Blood Filtration System for the Treatment of Severe Malaria Patients

用于治疗重症疟疾患者的血液过滤系统

基本信息

批准号：
8393331
负责人：
JAMES F. ANTAKI
金额：
$ 35.56万
依托单位：
ACCEL DIAGNOSTICS, LLC
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-09-01 至 2014-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8393331
关键词：
Address Adult Africa South of the Sahara Animal Testing Antimalarials Area Artemisinins Biomedical Engineering Blood Blood Circulation Blood Component Removal Blood Transfusion Blood Volume Blood donor Blood flow Cambodia Cause of Death Cells Cessation of life Child Childhood Clinical Combined Modality Therapy Computer Simulation Consumption Coupled Developed Countries Development Devices Disease Doctor of Philosophy Drug resistance Engineering Erythrocytes Excision Filtration Generations Goals Health Services Accessibility Health system Hematocrit procedure Hemorheology Hospitalization Hour In Vitro Intravenous Lead Legal patent Letters Life Liquid substance Magnetism Malaria Measures Medical Medical Device Medicine Morbidity - disease rate Motivation Parasitemia Parasites Parasitic infection Patients Pharmaceutical Preparations Pharmacotherapy Phase Physics Pilot Projects Plasmodium falciparum Principal Investigator Process Property Quinine Residual state Risk Small Business Innovation Research Grant Staging System Techniques Technology Thrombus Time Transfection Transfusion Translating Trauma Treatment Cost Tropical Disease United States National Institutes of Health Universities Water Whole Blood Exchange Transfusion Work World Health Organization analog artemisinine artesunate base blood filtration blood treatment commercialization conventional therapy cost design fetal in vivo innovative technologies mortality multidisciplinary novel operation pre-clinical prototype research clinical testing research study scale up simulation success theories trafficking wasting

项目摘要

Project Summary: The overall goal of the proposed project is to develop a novel blood filtration system, mPharesis", for the treatment of severe malaria patients. The World Health Organization estimates that each year approximately 300 million malaria episodes occur globally resulting in nearly one million deaths, 85% of which are children. The majority of deaths are caused by severe malaria. Severe malaria is a leading cause of pediatric morbidity, hospitalization, and mortality in Sub-Saharan Africa. It is responsible for more than 200,000 cases of fetal loss and more than 10,000 maternal deaths annually. Severe malaria also occurs in 5% of the nearly 30,000 imported malaria cases by travelers from endemic areas. Even when managed aggressively with intravenous antimalarial drugs (artesunate or quinine) mortality rates range between 10%-22%, and as high as 40% for the most complicated cases. Blood exchange transfusion (ET) and erythropheresis (EP) have been effectively used to significantly accelerate the clearance of malaria infected red blood cells from circulation. A large body of medical studies has shown that these treatments if available are beneficial. However, the current systems used to perform these therapies are not engineered to selectively separate the infected cells from the non infected. Thus, to remove these toxic infected cells the entire patient's blood is disposed - wasting in most cases between to 70%-95% of the healthy blood. This inefficacy results in larger than needed consumption of donor blood. Consequently, ET and EP therapies remain a prerogative of industrialized nations. This is precisely the motivation for developing the proposed mPharesis" system - a system that will allow the removal of toxic infected red blood cells from the patient's blood circulation with minimal or no use of donor blood. The mPharesis" filter operates by targeting these cells' unique (and well-known) magnetic properties. This system represents the first medical device of its kind to employ magnetic separation technology to clear these toxic cells from circulation. In this SBIR Phase 1 effort, we will complete the design verification of a first-generation mPharesis". This objective will be accomplished by entailing experimentation and numerical simulation, to achieve a prototype optimized for high-throughput, high separation efficiency, and low residual parasitic load. In specific, the successful completion of this Phase 1, will yield a working prototype, suitable for animal testing (in Phase 2), capable of reducing parasitic load (up to 40%) to less than 1.0% within a time period of 2-3 hours, and demonstrating satisfactory hemocompatibility. mPharesis" is intended for those millions of children and adults who have already reached the severe malaria stage, and will provide a life-saving measure for cases that do not respond well to conventional treatments - as too often occurs in the advanced severe stages of this deadly disease.

项目摘要：该项目的总体目标是开发一种新型血液过滤系统，mPharesis”，用于治疗严重疟疾患者。世界卫生组织据估计，全球每年大约发生 3 亿次疟疾发作，导致近一百万人死亡，其中 85% 是儿童。大多数死亡是由严重疟疾造成的。严重疟疾是撒哈拉以南地区儿童发病、住院和死亡的主要原因非洲。它造成了超过200,000例胎儿流产和超过10,000名孕产妇每年死亡人数。近3万例输入性疟疾病例中，5%为重症疟疾来自流行地区的旅行者。即使使用静脉注射抗疟药物积极治疗（青蒿琥酯或奎宁）死亡率在 10%-22% 之间，大多数人高达 40% 复杂的案件。换血（ET）和红细胞去除术（EP）已有效用于显着加速循环中感染疟疾的红细胞的清除。一个大量医学研究表明，这些治疗方法（如果可行）是有益的。然而，当前用于执行这些治疗的系统并未设计用于选择性分离感染者来自非感染者的细胞。因此，为了去除这些有毒的感染细胞，需要对患者的整个血液进行净化。处置 - 在大多数情况下浪费了 70%-95% 的健康血液。这种低效导致大于所需消耗的献血量。因此，ET 和 EP 疗法仍然是一种工业化国家的特权。这正是开发提议的动机 mPharesis”系统——一种可以从血液中去除有毒感染红细胞的系统患者的血液循环最少或不使用捐献血液。 mPharesis”过滤器的运行方式是针对这些细胞独特（且众所周知）的磁性。该系统代表了第一个同类医疗设备采用磁分离技术清除这些有毒细胞循环。在 SBIR 第一阶段工作中，我们将完成第一代的设计验证 mPharesis”。这一目标将通过实验和数值计算来实现模拟，以实现针对高通量、高分离效率和低功耗进行优化的原型残余寄生负载。具体来说，第一阶段的成功完成将产生一个可行的方案原型，适用于动物测试（第 2 阶段），能够将寄生负载（高达 40%）降低至更低 2-3小时内低于1.0%，并表现出令人满意的血液相容性。 mPharesis”旨在帮助数以百万计的已经处于严重疾病状态的儿童和成人疟疾阶段，并将为对传统药物反应不佳的病例提供挽救生命的措施治疗 - 这种致命疾病的严重晚期阶段经常发生。