Susceptibility of epidemic viruses to neuraminidase inhibitors and treatment-emergent resistance in the Japanese 2019-20 influenza season.

Naoki Tani, Naoki Kawai, Yong Chong, Takuma Bando, Norio Iwaki, Seizaburo Kashiwagi, Hideyuki Ikematsu

Journal: The Journal of infection 2022;84(2):151-157

PMID: 34861350

Full Text on Elsevier Science View on PubMed

Abstract

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 (ICs) 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 IC 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 IC 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.

Address: Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-Ku, Fukuoka 812-8582, Japan. Electronic address: [email protected].; Japan Physicians Association, Tokyo Medical Association Building 3F, 2-5 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-0062, Japan.; Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-Ku, Fukuoka 812-8582, Japan.; Japan Physicians Association, Tokyo Medical Association Building 3F, 2-5 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-0062, Japan; Ricerca Clinica Co., 2-18-30 Hakataekihigashi, Hakata-ku, Fukuoka 812-0013, Japan.

DOI: 10.1016/j.jinf.2021.11.020

Link outs

Free resources

Medical:

https://medlineplus.gov/h1n1fluswineflu.html

Subscription / membership required

Full Text Sources:

MeSH Terms: Antiviral Agents, Cyclopentanes, Drug Resistance, Viral, Humans, Influenza A Virus, H1N1 Subtype, Influenza A Virus, H3N2 Subtype, Influenza, Human, Japan, Neuraminidase, Oseltamivir, Prospective Studies, Seasons