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      Oseltamivir-Resistant Influenza Virus A (H1N1), Europe, 2007–08 Season

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          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          A high level of virus circulation and introduction of an antigenic drift variant in a susceptible population contributed to the spread of resistant virus.

          Abstract

          In Europe, the 2007–08 winter season was dominated by influenza virus A (H1N1) circulation through week 7, followed by influenza B virus from week 8 onward. Oseltamivir-resistant influenza viruses A (H1N1) (ORVs) with H275Y mutation in the neuraminidase emerged independently of drug use. By country, the proportion of ORVs ranged from 0% to 68%, with the highest proportion in Norway. The average weighted prevalence of ORVs across Europe increased gradually over time, from near 0 in week 40 of 2007 to 56% in week 19 of 2008 (mean 20%). Neuraminidase genes of ORVs possessing the H275Y substitution formed a homogeneous subgroup closely related to, but distinguishable from, those of oseltamivir-sensitive influenza viruses A (H1N1). Minor variants of ORVs emerged independently, indicating multiclonal ORVs. Overall, the clinical effect of ORVs in Europe, measured by influenza-like illness or acute respiratory infection, was unremarkable and consistent with normal seasonal activity.

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          Most cited references30

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          Resistant influenza A viruses in children treated with oseltamivir: descriptive study.

          Oseltamivir is an effective inhibitor of influenza virus neuraminidase. Although viruses resistant to oseltamivir emerge less frequently than those resistant to amantadine or rimantadine, information on oseltamivir-resistant viruses arising during clinical use of the drug in children is limited. Our aim was to investigate oseltamivir resistance in a group of children treated for influenza. We analysed influenza A viruses (H3N2) collected from 50 children before and during treatment with oseltamivir. We sequenced the genes for neuraminidase and haemagglutinin and studied the mutant neuraminidases for their sensitivity to oseltamivir carboxylate. We found neuraminidase mutations in viruses from nine patients (18%), six of whom had mutations at position 292 (Arg292Lys) and two at position 119 (Glu119Val), which are known to confer resistance to neuraminidase inhibitors. We also identified another mutation (Asn294Ser) in one patient. Sensitivity testing to oseltamivir carboxylate revealed that the neuraminidases of viruses that have an Arg292Lys, Glu119Val, or Asn294Ser mutation were about 10(4)-10(5)-fold, 500-fold, or 300-fold more resistant than their pretreatment neuraminidases, respectively. Oseltamivir-resistant viruses were first detected at day 4 of treatment and on each successive day of the study. More than 10(3) infectious units per mL of virus were detected in some of the patients who did not shed drug-resistant viruses, even after 5 days of treatment. Oseltamivir-resistant mutants in children being treated for influenza with oseltamivir arise more frequently than previously reported. Furthermore, children can be a source of viral transmission, even after 5 days of treatment with oseltamivir.
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            The war against influenza: discovery and development of sialidase inhibitors.

            The threat of a major human influenza pandemic, in particular from highly aggressive strains such as avian H5N1, has emphasized the need for therapeutic strategies to combat these pathogens. At present, two inhibitors of sialidase (also known as neuraminidase), a viral enzyme that has a key role in the life cycle of influenza viruses, would be the mainstay of pharmacological strategies in the event of such a pandemic. This article provides a historical perspective on the discovery and development of these drugs--zanamivir and oseltamivir--and highlights the value of structure-based drug design in this process.
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              The global impact of influenza on morbidity and mortality.

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                Author and article information

                Journal
                Emerg Infect Dis
                EID
                Emerging Infectious Diseases
                Centers for Disease Control and Prevention
                1080-6040
                1080-6059
                April 2009
                : 15
                : 4
                : 552-560
                Affiliations
                [1]Netherlands Institute for Health Services Research, Utrecht, the Netherlands (A. Meijer, J. Paget)
                [2]National Institute for Public Health and the Environment, Bilthoven, the Netherlands (A. Meijer, J. van de Kassteele)
                [3]European Surveillance Network for Vigilance against Viral Resistance (A. Lackenby, B. Lina, S. van der Werf, A. Hay, M. Zambon)
                [4]Health Protection Agency, London, UK (A. Lackenby, M. Zambon)
                [5]Norwegian Institute of Public Health, Oslo, Norway (O. Hungnes); Centre National de Référence des Virus Influenza (Région Sud), Lyon, France (B. Lina)
                [6]Centre National de Référence des Virus Influenza (Région Nord), Paris, France (S. van der Werf)
                [7]Robert Koch Institute, Berlin, Germany (B. Schweiger)
                [8]Laboratoire National de Santé, Luxembourg, Luxembourg (M. Opp)
                [9]World Health Organization Collaborating Centre Medical Research Council/National Institute of Medical Research, London (A. Hay)
                Author notes
                Address for correspondence: Adam Meijer, Centre for Infectious Disease Control, National Institute for Public Health and the Environment, PO Box 1, 3720 BA Bilthoven, the Netherlands; email: adam.meijer@ 123456rivm.nl
                Article
                08-1280
                10.3201/eid1504.081280
                2671453
                19331731
                20c80866-8714-4d8e-bc59-b151ee37d06a
                History
                Categories
                Research

                Infectious disease & Microbiology
                research,influenza a virus,surveillance,epidemiology,antiviral agents,h1n1,europe,oseltamivir,viruses,antimicrobial resistance

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