TY  - JOUR
T1  - EMergence of influenza b viruses with reduced sensitivity to neuraminidase inhibitors
AU  - Hatakeyama S, Sugaya N, Ito M, et al
Y1  - 2007/04/04
N1  - 10.1001/jama.297.13.1435
JO  - JAMA
SP  - 1435
EP  - 1442
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  - 0098-7484
M3  - doi: 10.1001/jama.297.13.1435
UR  - http://dx.doi.org/10.1001/jama.297.13.1435
ER  -