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Antiviral Res. 2017 Oct;146:12-20. doi: 10.1016/j.antiviral.2017.08.004. Epub 2017 Aug 10.

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

Author information

1
WHO Collaborating Center for Surveillance, Epidemiology and Control of Influenza, Centers for Disease Control and Prevention (CDC), 1600 Clifton RD NE, MS-G16, Atlanta, GA, 30329, United States. Electronic address: lgubareva@cdc.gov.
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 Disease Control and Prevention (CDC), 1600 Clifton RD NE, MS-G16, Atlanta, GA, 30329, United States.
5
WHO Collaborating Centre for Reference and Research on Influenza, National Institute for Viral Disease Control and Prevention, Collaboration Innovation Centre for Diagnosis and Treatment of Infectious Diseases, 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
National Infection Service, Public Health England, London, NW9 5HT, United Kingdom.
8
WHO Collaborating Centre for Reference and Research on Influenza, At the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, 3000, Australia.
9
Public Health Laboratory Centre, 382 Nam Cheong Street, Hong Kong, China.
10
Division of Health Emergencies and Communicable Diseases, World Health Organization Regional Office for Europe, UN City, Marmorvej 51, DK-2100, Copenhagen, Denmark.
11
Influenza Pathogenesis and Antiviral Resistance Laboratory, National Institute of Health, Av. Padre Cruz, 1649-016, Lisboa, Portugal; Faculdade de Farmácia, Universidade de Lisboa, Av. Prof Gama Pinto, 1649-016, Lisboa, Portugal.
12
National Influenza Center, Laboratorio de Virus Respiratorios, Oswaldo Cruz Institute/FIOCRUZ, Rio de Janeiro, Brazil.
13
WHO Collaborating Centre for Reference and Research on Influenza, National Institute of Infectious Diseases, Gakuen 4-7-1, Musashimurayama, Tokyo, 208-0011, Japan.
14
National Institute for Public Health and the Environment, PO Box 1, 3720 BA, Bilthoven, The Netherlands.

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.

KEYWORDS:

Inhibitor; Markers; Neuraminidase; Resistance; Surveillance; Susceptibility

PMID:
28802866
PMCID:
PMC5667636
DOI:
10.1016/j.antiviral.2017.08.004
[Indexed for MEDLINE]
Free PMC Article

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