#Oseltamivir #resistance in #severe #influenza A #H1N1pdm09 #pneumonia and #ARDS: a #French multicenter observational cohort study (Clin Infect Dis., abstract)

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

Clin Infect Dis. 2019 Sep 20. pii: ciz904. doi: 10.1093/cid/ciz904. [Epub ahead of print]

Oseltamivir resistance in severe influenza A(H1N1)pdm09 pneumonia and acute respiratory distress syndrome: a French multicenter observational cohort study.

Behillil S1, May F2,3, Fourati S4, Luyt CE5, Chicheportiche T5, Sonneville R6, Tandjaoui-Lambiotte Y7, Roux D8, Guérin L9, Mayaux J10, Maury E11, Ferré A12, Georger JF13, Voiriot G14, Enouf V1, van der Werf S1, Dessap AM2,3, de Prost N2,3.

Author information: 1 Unité de Génétique Moléculaire des Virus à ARN et Centre National de Référence des Virus des Infections Respiratoires (dont la grippe), Institut Pasteur, Université Paris Diderot, Sorbonne Paris Cité, Paris, France. 2 Service de Réanimation Médicale, Hôpitaux Universitaires Henri Mondor-Albert Chenevier, Assistance Publique-Hôpitaux de Paris, Créteil, France. 3 Groupe de Recherche Clinique CARMAS, Université Paris-Est Créteil, IMRB, Créteil,  France. 4 Département de Microbiologie, Hôpitaux Universitaires Henri Mondor-Albert Chenevier, Assistance Publique-Hôpitaux de Paris, Créteil, France. 5 Service de Médecine Intensive Réanimation, Hôpital de La Pitié Salpétrière, Assistance Publique-Hôpitaux de Paris, Paris, France. 6 Service de Médecine Intensive Réanimation, Hôpital Bichat Claude Bernard, Assistance Publique-Hôpitaux de Paris, Paris, France. 7 Service de Réanimation médico-chirurgicale, Hôpital Avicenne, Assistance Publique-Hôpitaux de Paris, Bobigny, France. 8 Service de réanimation médico-chirurgicale, Hôpital Louis Mourier, Assistance Publique-Hôpitaux de Paris, Colombes,  France; IAME, Université Paris Diderot, Paris, France. 9 Service de réanimation médicale, Hôpital Bicètre, Assistance Publique-Hôpitaux de Paris, Le Kremlin-Bicètre, France. 10 Service de Réanimation Médicale et Pneumologie, Hôpital de La Pitié Salpétrière, Assistance Publique-Hôpitaux de Paris, Paris, France. 11 Service de Réanimation Médicale, Hôpital Saint-Antoine, Assistance Publique-Hôpitaux de Paris, Paris, France. 12 Service de Réanimation, Centre hospitalier de Versailles, Le Chesnay, France. 13 Service de Réanimation, Centre hospitalier Intercommunal de Villeneuve Saint-Georges, Villeneuve Saint-Georges, France. 14 Service de Réanimation Médicale, Hôpital Tenon, Assistance Publique-Hôpitaux de Paris, Paris, France.



In a multicenter cohort study including 22 oseltamivir-treated patients with influenza A(H1N1)pdm09 acute respiratory distress syndrome, prevalence of the H275Y substitution in the neuraminidase, responsible for highly reduced sensitivity to oseltamivir, was 23%. Patients infected with the H275Y mutant virus had higher day-28 mortality than others (80% vs 12%; p=0.011).

© 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.

KEYWORDS: Influenza A Virus, H1N1 Subtype; Oseltamivir; Pneumonia, Viral; Respiratory Distress Syndrome, Adult

PMID: 31538643 DOI: 10.1093/cid/ciz904

Keywords: Seasonal Influenza; H1N1pdm09; Antivirals; Drugs Resistance; Oseltamivir; Pneumonia; ARDS; France.



Experimental #H1N1pdm09 #infection in #pigs mimics #human seasonal #influenza #infections (PLoS One, abstract)

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


Experimental H1N1pdm09 infection in pigs mimics human seasonal influenza infections

Theresa Schwaiger, Julia Sehl, Claudia Karte, Alexander Schäfer, Jane Hühr, Thomas C. Mettenleiter, Charlotte Schröder, Bernd Köllner, Reiner Ulrich, Ulrike Blohm

Published: September 20, 2019 / DOI: https://doi.org/10.1371/journal.pone.0222943



Pigs are anatomically, genetically and physiologically comparable to humans and represent a natural host for influenza A virus (IAV) infections. Thus, pigs may represent a relevant biomedical model for human IAV infections. We set out to investigate the systemic as well as the local immune response in pigs upon two subsequent intranasal infections with IAV H1N1pdm09. We detected decreasing numbers of peripheral blood lymphocytes after the first infection. The simultaneous increase in the frequencies of proliferating cells correlated with an increase in infiltrating leukocytes in the lung. Enhanced perforin expression in αβ and γδ T cells in the respiratory tract indicated a cytotoxic T cell response restricted to the route of virus entry such as the nose, the lung and the bronchoalveolar lavage. Simultaneously, increasing frequencies of CD8αα expressing αβ T cells were observed rapidly after the first infection, which may have inhibited uncontrolled inflammation in the respiratory tract. Taking together, the results of this study demonstrate that experimental IAV infection in pigs mimics major characteristics of human seasonal IAV infections.


