1887
Rapid communication Open Access
Like 1

Abstract

A community cluster of influenza A(H3N2) caused by viruses with an E199G substitution in PA was detected in Nara, Japan, between February and March 2023. The three patients with these mutant viruses had not received antiviral treatment before specimen collection but patients in the same hospital had. The sequences of the mutant viruses were closely related, suggesting clonal spread in Nara. They showed reduced susceptibility to baloxavir in vitro; however, the clinical significance of the PA E199G substitution remains unclear.

Loading

Article metrics loading...

/content/10.2807/1560-7917.ES.2023.28.39.2300501
2023-09-28
2024-02-28
http://instance.metastore.ingenta.com/content/10.2807/1560-7917.ES.2023.28.39.2300501
Loading
Loading full text...

Full text loading...

/deliver/fulltext/eurosurveillance/28/39/eurosurv-28-39-1.html?itemId=/content/10.2807/1560-7917.ES.2023.28.39.2300501&mimeType=html&fmt=ahah

References

  1. Takashita E, Kawakami C, Ogawa R, Morita H, Fujisaki S, Shirakura M, et al. Influenza A(H3N2) virus exhibiting reduced susceptibility to baloxavir due to a polymerase acidic subunit I38T substitution detected from a hospitalised child without prior baloxavir treatment, Japan, January 2019. Euro Surveill. 2019;24(12):1900170.  https://doi.org/10.2807/1560-7917.ES.2019.24.12.1900170  PMID: 30914078 
  2. Takashita E, Ichikawa M, Morita H, Ogawa R, Fujisaki S, Shirakura M, et al. Human-to-human transmission of influenza A(H3N2) virus with reduced susceptibility to baloxavir, Japan, February 2019. Emerg Infect Dis. 2019;25(11):2108-11.  https://doi.org/10.3201/eid2511.190757  PMID: 31436527 
  3. Takashita E, Abe T, Morita H, Nagata S, Fujisaki S, Miura H, et al. Influenza A(H1N1)pdm09 virus exhibiting reduced susceptibility to baloxavir due to a PA E23K substitution detected from a child without baloxavir treatment. Antiviral Res. 2020;180:104828.  https://doi.org/10.1016/j.antiviral.2020.104828  PMID: 32574689 
  4. Takashita E, Watanabe S, Hasegawa H, Kawaoka Y. Are twindemics occurring? Influenza Other Respir Viruses. 2023;17(1):e13090.  https://doi.org/10.1111/irv.13090  PMID: 36567444 
  5. Govorkova EA, Takashita E, Daniels RS, Fujisaki S, Presser LD, Patel MC, et al. Global update on the susceptibilities of human influenza viruses to neuraminidase inhibitors and the cap-dependent endonuclease inhibitor baloxavir, 2018-2020. Antiviral Res. 2022;200:105281.  https://doi.org/10.1016/j.antiviral.2022.105281  PMID: 35292289 
  6. Omoto S, Speranzini V, Hashimoto T, Noshi T, Yamaguchi H, Kawai M, et al. Characterization of influenza virus variants induced by treatment with the endonuclease inhibitor baloxavir marboxil. Sci Rep. 2018;8(1):9633.  https://doi.org/10.1038/s41598-018-27890-4  PMID: 29941893 
  7. Gubareva LV, Mishin VP, Patel MC, Chesnokov A, Nguyen HT, De La Cruz J, et al. Assessing baloxavir susceptibility of influenza viruses circulating in the United States during the 2016/17 and 2017/18 seasons. Euro Surveill. 2019;24(3):1800666.  https://doi.org/10.2807/1560-7917.ES.2019.24.3.1800666  PMID: 30670144 
  8. Takashita E, Fujisaki S, Yokoyama M, Shirakura M, Morita H, Nakamura K, et al. In vitro characterization of multidrug-resistant influenza A(H1N1)pdm09 viruses carrying a dual neuraminidase mutation isolated from immunocompromised patients. Pathogens. 2020;9(9):725.  https://doi.org/10.3390/pathogens9090725  PMID: 32887429 
  9. Takashita E. Influenza polymerase inhibitors: mechanisms of action and resistance. Cold Spring Harb Perspect Med. 2021;11(5):a038687.  https://doi.org/10.1101/cshperspect.a038687  PMID: 32122918 
  10. Hayden FG, Sugaya N, Hirotsu N, Lee N, de Jong MD, Hurt AC, et al. Baloxavir marboxil for uncomplicated influenza in adults and adolescents. N Engl J Med. 2018;379(10):913-23.  https://doi.org/10.1056/NEJMoa1716197  PMID: 30184455 
  11. Kiso M, Mitamura K, Sakai-Tagawa Y, Shiraishi K, Kawakami C, Kimura K, et al. Resistant influenza A viruses in children treated with oseltamivir: descriptive study. Lancet. 2004;364(9436):759-65.  https://doi.org/10.1016/S0140-6736(04)16934-1  PMID: 15337401 
  12. Hirotsu N, Sakaguchi H, Sato C, Ishibashi T, Baba K, Omoto S, et al. Baloxavir marboxil in Japanese pediatric patients with influenza: safety and clinical and virologic outcomes. Clin Infect Dis. 2020;71(4):971-81.  https://doi.org/10.1093/cid/ciz908  PMID: 31538644 
  13. Sato M, Takashita E, Katayose M, Nemoto K, Sakai N, Hashimoto K, et al. Detection of variants with reduced baloxavir marboxil susceptibility after treatment of children with influenza a during the 2018-2019 influenza season. J Infect Dis. 2020;222(1):121-5.  https://doi.org/10.1093/infdis/jiaa061  PMID: 32034420 
  14. Sato M, Takashita E, Katayose M, Nemoto K, Sakai N, Fujisaki S, et al. Detection of variants with reduced baloxavir marboxil and oseltamivir susceptibility in children with influenza A during the 2019-2020 influenza season. J Infect Dis. 2021;224(10):1735-41.  https://doi.org/10.1093/infdis/jiab196  PMID: 33837427 
  15. Uehara T, Hayden FG, Kawaguchi K, Omoto S, Hurt AC, De Jong MD, et al. Treatment-emergent influenza variant viruses with reduced baloxavir susceptibility: impact on clinical and virologic outcomes in uncomplicated influenza. J Infect Dis. 2020;221(3):346-55. PMID: 31309975 
  16. Ministry of Health, Labour, and Welfare, Japan. Notification on stable supply of influenza antivirals. Tokyo: Ministry of Health, Labour, and Welfare; 2023. Japanese. Available from: https://www.mhlw.go.jp/stf/seisakunitsuite/bunya/kenkou_iryou/kenkou/kekkaku-kansenshou01/jichitai.html
/content/10.2807/1560-7917.ES.2023.28.39.2300501
Loading

Data & Media loading...

Submit comment
Close
Comment moderation successfully completed
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error