Characterization of Respiratory Pathogens in Transplant Patients

描述(申请人提供)：免疫功能低下的患者，包括那些接受了造血干细胞(HSCT)和实体器官(SOT)移植的患者，患由呼吸道病原体引起的严重疾病的风险显著增加。这些患者对更广泛的微生物有更大的易感性，并经常出现更晚期的疾病。此外，他们往往有较高的机体负担，并被多种病原体感染，要么作为主要感染源，要么作为继发性感染并发症。此外，由于宿主对感染性病原体的免疫反应受损，基于免疫的诊断策略(如血清学)可能不可靠。虽然分子分析提供了提高灵敏度和特异度的优势，但大多数呼吸道样本的检测都是通过单链聚合酶链式反应完成的，这些检测是由发出的专业实验室进行的，需要几天或更长时间才能得出结果。由于缺乏对各种呼吸道病原体的快速诊断检测，往往导致针对性抗微生物疗法的启动延迟，这可能导致发病率和死亡率的增加。事实上，移植和免疫功能低下的患者提供了一个重大的诊断挑战和巨大的未得到满足的临床需求。这项第一阶段SBIR研究的目标是测试来自Brigham&Women‘s Hospital/Dana-Farber癌症研究所的300名成年HSCT/SOT患者的呼吸道样本，该系统具有在一小时内实时检测22种呼吸道病原体的能力。具体地说，我们将比较FilmArray RP系统的诊断性能与目前使用的CLIA批准的移植患者呼吸道病原体的临床诊断方法，包括HSCT和SOT，通过鼻咽抽吸(NPA)和支气管肺泡灌洗(BAL)采样。我们预计，这项第一阶段研究的结果将导致一项创新的第二阶段研究，届时将测试一种旨在检测一组扩大的呼吸道病原体的多重PCR袋。FilmArray RP系统的成功测试最终可能会改善对免疫受损患者群体的管理，并可能导致医疗保健服务的总体成本下降。公共卫生相关性：未诊断的呼吸道病原体是器官移植患者的一个主要问题，因为他们的免疫系统往往不能完全发挥作用。爱达荷州科技公司开发了一种诊断系统(称为FilmArray)，该系统可以快速(1小时)检测大量呼吸道病原体，操作人员只需最少的努力。我们将测试FilmArray可以帮助诊断移植患者的呼吸道症状，从而改进治疗的想法。

DESCRIPTION (provided by applicant): Immunocompromised patients including those who have undergone hematopoietic stem cell (HSCT) and solid organ (SOT) transplants are at markedly increased risk for severe disease caused by respiratory pathogens. These patients have greater susceptibility to a broader range of organisms and frequently present with more advanced disease. In addition, they often have higher organism burden and are infected with multiple pathogens either as primary infectious agents or as a secondary infectious complication. Moreover, because of an impaired host immunologic response to infectious agents, immune based diagnostic strategies such as serology can be unreliable. While molecular assays offer the advantage of improved sensitivity and specificity, most testing of respiratory samples is done by singleplex PCR that are performed by send-out specialty laboratories and take several days or more before results are available. The lack of rapid diagnostic testing for a wide range of respiratory pathogens often results in a delay in initiation of targeted anti-microbial therapies, which can result in increased morbidity and mortality. Indeed, transplant and immunocompromised patients provide a significant diagnostic challenge and a great unmet clinical need. The goal of this Phase I SBIR study is to test 300 respiratory samples from adult HSCT/SOT patients followed at Brigham & Women's Hospital/Dana-Farber Cancer Institute using a multiplex PCR (FilmArray RP) system that features the real-time capacity of detecting 22 respiratory pathogens within one hour. Specifically, we will compare the diagnostic performance of the FilmArray RP system to currently used CLIA approved clinical diagnostic assays for respiratory pathogens in transplant patients, both HSCT and SOT, sampled by nasopharyngeal aspirate (NPA) and by bronchoalveolar lavage (BAL). We anticipate that the results from this Phase I study will lead to an innovative Phase II study where a multiplex PCR pouch designed to detect an expanded panel of respiratory pathogens will be tested. The successful testing of the FilmArray RP system could ultimately lead to improved management of this immunocompromised patient population and potentially lead to an overall deceased cost in health care delivery. PUBLIC HEALTH RELEVANCE: Undiagnosed respiratory pathogens are a major problem for organ transplant patients because their immune systems are often not fully functional. Idaho Technology Incorporated has developed a diagnostic system (termed FilmArray) that can rapidly (<1 hour) detect a large number of respiratory pathogens with minimal operator effort. We will test the idea that FilmArray can aid in the diagnosis of respiratory symptoms in transplant patients and thus lead to improved treatment.