BioRad Galactomannan EIA for Diagnosis of Aspergillosis

描述（由申请人提供）：Bio-Rad半乳甘露聚糖酶免疫测定法（GM EIA）将很快提交给FDA批准，作为诊断曲霉病的辅助手段，曲霉病是免疫抑制患者感染性死亡的常见原因。我们的初步研究表明，该检测也可用作筛查试验，以实现早期诊断;然而，尚未确定阳性的最佳截止值。定义临界值以优化性能对于具有不同感染表现（支气管内与侵入性）的患者至关重要，例如实体器官移植受者和儿童，他们似乎经常出现假阳性结果。本项目中提出的研究将定义在多个不同患者人群中使用GM EIA的参数，使用从成人异基因造血干细胞移植（HSCT）受者中正在进行的大型FHCRC纵向方案中获得的临床样本，以及从NIH申办的多中心试验中获得的样本。目的1将定义使用GM EIA作为成人同种异体HSCT患者曲霉菌病早期诊断试验的参数。将进行研究，以确定GM检测的下限，确定影响循环GM水平的临床因素，并确定GM EIA应用于非血液液体（支气管肺泡灌洗液和尿液）的作用。目标2将确定适当的阳性临界值，并表征GM EIA作为高风险实体器官移植受者曲霉病诊断检测的性能。为此，将在作为正在进行的CDC申办的多中心监测研究的伴随方案中进行纵向样本采集。目标3将确定使用GM EIA作为贫血儿童曲霉病早期诊断试验的参数。为了确定儿童阳性的适当临界值，将对从AML诱导化疗治疗后和脐带血移植后的曲霉病高风险儿童中获得的系列血清进行GM EIA。作为儿童肿瘤组和NHLBI脐带血移植研究正在进行的多中心研究的一部分，将执行配套方案以收集血清。通过在病例对照研究中测量GI完整性的替代标志物，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。该项目是由FHCRC研究人员，Bio-Rad实验室和CDC，NIAID和NHLBI支持的几个多中心网络的合作活动实现的。

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.