Emergence of Influenza B Viruses With Reduced Sensitivity to Neuraminidase Inhibitors

Hatakeyama, S.; Sugaya, Norio; Ito, Mutsumi; Yamazaki, Masahiko; Ichikawa, Masataka; Kimura, Kazuhiro; Kiso, Maki; Shimizu, Hideaki; Kawakami, Chiharu; Koike, Kazuo; Mitamura, Keiko; Kawaoka, Yoshihiro

doi:10.1001/jama.297.13.1435

Cited by 198 publications

(174 citation statements)

References 25 publications

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“…Oseltamvir is an oral drug, whereas zanamivir is inhaled; therefore, oseltamivir is the more extensively used. Although the prevalence of viruses resistant to these drugs is lower than that for the aminoadamantanes (7,8), a higher proportion of oseltamivir-resistant viruses has been detected among treated patients than was expected (9), and person-to-person transmission of oseltamivir-resistant influenza B viruses has occurred (10). Furthermore, oseltamivirresistant H1N1 viruses emerged during the 2007-2008 season (11), and currently most H1N1 viruses are oseltamivir-resistant (12,13).…”

mentioning

confidence: 99%

T-705 (favipiravir) activity against lethal H5N1 influenza A viruses

Kiso¹,

Takahashi

Sakai‐Tagawa³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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The neuraminidase inhibitors oseltamivir and zanamivi are used to treat H5N1 influenza. However, oseltamivir-resistant H5N1 viruses have been isolated from oseltamivir-treated patients. Moreover, reassortment between H5N1 viruses and oseltamvir-resistant human H1N1 viruses currently circulating could create oseltamivir-resistant H5N1 viruses, rendering the oseltamivir stockpile obsolete. Therefore, there is a need for unique and effective antivirals to combat H5N1 influenza viruses. The investigational drug T-705 (favipiravir; 6-fluoro-3-hydroxy-2-pyrazinecarboxamide) has antiviral activity against seasonal influenza viruses and a mouse-adapted H5N1 influenza virus derived from a benign duck virus. However, its efficacy against highly pathogenic H5N1 viruses, which are substantially more virulent, remains unclear. Here, we demonstrate that T-705 effectively protects mice from lethal infection with oseltamivir-sensitive or -resistant highly pathogenic H5N1 viruses. Furthermore, our biochemical analysis suggests that T-705 ribofuranosyl triphosphate, an active form of T-705, acts like purines or purine nucleosides in human cells and does not inhibit human DNA synthesis. We conclude that T-705 shows promise as a therapeutic agent for the treatment of highly pathogenic H5N1 influenza patients.

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mentioning

confidence: 99%

T-705 (favipiravir) activity against lethal H5N1 influenza A viruses

Kiso¹,

Takahashi

Sakai‐Tagawa³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

198

169

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“…Both isolates were collected from SARI patients without historical drug exposure. A few previous studies have revealed influenza B virus with reduced susceptibility to NAIs, particularly oseltamivir (2,21,22). As indicated by substantially higher oseltamivir IC50 values, influenza B viruses appear to be more sensitive to zanamivir than oseltamivir.…”

Section: Discussionmentioning

confidence: 96%

Detection of influenza B viruses with reduced sensitivity to neuraminidase inhibitor in Morocco during 2014/15 season

Elfalki

Ihazmad

Bimouhen

et al. 2016

East Mediterr Health J

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We monitored phenotypic and genotypic susceptibility of influenza viruses circulating in Morocco during 2014-2015 to oseltamivir and zanamivir. Throat and nasal swab specimens were collected from outpatients (with influenza-like illness) and inpatients (with severe acute respiratory illness) and tested for influenza viruses using real-time reverse transcription polymerase chain reaction. Positive samples were inoculated in MDCK cells and virus phenotypic susceptibility to neuraminidase inhibitors (NAIs) was assessed using fluorescent NA inhibition. Of 440 specimens, 135 were positive for influenza B Yamagata-like virus, 38 were A(H1N1)pdm09 and 25 were A(H3N2). Sixty influenza B viruses isolated from MDCK cells showed no significant resistance to NAIs. However, two of these strains, B/Morocco/176H/2015 and B/Morocco/CP10/2015, showed reduced susceptibility to oseltamivir. The two influenza B viruses with reduced susceptibility to oseltamivir show that ongoing NAI susceptibility surveillance is essential. 2015-

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“…CDC continues to recommend that adamantane drugs not be used for infl uenza treatment in the United States. Given the recent emergence of oseltamivir-resistant infl uenza A and B infections (15,16), ongoing monitoring of infl uenza virus susceptibility to adamantanes and neuraminidase inhibitors is essential.…”

Section: Discussionmentioning

confidence: 99%