Transplant Associated Infection Surveillance Network Phase II

描述（由申请方提供）：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。在过去的6年里，我们已经完成了一个前瞻性的23中心监测网络（TRANSNET），筛选了34,000多名移植受者，并确定了2100多例确诊和可能的侵袭性真菌感染（IFI）病例。这些数据使人们更好地了解了美国的疾病负担，并突出了移植组之间的一些主要差异。尽管TRANSNET作为一种疾病负担的测量方法有其价值，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）是评估与IFL发展相关的风险因素的及时和必要的下一步，并启动对重要非真菌病原体的前瞻性监测。我们在该项目中的成功可以通过来自3个研究中心的2个队列（肺移植受者和同种异体干细胞移植受者）中招募的大量患者以及在这两个高危组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）在美国3个移植中心对选定的OTR和HSCT进行前瞻性监测，以确定是否存在已证实和可能的IFL（伯明翰的亚拉巴马大学、密歇根大学和宾夕法尼亚大学）; 2）执行案件-在侵袭性霉菌感染高危患者中进行对照研究，以确定重要的医院和门诊风险因素，并提出建议预防; 3）开发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;以及4）建立真菌分离株和其他临床标本库。这些目标的实现将提供至关重要的见解，与IFL的发展和其他移植后感染并发症，特别是高风险患者的关键可改变的风险因素。此外，在多个地点建立标准监测方法将大大提高重要病原体数据收集的质量和便利性。最后，建立一个数据库对于开发和验证新的诊断检测方法将是非常宝贵的。 公共卫生相关性：在美国，器官和造血干细胞移植已成为一项日益重要的挽救成千上万人生命的措施。器官排斥反应、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。有关移植受者侵袭性真菌感染的重要问题仍然存在，包括确定真实的疾病负担以及确定与这些并发症发生相关的关键风险因素。此外，新的非真菌病原体的出现，特别是C。艰难性结肠炎、西尼罗河病毒、其他呼吸道病毒和多重耐药细菌的出现，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提出的一项及时而重要的倡议，旨在解决这些患者的一些更重要的问题。该申请涉及三个大型、整合良好的移植项目（亚拉巴马大学伯明翰分校、密歇根大学和宾夕法尼亚大学），这些项目在前瞻性监测方面具有丰富的经验，并有良好的合作记录。该联盟非常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.