BioRad Galactomannan EIA for Diagnosis of Aspergillosis

BioRad 半乳甘露聚糖 EIA 用于诊断曲霉病

• 批准号: 6602916
• 负责人: Kieren A. Marr
• 金额: $ 93.94万
• 依托单位: FRED HUTCHINSON CANCER RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-03-01 至 2008-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6602916
• 关键词: Aspergillus; acute myelogenous leukemia; artificial immunosuppression; aspergillosis; carbohydrate transport; clinical research; communicable disease diagnosis; cooperative study; diagnosis design /evaluation; early diagnosis; gastrointestinal absorption /transport; heart transplantation; hematopoietic tissue transplantation; homologous transplantation; human subject; immunologic assay /test; liver transplantation; longitudinal human study; lung transplantation; mannans; neutropenia; opportunistic infections; patient oriented research; stem cell transplantation

DESCRIPTION (provided by applicant): The Bio-Rad galactomannan enzyme immunoassay (GM EIA) will soon be submitted to the FDA for approval as an aid to diagnose aspergillosis, a frequent cause of infectious death in immunosuppressed patients. Our preliminary studies suggest that the assay may also be used as a screening test to enable early diagnoses; however, the optimal cut-offs for positivity have not been determined. Defining cut-offs to optimize performance is critical for patients who have different manifestations of infection (endobronchial vs. invasive), such as in solid organ transplant recipients, and in children, who appear to have frequent false-positive results. The studies proposed in this project will define parameters to use the GM EIA in multiple different patient populations, using clinical samples obtained from a large ongoing FHCRC longitudinal protocol in adult allogeneic hematopoietic stem cell transplant (HSCT) recipients, and samples obtained from multicenter trials sponsored by the NIH. Aim 1 will define parameters for use of the GM EIA as an early diagnostic test for aspergillosis in adult allogeneic HSCT patients. Studies will be performed to determine the lower limit of GM detection, identify clinical factors that impact levels of circulating GM, and to determine the role of GM EIA applied to non-blood fluids (bronchoalveolar lavage fluid and urine). Aim 2 will define appropriate cut-offs for positivity and characterize performance of the GM EIA as a diagnostic assay for aspergillosis in high-risk solid organ transplant recipients. To do this, longitudinal sample collection will be performed in a protocol conducted as a companion to an ongoing CDC-sponsored multicenter surveillance study. Aim 3 will define parameters for use of the GM EIA as an early diagnostic test for aspergillosis in neutropenic children. To determine the appropriate cut-offs for positivity in children, GM EIAs will be performed on serial sera obtained from children at high risk for aspergillosis after treatment with induction chemotherapy for AML, and after cord blood transplant. Companion protocols will be performed to collect sera as part of ongoing multicenter studies performed by the Children' s Oncology Group and the NHLBI Cord Blood Transplantation Study. Studies will be performed to determine if false-positivity of the GM EIA in children corresponds with gut translocation of GM during periods of mucositis, by measuring surrogate markers for GI integrity in a case-control study. This project is enabled by the cooperative activities of FHCRC investigators, Bio-Rad Laboratories, and several multicenter networks supported by the CDC, NIAID, and NHLBI.

描述（由申请人提供）：Bio-Rad Galactomannan酶免疫测定法（GM EIA）将很快提交FDA批准以帮助诊断Aspergillosis，这是免疫抑制患者的经常导致感染性死亡的经常原因。我们的初步研究表明，该测定也可以用作筛查测试以实现早期诊断。但是，尚未确定阳性的最佳临界值。定义临界值以优化性能对于感染表现不同的患者（支撑剂与侵入性）至关重要，例如在固体器官移植受者中以及似乎频繁的假阳性结果的儿童中。该项目中提出的研究将定义参数以在多个不同的患者人群中使用GM EIA，使用从成人成人同种异体造血干细胞移植（HSCT）接受者中获得的大型FHCRC纵向方案获得的临床样本，并从NIH赞助的多中心试验中获得的样品。 AIM 1将定义使用GM EIA作为成人同种异体HSCT患者曲霉病的早期诊断测试的参数。将进行研究以确定GM检测的下限，确定影响GM循环水平的临床因素，并确定应用于非血液液（支气管肺泡灌洗液和尿液）的GM EIA的作用。 AIM 2将定义适当的临界值，以表明GM EIA的性能为高危固体器官移植受者曲霉病的诊断测定。为此，将以作为正在进行的CDC赞助的多中心监视研究的协议中进行纵向样本收集。 AIM 3将定义使用GM EIA作为中性粒细胞减少儿童曲霉病的早期诊断测试的参数。为了确定儿童阳性的适当临界值，将对从具有AML诱导化学疗法和脐带血移植后从具有高风险的曲霉病的儿童获得的序列血清进行GM EIA。作为儿童肿瘤学组和NHLBI脐带血移植研究进行的正在进行的多中心研究的一部分，将执行伴侣方案以收集血清。将进行研究以确定儿童中GM EIA的假阳性是否与粘膜炎期间GM的肠道易位相对应，通过在病例对照研究中测量GI完整性的替代标记。 FHCRC研究人员，Bio-Rad Laboratories以及CDC，Niaid和NHLBI支持的几个多中心网络的合作活动启用了该项目。