In vitro neuraminidase inhibitory concentration (IC₅₀) of four neuraminidase inhibitors in the Japanese 2018–19 season: Comparison with the 2010–11 to 2017–18 seasons

To assess the extent of susceptibility to the four most commonly used neuraminidase inhibitors (NAIs) of the epidemic viruses in the 2018-19 Japanese influenza season, we measured the 50% inhibitory concentration (IC₅₀) of four NAIs, oseltamivir, zanamivir, peramivir, and laninamivir, for influenza virus isolates from patients and compared them with the results from the 2010–11 to 2017-18 seasons. Viral isolation was done with specimens obtained prior to and after treatment, and the type/subtype was determined by RT-PCR using type- and subtype-specific primers. The IC₅₀ was determined by a neuraminidase inhibition assay using a fluorescent substrate. Virus isolates, 51 A(H1N1)pdm09, 125 A(H3N2), and one B, were measured in the 2018-19 season and the geometric mean IC₅₀s of the four NAIs were quite comparable to the previous eight studied seasons. No A(H1N1)pdm09 with highly reduced sensitivity for oseltamivir was found in the 2018-19 season prior to drug administration, although such A(H1N1)pdm09 were found in two, two, and two samples in the 2010–11, 2013–14, and 2015-16 seasons, respectively. No isolates with highly reduced sensitivity to the four NAIs were found for A(H3N2) or B through the 2010–11 to 2018-19 seasons. Among 18 samples with A(H1N1)pdm09 virus isolated after NAI administration, highly reduced sensitivity to oseltamivir and peramivir was detected from one of the five patients treated with oseltamivir. These results suggest that the sensitivity to the four commonly used NAIs has been maintained, although viruses with highly reduced sensitivity to oseltamivir and peramivir have emerged in some adult patients treated with oseltamivir.