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GLOBAL UPDATE ON THE SUSCEPTIBILITY OF HUMAN INFLUENZA VIRUSES TO NEURAMINIDASE INHIBITORS, 2013–2014
Antiviral resistance
Neuraminidase inhibitors
Oseltamivir
Global analysis
Reduced susceptibility
Author
Takashita, Emi
Meijer, Adam
Lackenby, Angie
Gubareva, Larisa
Andrade, Helena Rebelo de
Besselar, Terry
Fry, Alicia
Gregory, Vicky
Leang, Sook-Kwan
Huang, Weijuan
Lo, Janice
Pereyaslov, Dmitriy
Siqueira, Marilda Agudo Mendonça Teixeira de
Wang, Dayan
Mak, Gannon C.
Zhang, Wenqing
Daniels, Rod S.
Hurt, Aeron C.
Tashiro, Masato
Meijer, Adam
Lackenby, Angie
Gubareva, Larisa
Andrade, Helena Rebelo de
Besselar, Terry
Fry, Alicia
Gregory, Vicky
Leang, Sook-Kwan
Huang, Weijuan
Lo, Janice
Pereyaslov, Dmitriy
Siqueira, Marilda Agudo Mendonça Teixeira de
Wang, Dayan
Mak, Gannon C.
Zhang, Wenqing
Daniels, Rod S.
Hurt, Aeron C.
Tashiro, Masato
Affilliation
World Health Organization Collaborating Centre for Reference and Research on Influenza. National Institute of Infectious Diseases. Musashimurayama, Tokyo, Japan.
National Institute for Public Health and the Environment. Bilthoven, Netherlands.
Public Health England Colindale. London, United Kingdom.
World Health Organization Collaborating Centre for the Surveillance, Epidemiology and Control of Influenza. Centers for Disease Control and Prevention. Atlanta, GA, USA.
Instituto Nacional de Saúde. Lisboa, Portugal / Universidade de Lisboa. Faculdade de Farmácia. Lisboa, Portugal.
World Health Organization. Global Influenza Programme. Geneva, Switzerland.
World Health Organization Collaborating Centre for the Surveillance, Epidemiology and Control of Influenza. Centers for Disease Control and Prevention. Atlanta, GA, USA.
World Health Organization Collaborating Centre for Reference and Research on Influenza. MRC-National Institute for Medical Research. London, United Kingdom.
World Health Organization Collaborating Centre for Reference and Research on Influenza, VIDRL, At the Peter Doherty Institute for Infection and Immunit. Melbourne, Australia.
World Health Organization Collaborating Centre for Reference and Research on Influenza. Chinese National Influenza Center. National Institute for Viral Disease Control and Prevention. Chinese Center for Disease Control and Prevention. Beijng, China.
Public Health Laboratory Centre. Hong Kong, China.
World Health Organization Regional Office for Europe. Division of Communicable Diseases, Health Security & Environment. Copenhagen, Denmark.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Vírus Respiratórios e do Sarampo. Rio de Janeiro, RJ, Brasil.
World Health Organization Collaborating Centre for Reference and Research on Influenza. Chinese National Influenza Center. National Institute for Viral Disease Control and Prevention. Chinese Center for Disease Control and Prevention. Beijng, China.
Public Health Laboratory Centre. Hong Kong, China.
World Health Organization. Global Influenza Programme. Geneva, Switzerland.
World Health Organization Collaborating Centre for Reference and Research on Influenza.
World Health Organization Collaborating Centre for Reference and Research on Influenza. VIDRL, At the Peter Doherty Institute for Infection and Immunity. Melbourne, Australia / University of Melbourne, Melbourne School of Population and Global Health, Melbourne, Australia.
World Health Organization Collaborating Centre for Reference and Research on Influenza. National Institute of Infectious Diseases. Musashimurayama, Tokyo, Japan.
National Institute for Public Health and the Environment. Bilthoven, Netherlands.
Public Health England Colindale. London, United Kingdom.
