Oseltamivir-Resistant Influenza Virus A (H1N1), Europe, 2007–08 Season

Abstract

In Europe, the 2007-08 winter season was dominated by infl uenza virus A (H1N1) circulation through week 7, followed by infl uenza B virus from week 8 onward. Oseltamivir-resistant infl uenza viruses A (H1N1) (ORVs) with H275Y mutation in the neuraminidase emerged independently of drug use. By country, the proportion of ORVs ranged from 0% to 68%, with the highest proportion in Norway. The average weighted prevalence of ORVs across Europe increased gradually over time, from near 0 in week 40 of 2007 to 56% in week 19 of 2008 (mean 20%). Neuraminidase genes of ORVs possessing the H275Y substitution formed a homogeneous subgroup closely related to, but distinguishable from, those of oseltamivir-sensitive infl uenza viruses A (H1N1). Minor variants of ORVs emerged independently, indicating multiclonal ORVs. Overall, the clinical effect of ORVs in Europe, measured by infl uenza-like illness or acute respiratory infection, was unremarkable and consistent with normal seasonal activity.

Five years of monitoring for the emergence of oseltamivir resistance in patients with influenza A infections in the Influenza Resistance Information Study

“…This resistant virus eventually displaced the NAI‐susceptible H1N1 virus rendering virtually all seasonal H1N1 viruses highly resistant to oseltamivir 8, 9. This emergence was not related to the use of antivirals 10, 11. The resistant H1N1 virus was then replaced during the 2009‐2010 pandemic by the influenza A H1N12009pdm virus, which was oseltamivir sensitive 12…”

Impact of Potential Permissive Neuraminidase Mutations on Viral Fitness of the H275Y Oseltamivir-Resistant Influenza A(H1N1)pdm09 VirusIn Vitro, in Mice and in Ferrets

“…Thus, exposure of individuals infected with A(H1N1)pdm09 V241I/N369K viruses to oseltamivir during prophylaxis or treatment courses may rapidly select for the H275Y mutation, which could constitute a serious public health threat. Moreover, exposure to NAIs is not necessary to select for the H275Y mutation if permissive mutations are already present in the NA gene, as exemplified by the emergence and global dissemination of oseltamivir-resistant A/Brisbane/59/2007-like variants (9,35).…”

Characterization of Human Influenza Viruses in Lebanon during 2010-2011 and 2011-2012 Post-Pandemic Seasons

“…Neuraminidase inhibitors (NAIs), including oseltamivir and zanamivir, became the drugs of choice for treatment of H3N2 influenza infections [9]. The utility of oseltamivir in treating influenza was jeopardized by the worldwide rapid emergence of oseltamivir-resistant seasonal H1N1 viruses during 2007 through 2009 [6,7]. Nonetheless, this virus was soon replaced by the H1N1p virus, which is largely sensitive to oseltamivir but resistant to amantadine [10].…”

“…In addition to their antigenic evolution, influenza viruses evolve under drug pressure or natural selection, and new virus populations that are resistant to treatment occasionally evolve and sometimes prevail if viral fitness is maintained [6,7]. As a result, the use of antiviral drugs like amantadine, an M2-channel inhibitor, has been largely limited due to the surge of amantadine-resistant H3N2 influenza viruses [8].…”