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

第一阶段应用的目的是开发和评估sMAC横向流 细菌性脑膜炎（BM）的检测诊断工具。发展迅速， 中枢神经系统细菌感染的敏感性和特异性临床诊断 系统（CNS），如BM和分流感染，易于使用且具有成本效益， 将大大改善美国和全球的医疗保健。我们已经确定了 生物标志物，可溶性膜攻击复合物（sMAC），1）准确诊断 CNS感染，2）在随访检测中提供预后价值，3）具有潜在的 监测接受治疗性治疗以阻断补体的患者的价值 激活，从而形成sMAC。 CNS中的细菌感染是一种危及生命的疾病，需要快速治疗。 诊断和适当的治疗，以减少发病率和防止死亡。数百万 在北美、欧洲和亚洲， 一年后，怀疑细菌性脑膜炎。在撒哈拉以南非洲，细菌性脑膜炎是一种 严重的健康威胁，每年造成数万人死亡。缺乏训练有素的 医务人员和实验室资源限制了诊断能力， 该地区的相应待遇。此外，BM经常发生在儿童中 采用脑脊液（CSF）分流术治疗脑积水。关联 据估计，美国每年的卫生支出为20亿美元， 根据最近一项国际研究的评估，失败率仍然很高， 30天和1年分流失败率分别为12.9%和28.8%。 诊断BM的方法是耗时的，不总是特异性的， 贵了细菌培养是诊断的金标准， 阴性率（10-20%），同时检测CSF蛋白、葡萄糖水平和 白色血细胞浸润（WBC）通常不确定。这些测试可 增加了昂贵的技术PCR和成像技术。微分 尽管取得了这些进展，但脑膜炎的诊断仍然具有挑战性， 其他神经系统疾病可能使诊断复杂化的资源贫乏环境。 成功完成该测定将解决与该方法相关的许多问题。 目前的金标准测试，大大减少测试结果的时间，增加 灵敏度，并降低临床实验室费用。

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.