Remaining #effect of #influenza #vaccines received in prior #seasons (J Infect Dis., abstract)

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

Remaining effect of influenza vaccines received in prior seasons

Iván Martínez-Baz, Ana Navascués, Itziar Casado, Aitziber Aguinaga, Carmen Ezpeleta, Jesús Castilla

The Journal of Infectious Diseases, jiz266,

Published: 20 May 2019



This study evaluates the remaining effect of influenza vaccines received in the 5 prior seasons. During 7 influenza seasons 8933 patients were enrolled and 47% were confirmed for influenza. As compared to unvaccinated individuals in the current and 5 prior seasons, vaccination was protective when the last dose had been received in the current season (40%; 95%CI, 32-47), and one (42%; 95%CI, 27-54), 2-3 (35%; 95%CI, 16-49) or 4-5 seasons before (31%; 95%CI, 4-51). This effect lasted less in the elderly and chronic patients. On average, several recent prior doses were as protective as current season vaccination.

influenza, influenza vaccine, vaccination history, repeated vaccination, vaccine effectiveness, case-control study, test-negative study

Topic: influenza – influenza vaccines – vaccination – vaccines – elderly

Issue Section: Brief Report

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

This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (

Keywords: Seasonal Influenza; Vaccines.



#Mucosal #Immunity against #Neuraminidase Prevents #Influenza B Virus #Transmission in Guinea Pigs (mBio, abstract)

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

Mucosal Immunity against Neuraminidase Prevents Influenza B Virus Transmission in Guinea Pigs

Meagan McMahon, Ericka Kirkpatrick, Daniel Stadlbauer, Shirin Strohmeier, Nicole M. Bouvier, Florian Krammer

Stacey Schultz-Cherry, Editor

DOI: 10.1128/mBio.00560-19



Despite efforts to control influenza virus infection and transmission, influenza viruses still cause significant morbidity and mortality in the global human population each year. Most of the current vaccines target the immunodominant hemagglutinin surface glycoprotein of the virus. However, reduced severity of disease and viral shedding have also been linked to antibodies targeting the second viral surface glycoprotein, the neuraminidase. Importantly, antineuraminidase immunity was shown to be relatively broad, in contrast to vaccine-induced antibodies to the hemagglutinin head domain. In this study, we assessed recombinant neuraminidase protein vaccination for its ability to prevent or limit virus transmission. We vaccinated guinea pigs either intramuscularly or intranasally with a recombinant influenza B virus neuraminidase to assess whether neuraminidase vaccination via these routes could prevent transmission of the homologous virus to a naive recipient. Guinea pigs vaccinated with neuraminidase showed reduced virus titers; however, only vaccination via the intranasal route fully prevented virus transmission to naive animals. We found high levels of antineuraminidase antibodies capable of inhibiting neuraminidase enzymatic activity in the nasal washes of intranasally vaccinated animals, which may explain the observed differences in transmission. We also determined that mucosal immunity to neuraminidase impaired the transmission efficiency of a heterologous influenza B virus, although to a lesser extent. Finally, we found that neuraminidase-vaccinated animals were still susceptible to infection via the airborne and contact transmission routes. However, significantly lower virus titers were detected in these vaccinated recipients. In summary, our data suggest that supplementing vaccine formulations with neuraminidase and vaccinating via the intranasal route may broadly prevent transmission of influenza B viruses.



Recently, the protective effect of anti-neuraminidase immunity has been highlighted by several studies in humans and animal models. However, so far the role that anti-neuraminidase immunity plays in inhibition of virus transmission has not been explored. In addition, neuraminidase has been ignored as an antigen for influenza virus vaccines. We show here that neuraminidase-based vaccines can inhibit the transmission of influenza virus. Therefore, neuraminidase should be considered as an antigen for improved influenza virus vaccines that not only protect individuals from disease but also inhibit further spread of the virus in the population.

Keywords: Seasonal Influenza; Influenza B; Vaccines; Animal models.


Excess #mortality is associated with #influenza A (#H1N1) in patients with #SARI (J Clin Virol., abstract)

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

J Clin Virol. 2019 May 8;116:62-68. doi: 10.1016/j.jcv.2019.05.003. [Epub ahead of print]

Excess mortality is associated with influenza A (H1N1) in patients with severe acute respiratory illness.

Lobo SM1, Watanabe ASA2, Salomão MLM3, Queiroz F3, Gandolfi JV4, de Oliveira NE4, Covello LHS4, Sacillotto GH4, de Godoy LG4, Simões ES4, Frini ICM4, Da Silva Teixeira RER4, Furlan NP4, Dutra KR4, Nogueira ML2.

Author information: 1 Intensive Care Division – Hospital De Base -FAMERP, São José Do Rio Preto, SP – Brasil. Electronic address: 2 Virology Laboratory – Famerp, São José Do Rio Preto SP – Brasil; Epidemiology Department – FAMERP, São José Do Rio Preto, SP – Brasil. 3 Department Of Epidemiology – FAMERP, São José Do Rio Preto SP – Brasil; Intensive Care Division – Hospital De Base – Famerp, São José Do Rio Preto, SP – Brasil. 4 Intensive Care Division – Hospital De Base -FAMERP, São José Do Rio Preto, SP – Brasil.




