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: 8427977
• 负责人: Evan Martin Bloch
• 金额: $ 25.01万
• 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 2015-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8427977
• 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（由申请方提供）：巴贝虫病是一种蜱传的红细胞内原生动物感染，由巴贝虫属成员引起。输血传播的巴贝虫病（TTB）有很好的描述：仅在美国就报告了162例TTB病例，绝大多数是由小Babalemotti引起的，这是美国东北部和中西部地区的广泛流行病。自然获得性和TTB的增加导致了B。Microti被指定为美国血液安全的最重要传染性风险，目前还没有有效的筛查策略。围绕B的流行病学、传播性和免疫发病机制的不确定性。microti仍然是制定可行的缓解战略的一个障碍。最近的证据表明，输血传播可能是由一个子集的慢性寄生虫血症献血者不成比例。这促使我们的目标：1）确定B的比例。microti血清阳性供体，其发展为慢性与短暂/消退的感染，和2）建立由从B获得的纵向样品组成的标本库。microti血清和/或PCR阳性的献血者进行进一步的表征，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，这些研究将于2012年（SBIR）和2013年（IND）7月至9月在纽约筛选20，000份献血，使用原型高灵敏度和特异性ELISA检测B抗体。显微镜除IFA和外周血涂片检查（PBS）外，血清反应性样本将使用新型、高灵敏度的真实的实时PCR检测进行补充检测。根据R21，我们计划招募这些血清反应性供体（n=100），并在1年的随访期间进行连续血液采样和临床症状/风险因素问卷调查。在每次随访访视时，我们将进行ELISA、PCR、IFA和PBS检测，并重复进行临床问卷调查。我们还将 招募先前与TTB病例有关的供体（n=10）和在自我报告巴贝虫病史后被推迟的供体。测试后，剩余整体 每次随访的血液和血浆将被冷冻并存档在储存库中，以备将来表征。指数和随访结果（ELISA和PCR）的相关性将使感染风险分类为：慢性感染（ELISA+/PCR+），短暂感染（指数PCR+/随访PCR -）和远程暴露（指数和随访PCR-）。这种分类为筛选方法（血清学与PCR）的选择以及推迟和恢复的政策提供了信息。我们打算在将来的提交中使用样本库来确定慢性与短暂感染的遗传和免疫决定因素。