scholarly journals Oseltamivir resistance in an influenza A (H3N2) virus isolated from an immunocompromised patient during the 2014–2015 influenza season in Alberta, Canada

2016 ◽  
Vol 10 (6) ◽  
pp. 532-535 ◽  
Author(s):  
Ahsan Chaudhry ◽  
Nathalie Bastien ◽  
Yan Li ◽  
Allison Scott ◽  
Kanti Pabbaraju ◽  
...  
Keyword(s):  
Influenza A ◽  
Influenza Season ◽  
Immunocompromised Patient ◽  
H3n2 Virus ◽  
Oseltamivir Resistance

scholarly journals Cell Culture-Selected Substitutions in Influenza A(H3N2) Neuraminidase Affect Drug Susceptibility Assessment

2013 ◽  
Vol 57 (12) ◽  
pp. 6141-6146 ◽  
Author(s):  
Daisuke Tamura ◽  
Ha T. Nguyen ◽  
Katrina Sleeman ◽  
Marnie Levine ◽  
Vasiliy P. Mishin ◽  
...  
Keyword(s):  
Mdck Cell ◽  
Influenza A ◽  
Mdck Cells ◽  
Clinical Sample ◽  
Fold Increase ◽  
Drug Susceptibility ◽  
H3n2 Virus ◽  
Oseltamivir Resistance ◽  
Viral Propagation ◽  
Drug Resistance Profile

ABSTRACTAssessment of drug susceptibility has become an integral part of influenza virus surveillance. In this study, we describe the drug resistance profile of influenza A(H3N2) virus, A/Mississippi/05/2011, collected from a patient treated with oseltamivir and detected via surveillance. An MDCK cell-grown isolate of this virus exhibited highly reduced inhibition by the neuraminidase (NA) inhibitors (NAIs) oseltamivir (8,005-fold), zanamivir (813-fold), peramivir (116-fold), and laninamivir (257-fold) in the NA inhibition assay. Sequence analysis of its NA gene revealed a known oseltamivir-resistance marker, the glutamic acid-to-valine substitution at position 119 (E119V), and an additional change, threonine to isoleucine at position 148 (T148I). Unlike E119V, T148I was not detected in the clinical sample but acquired during viral propagation in MDCK cells. Using recombinant proteins, T148I by itself was shown to cause only a 6-fold increase in the zanamivir 50% inhibitory concentration (IC50) and had no effect on inhibition by other drugs. The T148I substitution reduced NA activity by 50%, most likely by affecting the positioning of the 150 loop at the NA catalytic site. Using pyrosequencing, changes at T148 were detected in 35 (23%) of 150 MDCK cell-grown A(H3N2) viruses tested, which was lower than the frequency of changes at D151 (85%), an NA residue previously implicated in cell selection. We demonstrate that culturing of the A(H3N2) viruses (n= 11) at a low multiplicity of infection delayed the emergence of the NA variants with changes at position 148 and/or 151, especially when conducted in MDCK-SIAT1 cells. Our findings highlight the current challenges in monitoring susceptibility of influenza A(H3N2) viruses to the NAI class of antiviral drugs.

scholarly journals H3N2 Virus as Causative Agent of ARDS Requiring Extracorporeal Membrane Oxygenation Support

2014 ◽  
Vol 2014 ◽  
pp. 1-3
Author(s):  
Adriano Peris ◽  
Giovanni Zagli ◽  
Pasquale Bernardo ◽  
Massimo Bonacchi ◽  
Morena Cozzolino ◽  
...  
Keyword(s):  
Intensive Care Unit ◽  
Extracorporeal Membrane Oxygenation ◽  
Influenza A ◽  
Seasonal Influenza ◽  
Influenza Season ◽  
Influenza Viruses ◽  
H3n2 Virus ◽  
Membrane Oxygenation ◽  
Viral Aetiology ◽  
Increased Risk

Pandemic influenza virus A(H1N1) 2009 was associated with a higher risk of viral pneumonia in comparison with seasonal influenza viruses. The influenza season 2011-2012 was characterized by the prevalent circulation of influenza A(H3N2) viruses. Whereas most H3N2 patients experienced mild, self-limited influenza-like illness, some patients were at increased risk for influenza complications because of age or underlying medical conditions. Cases presented were patients admitted to the Intensive Care Unit (ICU) of ECMO referral center (Careggi Teaching Hospital, Florence, Italy). Despite extracorporeal membrane oxygenation treatment (ECMO), one patient with H3N2-induced ARDS did not survive. Our experience suggests that viral aetiology is becoming more important and hospitals should be able to perform a fast differential diagnosis between bacterial and viral aetiology.

