Single Well MPCR Donor Screen to ID Blood Pathogens

单孔 MPCR 供体筛查以识别血液病原体

• 批准号: 7561700
• 负责人: RAYMOND RANKEN
• 金额: $ 40.68万
• 依托单位: IBIS BIOSCIENCES, INC.
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-04-01 至 2011-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7561700
• 关键词: Biological Assay; Birds; Blinded; Blood; Blood Banks; Blood Screening; Blood-Borne Pathogens; Cessation of life; Chagas Disease; Chronic; Communicable Diseases; Dengue Virus; Detection; Donor Selection; Extended Family; Flavivirus; HIV; HIV-1; HIV-2; Hepatitis A Virus; Hepatitis B Virus; Hepatitis C virus; Herpesvirus 1; Human; Infection; Malaria; Mass Spectrum Analysis; Microbe; Names; New Agents; Nucleic Acid Amplification Tests; Parasites; Parvovirus; Phase; Phase II Clinical Trials; Plasmodium; Plasmodium malariae; Principal Investigator; Reagent; Research; Sampling; Screening procedure; Specimen; System; Technology; Testing; Time; Transfusion; Transplant Recipients; Trypanosoma; Trypanosoma cruzi; Tube; Variant; Vascular blood supply; West Nile virus; Work; hazard; influenzavirus; member; pathogen; programs

DESCRIPTION (provided by applicant): In recent decades the blood supply has been periodically contaminated by emerging infectious microbes with sometimes devastating consequences. Pathogens, such as human immunodeficiency virus (HIV) and hepatitis C virus (HCV), have caused many thousands of chronic infections and deaths in transfusion and transplant recipients prior to the implementation of post-tragedy screening. Although the current "hindsight" approach has resulted in a blood supply that is safe from known hazards, it is still vulnerable to unanticipated pathogens. We propose to validate a proactive approach to protect the blood supply against newly emerging agents and new strains of existing agents and, at the same time, enhance protection against agents that are already of concern. We will develop a high-throughput nucleic acid test for analysis on the Ibis T5000 mass spectroscopy platform; the single-tube assay will use inexpensive reagents and provide detection of the known blood-borne pathogens, new strains of these pathogens, and pathogens of concern that are not currently detected. The Ibis T5000 technology is uniquely suited to the fast, sensitive, and accurate detection and identification of known and newly emerging pathogens. This capability was successfully demonstrated during the Phase I portion of this work by the creation of a single assay that has the ability to readily detect members of the extended families of six pathogens. In the proposed Phase II study, we will complete the assembly of a comprehensive screening test that will cover a variety of pathogens. We will first develop and validate primer pairs for the detection of parasites associated with Chagas disease (Trypanosoma cruzi) and malaria (Plasmodium species, including falciparum, vivax, ovale and malariae). We will then validate the final single- tube multiplex blood screening test that will allow identification of all strains and variants of HIV-1 (Group M, subtypes A-G; Groups N and O), HIV-2, HTLV 1-3, HCV, HBV, all known flaviviruses (including the West Nile and Dengue viruses), all influenza viruses (including human and avian), parvoviruses (including B19), hepatitis A virus, human herpes viruses (1-3, 5,8, excluding EBV), trypanosomes, and Plasmodium species. Both calibrant and positive controls will be produced to support this assay. This screen will be fully validated and the system tested with large numbers of blinded samples and a large number of samples from blood bank specimens. The technology is extensible to a much broader range of pathogens and will eventually provide a "seamless net" to protect the blood supply from pathogens that cause infectious disease.

描述（由申请人提供）：近几十年来，血液供应已被新兴的感染性微生物定期污染，有时会带来毁灭性的后果。病原体，例如人类免疫缺陷病毒（HIV）和丙型肝炎病毒（HCV），在实施后交通筛查之前，在输血和移植受者中引起了数千种慢性感染和死亡。尽管目前的“事后”方法导致血液供应免受已知危害的影响，但它仍然容易受到意外病原体的影响。我们建议验证一种积极主动的方法，以保护血液供应对新出现的代理和现有代理的新菌株，同时增强对已经令人关注的药物的保护。我们将开发一个高通量核酸测试，以在IBIS T5000质谱平台上进行分析；单管测定法将使用廉价的试剂，并提供已知的血源性病原体，这些病原体的新菌株以及目前尚未检测到的病原体的检测。 IBIS T5000技术非常适合快速，敏感，准确的检测和鉴定，对已知和新兴病原体的鉴定。在这项工作的第一阶段部分成功证明了这一能力，该方法通过创建一个可以轻松检测六种病原体的大家庭成员的单个测定法。在拟议的II期研究中，我们将完成涵盖各种病原体的综合筛查测试的组装。我们将首先开发和验证引物对检测与chagas疾病（Cruzi锥虫）和疟疾（包括恶性菌，Vivax，ovale和Malariae）相关的寄生虫。然后，我们将验证最终的单管多重血液筛查测试，该测试将允许鉴定HIV-1的所有菌株和变体（组M，亚型A-G；组N和O组），HIV-2，HTLV 1-3，HCV，HCV，HCV，HCV， HBV，所有已知的黄病毒（包括西尼罗河和登革热病毒），所有流感病毒（包括人和鸟类），细小病毒（包括B19），乙型肝炎病毒，人类疱疹病毒（1-3，5,8，不包括EBV），不包括EBV） ，锥虫和疟原虫。将产生校准和阳性对照以支持该测定法。该屏幕将得到充分验证，并用大量盲样样品和大量来自血库标本的样品进行了测试。该技术可扩展到更广泛的病原体，并最终将提供“无缝网络”，以保护血液供应免受引起传染病的病原体的影响。