title: Recombinant human activated protein C for the postexposure treatment of Ebola hemorrhagic fever.
abstract: BACKGROUND
  Infection of primates with Zaire ebolavirus (ZEBOV) leads to hypotension, coagulation disorders, and an impaired immune response and, in many ways, resembles severe sepsis. Rapid decreases in plasma levels of protein C are a prominent feature of severe sepsis and ZEBOV hemorrhagic fever (ZHF). Currently, recombinant human activated protein C (rhAPC [Xigris; Eli Lilly]) is licensed for treating human patients with severe sepsis who are at high risk of death. The aim of this study was to test the efficacy of rhAPC as a potential treatment for ZHF.
  
  
  METHODS
  Fourteen rhesus macaques were challenged with a uniformly lethal dose of ZEBOV; 11 of these monkeys were treated by intravenous infusion with rhAPC beginning 30-60 min after challenge and continuing for 7 days. Three control monkeys received sterile saline in parallel.
  
  
  RESULTS
  All 3 control monkeys died on day 8, whereas 2 of the 11 rhAPC-treated monkeys survived. The mean time to death for the rhAPC-treated monkeys that did not survive ZEBOV challenge was 12.6 days. The difference in survival was significant when the rhAPC-treated monkeys were compared with historical controls.
  
  
  CONCLUSIONS
  The experimental findings provide evidence that ZHF and severe sepsis share underlying mechanisms and may respond to the same therapies.
authors.affiliation: Virology Division, US Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD, USA.
authors.forename: Lisa E
authors.initials: LE
authors.lastname: Hensley
authors.forename: Edward L
authors.initials: EL
authors.lastname: Stevens
authors.forename: S Betty
authors.initials: SB
authors.lastname: Yan
authors.forename: Joan B
authors.initials: JB
authors.lastname: Geisbert
authors.forename: William L
authors.initials: WL
authors.lastname: Macias
authors.forename: Tom
authors.initials: T
authors.lastname: Larsen
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Daddario-DiCaprio
authors.forename: Gail H
authors.initials: GH
authors.lastname: Cassell
authors.forename: Peter B
authors.initials: PB
authors.lastname: Jahrling
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Geisbert
mesh_terms: D000818:Animals; D002405:Catheterization, Central Venous; D004195:Disease Models, Animal; D029043:Ebolavirus / Q000302:isolation & purification*; D019142:Hemorrhagic Fever, Ebola / Q000188:drug therapy*; D008253:Macaca mulatta; D009842:Oligopeptides / Q000627:therapeutic use; D011323:Primates; D011486:Protein C / Q000008:administration & dosage / Q000235:genetics / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use
chemical_list: D009842:Oligopeptides; D011486:Protein C; D011994:Recombinant Proteins; C047135:protein C activator peptide