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Antiviral Res. 2018 Sep;157:38-46. doi: 10.1016/j.antiviral.2018.07.001. Epub 2018 Jul 3.

Global update on the susceptibility of human influenza viruses to neuraminidase inhibitors and status of novel antivirals, 2016-2017.

Author information

1
National Infection Service, Public Health England, London, NW9 5HT, United Kingdom. Electronic address: angie.lackenby@phe.gov.uk.
2
Global Influenza Programme, World Health Organization, Avenue Appia 20, 1211, Geneva 27, Switzerland.
3
The Francis Crick Institute, Worldwide Influenza Centre (WIC), WHO Collaborating Centre for Reference and Research on Influenza, 1 Midland Road, London, NW1 1AT, United Kingdom.
4
WHO Collaborating Center for Surveillance, Epidemiology and Control of Influenza, Centers for Diseases Control and Prevention (CDC), 1600 Clifton RD NE, MS-G16, Atlanta, GA, 30329, USA.
5
WHO Collaborating Centre for Reference and Research on Influenza, National Institute for Viral Disease Control and Prevention, China CDC, Beijing, China.
6
WHO Collaborating Centre for Reference and Research on Influenza, At the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, 3000, Australia; Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria, 3010, Australia.
7
WHO Collaborating Centre for Reference and Research on Influenza, At the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, 3000, Australia.
8
Bioinformatics Institute, Agency for Science, Technology and Research, 30 Biopolis Street, #07-01, Matrix, Singapore, 138671, Singapore.
9
Public Health Laboratory Centre, Centre for Health Protection, Department of Health, 382 Nam Cheong Street, Hong Kong, China.
10
Bioinformatics Institute, Agency for Science, Technology and Research, 30 Biopolis Street, #07-01, Matrix, Singapore, 138671, Singapore; Department of Biological Sciences, National University of Singapore, 14 Science Drive 4, Singapore, 117543, Singapore; National Public Health Laboratory, Ministry of Health, 3 Biopolis Drive, Synapse #05-14 to 16, Singapore, 138623, Singapore.
11
WHO Collaborating Centre for Reference and Research on Influenza, National Institute of Infectious Diseases, Gakuen 4-7-1, Musashimurayama, Tokyo, 208-0011, Japan.
12
Division of Communicable Diseases, Health Security, & Environment, World Health Organization Regional Office for Europe, UN City, Marmorvej 51, DK-2100, Copenhagen Ø, Denmark.
13
National Institute for Public Health and the Environment, PO Box 1, 3720 BA, Bilthoven, The Netherlands.

Abstract

A total of 13672 viruses, collected by World Health Organization recognised National Influenza Centres between May 2016 and May 2017, were assessed for neuraminidase inhibitor susceptibility by four WHO Collaborating Centres for Reference and Research on Influenza and one WHO Collaborating Centre for the Surveillance Epidemiology and Control of Influenza. The 50% inhibitory concentration (IC50) was determined for oseltamivir and zanamivir for all viruses, and for peramivir and laninamivir in a subset (n = 8457). Of the viruses tested, 94% were obtained from the Western Pacific, Americas and European WHO regions, while limited viruses were available from the Eastern Mediterranean, African and South East Asian regions. Reduced inhibition (RI) by one or more neuraminidase inhibitor was exhibited by 0.2% of viruses tested (n = 32). The frequency of viruses with RI has remained low since this global analysis began (2015/16: 0.8%, 2014/15: 0.5%; 2013/14: 1.9%; 2012/13: 0.6%) but 2016/17 has the lowest frequency observed to date. Analysis of 13581 neuraminidase sequences retrieved from public databases, of which 5243 sequences were from viruses not included in the phenotypic analyses, identified 58 further viruses (29 without phenotypic analyses) with amino acid substitutions associated with RI by at least one neuraminidase inhibitor. Bringing the total proportion to 0.5% (90/18915). This 2016/17 analysis demonstrates that neuraminidase inhibitors remain suitable for treatment and prophylaxis of influenza virus infections, but continued monitoring is important. An expansion of surveillance testing is paramount since several novel influenza antivirals are in late stage clinical trials with some resistance already having been identified.

KEYWORDS:

Influenza; Inhibitor; Neuraminidase; Resistance; Surveillance; Susceptibility

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