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Neuraminidase inhibitor resistance after oseltamivir treatment of acute influenza A and B in children.

Abstract

BACKGROUND

Oseltamivir, a specific influenza neuraminidase inhibitor, is an effective treatment for seasonal influenza. Emergence of drug-resistant influenza viruses after treatment has been reported, particularly in children in Japan, where the dosing schedule is different from that used throughout the rest of the world. We investigated the emergence of drug-resistant infection in children treated with a tiered weight-based dosing regimen.

METHODS

We analyzed sequential clinical nasopharyngeal samples, obtained before and after tiered weight-based oseltamivir therapy, from children with acute influenza during 2005-2007. We isolated viruses, tested for drug resistance with use of a fluorescence-based neuraminidase inhibition assay, performed neuraminidase gene sequencing, and determined quantitative viral loads.

RESULTS

Sixty-four children (34 with influenza A subtype H3N2, 11 with influenza A subtype H1N1, and 19 with influenza B virus) aged 1-12 years (median age, 3 years, 1 month) were enrolled. By days 4-7 after initiation of treatment, of 64 samples tested, 47 (73.4%) and 26 (40.6%) had virus detectable by reverse-transcriptase polymerase chain reaction and culture, respectively. By days 8-12 after initiation of treatment, of 53 samples tested, 18 (33.9%) and 1 (1.8%) had virus detectable by reverse-transcriptase polymerase chain reaction and culture, respectively. We found no statistically significant differences in the reduction of viral shedding or time to clearance of virus between viral subtypes. Antiviral-resistant viruses were recovered from 3 (27.3%) of 11 children with influenza A subtype H1N1, 1 (2.9%) of 34 children with influenza A subtype H3N2, and 0 (0%) of 19 children with influenza B virus, all of whom were treated with oseltamivir (P = .004). There was no evidence of prolonged illness in children infected with drug-resistant virus.

CONCLUSIONS

Drug resistance emerges at a higher rate in influenza A subtype H1N1 virus than in influenza A subtype H3N2 or influenza B virus after tiered weight-based oseltamivir therapy. Virological surveillance for patterns of drug resistance is essential for determination of antiviral treatment strategies and for composition of pandemic preparedness stockpiles.

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  • Authors+Show Affiliations

    ,

    Infectious Diseases Unit, Leicester Royal Infirmary, Leicester, UK. iain.stephenson@uhl-tr.nhs.uk

    , , , , , , , ,

    Source

    MeSH

    Antiviral Agents
    Child
    Child, Preschool
    Drug Resistance, Viral
    Female
    Humans
    Infant
    Influenza A Virus, H1N1 Subtype
    Influenza A Virus, H3N2 Subtype
    Influenza A virus
    Influenza B virus
    Influenza, Human
    Male
    Microbial Sensitivity Tests
    Neuraminidase
    Oseltamivir
    Sequence Analysis, DNA
    Viral Load
    Viral Proteins

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    19133796

    Citation

    Stephenson, Iain, et al. "Neuraminidase Inhibitor Resistance After Oseltamivir Treatment of Acute Influenza a and B in Children." Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America, vol. 48, no. 4, 2009, pp. 389-96.
    Stephenson I, Democratis J, Lackenby A, et al. Neuraminidase inhibitor resistance after oseltamivir treatment of acute influenza A and B in children. Clin Infect Dis. 2009;48(4):389-96.
    Stephenson, I., Democratis, J., Lackenby, A., McNally, T., Smith, J., Pareek, M., ... Zambon, M. (2009). Neuraminidase inhibitor resistance after oseltamivir treatment of acute influenza A and B in children. Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America, 48(4), pp. 389-96. doi:10.1086/596311.
    Stephenson I, et al. Neuraminidase Inhibitor Resistance After Oseltamivir Treatment of Acute Influenza a and B in Children. Clin Infect Dis. 2009 Feb 15;48(4):389-96. PubMed PMID: 19133796.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Neuraminidase inhibitor resistance after oseltamivir treatment of acute influenza A and B in children. AU - Stephenson,Iain, AU - Democratis,Jane, AU - Lackenby,Angie, AU - McNally,Teresa, AU - Smith,James, AU - Pareek,Manish, AU - Ellis,Joanna, AU - Bermingham,Alison, AU - Nicholson,Karl, AU - Zambon,Maria, PY - 2009/1/13/entrez PY - 2009/1/13/pubmed PY - 2009/9/1/medline SP - 389 EP - 96 JF - Clinical infectious diseases : an official publication of the Infectious Diseases Society of America JO - Clin. Infect. Dis. VL - 48 IS - 4 N2 - BACKGROUND: Oseltamivir, a specific influenza neuraminidase inhibitor, is an effective treatment for seasonal influenza. Emergence of drug-resistant influenza viruses after treatment has been reported, particularly in children in Japan, where the dosing schedule is different from that used throughout the rest of the world. We investigated the emergence of drug-resistant infection in children treated with a tiered weight-based dosing regimen. METHODS: We analyzed sequential clinical nasopharyngeal samples, obtained before and after tiered weight-based oseltamivir therapy, from children with acute influenza during 2005-2007. We isolated viruses, tested for drug resistance with use of a fluorescence-based neuraminidase inhibition assay, performed neuraminidase gene sequencing, and determined quantitative viral loads. RESULTS: Sixty-four children (34 with influenza A subtype H3N2, 11 with influenza A subtype H1N1, and 19 with influenza B virus) aged 1-12 years (median age, 3 years, 1 month) were enrolled. By days 4-7 after initiation of treatment, of 64 samples tested, 47 (73.4%) and 26 (40.6%) had virus detectable by reverse-transcriptase polymerase chain reaction and culture, respectively. By days 8-12 after initiation of treatment, of 53 samples tested, 18 (33.9%) and 1 (1.8%) had virus detectable by reverse-transcriptase polymerase chain reaction and culture, respectively. We found no statistically significant differences in the reduction of viral shedding or time to clearance of virus between viral subtypes. Antiviral-resistant viruses were recovered from 3 (27.3%) of 11 children with influenza A subtype H1N1, 1 (2.9%) of 34 children with influenza A subtype H3N2, and 0 (0%) of 19 children with influenza B virus, all of whom were treated with oseltamivir (P = .004). There was no evidence of prolonged illness in children infected with drug-resistant virus. CONCLUSIONS: Drug resistance emerges at a higher rate in influenza A subtype H1N1 virus than in influenza A subtype H3N2 or influenza B virus after tiered weight-based oseltamivir therapy. Virological surveillance for patterns of drug resistance is essential for determination of antiviral treatment strategies and for composition of pandemic preparedness stockpiles. SN - 1537-6591 UR - https://www.unboundmedicine.com/medline/citation/19133796/Neuraminidase_inhibitor_resistance_after_oseltamivir_treatment_of_acute_influenza_A_and_B_in_children_ L2 - https://academic.oup.com/cid/article-lookup/doi/10.1086/596311 DB - PRIME DP - Unbound Medicine ER -