Global update on the susceptibility of human influenza viruses to neuraminidase inhibitors, 2013–2014

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.

Mycophenolic acid, an immunomodulator, has potent and broad-spectrum in vitro antiviral activity against pandemic, seasonal and avian influenza viruses affecting humans

“…The effectiveness of neuraminidase inhibitors has been evaluated in several meta-analyses, but authors differed in their conclusions (Dobson et al, 2015;Jefferson et al, 2014;Muthuri et al, 2014). Furthermore, there is an increasing number of viral isolates resistant to neuraminidase inhibitors, and resistance can emerge during treatment (Cheng et al, 2012;Takashita et al, 2015;. Adamantanes are active against influenza A virus only, but are now rarely used because of resistance (Cheng et al, 2012).…”

Characterization of an A (H1N1)pdm09 Virus Imported from India in March 2015

“…1B) genes of A/Fukuoka/SDC1/2015 indicated that it originated in India during the outbreak. The Indian-origin A(H1N1)pdm09 and all Indian viruses analyzed in this study belong to genetic clade 6B that contains majority of the globally circulating influenza viruses (5,6). Three amino acids characteristic of the Indian viruses causing the worst outbreak, S84N in the HA protein, and V13I and I314M in the NA protein, were detected.…”

“…However, community clusters of oseltamivir and peramivir cross-resistant viruses occurred in Australia in 2011, and in Japan in 2013-2014, respectively (10,11). Significant numbers of these resistant viruses were also detected in the United States and China during the 2013-2014 season (6,12,13). The resistant viruses possessed an H275Y substitution in the NA protein.…”

Generation of a Genetically Stable High-Fidelity Influenza Vaccine Strain

“…L40P, V83A, and N146K substitutions in the NA were observed only with the PB1-wild type-6:2 virus following prolonged passaging. Mutant A(H1N1)pdm09 viruses with an amino acid substitution in NA at the Leu-40 or Val-83 residue were isolated in the 2013-2014 influenza season (31). There is currently no evidence that these substitutions exert specific functional effects.…”