Posts filed under ‘Influenza’

Respiratory Virus Infection During Pregnancy: Does It Matter?

The Journal of Infectious Diseases August 15, 2018 V.218 N.4 P.512-515


Janet A Englund; Helen Y Chu





August 13, 2018 at 6:24 pm

Characterization of influenza virus variants induced by treatment with the endonuclease inhibitor baloxavir marboxil.

Sci Rep. June 25, 2018 V.8 N.1 P.9633.      doi: 10.1038/s41598-018-27890-4.

Omoto S1, Speranzini V2, Hashimoto T3, Noshi T3, Yamaguchi H3, Kawai M3, Kawaguchi K3, Uehara T3, Shishido T3, Naito A3, Cusack S4.

Author information

1 Shionogi & Co., Ltd., Osaka, Japan.

2 European Molecular Biology Laboratory, Grenoble Outstation, Grenoble, France.

3 Shionogi & Co., Ltd., Osaka, Japan.

4 European Molecular Biology Laboratory, Grenoble Outstation, Grenoble, France.


Baloxavir acid (BXA), derived from the prodrug baloxavir marboxil (BXM), potently and selectively inhibits the cap-dependent endonuclease within the polymerase PA subunit of influenza A and B viruses. In clinical trials, single doses of BXM profoundly decrease viral titers as well as alleviating influenza symptoms. Here, we characterize the impact on BXA susceptibility and replicative capacity of variant viruses detected in the post-treatment monitoring of the clinical studies. We find that the PA I38T substitution is a major pathway for reduced susceptibility to BXA, with 30- to 50-fold and 7-fold EC50 changes in A and B viruses, respectively.

The viruses harboring the I38T substitution show severely impaired replicative fitness in cells, and correspondingly reduced endonuclease activity in vitro. Co-crystal structures of wild-type and I38T influenza A and B endonucleases bound to BXA show that the mutation reduces van der Waals contacts with the inhibitor. A reduced affinity to the I38T mutant is supported by the lower stability of the BXA-bound endonuclease. These mechanistic insights provide markers for future surveillance of treated populations.



June 30, 2018 at 5:47 pm

Approved: Baloxavir marboxil

WHO Drug Information 2018 V.32 N.1 P.32

One-dose treatment for influenza

Product name: Xofluza®

Dosage form: Tablet

Class: cap-dependent endonuclease inhibitor

Approval: Ministry of Health, Labour and Welfare (MHLW) of Japan

Use: Treatment of influenza types A and B

Benefits: Treatment requires only a single oral dose regardless of age.

Shionogi & Co. Ltd Press



June 30, 2018 at 5:45 pm

Summary of the international clinical GUIDELINES – Management of HAP and VAP. Europ Resp J

Europ Respiratory Journal April 2018 V.4 N.2

Antoni Torres, Michael S. Niederman, Jean Chastre, Santiago Ewig, Patricia Fernandez-Vandellos, Hakan Hanberger, Marin Kollef, Gianluigi Li Bassi, Carlos M. Luna, Ignacio Martin-Loeches, J. Artur Paiva, Robert C. Read, David Rigau, Jean François Timsit, Tobias Welte and Richard Wunderink




Europ Respiratory Journal April 2018 V.4 N.2

Editorials – Treating nosocomial pneumonia – what’s new



June 29, 2018 at 12:31 pm

Relative vaccine effectiveness of high-dose vs standard-dose influenza vaccines among Veterans Health Administration patients.

Journal of Infectious Diseases May 5,  2018  V.217 N.11 P.1718-1727  

Young-Xu Y et al.

We examined whether a high-dose inactivated influenza vaccine was more efficacious in preventing hospitalizations than a standard-dose vaccine in the Veterans Health Administration (VHA) senior population.


This study estimated the relative vaccine effectiveness (rVE) of high dose versus standard dose using a retrospective cohort of VHA patients 65 years of age or older in the 2015–2016 influenza season. To adjust for measured confounders, we matched each high-dose recipient with up to 4 standard-dose recipients vaccinated at the same location within a 2-week period and having 2 or more pre-existing medical comorbidities. We used the previous event rate ratio method (PERR), a type of difference-in-differences analysis, to adjust for unmeasured confounders.


