A prospective evaluation of chronic B.microti infection in seroreactive blood don

血清反应性血液中慢性田鼠乙型杆菌感染的前瞻性评估

• 批准号: 8700503
• 负责人: Evan Martin Bloch
• 金额: $ 20.18万
• 依托单位: VITALANT
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-07-15 至 2015-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8700503
• 关键词: Accounting; Acute; Algorithms; American; Antibodies; Archives; Babesia; Babesia microti; Babesiosis; Behavior; Biological Assay; Blood; Blood Donations; Blood Tests; Blood Transfusion; Blood donor; Blood specimen; Borrelia microti; Cessation of life; Chronic; Clinical; Data; Development; Diagnosis; Disease; Donor Selection; Enrollment; Enzyme-Linked Immunosorbent Assay; Epidemiology; Evaluation; Freezing; Funding; Future; Genetic; Genetic Determinism; Immune; Immunologics; Infection; Knowledge; Laboratories; Methodology; Microscopic; New York; Parasitemia; Parasites; Patient Self-Report; Patients; Plasma; Policies; Protozoan Infections; Publishing; Questionnaires; Recording of previous events; Red Cross; Relative (related person); Reporting; Research; Residual state; Risk; Risk Factors; Safety; Sampling; Seasons; Serologic tests; Serological; Small Business Innovation Research Grant; Source; Specimen; Symptoms; Testing; Ticks; Time; Transfusion; Uncertainty; United States; Vascular blood supply; Visit; Whole Blood; base; follow-up; indexing; member; novel; peripheral blood; prevent; prospective; prototype; public health relevance; repository; screening; transmission process

DESCRIPTION (provided by applicant): Babesiosis is a tick-borne, intraerythrocytic protozoan infection, caused by members of the Babesia genus. Transfusion-transmitted babesiosis (TTB) is well described: 162 cases of TTB have been reported in the US alone, the overwhelming majority caused by Babesia microti, which is widely endemic in the Northeastern and upper Midwestern US. An increase in naturally-acquired and TTB, has resulted in B. microti's designation as the foremost infectious risk to blood safety in the US for which an effective screening strategy is currently unavailable. Uncertainty surrounding the epidemiology, transmissibility and immunopathogenesis of B. microti remains an obstacle to development of a viable mitigation strategy. Recent evidence suggests that transfusion transmission may be caused disproportionately by a subset of chronically parasitemic blood donors. This has prompted our aims: 1) to determine the proportions of B. microti seropositive donors that develop chronic versus transient/resolved infections, and 2) to build a specimen repository composed of longitudinal samples obtained from B. microti sero- and or PCR-positive blood donors for future characterization in order to further our understanding of the mechanisms underlying chronic infection. We plan to leverage two independently funded, planned studies which will screen 20,000 blood donations in New York from July to September in 2012 (SBIR) and 2013 (IND), using a prototype highly sensitive and specific ELISA to detect antibodies against B. microti. Seroreactive samples will be subjected to supplementary testing using a novel, highly sensitive real- time PCR-based assay in addition to IFA and peripheral blood smear examination (PBS). Under the R21, we plan to enroll these seroreactive donors (n=100) and to conduct serial blood sampling and clinical symptom/risk factor questionnaire administration over 1 year of follow-up. At each follow-up visit, we will perform ELISA, PCR, IFA and PBS testing, in addition to repeated administration of the clinical questionnaire. We will also enroll donors that have previously been implicated in cases of TTB (n=10) and donors that have been deferred following their self-reporting a history of babesiosis. After testing, residual whole blood and plasma from each follow-up visit will be frozen and archived in a repository for future characterization. Correlation of the index and follow-up results (ELISA and PCR) will enable infectious-risk categorization into: chronic infection (ELISA+/PCR+), transient infection (index PCR+/follow-up PCR -) and remote exposure (index and follow-up PCR-). This categorization informs choice of screening methodology (serology vs. PCR) and policy of deferral and reinstatement. We intend to use the sample repository for a future submission to determine the genetic and immunologic determinants of chronic vs. transient infection.

描述(申请人提供)：巴贝斯虫病是一种由扁虱传播的红细胞内原生动物感染，由巴贝斯虫属成员引起。输血传播巴贝斯虫病(TTB)被很好地描述：仅在美国就报告了162例TTB病例，绝大多数是由在美国东北部和中西部北部广泛流行的微小巴贝斯虫引起的。自然获得性和结核分枝杆菌的增加导致微小杆菌被指定为美国血液安全的最大感染风险，目前还没有有效的筛查策略。围绕微小杆菌的流行病学、传播性和免疫致病机制的不确定性仍然是制定可行的缓解战略的障碍。最近的证据表明，输血传播可能不成比例地由长期寄生虫病献血者的一部分引起。这促使我们的目标是：1)确定微小杆菌血清阳性献血者发生慢性感染和一过性感染/缓解感染的比例，以及2)建立一个由微型杆菌血清和/或聚合酶链式反应阳性献血者的纵向样本组成的标本库，用于未来的鉴定，以加深我们对慢性感染机制的理解。我们计划利用两项独立资助的计划研究，这两项研究将于2012年(SBIR)和2013年(IND)从7月至9月在纽约筛查20,000份献血，使用一种高度敏感和特异的原型ELISA来检测针对微结核杆菌的抗体。除了IFA和外周血液涂片检查(PBS)外，血清反应样本将接受一种新的、高灵敏度的实时聚合酶链式反应检测。根据R21，我们计划招募这些血清反应阳性的献血者(n=100)，并进行为期一年的连续采血和临床症状/危险因素问卷调查。在每次随访时，除了重复发放临床问卷外，我们还将进行ELISA、PCR、IFA和PBS检测。我们还将 招募以前与结核病例有牵连的捐赠者(n=10)，以及在自我报告巴贝斯虫病病史后被推迟的捐赠者。经检验，残差整齐 每一次后续访问的血液和血浆将被冷冻并存档在储存库中，以供未来鉴定。将该指数与随访结果(酶联免疫吸附试验和聚合酶链式反应)相关联，可以将感染风险分类为：慢性感染(酶联免疫吸附试验+/聚合酶链式反应+)、暂时性感染(指数聚合酶链式反应+/后续聚合酶链式反应-)和远程暴露(指数和后续聚合酶链式反应-)。这种分类为筛查方法的选择(血清学与聚合酶链式反应)以及延期和恢复的政策提供了信息。我们打算在将来提交时使用样本库，以确定慢性感染和暂时性感染的遗传和免疫学决定因素。