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.

抽象的 由间日疟原虫引起的疟疾威胁着全球超过 20 亿人，并导致数千万人患病 每年。间日疟原虫疟疾的根治方法包括针对急性发作的治疗（血液裂殖杀灭） 并防止未来的攻击（催眠杀虫）。唯一可用的催眠药是 8-氨基喹啉，例如 伯氨喹或他非诺喹。然而，由于 8-氨基喹啉类药物的高浓度，临床医生通常不会开具 8-氨基喹啉类药物处方。 具有不同水平的遗传性 6-磷酸葡萄糖脱氢酶 (G6PD) 的个体的患病率 (8%) 缺乏和8-氨基喹啉可导致中度患者危及生命的急性溶血性贫血 严重的 G6PD 缺陷。没有商用的即时护理 (POC) 测试可以量化 Hgb 和 G6PD 均来自指尖采血样本。 在第一阶段，我们成功达到了世界卫生组织和该计划概述的绩效 健康适当技术 (PATH)。全血和血浆检测结果显示优异 我们的 PreQuine 系统和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，其中将具有许多有价值的功能。首先，PreQuine 系统将由测试条组成 以及带有板载温度校正算法的手持式仪表。其次，PreQuine 系统将 坚固耐用、低成本、微创，广泛用于临床环境、公共卫生实验室和目标 外展计划。为了完成 PreQuine 系统的开发，我们将： (1) 完成测定 通过评估生物活性成分进行开发。将测试三种市售心肌黄酶 确保 (1) 在最佳 pH 值下具有高度活性 (2) 长期稳定性； (3) 没有抑制作用 马来酰亚胺的存在； (2)试纸条从手工组装过渡到半自动组装。 这将通过优化将条带涂布、分切和层压成 5-up 卡的工艺能力来实现 库存。; (3) 纳入温度修正系数 (TFC)。 PreQuine系统必须启用功能 工作温度为18°C至40°C。 TFC 将被合并到软件中并纠正 温度差异。最后，(4)PreQuine系统的验证。 G6PD 和 Hgb 水平验证 将证明制造的测试条与参考方法之间的一致性。一旦验证并 PreQuine 系统商业化后将提供护理点诊断工具来识别 G6PD 缺陷 能够或不能耐受 8-氨基喹啉治疗的个体，这将改变疟疾治疗 根除间日疟原虫和卵形疟原虫疟疾的策略和援助。