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

J Clin Virol. 2008 Jan;41(1):25-8. doi: 10.1016/j.jcv.2007.10.019. Epub 2007 Dec 4.

Abstract

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.

Study design: 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.

Conclusion: Resistant influenza strains to NAIs are circulating at a stable and low level of 1% since the introduction of NAIs in clinical practice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Substitution
  • Antiviral Agents / pharmacology*
  • Drug Resistance, Viral*
  • France
  • Humans
  • Influenza A Virus, H1N1 Subtype / drug effects*
  • Influenza A Virus, H1N1 Subtype / genetics
  • Influenza A Virus, H1N1 Subtype / isolation & purification*
  • Influenza B virus / drug effects*
  • Influenza B virus / isolation & purification*
  • Influenza, Human / virology*
  • Inhibitory Concentration 50
  • Microbial Sensitivity Tests
  • Mutation, Missense
  • Neuraminidase / genetics
  • Oseltamivir / pharmacology
  • Sequence Analysis, DNA
  • Viral Proteins / genetics
  • Zanamivir / pharmacology

Substances

  • Antiviral Agents
  • Viral Proteins
  • Oseltamivir
  • Neuraminidase
  • Zanamivir