scholarly journals Surveillance of influenza viruses isolated from travellers at Nagoya International Airport

2000 ◽  
Vol 124 (3) ◽  
pp. 507-514 ◽  
Author(s):  
K. SATO ◽  
T. MORISHITA ◽  
E. NOBUSAWA ◽  
Y. SUZUKI ◽  
Y. MIYAZAKI ◽  
...  
Keyword(s):  
Influenza A ◽  
Respiratory Symptoms ◽  
H1n1 Virus ◽  
Influenza Season ◽  
Influenza Viruses ◽  
H3n2 Virus ◽  
Influenza B ◽  
International Airport ◽  
Quarantine Station ◽  
Virus Strains

In order to conduct a survey of influenza viruses entering Japan via travellers arriving by airplanes, gargle solutions were collected from passengers who reported to the quarantine station of Nagoya International Airport complaining of respiratory symptoms. From 504 samples collected between August 1996 and March 1999, 30 influenza virus strains were isolated. Twenty-eight of the isolates were influenza A (H3N2) viruses and two were influenza B viruses. No H1N1 virus was isolated. Among 28 isolates of H3N2 virus, 3 strains were obtained outside the influenza season. Nucleotide sequences of the haemagglutinin (HA) genes of these isolates along with those from domestic patients were analysed in order to determine the influence of imported influenza viruses by travellers on epidemics in Japan. From the phylogenetic and chronological aspects, the possibility was suggested in one case in 1997/8 and two in the 1998/9 season that imported virus by travellers may have influenced the domestic influenza epidemics.

scholarly journals Surveillance for Neuraminidase Inhibitor Resistance among Human Influenza A and B Viruses Circulating Worldwide from 2004 to 2008

2008 ◽  
Vol 52 (9) ◽  
pp. 3284-3292 ◽  
Author(s):  
Tiffany G. Sheu ◽  
Varough M. Deyde ◽  
Margaret Okomo-Adhiambo ◽  
Rebecca J. Garten ◽  
Xiyan Xu ◽  
...  
Keyword(s):  
United States ◽  
Influenza A ◽  
Neuraminidase Inhibitor ◽  
The United States ◽  
H3n2 Virus ◽  
Influenza B ◽  
Close Monitoring ◽  
Oseltamivir Resistance ◽  
H3n2 Influenza ◽  
Inhibitor Resistance

ABSTRACT The surveillance of seasonal influenza virus susceptibility to neuraminidase (NA) inhibitors was conducted using an NA inhibition assay. The 50% inhibitory concentration values (IC50s) of 4,570 viruses collected globally from October 2004 to March 2008 were determined. Based on mean IC50s, A(H3N2) viruses (0.44 nM) were more sensitive to oseltamivir than A(H1N1) viruses (0.91 nM). The opposite trend was observed with zanamivir: 1.06 nM for A(H1N1) and 2.54 nM for A(H3N2). Influenza B viruses exhibited the least susceptibility to oseltamivir (3.42 nM) and to zanamivir (3.87 nM). To identify potentially resistant viruses (outliers), a threshold of a mean IC50 value + 3 standard deviations was defined for type/subtype and drug. Sequence analysis of outliers was performed to identify NA changes that might be associated with reduced susceptibility. Molecular markers of oseltamivir resistance were found in six A(H1N1) viruses (H274Y) and one A(H3N2) virus (E119V) collected between 2004 and 2007. Some outliers contained previously reported mutations (e.g., I222T in the B viruses), while other mutations [e.g., R371K and H274Y in B viruses and H274N in A(H3N2) viruses) were novel. The R371K B virus outlier exhibited high levels of resistance to both inhibitors (>100 nM). A substantial variance at residue D151 was observed among A(H3N2) zanamivir-resistant outliers. The clinical relevance of newly identified NA mutations is unknown. A rise in the incidence of oseltamivir resistance in A(H1N1) viruses carrying the H274Y mutation was detected in the United States and in other countries in the ongoing 2007 to 2008 season. As of March 2008, the frequency of resistance among A(H1N1) viruses in the United States was 8.6% (50/579 isolates). The recent increase in oseltamivir resistance among A(H1N1) viruses isolated from untreated patients raises public health concerns and necessitates close monitoring of resistance to NA inhibitors.

scholarly journals Vaccine effectiveness against influenza-associated hospitalizations among adults, 2018-2019, US Hospitalized Adult Influenza Vaccine Effectiveness Network

