Recent Ebola virus (EBOV) outbreaks in West Africa and the Democratic Republic of the Congo have highlighted the urgent need for approval of medical countermeasures for treatment and prevention of EBOV disease (EVD). Until recently, when successes were achieved in characterizing the efficacy of multiple experimental EVD therapeutics in humans, the only feasible way to obtain data regarding potential clinical benefits of candidate therapeutics was by conducting well-controlled animal studies. Nonclinical studies are likely to continue to be important tools for screening and development of new candidates with improved pharmacological properties. Here, we describe a natural history study to characterize the time course and order of progression of the disease manifestations of EVD in rhesus monkeys. In 12 rhesus monkeys exposed by the intramuscular route to 1000 plaque-forming units of EBOV, multiple endpoints were monitored for 28 days following exposure. The disease progressed rapidly with mortality events occurring 7-10 days after exposure. Key disease manifestations observed consistently across the infected animals included, but were not limited to, viremia, fever, systemic inflammation, coagulopathy, lymphocytolysis, renal tubular necrosis with mineralization, and hepatocellular degeneration and necrosis.

中文翻译：

---

恒河猴中埃博拉病毒病（EVD）的特征，用于开发EVD治疗药物。

西非和刚果民主共和国最近爆发埃博拉病毒（EBOV），突显了迫切需要批准用于治疗和预防EBOV疾病（EVD）的医学对策。直到最近，当成功表征多种实验性EVD治疗剂在人体中的功效时，获得有关候选治疗剂潜在临床益处的数据的唯一可行方法是进行良好控制的动物研究。非临床研究可能继续成为筛选和开发具有改善药理学性质的新候选药物的重要工具。在这里，我们描述了一项自然史研究，以表征恒河猴EVD疾病表现的时程和进展顺序。在通过肌内途径暴露于1000噬斑形成单位的EBOV的12只恒河猴中，在暴露后28天监测了多个终点。该病进展迅速，暴露后7-10天发生死亡事件。在感染动物中始终观察到的主要疾病表现包括但不限于病毒血症，发烧，全身性炎症，凝血病，淋巴细胞溶解，肾小管坏死伴矿化以及肝细胞变性和坏死。