This is an application for a K23 award for Dr. Adithya Cattamanchi, a pulmonologist at the University of California, San Francisco. This K23 award will provide Dr. Cattamanchi with the support necessary to accomplish the following goals: (1) to develop an indepenent patient-centered translational research career focused on tuberculosis (TB);(2) to conduct clinical investigations of immunodiagnostic tests for TB in an international setting;(3) to implement advanced biostatistical methods in clinical studies;and (4) to develop theoretical and practical skills in applied T-cell immunology. To achieve these goals, Dr. Cattamanchi has assembled a mentoring team comprised of a primary mentor, Dr. Phillip Hopewell, a leading expert in translational TB research, and three co-mentors: Dr. Laurence Huang, who conducts clinical investigations of the pulmonary complications of HIV;Dr. Dennis Osmond, an expert in study design and current state-of-theart biostatistical analysis;and Dr. Huyen Cao, an expert in applied T-cell immunology. Dr. Cattamanchi's research will focus on a lung-based approach to immunodiagnosis of active TB. The proposed research will expand on recent data suggesting that (1) local rather than peripheral T-cell cytokine responses can better discriminate active TB from both LTBI and other respiratory infections and (2) T-cell cytokine responses may be useful in monitoring response to TB treatment. The proposed study will enroll a large cohort of HIV-infected pulmonary TB suspects to address the following specific aims: (1) To compare the performance of local and peripheral T-cell interferon-gamma release assay responses for the diagnosis of pulmonary TB in HIV-infected patients with negative sputum smear microscopy and (2) To define the M. TB-specific T-cell cytokine profile during the course of TB treatment in HIV-infected patients with active pulmonary TB. The participants will be drawn from a separate, NHLBI-funded study of the causes of pneumonia in HIV-infected patients in Kampala, Uganda. Peripheral blood, BAL fluid, and oral wash specimens will be used to measure T-cell cytokine responses and stored for future immunologic analyses. This proposal is consistent with the NHLBI's mission to study pulmonary immune responses in HIVassociated pulmonary infections. The study may lead to new and improved approaches to diagnosing and treating active TB in sub-Saharan Africa and other parts of the world.
The study may lead to new and improved approaches to diagnosing and treating active TB in sub-Saharan Africa and other parts of the world. The study may also help identify new markers to predict response to TB therapy. This may help accelerate evaluation of new drugs, making them available at the bedside where they are urgently needed.
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|Blount, Robert J; Tran, Minh-Chi; Everett, Charles K et al. (2016) Tuberculosis progression rates in U.S. Immigrants following screening with interferon-gamma release assays. BMC Public Health 16:875|
|Katagira, Winceslaus; Walter, Nicholas D; Den Boon, Saskia et al. (2016) Empiric TB Treatment of Severely Ill Patients With HIV and Presumed Pulmonary TB Improves Survival. J Acquir Immune Defic Syndr 72:297-303|
|Cattamanchi, Adithya; Miller, Cecily R; Tapley, Asa et al. (2015) Health worker perspectives on barriers to delivery of routine tuberculosis diagnostic evaluation services in Uganda: a qualitative study to guide clinic-based interventions. BMC Health Serv Res 15:10|
|Walter, Nicholas D; Dolganov, Gregory M; Garcia, Benjamin J et al. (2015) Transcriptional Adaptation of Drug-tolerant Mycobacterium tuberculosis During Treatment of Human Tuberculosis. J Infect Dis 212:990-8|
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|Tagmouti, Saloua; Slater, Madeline; Benedetti, Andrea et al. (2014) Reproducibility of interferon gamma (IFN-?) release Assays. A systematic review. Ann Am Thorac Soc 11:1267-76|
|Marquez, Carina; Davis, J Lucian; Katamba, Achilles et al. (2014) Assessing the quality of tuberculosis evaluation for children with prolonged cough presenting to routine community health care settings in rural Uganda. PLoS One 9:e105935|
|Chaisson, Lelia H; Roemer, Marguerite; Cantu, David et al. (2014) Impact of GeneXpert MTB/RIF assay on triage of respiratory isolation rooms for inpatients with presumed tuberculosis: a hypothetical trial. Clin Infect Dis 59:1353-60|
|Pai, Madhukar; Denkinger, Claudia M; Kik, Sandra V et al. (2014) Gamma interferon release assays for detection of Mycobacterium tuberculosis infection. Clin Microbiol Rev 27:3-20|
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