Detection & Viral Load Monitoring of Adenovirus

I期项目描述（由申请方提供）：腺病毒（AdV）日益被认为是可导致显著发病率和死亡率的病毒病原体，尤其是在免疫功能低下的患者中。 据报道，免疫功能低下患者的死亡率高达60%，肺炎为50%，肝炎为25%。 在这些患者中严重AdV感染的管理需要早期诊断，与其他疾病的区分以及在治疗后监测感染的能力。 不幸的是，快速，准确和定量诊断技术腺病毒不存在在这个时候。 ViraCor希望为临床医生提供一种新的诊断工具，这将彻底改变AdV感染的诊断和管理方式，从而降低死亡率。 该项目的目的是揭示定量，实时PCR技术是否可以应用于腺病毒，以产生一种诊断测试，可以提供准确和早期的病毒检测。 申请人的初步工作表明，针对AdV基因组的六邻体区域的引物对于病毒的分子检测将是高度敏感和特异的，所述六邻体区域为所有AdV所共有。 在完成研究表明引物可以检测大多数（如果不是所有的话）AdV毒株后，研究人员将继续优化标本类型、标本处理和DNA分离方法。 在这些方面存在潜在的显著差异，这可能会改变患者总病毒载量的整体印象。 同时，申请人将确定试验的性能特征：试验内和试验间条件的范围、线性、重现性和变异系数。 在达到这些目标后，研究者将去他们的研究合作者那里，从培养证实的AdV感染患者中获得回顾性标本，开始将定量实验室数据与临床表现相关联。 目的是显示优化标本的总病毒载量与临床表现的严重程度和进展相关。

DESCRIPTION OF PHASE I PROJECT (provided by applicant): Adenoviruses (AdVs) are increasingly recognized as viral pathogens that can cause significant morbidity and mortality, especially in the immunocompromised patient. Mortality rates in the immunocompromised patient have been reported to be as high as 60 percent for pneumonia, 50 percent for hepatitis and 25 percent overall. Management of serious AdV infections in these patients requires early diagnosis, differentiation from other conditions and the ability to monitor the infection after treatment. Unfortunately, rapid, accurate and quantitative diagnostic techniques for AdV do not exist at this time. ViraCor would like to offer the clinician a new diagnostic tool that will revolutionize the way AdV infections are diagnosed and managed, thereby reducing mortality rates. The aim of the project is to uncover whether quantitative, real-time PCR technology can be applied to AdV to produce a diagnostic test that can provide accurate and early detection of the virus. The applicants' preliminary work indicates that primers against the hexon region of the AdV genome, which is shared by all the AdVs, will be highly sensitive and specific for the molecular detection of the virus. Upon completion of the studies showing that the primers can detect most, if not all the AdV strains, the investigators will proceed to optimization of specimen types, specimen processing and DNA isolation methods. There are potentially significant differences in these areas, which could change the overall impression of total viral load in the patient. Concurrently, the applicants will be establishing performance characteristics of the assay: range, linearity, reproducibility, and coefficient of variation for intra-assay and inter-assay conditions. After meeting these goals the investigators will go to their study collaborators and obtain retrospective specimens from patients with culture proven AdV infections to begin correlation of quantitative laboratory data with clinical presentation. The goal is to show total viral load from optimized specimens correlates with severity and progression of the clinical picture.