Transplant Associated Infection Surveillance Network Phase II

描述（由申请人提供）：移植后感染是实体器官移植受者和造血干细胞移植受者发病和死亡的主要原因。在过去 6 年里，我们已经完成了一个由 23 个中心组成的前瞻性监测网络 (TRANSNET)，筛查了超过 34,000 名移植受者，并确定了超过 2100 例已证实和可能的侵袭性真菌感染 (IFI) 病例。这些数据提高了对美国疾病负担的了解，并强调了移植群体之间的一些主要差异。尽管 TRANSNET 作为疾病负担的衡量标准很有价值，但它对重要危险因素进行病例对照试验的能力有限。 CDC 发起的器官移植感染检测和预防计划（2004-2009 年）是评估与 IFIs 发展相关的风险因素并启动对重要非真菌病原体的前瞻性监测的及时且必要的下一步。我们在该计划中的成功可以通过从 3 个地点纳入 2 个队列（肺移植受者和同种异体干细胞移植受者）的大量患者以及在这两个高风险群体中观察到的不同类型的感染来衡量。在本提案中，我们建议实现以下目标：1）在 3 个美国移植中心（阿拉巴马大学伯明翰分校、密歇根大学和宾夕法尼亚大学）对选定的 OTR 和 HSCT 进行前瞻性监测，以发现已证实和可能的 IFIs； 2) 在侵袭性霉菌感染高风险患者中进行病例对照研究，以确定显着的院内和门诊风险因素，并制定预防建议； 3) 制定对选定的非真菌病原体（即艰难梭菌、巨细胞病毒、西尼罗河病毒、呼吸道病毒和选定的多重耐药细菌）进行前瞻性监测的方法； 4) 建立真菌分离株和其他临床标本库。这些目标的实现将为了解与尤其是高危患者中发生 IFIs 和其他移植后感染并发症相关的关键可改变风险因素提供至关重要的见解。此外，建立跨多个地点的标准监测方法将显着提高重要病原体数据收集的质量和便利性。最后，银行的建立对于开发和验证新的诊断方法具有不可估量的价值。 公共健康相关性：在美国，器官和造血干细胞移植已成为每年成千上万人的一项日益重要的挽救生命的措施。器官排斥、移植物抗宿主病和移植后感染并发症，特别是侵袭性真菌感染，是与该人群发病率和死亡率相关的关键因素。关于移植受者侵袭性真菌感染的重要问题仍然存在，包括确定疾病的真正负担并确定与这些并发症发生相关的关键危险因素。此外，新的非真菌病原体的出现，特别是艰难梭菌结肠炎、西尼罗河病毒、其他呼吸道病毒和多重耐药细菌，要求重新关注移植后时期。因此，器官移植感染检测和预防计划（OTIP）是疾病预防控制中心为解决这些患者中一些更重要的问题而提出的一项及时而重要的举措。该申请涉及三个大型、整合良好的移植项目（阿拉巴马大学伯明翰分校、密歇根大学和宾夕法尼亚大学），在前瞻性监测方面拥有丰富的经验和出色的合作记录。该联盟完全有能力实现本公告中提出的目标。

DESCRIPTION (provided by applicant): Infections in the post-transplant period are a leading cause of morbidity and mortality among solid organ transplant recipients and hematopoietic stem cell transplant recipients. In the last 6 years we have completed a prospective 23 center surveillance network (TRANSNET), screening over 34,000 transplant recipients and identifying over 2100 proven and probable cases of invasive fungal infection (IFI). These data have led to improved understanding of the disease burden in the U.S. and has highlighted some of the major differences among transplant groups. Despite its value as a measure of disease burden, TRANSNET had limited ability to perform case-control trials of important risk factors. The CDC- sponsored initiative Organ Transplant Infection Detection and Prevention Program (2004-2009) was a timely and necessary next step toward the assessment of risk factors associated with the development of IFls, and to initiate prospective surveillance for important non-fungal pathogens. Our success in this program can be measured by the large numbers of patients enrolled into 2 cohorts (lung transplant recipients and allogeneic stem cell transplant recipients) from 3 sites, and the diverse types of infection observed among each of these two high risk groups. In this proposal, we propose to achieve the following aims: 1) to perform prospective surveillance among selected OTRs and HSCTs for proven and probable IFls at 3 US transplant centers (University of Alabama at Birmingham, University of Michigan, and University of Pennsylvania); 2) to perform case-control studies among patients at high risk for invasive mould infections to identify significant nosocomial and outpatient risk factors and to establish recommendations for prevention; 3) to develop methodologies for conducting prospective surveillance for selected non-fungal pathogens (i.e. C.difficile, cytomegalovirus, West Nile virus, respiratory viruses, and selected multiresistant bacteria); and 4) to establish a bank for fungal isolates and other clinical specimens. The achievement of these goals will provide critically important insights into the key modifiable risk factors associated with the development of IFls and other post-transplantation infectious complications in especially high-risk patients. Moreover, the establishment of standard surveillance methodology across multiple sites will significantly improve the quality and ease of data collection for important pathogens. Finally, the establishment of a bank will be invaluable in the development and validation of newer diagnostic assays. PUBLIC HEALTH RELEVANCE: Organ and hematopoietic stem cell transplantation has become an increasingly important and life saving measure for thousands of persons each year in the United States. Organ rejection, graft vs. host disease, and post-transplantation infections complications, especially invasive fungal infection, are the key factors related to morbidity and mortality in this population. Important questions remain concerning invasive fungal infections in transplant recipients, including determining the real burden of disease and identifying key risk factors associated with development of these complications. Moreover, the emergence of new non-fungal pathogens, especially C. difficile colitis, West Nile virus, other respiratory viruses, and multiresistant bacteria, dictates renewed focus on the post-transplant period. Thus, the Organ Transplant Infection Detection and Prevention Program (OTIP) is a timely and important initiative put forth by the CDC to address some of the more important issues in these patients. This application involves three large, well-integrated transplant programs (University of Alabama at Birmingham, University of Michigan and University of Pennsylvania) with strong experience in prospective surveillance and excellent record of collaboration. This consortium is very well positioned to accomplish the goals set forth in this announcement.