Citation: Schwaiger T, Sehl J, Karte C, Schäfer A, Hühr J, Mettenleiter TC, et al. (2019) Experimental H1N1pdm09 infection in pigs mimics human seasonal influenza infections. PLoS ONE 14(9): e0222943. https://doi.org/10.1371/journal.pone.0222943

Editor: Balaji Manicassamy, University of Iowa, UNITED STATES

Received: May 28, 2019; Accepted: September 10, 2019; Published: September 20, 2019

Copyright: © 2019 Schwaiger et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All relevant data are within the manuscript and its Supporting Information files.

Funding: This study was funded by Federal Excellence Initiative of Mecklenburg Western Pomerania and European Social Fund (ESF) Grant KoInfekt (ESF_14-BM-A55-00xx_16) to TCM.

Competing interests: The authors have declared that no competing interests exist.

Keywords: Seasonal Influenza; H1N1pdm09; Human; Pigs; Animal models.


A novel #reassortant #influenza A (#H1N1) virus #infection in #swine in #Shandong Province, eastern #China (Transbound Emerg Dis., abstract)

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

Transbound Emerg Dis. 2019 Sep 19. doi: 10.1111/tbed.13360. [Epub ahead of print]

A novel reassortant influenza A (H1N1) virus infection in swine in Shandong Province, eastern China.

Yu Z1,2,3, Cheng K4, He H5, Wu J1,2,3.

Author information: 1 Poultry Institute, Shandong Academy of Agricultural Sciences, Jinan, 250023, China. 2 Shandong Provincial Key Laboratory of Poultry Diseases Diagnosis and Immunology. 3 Poultry Breeding Engineering Technology Center of Shandong Province. 4 Dairy Cattle Research Center, Shandong Academy of Agricultural Sciences, Jinan, 250132, China. 5 College of Life Sciences, Shandong Normal University, Jinan, 250014, China.



Influenza A (H1N1) viruses are distributed worldwide and pose a threat to public health. Swine, as a natural host and mixing vessel of influenza A (H1N1) virus, play a critical role in the transmission of this virus to humans. Furthermore, swine influenza A (H1N1) viruses have provided all eight genes or some genes to the genomes of influenza strains that historically have caused human pandemics. Hence, persistent surveillance of influenza A (H1N1) virus in swine herds could contribute to the prevention and control of this virus. Here, we report a novel reassortant influenza A (H1N1) virus generated by reassortment between 2009 pandemic H1N1 viruses and swine viruses. We also found that this virus is prevalent in swine herds in Shandong Province, eastern China. Our findings suggest that surveillance of the emergence of the novel reassortant influenza A (H1N1) virus in swine is imperative.

© 2019 Blackwell Verlag GmbH.

KEYWORDS: H1N1; human; influenza; reassortant; swine

PMID: 31535780 DOI: 10.1111/tbed.13360

Keywords: Seasonal Influenza; Swine Influenza; H1N1; H1N1pdm09; Pigs; Reassortant strain; Shandong; China.


#Medical #Outcomes in Women Who Became #Pregnant after #Vaccination with a #VLP Experimental #Vaccine against #Influenza A (#H1N1) 2009 Virus Tested during 2009 #Pandemic Outbreak (Viruses, abstract)

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

Viruses. 2019 Sep 17;11(9). pii: E868. doi: 10.3390/v11090868.

Medical Outcomes in Women Who Became Pregnant after Vaccination with a Virus-Like Particle Experimental Vaccine against Influenza A (H1N1) 2009 Virus Tested during 2009 Pandemic Outbreak.

Cérbulo-Vázquez A1, Arriaga-Pizano L2, Cruz-Cureño G3, Boscó-Gárate I4, Ferat-Osorio E5, Pastelin-Palacios R6, Figueroa-Damian R7, Castro-Eguiluz D8, Mancilla-Ramirez J9, Isibasi A10, López-Macías C11,12,13.