Acute respiratory infections caused by viruses are among the leading causes of morbidity and mortality. The inflammatory response that follows viral infection is important for the control of virus proliferation. However, if overwhelming, may be associated with complicated outcomes.


We assessed the clinical characteristics of patients with severe acute respiratory illness (SARI) evolving to acute respiratory distress syndrome (ARDS) and the factors related to death.


Prospective study in 273 adult patients with SARI performed in a university-affiliated 800-bed hospital serving an area of epidemiologic vigilance of 102 municipalities and more than 2 million inhabitants. Influenza A (H1N1) 2009 (A/H1N1), influenza A H3N2, and influenza B were tested in all patients by RT-PCR.


The overall hospital mortality rate was 17.6%. A total of 30.4% of patients tested positive for influenza A/H1N1. Patients with SARI that evolved to ARDS took significantly longer to take the first dose of oseltamivir (6.0 vs 1.0 days, p=0.002). Patients with H1N1 positive tests had almost 3 times higher probability of death, despite having significantly less comorbidities (p=0.027). The influenza A/H1N1 pdm09 vaccine reduced the odds of death by 78%. Nonsurvivors had a more intense inflammatory response than did survivors at 48 h (C-reactive protein: 31.0 ± 17.5 vs. 14.6 ± 8.9 mg/dl, p=0.001) as well as a more positive fluid balance.


Hospital mortality associated with influenza H1N1-associated SARI and ARDS continued to be high years after the 2009 pandemic in a population with low vaccine coverage. Antiviral treatment started more than two days after onset of symptoms was more frequently associated with ARDS and death and, having had vaccine against influenza A (H1N1) was a factor independently related to survival.

Copyright © 2019 Elsevier B.V. All rights reserved.

KEYWORDS: Acute respiratory distress syndrome; C-reactive protein; Influenza A virus; Severe acute respiratory illness; Viral pneumonia

PMID: 31103803 DOI: 10.1016/j.jcv.2019.05.003

Keywords: Seasonal Influenza; H1N1pdm09; ARDS; SARI.


#Effectiveness of the #Neuraminidase #Inhibitors: The Supporting #Evidence Increases (J Infect Dis., summary)

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

Effectiveness of the Neuraminidase Inhibitors: The Supporting Evidence Increases

Arnold S Monto

The Journal of Infectious Diseases, jiz157,

Published: 20 May 2019

Issue Section: Editorial Commentary


The neuraminidase inhibitors (NAIs) zanamivir and oseltamivir were the first in that class of influenza antivirals to receive approval by the Food and Drug Administration, with both approved at the turn of the last century [1, 2] The regulatory approvals, for both prophylaxis and treatment of uncomplicated influenza, occurred after standard review of studies. The 2 drugs target nearby sites in the enzymatically active pocket of the virus but are very different in their route of administration and pharmacokinetics [1, 2]. Despite these differences, the results of the clinical trials of both were remarkably similar in terms of the characteristics of prophylactic efficacy and of treatment effects. Recruitment of cases to the treatment studies was based on clinical criteria but was limited to the influenza season; these cases were the intent-to-treat population [3–5]. The studies were done before use of polymerase chain reaction analysis had become accepted for influenza diagnosis, so the standard method of detecting the infecting virus was by cell culture.




Potential conflicts of interest.

A. S. M. reports personal fees from Roche outside the submitted work. The author has submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Keywords: Antivirals; Oseltamivir; Zanamivir; Peramivir; Influenza A; Pandemic Influenza.


In vitro #neuraminidase inhibitory concentration (#IC50) of four neuraminidase inhibitors in the #Japanese 2017-18 #season: Comparison with the 2010-11 to 2016-17 seasons (J Infect Chemother., abstract)

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

J Infect Chemother. 2019 May 14. pii: S1341-321X(19)30099-6. doi: 10.1016/j.jiac.2019.04.007. [Epub ahead of print]

In vitro neuraminidase inhibitory concentration (IC50) of four neuraminidase inhibitors in the Japanese 2017-18 season: Comparison with the 2010-11 to 2016-17 seasons.

Ikematsu H1, Kawai N2, Chong Y3, Bando T2, Iwaki N2, Kashiwagi S2.

Author information: 1 Japan Physicians Association, Tokyo, Japan; Ricerca Clinica Co., Fukuoka, Japan. Electronic address: 2 Japan Physicians Association, Tokyo, Japan. 3 Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.



To assess the extent of susceptibility to the four most commonly used neuraminidase inhibitors (NAIs) of the viruses epidemic in the 2017-18 Japanese influenza season, we measured the 50% inhibitory concentration (IC50) for influenza virus isolates from patients and compared them with the results from the 2010-11 to 2016-17 seasons. Viral isolation was done with specimens obtained prior to treatment, and the type and subtype was determined by RT-PCR using type- and subtype-specific primers. The IC50 was determined by a neuraminidase inhibition assay using a fluorescent substrate. A total of 237 virus isolates, 50 A(H1N1)pdm09, 92 A(H3N2), and 95 B were measured. No A(H1N1)pdm09 with highly reduced sensitivity for oseltamivir was found in the 2017-18 season. No isolates with highly reduced sensitivity to the four NAIs have been found for A(H3N2) or B from the 2010-11 to 2017-18 seasons. The geometric mean IC50s of the four NAIs were quite consistent during the eight studied seasons. These results indicate that the sensitivity to the four commonly used NAIs has been maintained.

