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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23HL094141-05
Application #
8451422
Study Section
Special Emphasis Panel (ZHL1-CSR-R (F1))
Program Officer
Colombini-Hatch, Sandra
Project Start
2009-04-09
Project End
2014-03-31
Budget Start
2013-04-01
Budget End
2014-03-31
Support Year
5
Fiscal Year
2013
Total Cost
$152,446
Indirect Cost
$10,196
Name
University of California San Francisco
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
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Cattamanchi, Adithya; Walter, Nicholas D; Metcalfe, John Z et al. (2013) A transcriptional signature for active TB: have we found the needle in the haystack? PLoS Med 10:e1001539
Tapley, Asa; Switz, Neil; Reber, Clay et al. (2013) Mobile digital fluorescence microscopy for diagnosis of tuberculosis. J Clin Microbiol 51:1774-8

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