To devise more effective means to reduce spread of tuberculosis (TB) in the U.S., it is critical to understand the transmission dynamics of drug-resistant and drug-susceptible TB in different socioeconomic settings, including small cities, rural areas and locations where foreign-born persons enter the U.S. To address these issues, the investigators propose a population-based molecular epidemiologic study of TB along the U.S.-Mexico border. They hypothesize that: (1) the transmission dynamics of TB in small cities and rural areas differ from those in large cities; (2) Prospective use of molecular epidemiology will delineate the transmission dynamics of drug- susceptible and drug-resistant TB; (3) A rapid method of RFLP analysis of M. tb isolates will enhance timely detection of TB outbreaks.
Our specific aims are-1. To determine the nature of epidemiologic links between patients who are infected with the same M. tb strain, and to identify locations and settings where TB is transmitted, including an analysis of transmission across the U.S.-Mexico border. This will be achieved by correlating detailed clinical and epidemiologic data on TB patients with results of RFLP analysis of M. tb isolates. 2. To characterize the development and transmission dynamics of drug- resistant TB, including comparison of the transmission potential of M. tb isolates with or without katG mutations. This will be achieved by evaluation of drug susceptibility patterns, clinical and epidemiologic data, RFLP results and sequencing of the katG gene. 3. To evaluate the utility of spoligotyping, a rapid method of RFLP analysis, to identify unsuspected TB outbreaks and guide public health interventions to reduce TB transmission. Spoligotyping will be adapted for use in clinical samples and early mycobacterial cultures, then prospectively applied to all M. tb isolates. This study will provide insight into the transmission dynamics of TB in mixed urban/rural areas. It will evaluate the relationship between katG mutations and transmission potential, providing clues to the mechanisms underlying mycobacterial virulence. Finally, it will determine if rapid RFLP methods can contribute to TB control efforts. The knowledge gained will permit refinement of TB control strategies along the U.S.-Mexico border and in Latin America.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI044935-04
Application #
6653097
Study Section
Bacteriology and Mycology Subcommittee 2 (BM)
Program Officer
Sizemore, Christine F
Project Start
2000-09-15
Project End
2005-05-31
Budget Start
2003-06-01
Budget End
2004-05-31
Support Year
4
Fiscal Year
2003
Total Cost
$244,933
Indirect Cost
Name
University of Texas Health Center at Tyler
Department
Anatomy/Cell Biology
Type
Other Domestic Higher Education
DUNS #
800772337
City
Tyler
State
TX
Country
United States
Zip Code
75708
Wu, Shiping; Barnes, Peter F; Samten, Buka et al. (2009) Activation of the eis gene in a W-Beijing strain of Mycobacterium tuberculosis correlates with increased SigA levels and enhanced intracellular growth. Microbiology 155:1272-81
Garg, Ankita; Barnes, Peter F; Porgador, Angel et al. (2006) Vimentin expressed on Mycobacterium tuberculosis-infected human monocytes is involved in binding to the NKp46 receptor. J Immunol 177:6192-8
Shams, Homayoun; Weis, Stephen E; Klucar, Peter et al. (2005) Enzyme-linked immunospot and tuberculin skin testing to detect latent tuberculosis infection. Am J Respir Crit Care Med 172:1161-8
Samten, Buka; Howard, Susan T; Weis, Steven E et al. (2005) Cyclic AMP response element-binding protein positively regulates production of IFN-gamma by T cells in response to a microbial pathogen. J Immunol 174:6357-63
Vankayalapati, Ramakrishna; Garg, Ankita; Porgador, Angel et al. (2005) Role of NK cell-activating receptors and their ligands in the lysis of mononuclear phagocytes infected with an intracellular bacterium. J Immunol 175:4611-7
Shams, Homayoun; Klucar, Peter; Weis, Steven E et al. (2004) Characterization of a Mycobacterium tuberculosis peptide that is recognized by human CD4+ and CD8+ T cells in the context of multiple HLA alleles. J Immunol 173:1966-77
Safi, Hassan; Barnes, Peter F; Lakey, David L et al. (2004) IS6110 functions as a mobile, monocyte-activated promoter in Mycobacterium tuberculosis. Mol Microbiol 52:999-1012
Vankayalapati, Ramakrishna; Klucar, Peter; Wizel, Benjamin et al. (2004) NK cells regulate CD8+ T cell effector function in response to an intracellular pathogen. J Immunol 172:130-7
Wu, Shiping; Howard, Susan T; Lakey, David L et al. (2004) The principal sigma factor sigA mediates enhanced growth of Mycobacterium tuberculosis in vivo. Mol Microbiol 51:1551-62
Safi, Hassan; Gormus, Bobby J; Didier, Peter J et al. (2003) Spectrum of manifestations of Mycobacterium tuberculosis infection in primates infected with SIV. AIDS Res Hum Retroviruses 19:585-95

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