Detection of human influenza A (H1N1) and B strains with reduced sensitivity to neuraminidase inhibitors.
BACKGROUND
Neuraminidase inhibitors (NAIs) have been used since 2005 in France.


OBJECTIVE
Influenza viruses isolated in hospital and community cases in winter 2005-2006 were evaluated for their sensitivity to NAIs.


METHODS
Isolates 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.


RESULTS
Out 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.


CONCLUSIONS
Resistant influenza strains to NAIs are circulating at a stable and low level of 1% since the introduction of NAIs in clinical practice.
Virologie et Pathologie humaine, CNRS FRE 3011, Université Lyon 1, 7 rue Guillaume Paradin, 69372 Lyon cedex 08, France. vanessa.escuret@chu-lyon.fr <vanessa.escuret@chu-lyon.fr>
Vanessa
V
Escuret
Emilie
E
Frobert
Maude
M
Bouscambert-Duchamp
Murielle
M
Sabatier
Isidore
I
Grog
Martine
M
Valette
Bruno
B
Lina
Florence
F
Morfin
Olivier
O
Ferraris
D019943:Amino Acid Substitution; D000998:Antiviral Agents / Q000494:pharmacology*; D024882:Drug Resistance, Viral; D005602:France; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification*; D009981:Influenza B virus / Q000187:drug effects* / Q000302:isolation & purification*; D007251:Influenza, Human / Q000821:virology*; D020128:Inhibitory Concentration 50; D008826:Microbial Sensitivity Tests; D020125:Mutation, Missense; D009439:Neuraminidase / Q000235:genetics; D053139:Oseltamivir / Q000494:pharmacology; D017422:Sequence Analysis, DNA; D014764:Viral Proteins / Q000235:genetics; D053243:Zanamivir / Q000494:pharmacology
D000998:Antiviral Agents; D014764:Viral Proteins; D053139:Oseltamivir; D009439:Neuraminidase; D053243:Zanamivir