1. Emergence of influenza B viruses with reduced sensitivity to neuraminidase inhibitors.
- Author
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Hatakeyama S, Sugaya N, Ito M, Yamazaki M, Ichikawa M, Kimura K, Kiso M, Shimizu H, Kawakami C, Koike K, Mitamura K, and Kawaoka Y
- Subjects
- Adolescent, Adult, Amino Acid Substitution, Child, Child, Preschool, Female, Hemagglutinins genetics, Humans, Infant, Influenza A Virus, H3N2 Subtype, Influenza A Virus, H5N1 Subtype, Influenza B virus genetics, Japan, Male, Middle Aged, Mutation, Missense, Neuraminidase genetics, Oseltamivir therapeutic use, Prevalence, Seasons, Antiviral Agents therapeutic use, Drug Resistance, Viral genetics, Enzyme Inhibitors therapeutic use, Influenza B virus drug effects, Influenza, Human drug therapy, Influenza, Human epidemiology, Influenza, Human transmission, Influenza, Human virology, Neuraminidase antagonists & 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.
- Published
- 2007
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