Author information: 1 Facultad de Medicina, Plan de Estudios Combinados en Medicina (MD, PhD Program), Universidad Nacional Autónoma de México, Mexico City CP 04510, Mexico. cerbulo@unam.mx. 2 Unidad de Investigación Médica en Inmunoquímica, Hospital de Especialidades del Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social (IMSS), Mexico City CP 06720, Mexico. landapi@hotmail.com. 3 Escuela Nacional de Ciencias Biológicas, Programa de Inmunología, Instituto Politécnico Nacional, Mexico City CP 11340, Mexico. gabrielacruz30@gmail.com. 4 Unidad de Investigación Médica en Inmunoquímica, Hospital de Especialidades del Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social (IMSS), Mexico City CP 06720, Mexico. ibosco45@hotmail.com. 5 Servicio de Cirugía Gastrointestinal, Unidad Médica de Alta Especialidad, Hospital de Especialidades Dr Bernardo Sepúlveda Gutiérrez, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social (IMSS), Mexico City CP 06720, Mexico. eduardoferat@prodigy.net.mx. 6 Departamento de Biología, Facultad de Química, Universidad Nacional Autónoma de México, Mexico City CP 04510, Mexico. rodolfop@unam.mx. 7 Departamento de Infectología, Instituto Nacional de Perinatología, Mexico City CP 11000, Mexico. rfd6102@yahoo.com.mx. 8 Consejo Nacional de Ciencia y Tecnología (CONACYT)- Departamento de Investigación Clínica, Instituto Nacional de Cancerología, Mexico City CP 14080, Mexico. angeldenisse@gmail.com. 9 Escuela Superior de Medicina, Instituto Politécnico Nacional; Hospital de la Mujer, Secretaria de Sauld, Mexico City CP 11340, Mexico. javiermancilla@hotmail.com. 10 Unidad de Investigación Médica en Inmunoquímica, Hospital de Especialidades del Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social (IMSS), Mexico City CP 06720, Mexico. isibasi@prodigy.net.mx. 11 Unidad de Investigación Médica en Inmunoquímica, Hospital de Especialidades del Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social (IMSS), Mexico City CP 06720, Mexico. constantino@sminmunologia.mx. 12 Visiting Professor of Immunology, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7LF, UK. constantino@sminmunologia.mx. 13 Mexican Translational Immunology Research Group, Federation of Clinical Immunology Societies Centers of Excellence, National Autonomous University of Mexico, Mexico City 04510, Mexico. constantino@sminmunologia.mx.



The clinical effects and immunological response to the influenza vaccine in women who later become pregnant remain to be thoroughly studied. Here, we report the medical outcomes of 40 women volunteers who became pregnant after vaccination with an experimental virus-like particle (VLP) vaccine against pandemic influenza A(H1N1)2009 (influenza A(H1N1)pdm09) and their infants. When included in the VLP vaccine trial, none of the women were pregnant and were randomly assigned to one of the following groups: (1) placebo, (2) 15 μg dose of VLP vaccine, or (3) 45 μg dose of VLP vaccine. These 40 women reported becoming pregnant during the follow-up phase after receiving the placebo or VLP vaccine. Women were monitored throughout pregnancy and their infants were monitored until one year after birth. Antibody titers against VLP were measured in the mothers and infants at delivery and at six months and one year after birth. The incidence of preeclampsia, fetal death, preterm delivery, and premature rupture of membranes was similar among groups. All vaccinated women and their infants elicited antibody titers (≥1:40). Women vaccinated prior to pregnancy had no adverse events that were different from the nonvaccinated population. Even though this study is limited by the sample size, the results suggest that the anti-influenza A(H1N1)pdm09 VLP experimental vaccine applied before pregnancy is safe for both mothers and their infants.

KEYWORDS: antibody titers; influenza A(H1N1)pdm09; pregnant women; vaccination; virus-like particle

PMID: 31533277 DOI: 10.3390/v11090868

Keywords: Pandemic Influenza; H1N1pdm09; Vaccines; Pregnancy.


#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.


#Influenza Viruses in #Mice: Deep #Sequencing Analysis of Serial Passage and Effects of #Sialic Acid Structural #Variation (J Virol., abstract)

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

Influenza Viruses in Mice: Deep Sequencing Analysis of Serial Passage and Effects of Sialic Acid Structural Variation

Brian R. Wasik, Ian E.H. Voorhees, Karen N. Barnard, Brynn K. Alford-Lawrence, Wendy S. Weichert, Grace Hood, Aitor Nogales, Luis Martínez-Sobrido, Edward C. Holmes, Colin R. Parrish

