title: Evaluation of influenza virus antiviral susceptibility testing in Europe: results from the first external quality assessment exercise.
abstract: BACKGROUND
  The first antiviral susceptibility testing external quality assessment (EQA) was held for European influenza reference laboratories during winter 2010/11.
  
  
  OBJECTIVE
  To assess European network influenza antiviral susceptibility testing capability and provide participants with an independent performance evaluation.
  
  
  METHODS
  The EQA panel contained ten coded specimens of inactivated human influenza A and B viruses with reduced susceptibility to neuraminidase inhibitors (NAI), or adamantanes. Twenty-four laboratories from 19 member states of the WHO European region analysed the panel using phenotypic (determination of 50% inhibitory concentration (IC(50)) values by neuraminidase (NA) enzyme inhibition assay) and/or genotypic methods.
  
  
  RESULTS
  All 24 laboratories returned genotypic data for A(H1N1)pdm09 influenza virus, 18 (75%) for former seasonal A(H1N1), 16 (67%) for A(H3N2) and 15 (63%) for influenza B virus, correctly identifying NAI or adamantane reduced susceptibility-associated substitutions in the NA (mean 84%; range 52-100%) or M2 (mean 85%; range 73-94%), respectively. Thirteen laboratories (54%) returned phenotypic NAI susceptibility data. Despite inter-laboratory and inter-assay IC(50) value variation, all 13 laboratories correctly identified oseltamivir reduced susceptibility/resistance in pure preparations of A(H1N1) oseltamivir-resistant viruses. However, only 11 (85%) identified oseltamivir reduced susceptibility/resistance in a mixture of A(H1N1)pdm09 oseltamivir-sensitive/-resistant viruses. Furthermore, 3 laboratories (23%) considered oseltamivir-sensitive influenza B virus reduced susceptible/resistant.
  
  
  CONCLUSIONS
  Detection of NA-H275Y in A(H1N1) viruses was achieved by most laboratories. IC(50) values and interpretation thereof varied for a sensitive/resistant virus mixture and for influenza B virus. The results of this exercise will assist harmonisation of antiviral susceptibility testing, interpretation and reporting within the European network through targeted training.
authors.affiliation: Health Protection Agency, London NW9 5EQ, UK.
authors.forename: C I
authors.initials: CI
authors.lastname: Thompson
authors.forename: A
authors.initials: A
authors.lastname: Lackenby
authors.forename: R S
authors.initials: RS
authors.lastname: Daniels
authors.forename: J W
authors.initials: JW
authors.lastname: McCauley
authors.forename: D
authors.initials: D
authors.lastname: Pereyaslov
authors.forename: E K
authors.initials: EK
authors.lastname: Broberg
authors.forename: A
authors.initials: A
authors.lastname: Meijer
authors.forename: M C
authors.initials: MC
authors.lastname: Zambon
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology*; D005060:Europe; D005838:Genotype; D009980:Influenza A virus / Q000187:drug effects* / Q000235:genetics; D009981:Influenza B virus / Q000187:drug effects* / Q000235:genetics; D020128:Inhibitory Concentration 50; D059021:Laboratory Proficiency Testing; D008826:Microbial Sensitivity Tests / Q000592:standards*; D020125:Mutation, Missense
chemical_list: D000998:Antiviral Agents