Abstract
BackgroundAssessing susceptibility of influenza viruses to neuraminidase (NA) inhibitors (NAIs) is primarily done in NA inhibition (NI) assays, supplemented by NA sequence analysis. However, two factors present challenges for NI assay data interpretation: lack of established IC50 values indicative of clinically relevant resistance and insufficient harmonization of NI testing methodologies among surveillance laboratories. In 2012, the WHO working group on influenza antiviral susceptibility (WHO-AVWG) developed criteria to facilitate consistent interpretation and reporting of NI assay data.MethodsThe WHO-AVWG classification criteria were applied in interpreting NI assay data for two FDA-licensed NAIs, oseltamivir and zanamivir, for viruses collected in the United States during the 2011–2012 winter season.ResultsAll A (H1N1)pdm09 viruses (n = 449) exhibited normal inhibition by oseltamivir and zanamivir, with the exception of eight viruses (1·8%) with highly reduced inhibition by oseltamivir, which carried the H275Y marker of oseltamivir resistance. A (H3N2) viruses (n = 978) exhibited normal inhibition by both NAIs, except for one virus with highly reduced inhibition by zanamivir due to the cell culture-selected NA change, Q136K. Type B viruses (n = 343) exhibited normal inhibition by both drugs, except for an isolate with reduced inhibition by both NAIs that had the cell culture-selected A200T substitution.ConclusionsWHO-AVWG classification criteria allowed the detection of viruses carrying the established oseltamivir resistance marker, as well as viruses whose susceptibility was altered during propagation. These criteria were consistent with statistical-based criteria for detecting outliers and will be useful in harmonizing NI assay data among surveillance laboratories worldwide and in establishing laboratory correlates of clinically relevant resistance.
Highlights
Monitoring influenza antiviral susceptibility has become a vital part of virological surveillance within the WHO Global Influenza Surveillance and Response System (WHO-GISRS)
Administered oseltamivir and inhaled zanamivir are FDAapproved, while newer NAIs include intravenously administered peramivir,2 which is licensed in Japan, South Korea, and China, and the long-acting inhaled laninamivir (CS-8958), licensed in Japan
(H1N1) viruses were displaced by the A (H1N1) pdm09 viruses that emerged in April 2009.8 Resistance to oseltamivir has remained low among A (H1N1) pdm09 viruses circulating in the United States 9,10 and other countries
Summary
Monitoring influenza antiviral susceptibility has become a vital part of virological surveillance within the WHO Global Influenza Surveillance and Response System (WHO-GISRS). Neuraminidase (NA) inhibitors (NAIs) are currently the only class of antiviral drugs effective against influenza infections.. The unexpected emergence and global spread of oseltamivir-resistant A (H1N1) viruses carrying the H275Y mutation in the NA during 2007–2009 4–7 reinforced the importance of drug susceptibility surveillance. Assessing susceptibility of influenza viruses to neuraminidase (NA) inhibitors (NAIs) is primarily done in NA inhibition (NI) assays, supplemented by NA sequence analysis. Two factors present challenges for NI assay data interpretation: lack of established IC50 values indicative of clinically relevant resistance and insufficient harmonization of NI testing methodologies among surveillance laboratories. In 2012, the WHO working group on influenza antiviral susceptibility (WHO-AVWG) developed criteria to facilitate consistent interpretation and reporting of NI assay data
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call