title: The neuraminidase inhibitor oseltamivir is effective against A/Anhui/1/2013 (H7N9) influenza virus in a mouse model of acute respiratory distress syndrome.
abstract: 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.
authors.affiliation: Department of Infectious Diseases, St Jude Children's Research Hospital, Memphis, Tennessee.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Baranovich
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Burnham
authors.forename: Bindumadhav M
authors.initials: BM
authors.lastname: Marathe
authors.forename: Jianling
authors.initials: J
authors.lastname: Armstrong
authors.forename: Yi
authors.initials: Y
authors.lastname: Guan
authors.forename: Yuelong
authors.initials: Y
authors.lastname: Shu
authors.forename: Joseph Malik Sriyal
authors.initials: JM
authors.lastname: Peiris
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Webby
authors.forename: Robert G
authors.initials: RG
authors.lastname: Webster
authors.forename: Elena A
authors.initials: EA
authors.lastname: Govorkova
mesh_terms: D055371:Acute Lung Injury / Q000821:virology; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D000998:Antiviral Agents / Q000494:pharmacology*; D004195:Disease Models, Animal; D024882:Drug Resistance, Viral; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D064766:Influenza A Virus, H7N9 Subtype / Q000502:physiology*; D008168:Lung / Q000473:pathology / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D009439:Neuraminidase / Q000037:antagonists & inhibitors; D053139:Oseltamivir / Q000494:pharmacology*; D012128:Respiratory Distress Syndrome / Q000188:drug therapy* / Q000821:virology*; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000914:Antibodies, Viral; D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D053139:Oseltamivir; D009439:Neuraminidase
keywords: acute respiratory distress syndrome; efficacy; human influenza H7N9; neuraminidase inhibitor; oseltamivir; resistance