Highlights
- •Neuraminidase inhibitors (NAIs) susceptibility was maintained and no increase of resistant virus was found.
- •Treatment-emergent resistance was found in A(H1N1)pdm09 treated with oseltamivir.
- •H275Y mutants rapidly replaced the wild type after oseltamivir treatment.
Summary
Objectives
To investigate the susceptibility of epidemic influenza viruses to neuraminidase inhibitors
(NAIs) and the emergence of resistant viruses after treatment, a prospective, observational
study was done in the 2019-20 Japanese influenza season.
Methods
Influenza viruses were isolated before and twice after treatment, the first at day
5 and the second at day 10. The 50% inhibitory concentrations (IC50s) to oseltamivir, zanamivir, peramivir, and laninamivir were measured and compared
with those of 2010-11 to 2018-19 seasons. NA amino acid sequences were analyzed by
next generation sequencing (NGS).
Results
The IC50 geometric means of the NAIs for 128 A(H1N1)pdm09, 2 A(H3N2), and 33 B were comparable
to those of the previous seasons. Only 2 (1.6%) A(H1N1)pdm09 with significantly high
IC50 to oseltamivir were found pretreatment. No A(H3N2) or B had resistance. Treatment-emergent
oseltamivir resistance was found in 2 among 33 oseltamivir-treated A(H1N1)pdm09, only
at the second follow-up. The NGS indicated a rapid increase in the proportion of H275Y
to wild type, from 0% to almost 100% between days 5 and 10.
Conclusions
These results suggest the continued effectiveness of these NAIs for epidemic influenza
in Japan. Treatment-emergent resistant H275Y A(H1N1)pdm09 viruses were detected after
oseltamivir treatment, rapidly replacing the wild type.
Keywords
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Article info
Publication history
Published online: November 30, 2021
Accepted:
November 25,
2021
Identification
Copyright
© 2021 The British Infection Association. Published by Elsevier Ltd. All rights reserved.
