#Compressed #Influenza #Vaccination in #US Older Adults: A Decision Analysis (Am J Prev Med., abstract)

[Source: American Journal of Preventive Medicine, full page: (LINK). Abstract, edited.]

Compressed Influenza Vaccination in U.S. Older Adults: A Decision Analysis

Kenneth J. Smith, MD, MS, Glenson France, MA, Mary Patricia Nowalk, PhD, Jonathan M. Raviotta, MPH, Jay DePasse, BS, Angela Wateska, MPH, Eunha Shim, PhD, Richard K. Zimmerman, MD, MPH

DOI: https://doi.org/10.1016/j.amepre.2018.11.015

Published online: February 14, 2019




Tradeoffs exist between efforts to increase influenza vaccine uptake, including early season vaccination, and potential decreased vaccine effectiveness if protection wanes during influenza season. U.S. older adults increasingly receive vaccination before October. Influenza illness peaks vary from December to April.


A Markov model compared influenza likelihood in older adults with (1) status quo vaccination (August–May) to maximize vaccine uptake or (2) vaccination compressed to October–May (to decrease waning vaccine effectiveness impact). The Centers for Disease Control and Prevention data were used for influenza incidence and vaccination parameters. Prior analyses showed that absolute vaccine effectiveness decreased by 6%–11% per month, favoring later season vaccination. However, compressed vaccination could decrease overall vaccine uptake. Influenza incidence was based on average monthly incidence with earlier and later peaks also examined. Influenza strain distributions from two seasons were modeled in separate scenarios. Sensitivity analyses were performed to test result robustness. Data were collected and analyzed in 2018.


Compressed vaccination would avert ≥11,400 influenza cases in older adults during a typical season if it does not decrease vaccine uptake. However, if compressed vaccination decreases vaccine uptake or there is an early season influenza peak, more influenza can result. In probabilistic sensitivity analyses, compressed vaccination was never favored if it decreased absolute vaccine uptake by >5.5% in any scenario; when influenza peaked early, status quo vaccination was favored.


Compressed vaccination could decrease waning vaccine effectiveness and decrease influenza cases in older adults. However, this positive effect is negated when early season influenza peaks occur and diminished by decreased vaccine uptake that could occur with shortening the vaccination season.

© 2018 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

Keywords: Seasonal Influenza; Vaccines; USA.



#H5N8 and #H7N9 packaging signals constrain #HA #reassortment with a seasonal #H3N2 #influenza A virus (Proc Natl Acad Sci USA, abstract)

[Source: Proceedings of the National Academy of Sciences of the United States of America, full page: (LINK). Abstract, edited.]

H5N8 and H7N9 packaging signals constrain HA reassortment with a seasonal H3N2 influenza A virus

Maria C. White, Hui Tao, John Steel, and Anice C. Lowen

PNAS published ahead of print February 13, 2019 / DOI: https://doi.org/10.1073/pnas.1818494116

Edited by Peter Palese, Icahn School of Medicine at Mount Sinai, New York, NY, and approved January 17, 2019 (received for review October 26, 2018)



Influenza A viruses (IAV) can exchange genetic material in coinfected cells in a process termed reassortment. The last three IAV pandemic strains arose from reassortment events involving human and nonhuman IAVs. Because introduction of the hemagglutinin (HA) gene from a nonhuman virus is required for a pandemic, we addressed the compatibility of human and avian IAV. We show that sequence differences between human and avian HA genes limit the potential for reassortment. However, human IAV still incorporated heterologous HA genes at a low level in coinfected animals. This observed low level of incorporation could become significant if reassortant viruses had a fitness advantage within the host, such as resistance to preexisting immunity, and highlights the continued need for IAV surveillance.



Influenza A virus (IAV) has a segmented genome, which (i) allows for exchange of gene segments in coinfected cells, termed reassortment, and (ii) necessitates a selective packaging mechanism to ensure incorporation of a complete set of segments into virus particles. Packaging signals serve as segment identifiers and enable segment-specific packaging. We have previously shown that packaging signals limit reassortment between heterologous IAV strains in a segment-dependent manner. Here, we evaluated the extent to which packaging signals prevent reassortment events that would raise concern for pandemic emergence. Specifically, we tested the compatibility of hemagglutinin (HA) packaging signals from H5N8 and H7N9 avian IAVs with a human seasonal H3N2 IAV. By evaluating reassortment outcomes, we demonstrate that HA segments carrying H5 or H7 packaging signals are significantly disfavored for incorporation into a human H3N2 virus in both cell culture and a guinea pig model. However, incorporation of the heterologous HAs was not excluded fully, and variants with heterologous HA packaging signals were detected at low levels in vivo, including in naïve contact animals. This work indicates that the likelihood of reassortment between human seasonal IAV and avian IAV is reduced by divergence in the RNA packaging signals of the HA segment. These findings offer important insight into the molecular mechanisms governing IAV emergence and inform efforts to estimate the risks posed by H7N9 and H5N8 subtype avian IAVs.

influenza A virus – reassortment – packaging – zoonosis – antigenic shift

Keywords: Influenza A; Pandemic Influenza; Seasonal Influenza; Avian Influenza; Reassortant strain; H3N2; H5N8; H7N9; Animal models.


