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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