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

Lisa E. Hensley, Edward L. Stevens, S. Betty Yan, Joan B. Geisbert, William L. Macias, Tom Larsen, Kathleen M. Daddario-DiCaprio, Gail H. Cassell, Peter B. Jahrling, Thomas W. Geisbert

Research output: Contribution to journalArticle

123 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)S390-S399
JournalJournal of Infectious Diseases
Volume196
Issue numberSUPPL. 2
DOIs
StatePublished - Nov 15 2007
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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    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. (2007). Recombinant human activated protein C for the postexposure treatment of ebola hemorrhagic fever. Journal of Infectious Diseases, 196(SUPPL. 2), S390-S399. https://doi.org/10.1086/520598