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Emergence of an oseltamivir-resistant influenza A/H3N2 virus in an elderly patient receiving a suboptimal dose of antiviral prophylaxis.

ABSTRACT: We report the emergence of an influenza virus A/H3N2-E119V neuraminidase variant from an elderly patient with renal dysfunction who received a suboptimal dose of oseltamivir prophylaxis. In neuraminidase inhibition assays, the E119V variant showed a 413-fold increase in the 50% inhibitory oseltamivir concentration and grew at titers comparable to those of the wild type in vitro.

SUBMITTER: Roussy JF

PROVIDER: S-EPMC3838039 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature

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Emergence of an oseltamivir-resistant influenza A/H3N2 virus in an elderly patient receiving a suboptimal dose of antiviral prophylaxis.

Roussy Jean-François JF Abed Yacine Y Bouhy Xavier X Boivin Guy G

Journal of clinical microbiology 20131002 12

We report the emergence of an influenza virus A/H3N2-E119V neuraminidase variant from an elderly patient with renal dysfunction who received a suboptimal dose of oseltamivir prophylaxis. In neuraminidase inhibition assays, the E119V variant showed a 413-fold increase in the 50% inhibitory oseltamivir concentration and grew at titers comparable to those of the wild type in vitro. ...[more]

PMID: 24088848

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Project description:Influenza viruses can cause severe life threatening infections in high-risk patients, including young children, the elderly and patients with compromised immunity due to underlying medical conditions or immunosuppressive treatment. The impaired immunity of these patients causes prolonged virus infection and combined with antiviral treatment facilitates the emergence of viruses with resistance mutations. The diverse nature of their immune status makes them a challenging group to study the impact of influenza virus infection and the efficacy of antiviral therapy. Immunocompromised ferrets may represent a suitable animal model to assess influenza virus infection and antiviral treatment strategies in immunocompromised hosts. Here, ferrets were given a daily oral solution of mycophenolate mofetil, tacrolimus and prednisolone sodium phosphate to suppress their immune system. Groups of immunocompromised and immunocompetent ferrets were inoculated with an A/H3N2 influenza virus and were subsequently treated with Oseltamivir or left untreated. Quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) was performed on the throat and nose specimens to study virus replication during the course of infection. All immunocompromised ferrets had prolonged presence of viral RNA and a higher total amount of virus shedding compared to the immunocompetent ferrets. Although Oseltamivir reduced the total amount of virus shedding from the nose and throat of treated ferrets, it also resulted in the emergence of the neuraminidase R292K resistance substitution in all these animals, as determined by mutation specific RT-PCR and next-generation sequencing. No additional mutations that could be associated with the emergence of the R292K resistance mutation were detected. The immunocompromised ferret model can be used to study A/H3N2 virus shedding and is a promising model to study new antiviral strategies and the emergence of antiviral resistance in immunocompromised hosts.

Dataset Information

Emergence of an oseltamivir-resistant influenza A/H3N2 virus in an elderly patient receiving a suboptimal dose of antiviral prophylaxis.

Publications

Emergence of an oseltamivir-resistant influenza A/H3N2 virus in an elderly patient receiving a suboptimal dose of antiviral prophylaxis.

Similar Datasets

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