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Influenza viruses can mutate genetically and cause a range of respiratory ailments. The H275Y mutation in the neuraminidase (NA) gene reduces the effectiveness of oseltamivir, a widely used drug for the treatment of Influenza A and B virus infection. The World Health Organization (WHO) recommends single‐nucleotide polymorphism assays to detect this mutation. The present study aims to estimate the prevalence of H275Y mutation conferring oseltamivir resistance in Influenza A(H1N1)pdm09 virus among hospitalized patients from June 2014 to December 2021. Following the WHO protocol, allelic discrimination real‐time RT‐PCR was performed for 752 samples. Out of the 752 samples, 1 tested positive for Y275 gene mutation by allelic discrimination real‐time RT‐PCR. In samples of years 2020 and 2021, neither the H275 nor Y275 genotype was detected. Sequencing of the NA gene of all negative samples showed a mismatch between the NA sequence and the probes used in the allelic discrimination assay. Also, Y275 mutation was detected in only 1 sample from 2020. The prevalence of oseltamivir resistance was estimated as 0.27% among the Influenza A(H1N1)pdm09 patients during 2014−2021. The study highlights that the WHO‐recommended probes for detecting H275Y mutation may not be useful to detect 2020 and 2021 circulating strains of Influenza A(H1N1)pdm09, emphasizing the need for continuous monitoring of mutations in the influenza virus. [ABSTRACT FROM AUTHOR]

Few treatment options are available for oseltamivir‐resistant influenza. It has been proposed that baloxavir can be effective in this setting due to its distinct mechanism of action but clinical experience is lacking for immunocompromised patients. We report two such cases treated with baloxavir after failure of oseltamivir and detection of oseltamivir resistance mutations. Baloxavir/zanamivir combination therapy was effective in one patient, but persistent viral shedding was noted with baloxavir monotherapy in the other patient. [ABSTRACT FROM AUTHOR]

Background: Antiviral resistance in Norwegian influenza viruses is rare. Only one A(H1N1)pdm09 virus from May 2015 had been found resistant to oseltamivir since the introduction of these viruses in 2009. Objectives: Surveillance of antiviral resistance is part of the Norwegian surveillance system, to rapidly detect the development of antiviral‐resistant viruses and spread in the community. We describe the spread of oseltamivir‐resistant A(H1N1)pdm09 viruses in Norway in the 2016‐17 season, found as part of the routine surveillance. Methods: Influenza H1N1 viruses were analysed for antiviral resistance by pyrosequencing, neuraminidase susceptibility assay and by Sanger sequencing of the HA and NA genes. Results: During the 2015‐16 influenza season, 3% of all A(H1N1)pdm09 viruses screened for resistance in Norway were resistant to oseltamivir, possessing the H275Y substitution in the neuraminidase protein. In comparison, the overall frequency in Europe was 0.87%. Out of these, 37% (n = 10) were reported from Norway. Most cases in Norway were not related to antiviral treatment, and the cases were from several different locations of southern Norway. Genetic analysis revealed that resistant virus emerged independently on several occasions and that there was some spread of oseltamivir‐resistant influenza A(H1N1)6B.1 viruses in the community, characterised by a N370S substitution in the haemagglutinin and T48I in the neuraminidase. Conclusions: Our findings emphasise the importance of antiviral resistance surveillance in the community, not only in immunocompromised patients or other patients undergoing antiviral treatment. [ABSTRACT FROM AUTHOR]

The H275Y and E119D neuraminidase (NA) mutations constitute important molecular markers of resistance to NA inhibitors in A(H1N1) pdm09 viruses. We used reverse transcriptase-droplet digital PCR amplification (RT-ddPCR) to analyze quasi-species at codons 275 and 119 of the NA in A(H1N1) pdm09 viruses recovered from an immuncompromised patient who received oseltamivir and zanamivir therapies. RT-ddPCR assays detected and quantified H275Y and E119D mutations with an efficiency that was comparable to that of high throughput sequencing (HiSeq 2500 Illumina, San Diego, CA) technology. With its sensitivity and reproducibility, RT-ddPCR could be a reliable method for accurate detection and quantification of major NAI-resistance mutations in clinical settings. J. Med. Virol. 89:737-741, 2017. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

In an observational cohort study, we found that adults hospitalized for oseltamivir-resistant (H275Y) seasonal H1N1 influenza ( n = 46) were older than those infected with oseltamivir-susceptible strains ( n = 31) [74(IQR 59-83) versus 64(IQR 48-76) years; P = 0·045], and most had major comorbidities (78% versus 65%). Disease severity and clinical outcomes were comparable between the two groups: radiographic pneumonia 40-42%, supplemental oxygen use 47-48%, critical illness 11-13%, median duration of hospitalization 5-6 days, death rate 6-9%. Failure to receive effective antiviral therapy was associated with progression to critical illness (23% versus 0%, P = 0·016) and death (20% versus 0%, P = 0·033) in hospitalized patients with seasonal H1N1 influenza. [ABSTRACT FROM AUTHOR]

C. Renaud, S.A. Pergam, C. Polyak, R. Jain, J. Kuypers, J.A. Englund, L. Corey, M.J. Boeckh. Early emergence of an H275Y mutation in a hematopoietic cell transplant recipient treated with intravenous peramivir. Transpl Infect Dis 2010: 513-517. All rights reserved Oseltamivir resistance in pandemic 2009 influenza A/H1N1 is caused by the neuraminidase mutation H275Y. This mutation has also been associated with in vitro resistance to peramivir, but few clinical cases have been described to date. Using allele-specific real-time reverse transcriptase polymerase chain reaction assay for the H275Y mutation, we were able to identify resistant H1N1 in a hematopoietic cell transplant recipient receiving intravenous peramivir therapy, and through serial testing we determined the molecular evolution of resistance. This case demonstrates that an H275Y mutant population can emerge early and replicate in vivo under peramivir antiviral pressure to become the major viral population. [ABSTRACT FROM AUTHOR]