BACKGROUND: High mortality and uncertainty about the effectiveness of neuraminidase inhibitors (NAIs) in humans infected with influenza A(H7N9) viruses are public health concerns. METHODS: Susceptibility of N9 viruses to NAIs was determined in a fluorescence-based assay. The NAI oseltamivir (5, 20, or 80 mg/kg/day) was administered to BALB/c mice twice daily starting 24, 48, or 72 hours after A/Anhui/1/2013 (H7N9) virus challenge. RESULTS: All 12 avian N9 and 3 human H7N9 influenza viruses tested were susceptible to NAIs. Without prior adaptation, A/Anhui/1/2013 (H7N9) caused lethal infection in mice that was restricted to the respiratory tract and resulted in pulmonary edema and acute lung injury with hyaline membrane formation, leading to decreased oxygenation, all characteristics of human acute respiratory distress syndrome. Oseltamivir at 20 and 80 mg/kg protected 80% and 88% of mice when initiated after 24 hours, and the efficacy decreased to 70% and 60%, respectively, when treatment was delayed by 48 hours. Emergence of oseltamivir-resistant variants was not detected. CONCLUSIONS: H7N9 viruses are comparable to currently circulating influenza A viruses in susceptibility to NAIs. Based on these animal studies, early treatment is associated with improved outcomes.
BACKGROUND: High mortality and uncertainty about the effectiveness of neuraminidase inhibitors (NAIs) in humans infected with influenza A(H7N9) viruses are public health concerns. METHODS: Susceptibility of N9 viruses to NAIs was determined in a fluorescence-based assay. The NAI oseltamivir (5, 20, or 80 mg/kg/day) was administered to BALB/c mice twice daily starting 24, 48, or 72 hours after A/Anhui/1/2013 (H7N9) virus challenge. RESULTS: All 12 avian N9 and 3 humanH7N9 influenza viruses tested were susceptible to NAIs. Without prior adaptation, A/Anhui/1/2013 (H7N9) caused lethal infection in mice that was restricted to the respiratory tract and resulted in pulmonary edema and acute lung injury with hyaline membrane formation, leading to decreased oxygenation, all characteristics of human acute respiratory distress syndrome. Oseltamivir at 20 and 80 mg/kg protected 80% and 88% of mice when initiated after 24 hours, and the efficacy decreased to 70% and 60%, respectively, when treatment was delayed by 48 hours. Emergence of oseltamivir-resistant variants was not detected. CONCLUSIONS:H7N9 viruses are comparable to currently circulating influenza A viruses in susceptibility to NAIs. Based on these animal studies, early treatment is associated with improved outcomes.
Authors: Ron A M Fouchier; Peter M Schneeberger; Frans W Rozendaal; Jan M Broekman; Stiena A G Kemink; Vincent Munster; Thijs Kuiken; Guus F Rimmelzwaan; Martin Schutten; Gerard J J Van Doornum; Guus Koch; Arnold Bosman; Marion Koopmans; Albert D M E Osterhaus Journal: Proc Natl Acad Sci U S A Date: 2004-01-26 Impact factor: 11.205
Authors: J L McKimm-Breschkin; A Sahasrabudhe; T J Blick; M McDonald; P M Colman; G J Hart; R C Bethell; J N Varghese Journal: J Virol Date: 1998-03 Impact factor: 5.103
Authors: Jessica A Belser; Kortney M Gustin; Melissa B Pearce; Taronna R Maines; Hui Zeng; Claudia Pappas; Xiangjie Sun; Paul J Carney; Julie M Villanueva; James Stevens; Jacqueline M Katz; Terrence M Tumpey Journal: Nature Date: 2013-07-10 Impact factor: 49.962
Authors: Tatiana Baranovich; Jeremy C Jones; Marion Russier; Peter Vogel; Kristy J Szretter; Susan E Sloan; Patrick Seiler; Jose M Trevejo; Richard J Webby; Elena A Govorkova Journal: Antimicrob Agents Chemother Date: 2016-03-25 Impact factor: 5.191
Authors: Juliet Morrison; Laurence Josset; Nicolas Tchitchek; Jean Chang; Jessica A Belser; David E Swayne; Mary J Pantin-Jackwood; Terrence M Tumpey; Michael G Katze Journal: J Virol Date: 2014-07-02 Impact factor: 5.103
Authors: Victoria A Meliopoulos; Erik A Karlsson; Lisa Kercher; Troy Cline; Pamela Freiden; Susu Duan; Peter Vogel; Richard J Webby; Yi Guan; Malik Peiris; Paul G Thomas; Stacey Schultz-Cherry Journal: J Virol Date: 2014-09-10 Impact factor: 5.103
Authors: Elena A Govorkova; Tatiana Baranovich; Bindumadhav M Marathe; Lei Yang; Margaret A Taylor; Robert G Webster; Garry L Taylor; Helen Connaris Journal: Antimicrob Agents Chemother Date: 2014-12-22 Impact factor: 5.191