Emergence of Influenza B Viruses With Reduced Sensitivity to Neuraminidase Inhibitors

ContextVery 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.ObjectiveTo assess the prevalence and transmissibility of influenza B viruses with reduced sensitivity to neuraminidase inhibitors.Design, Setting, and PatientsInvestigation 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 MeasureSialidase 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.ResultsIn 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.ConclusionsIn 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.