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Task Order 2: Prospective Evaluation of immunogenetic and immunologic markers for susceptibility to M. tuberculosis infection and progression from M. tuberculosis infection to active TB

Task order 2 assesses human immunologic and genetic factors that may predispose persons to getting infected with M. tuberculosis if exposed and developing active TB disease if infected. In an effort to identify risk factors for Mycobacterium tuberculosis transmission from cases to contacts in various settings, the study also seeks to determine the characteristics of adults with active culture-positive pulmonary tuberculosis, their contacts, the environment in which contact occurred, and the organisms associated with defined rates of M. tuberculosis transmission.


American Lung Association of Metropolitan Chicago, Arkansas Department of Health, University of British Columbia, Charles Felton National Tuberculosis Center, Denver Department of Health and Hospitals, Emory University, University of Manitoba, Maryland Department of Health and Mental Hygiene, Mississippi State Department of Health, New Jersey Department of Health, and Tennessee Department of Health/Vanderbilt University.

Study Objectives

  1. Identify risk factors (case, contact, environmental, and organism-specific) for transmission of Mycobacterium tuberculosis from cases to contacts.
  2. Utilize data from this study to better define the following aspects of contact investigation:
    1. Extent of contact investigation needed in various settings;
    2. Extent of M. tuberculosis transmission for smear-positive vs. smear-negative TB cases;
    3. When and how to prioritize contact investigations;
    4. Which risk factor data should routinely be collected from cases;
    5. Time period of case infectiousness relative to specific symptoms;
    6. Which risk factor and exposure data should routinely be collected from contacts;
    7. Extent of M. tuberculosis transmission in various environments; and
    8. Which environmental data should routinely be collected during contact investigations
  3. Identify surrogate immunologic markers for protective immunity to Mycobacterium tuberculosis.
  4. Identify genetic determinants of susceptibility to tuberculosis infection and disease.

Study design

Incident cases of culture-positive pulmonary tuberculosis among persons 15 years of age and older reported from April 1, 1999 - April 1, 2000 (enrollment went through December 31, 2006) and all identified contacts of these cases were included. The prospective study involved case interviews, contact tuberculin skin test (TST) screening and interviews, laboratory record review, and data abstraction from medical records. Infected contacts were offered preventive therapy according to CDC recommendations. All identified contacts will be cross-matched with state TB registries at the end of study enrollment, one year after the end of enrollment, and two years after the end of enrollment to determine the proportion of patients who developed active TB subsequent to initial investigation. HIV testing was offered to all cases and contacts at the time of enrollment so that HIV status could be factored into decisions regarding anti-tuberculous therapy for cases and preventive therapy for contacts, and in order to stratify by HIV status when evaluating risk factors for TB infection and progression to TB disease among contacts. All cases and contacts will also be cross-matched to state HARS registries.

Study progress

Primary data collection is complete and analysis underway. Some secondary data collection is still ongoing.

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