2020 ◽  
Author(s):  
J M Ferdinands ◽  
M Gaglani ◽  
S Ghamande ◽  
E T Martin ◽  
D Middleton ◽  
...  
Keyword(s):  
Influenza Vaccine ◽  
Influenza A ◽  
Influenza Season ◽  
Respiratory Illness ◽  
Vaccine Effectiveness ◽  
H3n2 Virus ◽  
Influenza A H1n1 ◽  
The Us ◽  
Middle Aged Adults ◽  
Residual Confounding

Abstract We estimated vaccine effectiveness for prevention of influenza-associated hospitalizations among adults during the 2018-2019 influenza season. Adults admitted with acute respiratory illness to 14 hospitals of the US Hospitalized Adult Influenza Vaccine Effectiveness Network and testing positive for influenza were cases; patients testing negative were controls. Vaccine effectiveness was estimated using logistic regression and inverse probability of treatment weighting. We analyzed data from 2863 patients with mean age of 63 years. Adjusted VE against influenza A(H1N1)pdm09-associated hospitalization was 51% (95%CI 25, 68). Adjusted VE against influenza A(H3N2) virus-associated hospitalization was −2% (95%CI −65, 37) and differed significantly by age, with VE of −130% (95% CI −374, −27) among adults 18 to ≤56 years of age. Although vaccination halved the risk of influenza-A(H1N1)pdm09-associated hospitalizations, it conferred no protection against influenza A(H3N2)-associated hospitalizations. We observed negative VE for young-and middle-aged adults but cannot exclude residual confounding as a potential explanation.

scholarly journals Trivalent inactivated influenza vaccine effective against influenza A(H3N2) variant viruses in children during the 2014/15 season, Japan

2016 ◽  
Vol 21 (42) ◽  
Author(s):  
Norio Sugaya ◽  
Masayoshi Shinjoh ◽  
Chiharu Kawakami ◽  
Yoshio Yamaguchi ◽  
Makoto Yoshida ◽  
...  
Keyword(s):  
New York ◽  
Influenza Vaccine ◽  
Influenza A ◽  
Influenza Season ◽  
Influenza Virus Infection ◽  
Case Control ◽  
H3n2 Virus ◽  
Influenza B ◽  
Influenza A Viruses ◽  
Negative Case

The 2014/15 influenza season in Japan was characterised by predominant influenza A(H3N2) activity; 99% of influenza A viruses detected were A(H3N2). Subclade 3C.2a viruses were the major epidemic A(H3N2) viruses, and were genetically distinct from A/New York/39/2012(H3N2) of 2014/15 vaccine strain in Japan, which was classified as clade 3C.1. We assessed vaccine effectiveness (VE) of inactivated influenza vaccine (IIV) in children aged 6 months to 15 years by test-negative case–control design based on influenza rapid diagnostic test. Between November 2014 and March 2015, a total of 3,752 children were enrolled: 1,633 tested positive for influenza A and 42 for influenza B, and 2,077 tested negative. Adjusted VE was 38% (95% confidence intervals (CI): 28 to 46) against influenza virus infection overall, 37% (95% CI: 27 to 45) against influenza A, and 47% (95% CI: -2 to 73) against influenza B. However, IIV was not statistically significantly effective against influenza A in infants aged 6 to 11 months or adolescents aged 13 to 15 years. VE in preventing hospitalisation for influenza A infection was 55% (95% CI: 42 to 64). Trivalent IIV that included A/New York/39/2012(H3N2) was effective against drifted influenza A(H3N2) virus, although vaccine mismatch resulted in low VE.

scholarly journals Detection of E119V and E119I Mutations in Influenza A (H3N2) Viruses Isolated from an Immunocompromised Patient: Challenges in Diagnosis of Oseltamivir Resistance

2010 ◽  
Vol 54 (5) ◽  
pp. 1834-1841 ◽  
Author(s):  
M. Okomo-Adhiambo ◽  
G. J. Demmler-Harrison ◽  
V. M. Deyde ◽  
T. G. Sheu ◽  
X. Xu ◽  
...  
Keyword(s):  
Influenza A ◽  
Immunocompromised Patient ◽  
Oseltamivir Resistance

scholarly journals Genetic and antigenic characterisation of influenza A(H3N2) viruses isolated in Yokohama during the 2016/17 and 2017/18 influenza seasons

