Airborne pathogens form an interesting group of microbes, able to successfully disseminate, cause infection and disease. The proposed project will examine the mycobacterial factors associated with the transmission of Mycobacterium tuberculosis, one of the most important bacterial pathogens of humans. The continuing burden of M. tuberculosis infection and disease is a major public health concern, heightened by reports of drug-resistant strains and the interaction between M. tuberculosis and the human immunodecificiency virus (HIV). We will blend tools and methods from epidemiology, microbial pathogenesis and genomics in our research plan to generate new knowledge about the transmission of this important airborne pathogen. Cross-sectional and prospective cohort epidemiologic studies will be used to collect data and specimens from TB cases and their contacts. Using a combination of established microbiologic methods (sputum smear exams, culture, drug susceptibility testing, TST) and novel technologies (a cough aerosol sampling system and microarrays), we will identify the factors associated with the phenotypes of transmission and aerosolization. Using comparative genomic studies, we expect to identify specific genotypic markers correlated with these two important phenotypes. The field research will be performed at an established research site in Orizaba, Mexico, within a framework that promotes exchange of personnel and technology. Because the disease burden and applied research opportunities are in under-resourced countries, it is appropriate that the research be conducted there. We will use comparative genomic techniques developed at Stanford University to ascertain the genetic content of specific, well-characterized clones identified from the field site. Finally, we use statistical techniques and analyses to correlate specific genotypes with the observed phenotypes. We will perform a series of genomic analyses to address the question of whether all clones of M tuberculosis aerosolize equally and infection is purely opportunisitic (defined by host and environmental factors), or whether infection and disease are primarily caused by a subset of particularly aerosolizable and transmissible genotypes, unrepresentative of the population of clones as a whole. ? ?

Agency
National Institute of Health (NIH)
Institute
Fogarty International Center (FIC)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
5K01TW000001-05
Application #
6663780
Study Section
Microbiology and Infectious Diseases B Subcommittee (MID)
Program Officer
Jessup, Christine
Project Start
1999-09-30
Project End
2005-08-31
Budget Start
2003-09-01
Budget End
2004-08-31
Support Year
5
Fiscal Year
2003
Total Cost
$114,180
Indirect Cost
Name
Stanford University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305
Torres, Martha; García-García, Lourdes; Cruz-Hervert, Pablo et al. (2015) Effect of isoniazid on antigen-specific interferon-? secretion in latent tuberculosis. Eur Respir J 45:473-82
Bastos, Mayara L; Hussain, Hamidah; Weyer, Karin et al. (2014) Treatment outcomes of patients with multidrug-resistant and extensively drug-resistant tuberculosis according to drug susceptibility testing to first- and second-line drugs: an individual patient data meta-analysis. Clin Infect Dis 59:1364-74
Bonacci, Robert A; Cruz-Hervert, Luis Pablo; García-García, Lourdes et al. (2013) Impact of cigarette smoking on rates and clinical prognosis of pulmonary tuberculosis in Southern Mexico. J Infect 66:303-12
Migliori, G B; Sotgiu, G; Gandhi, N R et al. (2013) Drug resistance beyond extensively drug-resistant tuberculosis: individual patient data meta-analysis. Eur Respir J 42:169-179
Falzon, Dennis; Gandhi, Neel; Migliori, Giovanni B et al. (2013) Resistance to fluoroquinolones and second-line injectable drugs: impact on multidrug-resistant TB outcomes. Eur Respir J 42:156-68
Sullivan, Timothy; Ben Amor, Yanis (2013) What's in a name? The future of drug-resistant tuberculosis classification. Lancet Infect Dis 13:373-6
Jiménez-Corona, María Eugenia; Cruz-Hervert, Luis Pablo; García-García, Lourdes et al. (2013) Association of diabetes and tuberculosis: impact on treatment and post-treatment outcomes. Thorax 68:214-20
Ahuja, Shama D; Ashkin, David; Avendano, Monika et al. (2012) Multidrug resistant pulmonary tuberculosis treatment regimens and patient outcomes: an individual patient data meta-analysis of 9,153 patients. PLoS Med 9:e1001300
Cruz-Hervert, Luis Pablo; Garcia-Garcia, Lourdes; Ferreyra-Reyes, Leticia et al. (2012) Tuberculosis in ageing: high rates, complex diagnosis and poor clinical outcomes. Age Ageing 41:488-95
Marquina-Castillo, Brenda; García-García, Lourdes; Ponce-de-León, Alfredo et al. (2009) Virulence, immunopathology and transmissibility of selected strains of Mycobacterium tuberculosis in a murine model. Immunology 128:123-33

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