Copyright © 2019 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

KEYWORDS: 50% inhibitory concentration; Influenza virus; Neuraminidase inhibitor; Resistance; Surveillance

PMID: 31101530 DOI: 10.1016/j.jiac.2019.04.007

Keywords: Antivirals; Drugs Resistance; Oseltamivir; Zanamivir; Peramivir; Laninamivir; Japan; Seasonal Influenza; H1N1pdm09; H3N2; Influenza B.


#Oseltamivir induced Stevens-Johnson #syndrome/toxic #epidermal #necrolysis-case report (Medicine (Baltimore), abstract)

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

Medicine (Baltimore). 2019 May;98(19):e15553. doi: 10.1097/MD.0000000000015553.

Oseltamivir induced Stevens-Johnson syndrome/toxic epidermal necrolysis-case report.

Zuo W1,2, Wen LP1, Li J1, Mei D1, Fu Q1, Zhang B1.

Author information: 1 Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing. 2 Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education”, Yantai University, Yantai, China.




Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are 2 rare but life-threatening diseases characterized by detachment of epidermis, bullous skin lesions, and mucous membrane erosions. Drugs are highly suspected to be the causative agents. We report a case of SJS/TEN induced by oseltamivir, which is a very rare event.


A 9-year-old girl with upper respiratory tract infections presented with generalized maculopapular rash the second day after taking oseltamivir.


The diagnosis of SJS/TEN was made based on cytotoxic skin lesions and mucous membrane involvement.


After discontinuing of the drug and combination therapy of corticosteroid and human immunoglobulin initiation, the lesions were improved. Human leukocyte antigen (HLA) gene sequencing was done.


The girl was followed-up for 1 year. The skin and mucous membranes symptoms were relieved.


We report this case to attract attention to the rare but serious side effect of this antiviral drug.

PMID: 31083216 DOI: 10.1097/MD.0000000000015553

Keywords: Seasonal Influenza; Antivirals; Oseltamivir; Drugs safety; Steven-Johnson Syndrome.


#Naproxen Exhibits Broad Anti- #influenza Virus Activity in Mice by Impeding Viral Nucleoprotein Nuclear Export (Cell Rep., abstract)

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

Cell Rep. 2019 May 7;27(6):1875-1885.e5. doi: 10.1016/j.celrep.2019.04.053.

Naproxen Exhibits Broad Anti-influenza Virus Activity in Mice by Impeding Viral Nucleoprotein Nuclear Export.

Zheng W1, Fan W1, Zhang S1, Jiao P2, Shang Y3, Cui L4, Mahesutihan M4, Li J1, Wang D5, Gao GF6, Sun L7, Liu W4.

Author information: 1 CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China. 2 State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresourses & Laboratory of Animal Infectious Diseases, College of Animal Sciences and Veterinary Medicine, Guangxi University, Nanning 530004, China. 3 Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, College of Veterinary Medicine, Shandong Agricultural University, Tai’an 271018, China. 4 CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; Savaid Medical School, University of Chinese Academy of Sciences, Beijing 100049, China. 5 Chinese National Influenza Center (CNIC), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention (China CDC), Beijing 102206, China. 6 CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; Savaid Medical School, University of Chinese Academy of Sciences, Beijing 100049, China; Chinese National Influenza Center (CNIC), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention (China CDC), Beijing 102206, China.  7 CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; Savaid Medical School, University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address:



Naproxen is a non-steroidal anti-inflammatory drug that has previously been shown to exert antiviral activity against influenza A virus by inhibiting nucleoprotein (NP) binding to RNA. Here, we show that naproxen is a potential broad, multi-mechanistic anti-influenza virus therapeutic, as it inhibits influenza B virus replication both in vivo and in vitro. The anti-influenza B virus activity of naproxen is more efficient than that of the commonly used neuraminidase inhibitor oseltamivir in mice. Furthermore, the NP of influenza B virus (BNP) has a higher binding affinity to naproxen than influenza A virus NP (ANP). Specifically, naproxen targets the NP at residues F209 (BNP) and Y148 (ANP). This interaction antagonizes the nuclear export of NP normally mediated by the host export protein CRM1. This study reveals a crucial mechanism of broad-spectrum anti-influenza virus activity of naproxen, suggesting that the existing drug naproxen may be used as an anti-influenza drug.

Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.

KEYWORDS: CRM1; influenza virus; naproxen; nuclear export; nucleoprotein; vRNP

PMID: 31067470 DOI: 10.1016/j.celrep.2019.04.053

Keywords: Seasonal Influenza; Antivirals; NSAIDs; Naproxen; Animal models.