DOI: 10.1128/JVI.01039-19



Influenza A viruses have regularly jumped to new host species to cause epidemics or pandemics, an evolutionary process that involves variation in the viral traits necessary to overcome host barriers and facilitate transmission. Mice are not a natural host for influenza virus, but are frequently used as models in studies of pathogenesis, often after multiple passages to achieve higher viral titers that result in clinical disease such as weight loss or death. Here we examine the processes of influenza A virus infection and evolution in mice by comparing single nucleotide variation of a human H1N1 pandemic virus, a seasonal H3N2 virus, and a H3N2 canine influenza virus during experimental passage. We also compared replication and sequence variation in wild-type mice expressing N-glycolylneuraminic acid (Neu5Gc) with that seen in mice expressing only N-acetylneuraminic acid (Neu5Ac). Viruses derived from plasmids were propagated in MDCK cells and then passaged in mice up to four times. Full genome deep sequencing of the plasmids, cultured viruses, and viruses from mice at various passages revealed only small numbers of mutational changes. The H3N2 canine influenza virus showed increases in frequency of sporadic mutations in the PB2, PA, and NA segments. The H1N1 pandemic virus grew well in mice, and while it exhibited the maintenance of some minority mutations, there was no clear evidence for adaptive evolution. The H3N2 seasonal virus did not establish in the mice. Finally, there were no clear sequence differences associated with the presence or absence of Neu5Gc.



Mice are commonly used as a model to study the growth and virulence of influenza A viruses in mammals, but are not a natural host and have distinct sialic acid receptor profiles compared to humans. Using experimental infections with different subtypes of influenza A virus derived from different hosts we found that evolution of influenza A virus in mice did not necessarily proceed through the linear accumulation of host-adaptive mutations, that there was variation in the patterns of mutations detected in each repetition, and the mutation dynamics depended on the virus examined. In addition, variation in the viral receptor, sialic acid, did not affect influenza evolution in this model. Overall, our results show that while mice provide a useful animal model for influenza pathology, host passage evolution will vary depending on the specific virus tested.

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

Keywords: Influenza A; H1N1pdm09; H3N2; Animal models.


#Molecular characterization of #influenza A #H1N1pdm09 viruses circulating at various geographical locations in #India, 2017 (Indian J Med Res., abstract)

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

Indian J Med Res. 2019 Jun;149(6):783-789. doi: 10.4103/ijmr.IJMR_925_18.

Molecular characterization of influenza A(H1N1)pdm09 viruses circulating at various geographical locations in India, 2017.

Potdar V1, Vijay N2, Gupta N3, Arunkumar G4, Borkakoty B5, Malhotra B6, Rabha D7, Hinge D1, Kaur H2, Chadha M1; for VRDL Team.

Author information: 1 Influenza Group, ICMR-National Institute of Virology, Pune, India. 2 Department of Health Research, Ministry of Health & Family Welfare, Government of India, New Delhi, India. 3 Division of Epidemiology & Communicable Diseases, Indian Council of Medical Research, Headquarters, New Delhi, India. 4 Manipal Institute of Virology, Manipal Academy of Higher Education (Deemed to be University), Manipal, India. 5 ICMR-Regional Medical Research Center, Dibrugarh, India. 6 Department of Microbiology, Sawai Man Singh Medical College, Jaipur, India. 7 Department of Microbiology, Guwahati Medical College, Guwahati, India.




Influenza virological surveillance is an essential tool for the early detection of novel genetic variants of epidemiologic and clinical significance. This study was aimed to genetically characterize A(H1N1)pdm09 virus circulating in 2017 and to compare it with the global data.


The regional/State Viral Research and Diagnostic Laboratories (VRDLs) provided influenza diagnosis for referred clinical samples and shared influenza A(H1N1)pdm09 positives with the Indian Council of Medical Research-National Institute of Virology (ICMR-NIV), Pune, India, for hemagglutinin (HA) gene phylogenetic analysis. Sites at Manipal, Jaipur and Dibrugarh performed the sequencing and shared the sequence data for analysis. The antiviral susceptibility of influenza viruses was assessed for known molecular marker H275Y at the ICMR-NIV, Pune.


All the eight VRDLs had well-established influenza diagnostic facilities and showed increased activity of influenza A(H1N1)pdm09 during 2017. Phylogenetic analysis showed that the viruses from the different regions of the country were similar to A/Michigan/45/2015 strain which was the 2017-2018 recommended vaccine strain and were clustered with the globally circulating clade 6B.1 with signature mutations S84N, S162N and I216T. The clade 6B.1 showed further subgrouping with additional mutations S74R, S164T and I295V; however, there was no significant association between the presence of these mutations and severity of disease due to influenza. All the study viruses were sensitive to oseltamivir.


During the study period, all the study sites reported globally circulating A/Michigan/45/2015 vaccine strain of influenza A(H1N1)pdm09 viruses and remained sensitive to oseltamivir. Further genetic and antigenic characterization of influenza viruses is recommended to address public health concerns.

KEYWORDS: H275Y ; India; haemagglutinin protein; influenza A(H1N1)pdm09

PMID: 31496532 DOI: 10.4103/ijmr.IJMR_925_18

Keywords: Seasonal Influenza; H1N1pdm09; India.