Project Summary Childhood TB is estimated to contribute 10-15% of the disease burden in high-burden settings, with approx- imately a million cases per year in 2010 worldwide. Existing gold-standard diagnostic culture tools fail to confirm TB in most children, who typically have low bacterial counts and cannot produce sputum. More sensitive and child-friendly diagnostic tools are urgently needed to diagnose TB in children. Chronus Pharmaceuticals pro- poses to develop a robust, minimally invasive, serum-based diagnostic tool that detects active TB in children. Our technology is based on the detection of pathogen modifications of a host lipoprotein MtLDL, using a low cost and easy-to-use antibody diagnostic technology, enzyme-linked immunosorbent assay (ELISA). The ELISA technology format will be commercialized for MtLDL as a test for childhood TB disease to help identify the ap- proximately one million new pediatric cases each year and prevent the more than 100,000 pediatric deaths that occur each year from TB. We will demonstrate that antibody-based detection of MtLDL in patient blood will provide specific detection of TB disease in both HIV+ and HIV- children. Aim 1 focuses on establishing inde- pendence of MtLDL detection from possible interfering substances. Aim 2 is to quantitate patient MtLDL levels that occur with active TB disease. Upon completion of Phase I, we will undertake GMP compliant production of kits for expanded clinical testing to validate the assay. Chronus Pharmaceuticals will utilize an antibody diagnos- tic OEM to produce kits. We will partner with the NIH Clinical trials network researchers (IMPAACT/ACTG) who provided validation samples used in this proposal to distribute and sell diagnostic kits to clinicians in pediatric TB endemic countries.