@article{eab56891ce9044b1b1fbe1bfaa259f5f,
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.",
author = "Hensley, {Lisa E.} and Stevens, {Edward L.} and Yan, {S. Betty} and Geisbert, {Joan B.} and Macias, {William L.} and Tom Larsen and Daddario-DiCaprio, {Kathleen M.} and Cassell, {Gail H.} and Jahrling, {Peter B.} and Geisbert, {Thomas W.}",
note = "Funding Information: Supplement sponsorship. This article was published as part of a supplement entitled “Filoviruses: Recent Advances and Future Challenges,” sponsored by the Public Health Agency of Canada, the National Institutes of Health, the Canadian Institutes of Health Research, Cangene, CUH2A, Smith Carter, Hemisphere Engineering, Crucell, and the International Centre for Infectious Diseases. Funding Information: Financial support: Defense Threat Reduction Agency; Medical Chemical/ Biological Defense Research Program, US Army Medical Research and Material Command (project no. 02-4-4J-081). Supplement sponsorship is detailed in the Acknowledgments. Funding Information: We thank Denise Braun for technical assistance. We also thank Scott Gamble and Kenneth Jacobsen for surgical and veterinary care support and Jim LeDuc for helpful discussions. The study was supported by the Medical Chemical/Biological Defense Research Program, U.S. Army Medical Research and Material Command (project no. 02-4-4J-081). Animal research was conducted at United States Army Medical Research Institute for Infectious Diseases in compliance with the Animal Welfare Act and other federal statues and regulations relating to animals and experiments involving animals and adheres to the principles stated in the Guide for the Care and Use of Laboratory Animals, National Research Council, 1996. The facility is fully accredited by the Association for Assessment and Accreditation of Laboratory Animal Care International.",
year = "2007",
month = nov,
day = "15",
doi = "10.1086/520598",
language = "English (US)",
volume = "196",
pages = "S390--S399",
journal = "Journal of Infectious Diseases",
issn = "0022-1899",
publisher = "Oxford University Press",
number = "SUPPL. 2",
}