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.


Annual #report on #influenza viruses received and tested by the #Melbourne #WHO CC for #Reference and Research on Influenza in 2016 (Commun Dis Intell (2018), abstract)

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

Commun Dis Intell (2018). 2019 Feb 1;43. doi: 10.33321/cdi.2019.43.5.

Annual report on influenza viruses received and tested by the Melbourne WHO Collaborating Centre for Reference and Research on Influenza in 2016

Leung VK1, Deng YM1, Kaye M1, Leang SK1, Gillespie L1, Chow MK1.

Author information: 1 WHO Collaborating Centre for Reference and Research on Influenza



As part of its role in the World Health Organization’s (WHO) Global Influenza Surveillance and Response System (GISRS), the WHO Collaborating Centre for Reference and Research on Influenza in Melbourne received a total of 4,247 human influenza positive samples during 2016. Viruses were analysed for their antigenic, genetic and antiviral susceptibility properties and also propagated in qualified cells and hens eggs for potential seasonal influenza vaccine virus candidates. In 2016, influenza A(H3) viruses predominated over influenza A(H1)pdm09 and B viruses, accounting for a total of 51% of all viruses analysed. The vast majority of A(H1)pdm09, A(H3) and influenza B viruses analysed at the Centre were found to be antigenically similar to the respective WHO recommended vaccine strains for the Southern Hemisphere in 2016. However, phylogenetic analysis of a selection of viruses indicated that the majority of circulating A(H3) viruses had undergone some genetic drift relative to the WHO recommended strain for 2016. Of more than 3,000 samples tested for resistance to the neuraminidase inhibitors oseltamivir and zanamivir, six A(H1)pdm09 viruses and two B/Victoria lineage viruses showed highly reduced inhibition to oseltamivir.

© Commonwealth of Australia CC BY-NC-ND

PMID: 30739429

Keywords: Seasonal Influenza; Vaccines; Antivirals; Drugs Resistance; Australia.


#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.


The #future of #influenza #forecasts (Proc Natl Acad Sci USA, summary)

[Source: Proceedings of the National Academy of Sciences of the United States of America, full page: (LINK). Summary, edited.]

The future of influenza forecasts

Cécile Viboud and Alessandro Vespignani

PNAS published ahead of print February 8, 2019 / DOI: https://doi.org/10.1073/pnas.1822167116

See related content: A collaborative multiyear, multimodel assessment of seasonal influenza forecasting in the United States – Jan 15, 2019



Recent years have seen a growing interest in generating real-time epidemic forecasts to help control infectious diseases, prompted by a succession of global and regional outbreaks. Increased availability of epidemiological data and novel digital data streams such as search engine queries and social media (1, 2), together with the rise of machine learning and sophisticated statistical approaches, have injected new blood into the science of outbreak forecasts (3, 4). In parallel, mechanistic transmission models have benefited from computational advances and extensive data on the mobility and sociodemographic structure of human populations (5, 6). In this rapidly advancing research landscape, modeling consortiums have generated systematic model comparisons of the impact of new interventions and ensemble predictions of outbreak trajectory, for use by decision makers (7⇓⇓⇓⇓–12). Despite the rapid development of disease forecasting as a discipline, however, and the interest of public health policy makers in making better use of analytics tools to control outbreaks, forecasts are rarely operational in the same way that weather forecasts, extreme events, and climate predictions are. The influenza study by Reich et al. (13) in PNAS is a unique example of multiyear infectious disease forecasts featuring a variety of modeling approaches, with consistent model formulations and forecasting targets throughout the 7-y study period (13). This is a major improvement over previous model comparison studies that used different targets and time horizons and sometimes different epidemiological datasets.

While there is considerable interest among modelers in advancing the science of disease forecasts, the level of confidence of the public health community in exploiting these predictions in real-world situations remains unclear. The disconnect is in part due to poor understanding of modeling concepts by policy experts, which is compounded by a lack of a well-established operational framework for using and …



1 To whom correspondence should be addressed. Email: viboudc@mail.nih.gov.

Keywords: Seasonal Influenza.


#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.