A user-friendly point-of-care device for G6PDH determination

用于 G6PDH 测定的用户友好型床旁设备

• 批准号: 9922841
• 负责人: Robert Harper
• 金额: $ 57.42万
• 依托单位: ANALYTICAL DIAGNOSTIC SOLUTIONS, INC.
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-02-08 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9922841
• 关键词: Acute; Affect; Agreement; Algorithms; Aminoquinolines; Anemia; Bedside Testings; Biological Assay; Blood; Blood Tests; Clinical; Color; Computer software; Development; Devices; Diagnosis; Diagnostic; Drops; Electrons; Ensure; Enzymes; Evaluation; Fingers; Future; Glucosephosphate Dehydrogenase; Glucosephosphate Dehydrogenase Deficiency; Guidelines; Hand; Health; Hemoglobin; Hemoglobin concentration result; Hemolytic Anemia; High Prevalence; In Vitro; Individual; Inherited; Life; Life Experience; Light; Malaria; Maleimides; Measurement; Mediating; Mediator of activation protein; Membrane; Methods; Patients; Performance; Phase; Plasma; Plasmodium ovale; Plasmodium vivax; Primaquine; Process; Program Appropriateness; Public Health; Reagent; Sampling; Sensitivity and Specificity; System; Technology; Temperature; Test Result; Testing; Treatment Protocols; Validation; Vivax Malaria; Whole Blood; World Health Organization; assay development; base; blind; commercialization; cost; cost effective; cryogenics; design; dihydrolipoamide dehydrogenase; enzyme activity; meter; minimally invasive; outreach program; point of care; point-of-care diagnostics; preservation; process optimization; prototype; rate of change; success; tool; treatment strategy; user-friendly

Abstract Malaria caused by Plasmodium vivax threatens over 2 billion people globally and sickens tens of millions annually. Radical cure for P. vivax malaria includes therapy aimed both at the acute attack (blood schizontocidal) and against future attacks (hypnozoitocidal). The only hypnozoitocides available are 8-aminoquinolines such as primaquine or tafenoquine. However, clinicians often do not prescribe 8-aminoquinolines due to the high prevalence (8%) of individuals with various levels of inherited Glucose-6-phosphate dehydrogenase (G6PD) deficiencies and 8-aminoquinolines can cause life-threatening acute hemolytic anemia in patients with moderate to severe G6PD deficiencies. There are no commercially available point-of-care (POC) tests that can quantify both Hgb and G6PD from a finger-stick sample. In Phase I, we successfully met the performance as outlined by the World Health Organization and the Program for Appropriate Technology in Health (PATH). Results of whole blood and plasma testing revealed excellent concordance between our PreQuine System and current reference methods. In Phase II, we propose to manufacture a simple-to-use inexpensive device, the PreQuine System, that can be used in the field or clinical setting, which will have a number of valuable features. First, the PreQuine System will be comprised of test strips and a hand-held meter with an on-board temperature correction algorithm. Second, the PreQuine System will be rugged, low cost, and minimally invasive for broad use in clinical settings, public health labs and targeted outreach programs. To complete development of the PreQuine System, we will: (1) Finalize Assay Development by Assessing Bioactive Components. Three commercially available diaphorases will be tested to ensure (1) a high degree of activity at the optimal pH (2) long-term stability; and (3) no inhibition in the presence of maleimide; (2) Transition from Hand Assembly to Semi-Automated Assembly of Test Strips. This will be achieved by optimizing process capabilities of coating, slitting and laminating the strips into 5-up card stock.; (3) Incorporate a Temperature Correction Factor (TFC). The PreQuine system must be enable function in a working temperature of 18°C to 40°C. The TFC will be incorporated into the software and correct for temperature differences. Finally, (4) Validation of the PreQuine System. Validation for G6PD and Hgb levels will demonstrate concordance between the manufactured test strips and reference methods. Once validated and commercialized, the PreQuine System will provide point of care diagnostic tool to identify G6PD deficient individuals who can or cannot tolerate 8-aminoquinoline treatment, which will transform malaria treatment strategies and aid in the eradication of P.vivax and P. ovale malaria.

摘要 由间日疟原虫引起的疟疾威胁着全球20多亿人，并导致数千万人患病 每年一次。根治间日疟包括针对急性发作的治疗(血裂殖子杀灭) 以及抵御未来的攻击(催眠药)。唯一可用的催眠药是8-氨基喹啉类，如 伯喹或他苯喹。然而，临床医生往往不会开出8-氨基喹啉类药物的处方，因为 遗传性葡萄糖-6-磷酸脱氢酶(G6PD)不同水平个体的患病率(8%) 缺乏和8-氨基喹啉类药物可导致威胁生命的急性溶血性贫血患者的中度 严重的G6PD缺乏症。目前还没有商业上可用的护理点(POC)测试可以量化 手指样本中的HGB和G6PD。 在第一阶段，我们成功地达到了世界卫生组织和本方案概述的业绩 适用于健康的技术(PATH)。全血和血浆检测结果显示 我们的PreQuine系统与当前参考方法之间的一致性。在第二阶段，我们建议 制造一种简单易用、价格低廉的设备，PreQuine系统，可用于现场或临床 设置，这将具有许多有价值的功能。首先，PreQuine系统将由试纸组成 以及带有车载温度修正算法的手持式仪表。第二，PreQuine系统将 坚固耐用、低成本和微创，可广泛用于临床环境、公共卫生实验室和靶向 外展计划。为了完成PreQuine系统的开发，我们将：(1)完成分析 通过评估生物活性成分进行开发。将测试三种商业化的黄递酶 以确保(1)在最佳pH下的高度活性；(2)长期稳定性；以及(3)在 马来酰亚胺的存在；(2)测试条从手工组装过渡到半自动组装。 这将通过优化涂布、分切和层压的工艺能力来实现 加入温度修正系数(TFC)。必须启用PreQuine系统功能 在18°C至40°C的工作温度下，TFC将被集成到软件中并正确 温差。最后，(4)PreQuine系统的验证。G6PD和HGB水平的验证 将证明所制造的试纸和参考方法之间的一致性。一旦经过验证并 商业化后，PreQuine系统将提供看护点诊断工具，以确定G6PD缺陷 能够或不能耐受8-氨基喹啉治疗的个人，这将改变疟疾的治疗 根除间日疟原虫和卵形疟原虫的战略和援助。