Neuraminidase-inhibitor resistance testing for pandemic influenza A (H1N1) 2009 in Ontario, Canada

J Clin Virol. 2011 Mar;50(3):257-61. doi: 10.1016/j.jcv.2010.12.007. Epub 2011 Jan 19.

Abstract

Background: Oseltamivir resistance-associated H275Y mutation in the neuraminidase (NA) gene of pandemic influenza A (H1N1) 2009 was occasionally reported worldwide during the 2009-2010 influenza season. A significant proportion of those were found in immunocompromised or severely ill persons. This phenomenon remains infrequent and clear recommendations for resistance testing are lacking.

Objectives: Present the suggested clinical selection criteria for antiviral susceptibility testing for influenza in Canada and to describe the Ontarian experience during the 2009-2010 influenza season.

Study design: Using a defined algorithm, we prospectively screened for OsR with pyrosequencing and phenotypic testing during the 2009-2010 influenza season. Zanamivir resistance was screened using phenotypic and sequencing technique on selected occasions. Clinical data was gathered for the resistant cases.

Results: A total of 804 clinical H1N1 (2009) positive samples from Ontario were screened for oseltamivir resistance between June 2009 and March 2010. We identified oseltamivir resistance in 5 (0.6%) distinct patients aged 9-62 years. All the resistant strains bore the H275Y mutation. Susceptibility to zanamivir was maintained in all of them. Three patients harboring oseltamivir resistant strain were intensive care unit patients and four were immunocompromised. All were tested for susceptibility because of a repeat positive result for influenza A PCR.

Conclusion: Oseltamivir resistance was not frequent during the 2009-2010 influenza season but was identified with a systematic and prospective approach to resistance testing. In order to be as sensitive as possible in the detection of those few cases, we report the suggested indications for antiviral susceptibility testing in Canada.

MeSH terms

  • Adolescent
  • Adult
  • Amino Acid Substitution / genetics
  • Antiviral Agents / pharmacology*
  • Child
  • Drug Resistance, Viral*
  • Female
  • Humans
  • Influenza A Virus, H1N1 Subtype / drug effects*
  • Influenza A Virus, H1N1 Subtype / isolation & purification
  • Influenza, Human / virology*
  • Male
  • Middle Aged
  • Mutation, Missense
  • Neuraminidase / genetics
  • Ontario
  • Oseltamivir / pharmacology*
  • Viral Proteins / genetics
  • Young Adult

Substances

  • Antiviral Agents
  • Viral Proteins
  • Oseltamivir
  • NA protein, influenza A virus
  • Neuraminidase