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

描述（由申请人提供）：巴贝斯虫病是一种蜱传的红细胞内原生动物感染，由巴贝斯虫属成员引起。输血传播的巴贝斯虫病（TTB）有很好的描述：仅在美国就报告了162例TTB病例，绝大多数是由微小巴贝斯虫引起的，在美国东北部和中西部北部广泛流行。自然获得性和TTB的增加，导致微螺旋体被指定为美国血液安全的首要传染性风险，目前尚无有效的筛查策略。围绕微螺旋体的流行病学、传播性和免疫发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一部分慢性寄生虫献血者引起。这提示了我们的目标：1)确定微螺旋体血清阳性献血者发生慢性感染与短暂性/解决性感染的比例；2)建立一个由从微螺旋体血清和/或pcr阳性献血者获得的纵向样本组成的标本库，用于未来的表征，以进一步了解慢性感染的机制。我们计划利用两项独立资助的计划研究，这两项研究将在2012年7月至9月（SBIR）和2013年（IND）在纽约筛选20,000名献血者，使用原型高灵敏度和特异性ELISA检测针对微螺旋体的抗体。除IFA和外周血涂片检查（PBS）外，血清反应性样品将采用一种新型的、高灵敏度的实时pcr检测方法进行补充检测。在R21下，我们计划招募这些血清反应阳性的献血者（n=100），并在1年的随访期间进行连续采血和临床症状/危险因素问卷调查。在每次随访中，我们将进行ELISA、PCR、IFA和PBS检测，并重复进行临床问卷调查。我们也会

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.