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

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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.