Detection of a Peramivir-Resistant Influenza B/Yamagata-Lineage Virus Imported from Indonesia in Aichi, Japan, March 2019

摘要

In Japan，the four neuraminidase (NA) inhibitorsoseltamivir, peramivir,zanamivir, and laninamivir,as well as the cap-dependent endonuclease inhibitorbaloxavir,are used to treat influenza A and B virusinfections. We have been monitoring the susceptibilityof influenza viruses to these NA inhibitors nationwidesince the 2010-11 season. During the 2013-14 season,a large cluster of A(H1N1)pdm09 viruses exhibitingcross-resistance to oseltamivir and peramivir wasdetected in Sapporo，Japan; these resistant virusespossessed an H275Y substitution in their NA protein(1).The prevalence of H275Y mutant viruses was 29%in this area; however，the frequency of NA inhibitor-resistant A(H1N 1)pdm09 viruses has not increasedsince the ending of this cluster in Japan (0.9-1.9%).Baloxavir was approved in February 2018 and becamethe most-used influenza antiviral during the 2018-19season in Japan，during which we also initiated anationwide monitoring of the baloxavir susceptibilityof influenza viruses. We found that 2.3%(9/395) ofA(H1N1)pdm09 and 8.0% (34/424) of A (H3N2) virusespossessed amino acid substitutions associated withreduced susceptibility to baloxavir in the polymeraseacidic subunit (PA)(2).However， we did not detectany influenza B viruses that were resistant to the NAinhibitors or baloxavir. In March 2019, we detected thefirst case of an NA inhibitor-resistant influenza B virusin a patient who lived in Indonesia and returned briefly to Japan; here, we report the properties of this resistantvirus.