Inexpensive, sensitive and specific, point-of-care diagnostic for bacterial infections in the central nervous system

廉价、灵敏且特异的中枢神经系统细菌感染即时诊断

• 批准号: 9341823
• 负责人: Theresa N Schein
• 金额: $ 27.25万
• 依托单位: CNINE BIOSOLUTIONS, INC.
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-02-01 至 2019-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9341823
• 关键词: Adult; Affect; Africa South of the Sahara; Antibiotics; Antibodies; Asia; Bacteria; Bacterial Infections; Bacterial Meningitis; Biological Assay; Biological Markers; Buffers; Cellular Phone; Central Nervous System Bacterial Infections; Central Nervous System Infections; Cerebrospinal Fluid; Cerebrospinal Fluid Proteins; Cerebrospinal fluid shunts procedure; Child; Childhood; Clinical; Clinical Sensitivity; Companions; Complement; Complement Activation; Complement Membrane Attack Complex; Developing Countries; Development; Diagnosis; Diagnostic; Diagnostic tests; Differential Diagnosis; Ensure; Enzyme-Linked Immunosorbent Assay; Europe; FDA approved; Failure; Glucose; Gold; Guidelines; Health; Health Care Costs; Health Expenditures; Health Personnel; Healthcare; Healthcare Systems; Hospitalization; Hydrocephalus; Imaging Techniques; Individual; Infection; Infiltration; International; Laboratories; Lateral; Leukocytes; Life; Medical; Meningitis; Methods; Morbidity - disease rate; Nervous System Trauma; Neuraxis; North America; Outcome Study; Patient Care; Patient Monitoring; Patients; Phase; Publishing; Reader; Reagent; Research; Resources; Sampling; Secure; Sensitivity and Specificity; Shunt Device; Spinal Puncture; Survivors; Test Result; Testing; Therapeutic; Time; Toxic effect; Training; Treatment Cost; Viral; Work; accurate diagnosis; base; clinical diagnostics; clinical practice; cost; cost effective; design; diagnosis standard; diagnostic assay; follow-up; improved; killings; mortality; nervous system disorder; outcome forecast; pathogen; point of care; point-of-care diagnostics; preclinical evaluation; preclinical study; prevent; prognostic value; rapid diagnosis; standard of care; tool

The objective of this Phase I application is to develop and assess a sMAC lateral flow assay diagnostic tool for bacterial meningitis (BM). Development of rapid, highly sensitive and specific clinical diagnostic for bacterial infections in the central nervous system (CNS), such as BM and shunt infection, that are easy to use and cost-effective, would significantly improve healthcare in the US and worldwide. We have identified the biomarker, soluble membrane attack complex (sMAC), that 1) accurately diagnoses CNS infection, 2) provides prognostic value in follow-up testing, and 3) has potential value in monitoring patients undergoing therapeutic treatment to block complement activation and thus the formation of sMAC. Bacterial infections in the CNS are a life-threatening condition requiring rapid diagnosis and appropriate treatment to reduce morbidity and prevent mortality. Millions of individuals in the North America, Europe and Asia undergo lumbar puncture every year on suspicion of bacterial meningitis. In sub-Saharan Africa, bacterial meningitis is a significant health threat killing tens of thousands annually. The lack of sufficiently trained medical personnel and laboratory resources limits diagnostic capability and corresponding treatment in this region. Additionally, BM frequently occurs in children treated with cerebrospinal fluid (CSF) shunts to manage hydrocephalus. Associated health expenditures are estimated to cost $2 billion per year in the USA, and shunt failure rates remain high as assessed in a recent international study which documented 30 day and 1 year shunt failure rates of 12.9% and 28.8% respectively. Methods to diagnose BM, are time-consuming, not always specific, and can be expensive. Bacterial culturing, the gold standard for diagnosis, has a significant false negative rate (10-20%), while testing for changes in CSF protein, glucose levels, and white blood cell infiltration (WBC) are generally inconclusive. These tests can be augmented with expensive and technical PCR and imaging techniques. Differential diagnosis for meningitis remains challenging despite these advances, and is difficult in resource-poor settings where other neurological diseases can complicate diagnosis. Successful completion of this assay will solve many problems associated with the current gold-standard test by significantly reducing time to test results, increase sensitivity, and reduce clinical lab expenses.

此第一阶段应用程序的目标是开发和评估SMAC横向流动 细菌性脑膜炎(BM)检测诊断工具。快速、高度的发展 中枢神经系统细菌感染的敏感和特异临床诊断 BM和分流感染等易于使用且具有成本效益的系统(CNS)， 将显著改善美国和世界各地的医疗保健。我们已经确定了 生物标志物，可溶性膜攻击复合体(SMAC)，可1)准确诊断 CNS感染，2)在随访测试中提供预后价值，3)有潜力 监测接受补体封闭治疗的患者的价值 激活，从而形成SMAC。 中枢神经系统的细菌感染是一种危及生命的疾病，需要迅速 诊断和适当的治疗，以减少发病率和防止死亡。百万 北美、欧洲和亚洲的个人每年都会接受腰椎穿刺术 一年前因怀疑患有细菌性脑膜炎。在撒哈拉以南非洲，细菌性脑膜炎是一种 严重的健康威胁，每年导致数万人死亡。缺乏受过充分训练的人 医务人员和实验室资源限制了诊断能力和 在这一地区进行相应的治疗。此外，BM经常发生在儿童中 脑脊液分流术治疗脑积水。关联的 据估计，美国每年的医疗支出为20亿美元， 失败率仍然居高不下，正如最近一项国际研究所评估的那样，该研究记录了 术后30天和1年分流失败率分别为12.9%和28.8%。 诊断BM的方法很耗时，并不总是特定的，而且可以 很贵的。细菌培养，诊断的黄金标准，有一个重大的错误 阴性率(10%-20%)，同时检测脑脊液蛋白质、血糖水平和 白细胞渗出(WBC)通常不能确定。这些测试可以是 增加了昂贵和技术性的聚合酶链式反应和成像技术。差动 尽管取得了这些进展，脑膜炎的诊断仍然具有挑战性，而且在 资源匮乏的环境，其他神经疾病可能使诊断复杂化。 这项检测的成功完成将解决许多与 目前的金标准检测通过显著减少检测结果的时间，增加了 敏感度，并降低临床实验室费用。