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Clinical management and viral genomic diversity analysis of a child's influenza A(H1N1)pdm09 infection in the context of a severe combined immunodeficiency

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  • Clinical management and viral genomic diversity analysis of a child's influenza A(H1N1)pdm09 infection in the context of a severe combined immunodeficiency

    Antiviral Res. 2018 Oct 10. pii: S0166-3542(18)30307-3. doi: 10.1016/j.antiviral.2018.10.009. [Epub ahead of print]
    Clinical management and viral genomic diversity analysis of a child's influenza A(H1N1)pdm09 infection in the context of a severe combined immunodeficiency.

    Pichon M1, Picard C1, Simon B2, Gaymard A1, Renard C3, Massenavette B4, Malcus C5, Monneret G5, Morfin-Sherpa F1, Valette M1, Javouhey E4, Millat G6, Lina B1, Josset L1, Escuret V7.
    Author information

    Abstract

    INTRODUCTION:

    A child with severe combined immunodeficiency (SCID) had an influenza A(H1N1)pdm09 infection with viral excretion longer than 6 months, during 2013-2014 influenza season, despite cord blood transplantation and antiviral treatments.
    METHODS:

    Conventional real-time RT-PCR methods were used to estimate viral load and to detect the presence of the common N1 neuraminidase (NA) H275Y substitution responsible for oseltamivir resistance. Next-generation sequencing (NGS) of influenza viruses was performed retrospectively to characterize viral quasispecies in specimens.
    RESULTS:

    The patient was first treated with oral oseltamivir, leading to detection of low-levels of NA-H275Y substitution. Concomitant cord blood cell transplantation, intravenous administration of zanamivir and immunoglobulins led to an increase in white blood cells and influenza viral load decrease. A viral rebound occurred as soon as the antiviral treatment was discontinued. Eventually, influenza viral load was negated with immune reconstitution. NGS found influenza quasispecies harboring NA-E119A substitution (10.3%). Moreover, NGS showed that viral genomic diversity evolved under antiviral treatment and immune status.
    CONCLUSIONS:

    Conventional virological techniques were sufficient for influenza infection follow-up but NGS performances allowed characterization of viral variants evolution in this specific case of prolonged influenza virus infection. New and efficient treatments against influenza in immunocompromised patients are needed.
    Copyright ? 2018. Published by Elsevier B.V.


    KEYWORDS:

    Influenza A(H1N1)pdm09 virus; Intravenous zanamivir; NA-E119A substitution; NA-H275Y substitution; Next-generation sequencing; Oseltamivir resistance

    PMID: 30315875 DOI: 10.1016/j.antiviral.2018.10.009
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