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.

项目摘要：拟议项目的总体目标是开发一种新颖的血液过滤 系统，mpharesis”，用于治疗严重疟疾患者。世界卫生组织 估计每年大约3亿疟疾发作在全球发生，几乎导致 100万人死亡，其中85％是儿童。大多数死亡是由严重的疟疾引起的。 严重的疟疾是撒哈拉以下小儿发病，住院和死亡率的主要原因 非洲。它负责超过200,000例胎儿损失和10,000多个母亲 每年死亡。在近30,000例进口疟疾病例中，有5％发生严重疟疾。 来自流行地区的旅行者。即使用静脉抗疟药积极管理 （青臂或奎宁）死亡率在10％-22％之间，最高至40％ 复杂的情况。血液交换输血（ET）和红血病（EP）已有效 用于显着加速疟疾感染的红细胞循环的清除。一个 大量的医学研究表明，如果可用的话，这些治疗是有益的。但是， 用于执行这些疗法的当前系统没有设计用于选择性分开感染的 来自未感染的细胞。因此，要去除这些有毒感染的细胞，整个患者的血液是 处置 - 在大多数情况下浪费在健康血液的70％-95％之间。这种低效率导致 比供体血液所需的消费大。因此，ET和EP疗法仍然是 工业化国家的特权。这正是开发提议的动机 Mpharesis”系统 - 一种系统，将允许去除有毒感染的红细胞 患者的血液循环，最少或不使用供体血液。 mpharesis“滤波器通过 针对这些细胞的独特（和知名）磁性。该系统代表第一个 同类的医疗设备采用磁分离技术来清除这些有毒细胞 循环。在SBIR 1阶段的工作中，我们将完成第一代的设计验证 mpharesis”。这个目标将通过实验和数值来实现 模拟，以实现针对高通量，高分离效率和低较低的原型 残留的寄生负荷。具体而言，该阶段1的成功完成将产生工作 原型，适用于动物测试（在第2阶段），能够将寄生载荷（最高40％）降低到更少 在2-3小时的时间内，超过1.0％，表现出令人满意的血流相容性。 Mpharesis“适用于已经达到严重的几百万儿童和成人 疟疾阶段，并将为对常规反应不佳的病例提供挽救生命的措施 治疗 - 正如这种致命疾病的晚期严重阶段经常发生的那样。