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Emergence of influenza B viruses with reduced sensitivity to neuraminidase inhibitors.

Abstract

CONTEXT

Very little is known about the frequency of generation and transmissibility of influenza B viruses with reduced sensitivity to neuraminidase inhibitors. Furthermore, transmission of resistant virus, whether influenza A or B, has not been recognized to date.

OBJECTIVE

To assess the prevalence and transmissibility of influenza B viruses with reduced sensitivity to neuraminidase inhibitors.

DESIGN, SETTING, AND PATIENTS

Investigation of the neuraminidase inhibitor sensitivity of influenza B isolates from 74 children before and after oseltamivir therapy and from 348 untreated patients with influenza (including 66 adults) seen at 4 community hospitals in Japan during the 2004-2005 influenza season. Four hundred twenty-two viruses from untreated patients and 74 samples from patients after oseltamivir therapy were analyzed.

MAIN OUTCOME MEASURE

Sialidase inhibition assay was used to test the drug sensitivities of influenza B viruses. The neuraminidase and hemagglutinin genes of viruses showing reduced sensitivity to neuraminidase inhibitors were sequenced to identify mutations that have the potential to confer reduced sensitivity to these drugs.

RESULTS

In 1 (1.4%) of the 74 children who had received oseltamivir, we identified a variant with reduced drug sensitivity possessing a Gly402Ser neuraminidase substitution. We also identified variants with reduced sensitivity carrying an Asp198Asn, Ile222Thr, or Ser250Gly mutation in 7 (1.7%) of the 422 viruses from untreated patients. Review of the clinical and viral genetic information available on these 7 patients indicated that 4 were likely infected in a community setting, while the remaining 3 were probably infected through contact with siblings shedding the mutant viruses.

CONCLUSIONS

In this population, influenza B viruses with reduced sensitivity to neuraminidase inhibitors do not arise as frequently as resistant influenza A viruses. However, they appear to be transmitted within communities and families, requiring continued close monitoring.

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  • Authors+Show Affiliations

    ,

    Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.

    , , , , , , , , , ,

    Source

    JAMA 297:13 2007 Apr 04 pg 1435-42

    MeSH

    Adolescent
    Adult
    Amino Acid Substitution
    Antiviral Agents
    Child
    Child, Preschool
    Drug Resistance, Viral
    Enzyme Inhibitors
    Female
    Hemagglutinins
    Humans
    Infant
    Influenza A Virus, H3N2 Subtype
    Influenza A Virus, H5N1 Subtype
    Influenza B virus
    Influenza, Human
    Japan
    Male
    Middle Aged
    Mutation, Missense
    Neuraminidase
    Oseltamivir
    Prevalence
    Seasons

    Pub Type(s)

    Journal Article
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    17405969

    Citation

    TY - JOUR T1 - Emergence of influenza B viruses with reduced sensitivity to neuraminidase inhibitors. AU - Hatakeyama,Shuji, AU - Sugaya,Norio, AU - Ito,Mutsumi, AU - Yamazaki,Masahiko, AU - Ichikawa,Masataka, AU - Kimura,Kazuhiro, AU - Kiso,Maki, AU - Shimizu,Hideaki, AU - Kawakami,Chiharu, AU - Koike,Kazuhiko, AU - Mitamura,Keiko, AU - Kawaoka,Yoshihiro, PY - 2007/4/5/pubmed PY - 2007/4/7/medline PY - 2007/4/5/entrez SP - 1435 EP - 42 JF - JAMA JO - JAMA VL - 297 IS - 13 N2 - CONTEXT: Very little is known about the frequency of generation and transmissibility of influenza B viruses with reduced sensitivity to neuraminidase inhibitors. Furthermore, transmission of resistant virus, whether influenza A or B, has not been recognized to date. OBJECTIVE: To assess the prevalence and transmissibility of influenza B viruses with reduced sensitivity to neuraminidase inhibitors. DESIGN, SETTING, AND PATIENTS: Investigation of the neuraminidase inhibitor sensitivity of influenza B isolates from 74 children before and after oseltamivir therapy and from 348 untreated patients with influenza (including 66 adults) seen at 4 community hospitals in Japan during the 2004-2005 influenza season. Four hundred twenty-two viruses from untreated patients and 74 samples from patients after oseltamivir therapy were analyzed. MAIN OUTCOME MEASURE: Sialidase inhibition assay was used to test the drug sensitivities of influenza B viruses. The neuraminidase and hemagglutinin genes of viruses showing reduced sensitivity to neuraminidase inhibitors were sequenced to identify mutations that have the potential to confer reduced sensitivity to these drugs. RESULTS: In 1 (1.4%) of the 74 children who had received oseltamivir, we identified a variant with reduced drug sensitivity possessing a Gly402Ser neuraminidase substitution. We also identified variants with reduced sensitivity carrying an Asp198Asn, Ile222Thr, or Ser250Gly mutation in 7 (1.7%) of the 422 viruses from untreated patients. Review of the clinical and viral genetic information available on these 7 patients indicated that 4 were likely infected in a community setting, while the remaining 3 were probably infected through contact with siblings shedding the mutant viruses. CONCLUSIONS: In this population, influenza B viruses with reduced sensitivity to neuraminidase inhibitors do not arise as frequently as resistant influenza A viruses. However, they appear to be transmitted within communities and families, requiring continued close monitoring. SN - 1538-3598 UR - https://www.unboundmedicine.com/medline/citation/17405969/full_citation L2 - https://jamanetwork.com/journals/jama/fullarticle/10.1001/jama.297.13.1435 ER -