2019 ◽  
Vol 24 (6) ◽  
Author(s):  
Chiharu Kawakami ◽  
Seiya Yamayoshi ◽  
Miki Akimoto ◽  
Kazuya Nakamura ◽  
Hideka Miura ◽  
...  
Keyword(s):  
Immune Responses ◽  
Influenza A ◽  
Influenza Season ◽  
Glycosylation Site ◽  
H3n2 Virus ◽  
Amino Acid Substitutions ◽  
Antigenic Analysis ◽  
Glycosylation Sites ◽  
Identify Amino Acid ◽  
Human Immune

Background: Influenza A(H3N2) virus rapidly evolves to evade human immune responses, resulting in changes in the antigenicity of haemagglutinin (HA). Therefore, continuous genetic and antigenic analyses of A(H3N2) virus are necessary to detect antigenic mutants as quickly as possible. Aim: We attempted to phylogenetically and antigenically capture the epidemic trend of A(H3N2) virus infection in Yokohama, Japan during the 2016/17 and 2017/18 influenza seasons. Methods: We determined the HA sequences of A(H3N2) viruses detected in Yokohama, Japan during the 2016/17 and 2017/18 influenza seasons to identify amino acid substitutions and the loss or gain of potential N-glycosylation sites in HA, both of which potentially affect the antigenicity of HA. We also examined the antigenicity of isolates using ferret antisera obtained from experimentally infected ferrets. Results: Influenza A(H3N2) viruses belonging to six clades (clades 3C.2A1, 3C.2A1a, 3C.2A1b, 3C.2A2, 3C.2A3 and 3C.2A4) were detected during the 2016/17 influenza season, whereas viruses belonging to two clades (clades 3C.2A1b and 3C.2A2) dominated during the 2017/18 influenza season. The isolates in clades 3C.2A1a and 3C.2A3 lost one N-linked glycosylation site in HA relative to other clades. Antigenic analysis revealed antigenic differences among clades, especially clade 3C.2A2 and 3C.2A4 viruses, which showed distinct antigenic differences from each other and from other clades in the antigenic map. Conclusion: Multiple clades, some of which differed antigenically from others, co-circulated in Yokohama, Japan during the 2016/17 and 2017/18 influenza seasons.

scholarly journals Nanopore metagenomic sequencing of influenza virus directly from respiratory samples: diagnosis, drug resistance and nosocomial transmission, United Kingdom, 2018/19 influenza season

2021 ◽  
Vol 26 (27) ◽  
Author(s):  
Yifei Xu ◽  
Kuiama Lewandowski ◽  
Louise O Downs ◽  
James Kavanagh ◽  
Thomas Hender ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Influenza Virus ◽  
United Kingdom ◽  
Influenza A ◽  
Influenza Season ◽  
Sequence Data ◽  
Nosocomial Transmission ◽  
Molecular Diagnostic ◽  
Metagenomic Sequencing ◽  
Oseltamivir Resistance

Background Influenza virus presents a considerable challenge to public health by causing seasonal epidemics and occasional pandemics. Nanopore metagenomic sequencing has the potential to be deployed for near-patient testing, providing rapid infection diagnosis, rationalising antimicrobial therapy, and supporting infection-control interventions. Aim To evaluate the applicability of this sequencing approach as a routine laboratory test for influenza in clinical settings. Methods We conducted Oxford Nanopore Technologies (Oxford, United Kingdom (UK)) metagenomic sequencing for 180 respiratory samples from a UK hospital during the 2018/19 influenza season, and compared results to routine molecular diagnostic standards (Xpert Xpress Flu/RSV assay; BioFire FilmArray Respiratory Panel 2 assay). We investigated drug resistance, genetic diversity, and nosocomial transmission using influenza sequence data. Results Compared to standard testing, Nanopore metagenomic sequencing was 83% (75/90) sensitive and 93% (84/90) specific for detecting influenza A viruses. Of 59 samples with haemagglutinin subtype determined, 40 were H1 and 19 H3. We identified an influenza A(H3N2) genome encoding the oseltamivir resistance S331R mutation in neuraminidase, potentially associated with an emerging distinct intra-subtype reassortant. Whole genome phylogeny refuted suspicions of a transmission cluster in a ward, but identified two other clusters that likely reflected nosocomial transmission, associated with a predominant community-circulating strain. We also detected other potentially pathogenic viruses and bacteria from the metagenome. Conclusion Nanopore metagenomic sequencing can detect the emergence of novel variants and drug resistance, providing timely insights into antimicrobial stewardship and vaccine design. Full genome generation can help investigate and manage nosocomial outbreaks.

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