Detection of human influenza A (H1N1) and B strains with reduced sensitivity to neuraminidase inhibitors

BackgroundNeuraminidase inhibitors (NAIs) have been used since 2005 in France.ObjectiveInfluenza viruses isolated in hospital and community cases in winter 2005–2006 were evaluated for their sensitivity to NAIs.Study designIsolates were tested in duplicate with a fluorescence-based neuraminidase assay. The IC50 for oseltamivir or zanamivir was calculated for each strain. Mean IC50 (±S.D.) are expressed in nM. Viruses with IC50 superior or very superior to the upper limit (mean IC50 + 2.5 S.D.) were considered as outliers or resistant viruses, respectively. HA and NA genes for outliers, resistant strains and for a few sensitive strains were sequenced.ResultsOut of 225 B isolates, one was found resistant to both oseltamivir and zanamivir with a D197Y mutation in NA and eight isolates were outliers for oseltamivir and/or zanamivir. Out of 151 A (H1N1) isolates, one was found resistant to oseltamivir but sensitive to zanamivir with a H275Y mutation in NA, two isolates were resistant to zanamivir and three isolates were outliers for oseltamivir and/or zanamivir. New mutations were detected in outliers compared to sensitive viruses.ConclusionResistant influenza strains to NAIs are circulating at a stable and low level of 1% since the introduction of NAIs in clinical practice.