Global update on the susceptibility of human influenza viruses to neuraminidase inhibitors, 2015–2016

Larisa V Gubareva,Terry G Besselaar,Rod S Daniels,Alicia Fry,Vicki Gregory,Weijuan Huang,Aeron C Hurt,Patricia A Jorquera,Angie Lackenby,Sook-Kwan Leang,Janice Lo,Dmitriy Pereyaslov,Helena Rebelo-De-Andrade,Marilda M Siqueira,Emi Takashita,Takato Odagiri,Dayan Wang,Wenqing Zhang,Adam Meijer

doi:10.1016/j.antiviral.2017.08.004

Abstract

Four World Health Organization (WHO) Collaborating Centres for Reference and Research on Influenza and one WHO Collaborating Centre for the Surveillance, Epidemiology and Control of Influenza (WHO CCs) assessed antiviral susceptibility of 14,330 influenza A and B viruses collected by WHO-recognized National Influenza Centres (NICs) between May 2015 and May 2016. Neuraminidase (NA) inhibition assay was used to determine 50% inhibitory concentration (IC50) data for NA inhibitors (NAIs) oseltamivir, zanamivir, peramivir and laninamivir. Furthermore, NA sequences from 13,484 influenza viruses were retrieved from public sequence databases and screened for amino acid substitutions (AAS) associated with reduced inhibition (RI) or highly reduced inhibition (HRI) by NAIs. Of the viruses tested by WHO CCs 93% were from three WHO regions: Western Pacific, the Americas and Europe. Approximately 0.8% (n = 113) exhibited either RI or HRI by at least one of four NAIs.As in previous seasons, the most common NA AAS was H275Y in A(H1N1)pdm09 viruses, which confers HRI by oseltamivir and peramivir. Two A(H1N1)pdm09 viruses carried a rare NA AAS, S247R, shown in this study to confer RI/HRI by the four NAIs. The overall frequency of A(H1N1)pdm09 viruses containing NA AAS associated with RI/HRI was approximately 1.8% (125/6915), which is slightly higher than in the previous 2014-15 season (0.5%). Three B/Victoria-lineage viruses contained a new AAS, NA H134N, which conferred HRI by zanamivir and laninamivir, and borderline HRI by peramivir. A single B/Victoria-lineage virus harboured NA G104E, which was associated with HRI by all four NAIs. The overall frequency of RI/HRI phenotype among type B viruses was approximately 0.6% (43/7677), which is lower than that in the previous season.Overall, the vast majority (>99%) of the viruses tested by WHO CCs were susceptible to all four NAIs, showing normal inhibition (NI). Hence, NAIs remain the recommended antivirals for treatment of influenza virus infections. Nevertheless, our data indicate that it is prudent to continue drug susceptibility monitoring using both NAI assay and sequence analysis.

Highlights

The M2 channel blockers are no longer recommended for treating seasonal influenza due to prevalent resistance (Bright et al., 2005; Nelson et al, 2009)
This is the fourth global update on seasonal influenza susceptibility to NAIs conducted by the WHO-AVWG of Global Influenza Surveillance and Response System (GISRS)
The NAI assay data were generated by five WHO Collaborating Centres (CCs) on samples received from GISRS laboratories

Summary

Introduction

The M2 channel blockers are no longer recommended for treating seasonal influenza due to prevalent resistance (Bright et al., 2005; Nelson et al, 2009). To ensure consistency in interpreting and reporting of NAI assay data, the World Health Organization Expert Working Group on Surveillance of Influenza Antiviral Susceptibility (WHO-AVWG) introduced a set of criteria to define the antiviral susceptibility of viruses based on the fold change of their IC50. To this end, the IC50 of a test virus is compared to a reference IC50 (e.g. a median IC50 of viruses of the same type/subtype) to calculate a fold increase (WHO, 2012). In order to develop strategies for pandemic preparedness and ensure appropriate treatment and clinical management guidelines, it is essential to monitor susceptibility to individual NAIs of all influenza types, subtypes and lineages

Overall analysis of phenotypic antiviral susceptibility data from WHO CCs

Findings

Concluding remarks