Since January 1991 we have been using genotyping ot Mycobacterium tuberculosis together with conventional epidemiological approaches to elucidate the distribution and dynamics of tuberculosis in San Francisco. During this time we have refined and validated molecular epidemiological methods and applied these methods in a systematic series of studies that have been used to guide interventions tailored to the prevailing epidemiological circumstances. This study will extend our previous population-based, molecular epidemiologic studies of tuberculosis in support of the broad objective of eliminating tuberculosis in San Francisco that is caused by the transmission of Mycobacterium tuberculosis in San Francisco. This objective can be measured only by long-term application of molecular epidemiological methods. In addition, we propose to contribute to this objective by utilizing our detailed understanding of the dynamics of tuberculosis in San Francisco to examine genetic factors in both host and microbe that are associated with transmission of M. tuberculosis and progression of tuberculosis infection to clinical tuberculosis. In the proposed studies we will be combining state-of-the-art molecular epidemiology with recent advances in molecular biology, genomics, and computational biology in the setting of an effective tuberculosis control program to address some of the major current impediments to the elimination of the disease.
The specific aims have been divided into four closely related components, intended to examine the interrelationships between clinical and epidemiological features of tuberculosis and human host and microbial genetic events in a setting wherein findings can be translated quickly to tuberculosis control efforts.
The specific aims are divided as follows: 1) Identification and evaluation of tuberculosis control strategies; 2) Quantification of exposure and transmission; 3) Identification of host gene expression responses that distinguish susceptible and resistant persons; 4) Identification of mycobacterial factors associated with various outcomes following exposure to infectious tuberculosis. The components of these aims are all related to elucidating the factors related to transmission of M. tuberculosis and directed toward providing the scientific basis for measures designed to prevent transmission.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI034238-13
Application #
6892401
Study Section
Special Emphasis Panel (ZRG1-EDC-3 (01))
Program Officer
Sizemore, Christine F
Project Start
1993-04-01
Project End
2007-08-31
Budget Start
2005-06-01
Budget End
2007-08-31
Support Year
13
Fiscal Year
2005
Total Cost
$1,192,284
Indirect Cost
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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Kato-Maeda, Midori; Shanley, Crystal A; Ackart, David et al. (2012) Beijing sublineages of Mycobacterium tuberculosis differ in pathogenicity in the guinea pig. Clin Vaccine Immunol 19:1227-37

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