Ebola Hemorrhagic Fever: Novel Biomarker Correlates of Clinical Outcome
Ebola Hemorrhagic Fever: Novel Biomarker Correlates of Clinical Outcome
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DOI：
10.1093/infdis/jiu088
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发表时间：
2014-08-15
影响因子：
6.4
通讯作者：
Spiropoulou, Christina F.
中科院分区：
文献类型：
--
作者：
McElroy, Anita K.;Erickson, Bobbie R.;Spiropoulou, Christina F.
背景埃博拉出血热（EHF）在非洲零星发生，导致高死亡率。2000-2001年在乌干达古卢地区爆发的与苏丹病毒有关的EHF导致425例病例，其中216例经实验室确认，是有记录以来最大的EHF爆发。本次疫情的血清标本从采集之时起就保存在液氮中，可供分析。使用一系列多重测定来测试可用的样品，以测量55种生物标志物的浓度。对数据进行分析以确定所测试的生物标志物与出血性表现、病毒血症和/或死亡之间的统计学显著相关性。死亡、出血和病毒血症与几种趋化因子和细胞因子水平升高独立相关。死亡和出血与血栓调节蛋白和铁蛋白水平升高相关。出血也与可溶性细胞内粘附分子水平升高有关。病毒血症与组织因子和组织纤溶酶原激活物水平升高独立相关。最后，非致死性病例的样本中sCD 40 L水平较高。这些新的关联提供了对EHF病理生理学的更好理解，并为研究治疗干预的新的潜在靶点提供了起点。
Background. Ebola hemorrhagic fever (EHF) outbreaks occur sporadically in Africa and result in high rates of death. The 2000-2001 outbreak of Sudan virus-associated EHF in the Gulu district of Uganda led to 425 cases, of which 216 were laboratory confirmed, making it the largest EHF outbreak on record. Serum specimens from this outbreak had been preserved in liquid nitrogen from the time of collection and were available for analysis.Methods. Available samples were tested using a series of multiplex assays to measure the concentrations of 55 biomarkers. The data were analyzed to identify statistically significant associations between the tested biomarkers and hemorrhagic manifestations, viremia, and/or death.Results. Death, hemorrhage, and viremia were independently associated with elevated levels of several chemokines and cytokines. Death and hemorrhage were associated with elevated thrombomodulin and ferritin levels. Hemorrhage was also associated with elevated levels of soluble intracellular adhesion molecule. Viremia was independently associated with elevated levels of tissue factor and tissue plasminogen activator. Finally, samples from nonfatal cases had higher levels of sCD40L.Conclusions. These novel associations provide a better understanding of EHF pathophysiology and a starting point for researching new potential targets for therapeutic interventions.