Broad Detection of Infectious Agents in Blood by Microarrays and Deep Sequencing

通过微阵列和深度测序广泛检测血液中的传染性病原体

• 批准号: 8649071
• 负责人: Charles Yen Chiu
• 金额: $ 57.07万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-04-01 至 2016-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8649071
• 关键词: Acute; Age; American; Anaplasma; Babesia; Bacteria; Biological Assay; Blood; Blood Cells; Blood donor; Blood-Borne Pathogens; Borrelia; Cessation of life; Chagas Disease; Characteristics; Clinical; Clinical Microbiology; Clinical Sensitivity; Cytomegalovirus; Dengue Virus; Detection; Diagnostic; Ehrlichia; Ensure; Epidemiology; Fever; Genome; Genomics; Geographic Locations; Geography; Goals; HIV; HIV-1; Headache; Hepatitis; Hepatitis B; Human Herpesvirus 4; Human Parvovirus B19; Human T-lymphotropic virus 1; Individual; Infection; Infectious Agent; Investigation; Laboratories; Leishmania; Link; Malaria; Metagenomics; National Heart, Lung, and Blood Institute; Pathogen detection; Pathogenicity; Patients; Plasma; Plasmodium; Prevalence; Principal Investigator; Probability; Public Health; Red Cross; Relative (related person); Research; Safety; Sampling; Scientist; Sensitivity and Specificity; Serologic tests; Serum; Surveillance Program; Technology; Testing; Transfusion; Transfusion-Transmitted Virus; United States; United States National Institutes of Health; Vascular blood supply; Viral; Viral Load result; Virus; Whole Blood; base; deep sequencing; design; follow-up; genome sequencing; liver transplantation; novel; novel virus; pathogen; programs; public health relevance; repository; respiratory; screening; sex; tool; viral detection

DESCRIPTION (provided by applicant): Bloodborne infectious agents, including novel / emerging pathogens of concern, pose a continual threat to our blood supply and the safety of the 5 million transfusions performed annually in the United States. Here we propose to apply two state-of-the-art diagnostic technologies, a pan-viral microarray called the Virochip and massively parallel deep sequencing, to comprehensively identify infectious agents in blood. The Virochip will be expanded to cover bloodborne nonviral as well as viral pathogens, and we will rigorously assess analytical test characteristics (e.g. sensitivity, specificity, limits of detection, accuracy) for detection of pathogens associated with the most common bloodborne infections, including malaria, Chagas disease, HIV, hepatitis B/C, and dengue virus. The expanded Virochip and deep sequencing will then be used to launch a broad- spectrum surveillance program for bloodborne infectious agents. We will initially focus on analyzing serum samples from patients with nonA-E clinical hepatitis and deferred blood donors with post-donation acute illness such as fever - samples which carry a high a priori probability of harboring known / novel infectious agents. We will analyze random individual or pooled serum samples from donors matched by age, sex, and geographic location for infectious agents circulating in our blood supply. We will perform whole-genome sequencing and epidemiological screening by serology and PCR for any novel viruses identified in transfused blood. A major goal of this research is to assess the utility of Virochip and deep sequencing as comprehensive pathogen screening tools for ensuring transfusion safety. Identification of novel infectious agents in blood will also spur further detailed investigations into their epidemiology and pathogenicity. PUBLIC HEALTH RELEVANCE: Known as well as novel / emerging infectious agents continually threaten the safety of the 5 million transfusions performed annually in the United States, yet the lack of diagnostic tools able to comprehensively test for bloodborne pathogens or to identify novel / divergent strains has hindered surveillance efforts. This study proposes to investigate the utility of the Virochip, a pan-viral microarray, and massively parallel deep sequencing as complementary strategies for (1) broad-based detection of bloodborne pathogens, and (2) identification of novel / emerging infectious agents. The results from this study have the potential to advance these technologies for eventual FDA approval as broad-based screening tools to ensure transfusion safety, with significant clinical and public health implications. Identification of novel infectious agents in blood will also open up new avenues of research into their epidemiology and the threat that they pose to our blood supply.

描述（由申请人提供）：血源性传染原，包括新型/新出现的令人关注的病原体，对我们的血液供应和美国每年进行的 500 万次输血的安全构成持续威胁。在这里，我们建议应用两种最先进的诊断技术，一种称为 Virochip 的泛病毒微阵列和大规模并行深度测序，来全面识别血液中的感染因子。 Virochip 将扩展到涵盖血源性非病毒和病毒病原体，我们将严格评估分析测试特征（例如灵敏度、特异性、检测限、准确性），以检测与最常见的血源性感染相关的病原体，包括疟疾、恰加斯病、艾滋病毒、乙型/丙型肝炎和登革热病毒。扩展后的 Virochip 和深度测序将用于启动针对血源性传染源的广谱监测计划。我们首先将重点分析来自非甲型至戊型临床肝炎患者和患有献血后急性疾病（例如发烧）的延期献血者的血清样本，这些样本携带已知/新型传染原的先验概率很高。我们将分析来自与年龄、性别和地理位置相匹配的捐献者的随机个体或混合血清样本，以查找我们血液供应中循环的传染源。我们将通过血清学和PCR对输血中发现的任何新病毒进行全基因组测序和流行病学筛查。这项研究的一个主要目标是评估 Virochip 和深度测序作为综合病原体筛查工具确保输血安全的效用。血液中新型感染因子的鉴定也将促进对其流行病学和致病性的进一步详细研究。 公共卫生相关性：已知的以及新型/新出现的传染源持续威胁着美国每年进行的 500 万次输血的安全，但由于缺乏能够全面检测血源性病原体或识别新型/不同菌株的诊断工具，阻碍了监视工作。本研究拟探讨 Virochip（一种泛病毒微阵列）和大规模并行深度测序的实用性，作为以下补充策略：（1）广泛检测血源性病原体，以及（2）识别新型/新兴传染原。这项研究的结果有可能推动这些技术的发展，最终获得 FDA 批准作为广泛的筛查工具，以确保输血安全，具有重大的临床和公共卫生影响。血液中新型传染源的鉴定也将为研究其流行病学及其对我们血液供应造成的威胁开辟新的途径。