract)

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

Viruses. 2019 Jan 29;11(2). pii: E116. doi: 10.3390/v11020116.

Characterization of Host and Bacterial Contributions to Lung Barrier Dysfunction Following Co-infection with 2009 Pandemic Influenza and Methicillin Resistant Staphylococcus aureus.

Nickol ME1, Ciric J2, Falcinelli SD3, Chertow DS4,5, Kindrachuk J6.

Author information: 1 Laboratory of Emerging and Re-Emerging Viruses, Department of Medical Microbiology, University of Manitoba, Winnipeg, MB R3E 0J9, Canada. nickolm@myumanitoba.ca. 2 Laboratory of Emerging and Re-Emerging Viruses, Department of Medical Microbiology, University of Manitoba, Winnipeg, MB R3E 0J9, Canada. ciricj@myumanitoba.ca. 3 Department of Microbiology and Immunology, University of North Carolina Chapel Hill School of Medicine, Chapel Hill, NC 27599, USA. shane_falcinelli@med.unc.edu. 4 Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. chertowd@cc.nih.gov. 5 Critical Care Medicine Department, National Institutes of Health Clinical Center, Bethesda, MD 20892, USA. chertowd@cc.nih.gov. 6 Laboratory of Emerging and Re-Emerging Viruses, Department of Medical Microbiology, University of Manitoba, Winnipeg, MB R3E 0J9, Canada. Jason.Kindrachuk@umanitoba.ca.



Influenza viruses are a threat to global public health resulting in ~500,000 deaths each year. Despite an intensive vaccination program, influenza infections remain a recurrent, yet unsolved public health problem. Secondary bacterial infections frequently complicate influenza infections during seasonal outbreaks and pandemics, resulting in increased morbidity and mortality. Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA), is frequently associated with these co-infections, including the 2009 influenza pandemic. Damage to alveolar epithelium is a major contributor to severe influenza-bacterial co-infections and can result in gas exchange abnormalities, fluid leakage, and respiratory insufficiency. These deleterious manifestations likely involve both pathogen- and host-mediated mechanisms. However, there is a paucity of information regarding the mechanisms (pathogen- and/or host-mediated) underlying influenza-bacterial co-infection pathogenesis. To address this, we characterized the contributions of viral-, bacterial-, and host-mediated factors to the altered structure and function of alveolar epithelial cells during co-infection with a focus on the 2009 pandemic influenza (pdm2009) and MRSA. Here, we characterized pdm2009 and MRSA replication kinetics, temporal host kinome responses, modulation of MRSA virulence factors, and disruption of alveolar barrier integrity in response to pdm2009-MRSA co-infection. Our results suggest that alveolar barrier disruption during co-infection is mediated primarily through host response dysregulation, resulting in loss of alveolar barrier integrity.

KEYWORDS: 2009 pandemic; Staphylococcus aureus; alveolar epithelial cells; barrier function; co-infection; influenza; kinome; virulence factors

PMID: 30699912 DOI: 10.3390/v11020116

Keywords: Influenza A; H1N1pdm09; Staphylococcus aureus; MRSA.


Interim #estimates of 2018/19 #vaccine #effectiveness against #influenza A #H1N1pdm09, #Canada, January 2019 (Euro Surveill., abstract)

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

Interim estimates of 2018/19 vaccine effectiveness against influenza A(H1N1)pdm09, Canada, January 2019

Danuta M Skowronski1,2, Siobhan Leir1, Suzana Sabaiduc1, Michelle Murti3,4, James A Dickinson5, Romy Olsha3,Jonathan B Gubbay3,4, Matthew A Croxen6,7, Hugues Charest8, Tracy Chan1, Nathalie Bastien9, Yan Li9, Mel Krajden1,2, Gaston De Serres8,10,11

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 Provincial Laboratory for Public Health, Edmonton, Canada; 7 University of Alberta, Edmonton, Canada; 8 Institut National de Santé Publique du Québec, Quebec City, Canada; 9 National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Canada; 10 Laval University, Quebec City, Canada; 11 Centre Hospitalier Universitaire de Québec, Quebec City, Canada

Correspondence:  Danuta M Skowronski

Citation style for this article: Skowronski Danuta M, Leir Siobhan, Sabaiduc Suzana, Murti Michelle, Dickinson James A, Olsha Romy, Gubbay Jonathan B, Croxen Matthew A,Charest Hugues, Chan Tracy, Bastien Nathalie, Li Yan, Krajden Mel, De Serres Gaston. Interim estimates of 2018/19 vaccine effectiveness against influenza A(H1N1)pdm09, Canada, January 2019. Euro Surveill. 2019;24(4):pii=1900055. https://doi.org/10.2807/1560-7917.ES.2019.24.4.1900055

Received: 18 Jan 2019;   Accepted: 24 Jan 2019



Using a test-negative design, the Canadian Sentinel Practitioner Surveillance Network assessed interim 2018/19 vaccine effectiveness (VE) against predominant influenza A(H1N1)pdm09 viruses. Adjusted VE was 72% (95% confidence interval: 60 to 81) against medically attended, laboratory-confirmed influenza A(H1N1)pdm09 illness. This substantial vaccine protection was observed in all age groups, notably young children who appeared to be disproportionately affected. Sequence analysis identified heterogeneity in emerging clade 6B.1 viruses but no dominant drift variant.

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

Keywords: Seasonal Influenza; H1N1pdm09; Vaccines; Canada.


Assessing #baloxavir susceptibility of #influenza viruses circulating in the #USA during the 2016/17 and 2017/18 seasons (Euro Surveill., abstract)

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

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

Larisa V Gubareva1, Vasiliy P Mishin1, Mira C Patel1,2, Anton Chesnokov1, Ha T Nguyen1,2, Juan De La Cruz1,2, Sarah Spencer1, Angela P Campbell1, Mallory Sinner3, Heather Reid3, Rebecca Garten1, Jackie M Katz1, Alicia M Fry1, John Barnes1, David E Wentworth1

Affiliations: 1 Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention (CDC), Atlanta, United States of America 2 Battelle Memorial Institute, Atlanta, United States of America 3 Illinois Department of Public Health, Springfield, United States of America

Correspondence:  Larisa V Gubareva

Citation style for this article: Gubareva Larisa V, Mishin Vasiliy P, Patel Mira C, Chesnokov Anton, Nguyen Ha T, De La Cruz Juan , Spencer Sarah, Campbell Angela P, Sinner Mallory, Reid Heather, Garten Rebecca, Katz Jackie M, Fry Alicia M, Barnes John, Wentworth David E. Assessing baloxavir susceptibility of influenza viruses circulating in the United States during the 2016/17 and 2017/18 seasons. Euro Surveill. 2019;24(3):pii=1800666. https://doi.org/10.2807/1560-7917.ES.2019.24.3.1800666

Received: 12 Dec 2018;   Accepted: 16 Jan 2019



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.

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

Keywords: Seasonal Influenza; Antivirals; Drugs Resistance; Baloxavir; USA.