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Recombinant human activated protein C for the postexposure treatment of Ebola hemorrhagic fever

  1. Author:
    Hensley, L. E.
    Stevens, E. L.
    Yan, S. B.
    Geisbert, J. B.
    Macias, W. L.
    Larsen, T.
    Daddario-DiCaprio, K. M.
    Cassell, G. H.
    Jahrling, P. B.
    Geisbert, T. W.

  2. Author Address

    USA, Med Res Inst Infect Dis, Div Virol, Ft Detrick, MD 21702 USA. USA, Med Res Inst Infect Dis, Div Pathol, Ft Detrick, MD 21702 USA. NIH, NIAID, Integrated Res Facil, Ft Detrick, MD USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. Lilly Res Labs, Indianapolis, IN USA.;Geisbert, TW, Boston Univ, Sch Med, Dept Microbiol, 715 Albany St, Boston, MA 02118 USA.;geisbert@bu.edu
    1. Year: 2007
    2. Date: Nov
  2. Journal: Journal of Infectious Diseases
    1. 196
    2. Pages: S390-S399
  4. Type of Article: Article
  5. ISSN: 0022-1899
  1. 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.

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External Sources

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  2. DOI: 10.1086/520598
  3. View record in Web of Science®
  4. WOS: 000251090400038

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