The Malaria Transfusion Risk (MATRix) Study

疟疾输血风险 (MATRIx) 研究

• 批准号: 10153880
• 负责人: Evan Martin Bloch
• 金额: $ 17.61万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-05-03 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10153880
• 关键词: Accounting; Address; Adoption; Africa; Africa South of the Sahara; Age; Biological Assay; Blood; Blood Transfusion; Blood donor; Blood donor screening; Blood specimen; Characteristics; Clinical; Clinical Data; Clinical Trials; Clinical assessments; Complex; Cost Analysis; Country; Data; Demographic Factors; Department of Defense; Development; Donor Selection; Economics; Epidemiology; Expert Opinion; Funding; Geography; Human; Incidence; Individual; Infection; Infrastructure; International; Laboratories; Logistics; Malaria; Mentored Research Scientist Development Award; Mentors; Microscopy; Modality; Modeling; Molecular; Morbidity - disease rate; Nested PCR; Outcome; Parasitemia; Patients; Performance; Plasmodium; Policies; Population; Prevalence; Public Health; Publications; Publishing; Quality-Adjusted Life Years; Randomized; Research; Risk; Risk Factors; Running; Safety; Sample Size; Sampling; Seasons; Severities; Technology; Testing; Time; Transfusion; Travel; Uganda; Whole Blood; antibody test; antigen test; arm; base; comparative; comparative cost effectiveness; control trial; cost; cost effectiveness; cost-effectiveness evaluation; evidence base; experience; human subject; infection risk; insight; mortality; neglect; novel; pathogen; prevent; sample archive; sample collection; screening; sex; simulation; transcription mediated amplification; transmission process; vector-borne

PROJECT SUMMARY Globally, malaria (Plasmodium spp.) is the leading parasitic threat to humans and a major cause of morbidity and mortality. Despite longstanding recognition that Plasmodium species are transfusion transmissible, the burden and risk of transfusion-transmitted malaria (TTM) has not been well characterized and evidence-based policy to safeguard against TTM has not been determined. The advent of novel, molecular assays for blood donor screening could transform the existing approaches for TTM. We hypothesize that Blood donor screening for malaria using highly sensitive molecular assays in Uganda and other endemic countries will prevent a substantial proportion of transfusion-transmitted infections but will be cost-prohibitive and operationally unfeasible given associated donor loss. In contrast, molecular screening of blood donors in the US, will be cost-favorable when applied to those deferred for travel to endemic countries. To test this hypothesis, we will conduct the Malaria Transfusion Risk (MATRix) study to Aim 1) Evaluate donor prevalence of parasitemia and lab-based screening approaches to address TTM; Aim 2) Quantify the risk of TTM and identify demographic factors for TTM in a highly endemic country; and Aim 3) Compare the cost-effectiveness of different strategies to mitigate TTM to inform donor policies. The MATRix study will capitalize on a US Dept. of Defense-funded clinical trial that is underway in Uganda to evaluate (a) the feasibility of implementation of pathogen reduction technology (PRT) and (b) its impact on transfusion-transmitted infections following whole blood transfusions. The trial will soon begin collecting blood samples and demographic information from 3,500 donors and 2,000 transfusion recipients; recipients will be evaluated before- and after (days 2, 7, 28) transfusion. To address the MATRix study aims, we will use clinical data and archived samples from the PRT trial to (1a) compare performance characteristics of nested PCR, transcription-mediated amplification, antigen testing, microscopy and antibody testing, to detect Plasmodium spp. in Ugandan blood donors (n=3500) and (1b) describe the prevalence of Plasmodium seroreactivity and parasitemia by demographic and donor status. (2) Lab testing and clinical assessment of donor recipient pairs from the PRT trial control arm will enable quantification of incidence and clinical severity of TTM in recipients of blood from donors in Aim 1 (n=1000). We describe the risk of TTM by demographic, level of parasitemia and recipient clinical characteristics. Finally, a Markov-based decision analytic model will be used to evaluate TTM mitigation strategies drawing on input data from Aims 1 and 2, previous publication and/or local expert opinion to (3a) assess the cost-effectiveness of donor screening for TTM in Uganda by test modality and extent of implementation, while accounting for donor loss. It will also (3b) compare the cost-effectiveness of donor testing vs. risk-based deferral in the US. This study would guide global policy on TTM. It would also provide key insight into relative performance of the individual testing modalities for malaria, while offering insight into transmission dynamics and infectivity of TTM.

项目总结 在全球范围内，疟疾(疟疾spp.)是对人类的主要寄生虫威胁，也是致病的主要原因 和死亡率。尽管长期以来人们一直认为疟原虫是可以通过血液传播的，但 输血传播疟疾(TTM)的负担和风险尚未得到很好的描述和证据 防范TTM的政策尚未确定。新的血液分子分析方法的出现 捐献者筛选可以改变TTM的现有方法。我们假设献血者筛查 对于疟疾，在乌干达和其他流行国家使用高灵敏的分子分析将防止 很大一部分是通过输血传播的感染，但成本高昂，而且在操作上是不可行的 考虑到相关的捐赠者损失，这是不可行的。相比之下，美国对献血者的分子筛查将是 如果适用于那些因前往流行国家而被推迟旅行的人，则具有成本优势。为了检验这一假设，我们将 开展疟疾输血风险(MATRIX)研究，目的1)评估献血者寄生虫血症的患病率和 以实验室为基础的筛查方法，以应对TTM；目标2)量化TTM的风险并确定人口统计 在一个高度流行的国家导致TTM的因素；以及目标3)比较不同战略的成本效益 以减轻TTM，以便为捐助者政策提供信息。黑客帝国的研究将利用一个美国部门。国防部资助的 正在乌干达进行的临床试验，以评估(A)实施病原体减少的可行性 技术(PRT)和(B)其对全血输血后经输血传播感染的影响。 这项试验将很快开始从3500名献血者和2000名献血者那里收集血液样本和人口统计信息 输血受者；受者将在输血前和输血后(第2、7、28天)接受评估。要解决这个问题 矩阵研究的目的，我们将使用临床数据和PRT试验的存档样本来比较(1a) 套式聚合酶链式反应、转录介导扩增、抗原检测、显微镜检查的性能特征 和抗体检测，以检测疟原虫。乌干达献血者(n=3500)和(1b)描述 按人口学和捐献者状况分列的疟原虫血清反应性和寄生虫血症的患病率。(2)实验室检测 对PRT试验对照部门的捐赠者和接受者对的临床评估将使量化 目标1中受血者TTM的发生率和临床严重程度(n=1000)。我们描述了 TTM风险按人口学、寄生虫血症水平和受者临床特征分类。最后，一个基于马尔可夫的 决策分析模型将用于评估基于AIMS 1的输入数据的TTM缓解策略 和2、以前的出版物和/或当地专家意见，以(3a)评估捐赠者筛选的成本效益 按测试方式和执行程度对乌干达的TTM进行评估，同时考虑到捐助者的损失。它还将 (3B)比较美国捐献者检测与基于风险的延期治疗的成本效益。这项研究将指导 关于TTM的全球政策。它还将提供对各个测试的相对性能的关键洞察 疟疾的传播模式，同时提供对TTM的传播动态和传染性的洞察。