World Health Organization Collaborating Centre for the Surveillance, Epidemiology and Control of Influenza. Centers for Disease Control and Prevention. Atlanta, GA, USA.
Instituto Nacional de Saúde. Lisboa, Portugal / Universidade de Lisboa. Faculdade de Farmácia. Lisboa, Portugal.
World Health Organization. Global Influenza Programme. Geneva, Switzerland.
World Health Organization Collaborating Centre for the Surveillance, Epidemiology and Control of Influenza. Centers for Disease Control and Prevention. Atlanta, GA, USA.
World Health Organization Collaborating Centre for Reference and Research on Influenza. MRC-National Institute for Medical Research. London, United Kingdom.
World Health Organization Collaborating Centre for Reference and Research on Influenza, VIDRL, At the Peter Doherty Institute for Infection and Immunit. Melbourne, Australia.
World Health Organization Collaborating Centre for Reference and Research on Influenza. Chinese National Influenza Center. National Institute for Viral Disease Control and Prevention. Chinese Center for Disease Control and Prevention. Beijng, China.
Public Health Laboratory Centre. Hong Kong, China.
World Health Organization Regional Office for Europe. Division of Communicable Diseases, Health Security & Environment. Copenhagen, Denmark.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Vírus Respiratórios e do Sarampo. Rio de Janeiro, RJ, Brasil.
World Health Organization Collaborating Centre for Reference and Research on Influenza. Chinese National Influenza Center. National Institute for Viral Disease Control and Prevention. Chinese Center for Disease Control and Prevention. Beijng, China.
Public Health Laboratory Centre. Hong Kong, China.
World Health Organization. Global Influenza Programme. Geneva, Switzerland.
World Health Organization Collaborating Centre for Reference and Research on Influenza.
World Health Organization Collaborating Centre for Reference and Research on Influenza. VIDRL, At the Peter Doherty Institute for Infection and Immunity. Melbourne, Australia / University of Melbourne, Melbourne School of Population and Global Health, Melbourne, Australia.
World Health Organization Collaborating Centre for Reference and Research on Influenza. National Institute of Infectious Diseases. Musashimurayama, Tokyo, Japan.
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) tested 10,641 viruses collected by WHO-recognized National Influenza Centres between May 2013 and May 2014 to determine 50% inhibitory concentration (IC50) data for neuraminidase inhibitors (NAIs) oseltamivir, zanamivir, peramivir and laninamivir. In addition, neuraminidase (NA) sequence data, available from the WHO CCs and from sequence databases (n = 3206), were screened for amino acid substitutions associated with reduced NAI susceptibility. Ninety-five per cent of the viruses tested by the WHO CCs were from three WHO regions: Western Pacific, the Americas and Europe. Approximately 2% (n = 172) showed highly reduced inhibition (HRI) against at least one of the four NAIs, commonly oseltamivir, while 0.3% (n = 32) showed reduced inhibition (RI). Those showing HRI were A(H1N1)pdm09 with NA H275Y (n = 169), A(H3N2) with NA E119V (n = 1), B/Victoria-lineage with NA E117G (n = 1) and B/Yamagata-lineage with NA H273Y (n = 1); amino acid position numbering is A subtype and B type specific. Although approximately 98% of circulating viruses tested during the 2013–2014 period were sensitive to all four NAIs, a large community cluster of A(H1N1)pdm09 viruses with the NA H275Y substitution from patients with no previous exposure to antivirals was detected in Hokkaido, Japan. Significant numbers of A(H1N1)pdm09 NA H275Y viruses were also detected in China and the United States: phylogenetic analyses showed that the Chinese viruses were similar to those from Japan, while the United States viruses clustered separately from those of the Hokkaido outbreak, indicative of multiple resistance-emergence events. Consequently, global surveillance of influenza antiviral susceptibility should be continued from a public health perspective.
Keywords
Influenza virusAntiviral resistance
Neuraminidase inhibitors
Oseltamivir
Global analysis
Reduced susceptibility
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