Community spread and late season increased incidence of oseltamivir‐resistant influenza A(H1N1) viruses in Norway 2016

Abstract

Background Antiviral resistance in Norwegian influenza viruses is rare. Only one A(H1N1)pdm09 virus from May 2015 had been found resistant to oseltamivir since the introduction of these viruses in 2009. Objectives Surveillance of antiviral resistance is part of the Norwegian surveillance system, to rapidly detect the development of antiviral‐resistant viruses and spread in the community. We describe the spread of oseltamivir‐resistant A(H1N1)pdm09 viruses in Norway in the 2016‐17 season, found as part of the routine surveillance. Methods Influenza H1N1 viruses were analysed for antiviral resistance by pyrosequencing, neuraminidase susceptibility assay and by Sanger sequencing of the HA and NA genes. Results During the 2015‐16 influenza season, 3% of all A(H1N1)pdm09 viruses screened for resistance in Norway were resistant to oseltamivir, possessing the H275Y substitution in the neuraminidase protein. In comparison, the overall frequency in Europe was 0.87%. Out of these, 37% (n = 10) were reported from Norway. Most cases in Norway were not related to antiviral treatment, and the cases were from several different locations of southern Norway. Genetic analysis revealed that resistant virus emerged independently on several occasions and that there was some spread of oseltamivir‐resistant influenza A(H1N1)6B.1 viruses in the community, characterised by a N370S substitution in the haemagglutinin and T48I in the neuraminidase. Conclusions Our findings emphasise the importance of antiviral resistance surveillance in the community, not only in immunocompromised patients or other patients undergoing antiviral treatment.

Interferon Lambda Delays the Emergence of Influenza Virus Resistance to Oseltamivir

“…This substitution emerged first in the seasonal influenza A H1N1 (A/Brisbane/59/2007-like) strain in 2007 and rapidly spread to all H1N1 strains [13]. The 2009 H1N1pdm09 was fortunately sensitive to the drug although clusters of OS-resistant (OR) strains are detected at low frequency (<2%) [14][15][16][17][18], posing a threat of global spread of resistance as occurred with the seasonal pre-pandemic H1N1. In influenza wild-type strains, the NA active site changes shape to accommodate OS.…”

Pharmacokinetics and safety of a novel influenza treatment (baloxavir marboxil) in Korean subjects compared with Japanese subjects

“…Antiviral agents are usually prescribed to treat newly surfaced or variant viruses owing to their ability to target stable viral parts 5 . Neuraminidase inhibitors, including oseltamivir, are mainstay antiviral treatment against influenza, but a considerable emergence of variants resistant to oseltamivir warrants the development of new antiviral agents with novel mechanisms of action 6–8 . Moreover, antiviral drug‐resistant influenza viruses have been detected in South Korea 9,10 …”

Comprehensive assessment of amino acid substitutions in the trimeric RNA polymerase complex of influenza A virus detected in clinical trials of baloxavir marboxil

“…Neuraminidase inhibitors (NAIs: oseltamivir, zanamivir, peramivir) are widely used as the current treatment for influenza, 2 while adamantanes, M2 ion channel inhibitors, are no longer used due to widespread resistance in circulating influenza viruses. 3,4 While NAI-resistant A(H1N1)pdm09 viruses are currently only detected at a frequency of <1% among circulating viruses, 2 community clusters of such variant viruses have been detected, [5][6][7] emphasizing the need for antivirals with a novel mechanism of action.…”