We evaluated 104965 standard-dose and 125776 high-dose recipients; matching decreased the population to 49091 standard-dose and 24682 high-dose recipients. The matched, PERR-adjusted rVE was 25% (95% confidence interval [CI], 2%–43%) against influenza- or pneumonia-associated hospitalization, 7% (95% CI, −2% to 14%) against all-cause hospitalization, 14% (95% CI, −8% to 32%) against influenza- or pneumonia-associated outpatient visit, 5% (95% CI, 2%–8%) against all-cause outpatient visit, and 38% (95% CI, −5% to 65%) against laboratory-confirmed influenza.


In protecting senior VHA patients against influenza- or pneumonia-associated hospitalization, a high-dose influenza vaccine is more effective than a standard-dose vaccine.



May 31, 2018 at 8:30 am

Multicenter Evaluation of BioFire FilmArray Respiratory Panel 2 for Detection of Viruses and Bacteria in Nasopharyngeal Swab Samples

Journal of Clinical Microbiology June 2018 V.56 N.6

Amy L. Leber, Kathy Everhart, Judy A. Daly, Aubrey Hopper, Amanda Harrington, Paul Schreckenberger, Kathleen McKinley, Matthew Jones, Kristen Holmberg and Bart Kensinger

a Nationwide Children’s Hospital, Columbus, Ohio, USA

b Primary Children’s Medical Center, Salt Lake City, Utah, USA

c Loyola University Medical Center, Chicago, Illinois, USA

d BioFire Diagnostics, LLC, Salt Lake City, Utah, USA

The FilmArray Respiratory Panel 2 (RP2) is a multiplex in vitro diagnostic test for the simultaneous and rapid (∼45-min) detection of 22 pathogens directly from nasopharyngeal swab (NPS) samples. It contains updated (and in some instances redesigned) assays that improve upon the FilmArray Respiratory Panel (RP; version 1.7), with a faster run time. The organisms identified are adenovirus, coronavirus 229E, coronavirus HKU1, coronavirus NL63, coronavirus OC43, human metapneumovirus, human rhinovirus/enterovirus, influenza virus A, influenza virus A H1, influenza virus A H1-2009, influenza virus A H3, influenza virus B, parainfluenza virus 1, parainfluenza virus 2, parainfluenza virus 3, parainfluenza virus 4, respiratory syncytial virus, Bordetella pertussis, Chlamydia pneumoniae, and Mycoplasma pneumoniae. Two new targets are included in the FilmArray RP2: Middle East respiratory syndrome coronavirus and Bordetella parapertussis. This study provides data from a multicenter evaluation of 1,612 prospectively collected NPS samples, with performance compared to that of the FilmArray RP or PCR and sequencing. The overall percent agreement between the FilmArray RP2 and the comparator testing was 99.2%. The RP2 demonstrated a positive percent agreement of 91.7% or greater for detection of all but three analytes: coronavirus OC43, B. parapertussis, and B. pertussis. The FilmArray RP2 also demonstrated a negative percent agreement of ≥93.8% for all analytes. Of note, the adenovirus assay detects all genotypes, with a demonstrated increase in sensitivity. The FilmArray RP2 represents a significant improvement over the FilmArray RP, with a substantially shorter run time that could aid in the diagnosis of respiratory infections in a variety of clinical scenarios.



May 28, 2018 at 9:31 am

Westward Spread of Highly Pathogenic Avian Influenza A(H7N9) Virus among Humans, China

Emerging Infectious Diseases June 2018 V.24 N.6   

Yang et al.

Beijing Normal University, Beijing, China (Q. Yang, X. Tong, H. Tian); Shaanxi Provincial Centre for Disease Control and Prevention, Xi’an, China (W. Shi, L. Zhang, Y. Xu, J. Xu, S. Li, F. Liu, P. Yu); Xianyang Centre for Disease Control and Prevention, Xianyang, China (J. Zhang); Baoji Centre for Disease Control and Prevention, Baoji, China (K. Hu); Xi’an Centre for Disease Control and Prevention, Xi’an (C. Ma); Chinese Center for Disease Control and Prevention, Beijing (X. Zhao, X. Li); Chinese Academy of Forestry, Beijing (G. Zhang); University of Oxford, Oxford, UK (O.G. Pybus)

We report infection of humans with highly pathogenic avian influenza A(H7N9) virus in Shaanxi, China, in May 2017. We obtained complete genomes for samples from 5 patients and from live poultry markets or farms in 4 cities. Results indicate that H7N9 is spreading westward from southern and eastern China.



May 22, 2018 at 7:41 am

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