Recombinant Human Activated Protein C for the Postexposure Treatment of Ebola Hemorrhagic Fever
Bibliographic record
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.The filoviruses, Ebola virus (EBOV) and Marburg virus (MARV), represent an enigmatic family of viruses that cause severe and often lethal hemorrhagic fever [1-3].Currently, there are no vaccines or postexposure treatment modalities available for preventing or managing filoviral infections.There have been a number of attempts in clinical settings to improve the status of infected patients, and several strategies have been developed and tested in vitro and in animal models (reviewed in [4,5]).Potential conflicts of interest: S.B.Y, W.L.M., and G.H.C. are employees of Lilly Research Laboratories, which holds a license for using recombinant human activated protein C for treating human cases of severe sepsis at high risk of death.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".