The development of new diagnostic tools and more effective vaccines are essential to combat the global tuberculosis (TB) pandemic. The lack of a widely accessible screening test that is easy to perform without laboratory facilities is one of the main reas ons for the unacceptable delay in diagnosing pulmonary TB. The goal of this project is to develop, evaluate and validate a rapid, sensitive and inexpensive serological test for the detection of TB disease that is suitable for use in the developing world. It is crucial that a screening test detects only active disease because latent TB is prevalent, but not a target for treatment, in developing countries. Recent advances in proteomics and genomics make it possible to investigate a large repertoire of M. tuberculosis proteins for their ability to serve as diagnostic markers. Comparison of antigens recognized by antibodies from patients and community controls recruited from TB endemic regions will enable the identification of appropriate antigens that can be used to differentiate between active and latent infection. After demonstrating proof-of-principle the prototype ELISA assay will be transferred to a rapid assay platform and evaluated in the field by collaborative partners in settings with different TB epidemiology. A rapid screening test will make it possible to identify and selectively treat those with active TB disease at the local health care level thus reducing diagnostic delay and transmission. In addition, the test will be designed to differ entiate between TB and vaccine-induced immunity. Accurate diagnostic tools suitable for use in the developing world are essential for monitoring the efficacy of new candidate TB vaccines. The collaborative network and administrative structure of this proj ect are designed to achieve ideal cross-institutional interactions between Western and developing countries, technology transfer, decentralization and increasing local capacity to curb TB in endemic regions.