Pre-symptomatic diagnosis and treatment of filovirus diseases.
Pre-symptomatic diagnosis and treatment of filovirus diseases.
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DOI：
10.3389/fmicb.2015.00108
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发表时间：
2015
影响因子：
5.2
通讯作者：
Bavari S
中科院分区：
文献类型：
--
作者：
Shurtleff AC;Whitehouse CA;Ward MD;Cazares LH;Bavari S
丝状病毒是致命的人类病原体，其引起具有高病死率的严重疾病，并且没有可用的FDA批准的疫苗或治疗剂。诊断工具，包括抗体和分子为基础的测定，质谱，和下一代测序正在不断发展。使用聚合酶链反应（PCR）的检测已成为在疫情环境中检测丝状病毒的主要方法。在许多情况下，实时逆转录酶-PCR允许以最少的操作和设备进行丝状病毒的检测，并且可以在不到2小时内提供结果。在新的高度多样化的丝状病毒的情况下，随机引发的焦磷酸测序方法已被证明是有用的。理想情况下，诊断检测将允许在感染后尽早诊断丝状病毒感染，在症状开始之前，在已知暴露或流行病学爆发的情况下，或在感染后。如果测试可以提供一个早期明确的诊断，那么这个信息可以用来告知可能的治疗方法的选择。最近已经描述了几种令人兴奋的新候选疗法;一旦疾病迹象开始，在暴露后几天给予感染动物模型时具有治疗活性的分子。候选核苷类似物，小干扰RNA（siRNA）分子，磷酰二胺（PMO）分子，以及抗体和血液制品的治疗和治疗性疫苗的最新数据进行了讨论。对于丝状病毒研究人员和有兴趣为国家国防和公众提供治疗的政府机构来说，拥有正确的诊断工具来识别丝状病毒感染，以及在需要时进行治疗的可用疗法，是一个高度优先事项。为了最终取得成功，需要在这两个领域进行更多的研究，但在实现这些目标方面正在取得重大进展。
Filoviruses are virulent human pathogens which cause severe illness with high case fatality rates and for which there are no available FDA-approved vaccines or therapeutics. Diagnostic tools including antibody- and molecular-based assays, mass spectrometry, and next-generation sequencing are continually under development. Assays using the polymerase chain reaction (PCR) have become the mainstay for the detection of filoviruses in outbreak settings. In many cases, real-time reverse transcriptase-PCR allows for the detection of filoviruses to be carried out with minimal manipulation and equipment and can provide results in less than 2 h. In cases of novel, highly diverse filoviruses, random-primed pyrosequencing approaches have proved useful. Ideally, diagnostic tests would allow for diagnosis of filovirus infection as early as possible after infection, either before symptoms begin, in the event of a known exposure or epidemiologic outbreak, or post-symptomatically. If tests could provide an early definitive diagnosis, then this information may be used to inform the choice of possible therapeutics. Several exciting new candidate therapeutics have been described recently; molecules that have therapeutic activity when administered to animal models of infection several days post-exposure, once signs of disease have begun. The latest data for candidate nucleoside analogs, small interfering RNA (siRNA) molecules, phosphorodiamidate (PMO) molecules, as well as antibody and blood-product therapeutics and therapeutic vaccines are discussed. For filovirus researchers and government agencies interested in making treatments available for a nation’s defense as well as its general public, having the right diagnostic tools to identify filovirus infections, as well as a panel of available therapeutics for treatment when needed, is a high priority. Additional research in both areas is required for ultimate success, but significant progress is being made to reach these goals.
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