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

• 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
• 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

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.

项目概述：建议项目的总体目标是开发一种新型血液过滤器 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3亿起疟疾事件，导致近 100万人死亡，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科发病率、住院和死亡率的主要原因 非洲。它造成了20多万例胎儿流产和10,000多名产妇 每年的死亡人数。到#年，近30,000例输入性疟疾病例中也有5%发生严重疟疾 来自疫区的旅行者。即使在积极使用静脉注射抗疟疾药物的情况下 (青蒿琥酯或奎宁)死亡率在10%-22%之间，大多数高达40% 复杂的案子。换血(ET)和红细胞回输(EP)已经取得了有效的效果 用于显著加快受疟疾感染的红细胞从循环中的清除。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， 目前用于进行这些治疗的系统并没有被设计成有选择地分离感染者 来自非感染者的细胞。因此，要清除这些有毒的感染细胞，整个患者的血液 大多数情况下，丢弃的血液占健康血液的70%-95%。这种无效导致了 超过所需的献血者血液消耗量。因此，ET和EP疗法仍然是一种 工业化国家的特权。这正是发展建议中的 MPharesis“系统-该系统将允许将有毒的受感染的红细胞从 患者的血液循环最少或不使用捐献者的血液。MPharesis“过滤器的运行方式为 瞄准这些细胞独特的(和众所周知的)磁性。这一系统是世界上第一个 利用磁分离技术清除这些有毒细胞的同类医疗设备 发行量。在这项SBIR第一阶段的工作中，我们将完成第一代 这一目标将通过实验和数值计算来实现 仿真，实现了一个针对高通量、高分离效率和低成本进行优化的原型 剩余寄生负载。具体地说，这一阶段的成功完成将产生一个有效的 原型，适用于动物测试(第二阶段)，能够将寄生负载(高达40%)降至更低 在2-3小时的时间内超过1.0%，并表现出良好的血液相容性。 MPharesis“是为数百万已经达到严重疾病的儿童和成年人设计的 疟疾阶段，并将为常规治疗反应不佳的病例提供一种挽救生命的措施 治疗--通常发生在这种致命疾病的严重晚期。