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.
Bibliographical noteFunding Information:
We thank all laboratories, mostly NICs of the WHO GISRS ( http://www.who.int/influenza/gisrs_laboratory/national_influenza_centres/list/en/ ), which contributed to this global analysis by submitting influenza virus positive samples (clinical specimens or virus isolates) to WHO CCs for detailed characterisation. We gratefully acknowledge the authors, originating and submitting laboratories of the sequences submitted to the GISAID database ( Supplementary Table 3 ), and the sequences retrieved from the NCBI-IVR, that were included in this global analysis. The Tokyo WHO CC is supported by Grants-in-Aid for Emerging and Re-emerging Infectious Diseases from the Ministry of Health, Labour, and Welfare , Japan and by JSPS KAKENHI Grant number 26460816 . The London WHO CC is funded by the British Medical Research Council through programme U117512723. The Melbourne WHO CC is supported by the Australian Government Department of Health.
© 2015 The Authors. Published by Elsevier B.V.
- Antiviral resistance
- Global analysis
- Influenza virus
- Neuraminidase inhibitors
- Reduced susceptibility