Interferon-Gamma Release Assays in Tuberculosis (TB) - HIV Co-infected Children
Condition: Tuberculosis; HIV
MeSH terms: Tuberculosis
Study type: Observational

Summary: 
      Tuberculosis (TB) is a disease affecting the lungs that is caused by a germ spread by
      coughing. TB infection is currently diagnosed by a skin test that has limited accuracy. The
      purpose of this study is to look at the reliability of a new blood test for diagnosing TB
      infection in children. Study participants will include 300 HIV-infected (HIV infection is a
      viral infection that causes disease which destroys the body's ability to protect itself from
      infection and disease.) children and 500 HIV-uninfected children, ages 3 months to 5 years,
      residing in the Khayelitsha and Ravensmead/Uitsig Communities of the Western Cape Province,
      South Africa. Study procedures will include questionnaires, HIV and TB testing, which will be
      performed by blood and skin tests. Participants may be involved in study related procedures
      for up to 24 months.
    

Detailed description: 
      Although widely used, the tuberculin skin test (TST) has limited diagnostic accuracy for
      Mycobacterium tuberculosis (M. tb) infection. TST sensitivity is particularly limited in
      children with compromised immune status due to HIV (Human Immunodeficiency Virus) infection,
      young age and/or severe malnutrition. Very limited data exists regarding the diagnostic
      utility of Interferon Gamma Release Assays (IGRAs) to detect M. tb infection in children. The
      proposed study will address major gaps in current knowledge regarding the diagnosis of M. tb
      infection in HIV-infected children and may be a powerful tool to spur policy change that
      would dramatically improve health in children in countries endemic for tuberculosis (TB) and
      HIV. The primary objectives of the study will be to assess the agreement between the TST and
      IGRAs in HIV-infected and uninfected children less than or equal to age 5 and to assess the
      performance of TST and IGRAs across a standard gradient of M. tb exposure in HIV-infected and
      uninfected children less than or equal to age 5. The secondary objectives of the study will
      be to measure the impact of potential interaction and confounding variables on the TST and
      IGRAs in HIV-infected and uninfected children less than or equal to age 5 and to identify
      factors that modify children's response to the TST and IGRAs over time. This study is a
      prospective community-based study in a setting highly endemic for HIV and TB, the agreement
      between the TST and IGRAs will be assessed in 800 children, ages 3 months to 5 years, and the
      influence of M. tb exposure, HIV status, cellular immunity, nutritional status and age
      evaluated. Subjects will include HIV-infected (N=300) and uninfected (N=500) children with
      variable degrees of M. tb exposure. The inclusion of children with no known household TB
      contact will result in a measure of background community M. tb exposure in a setting with
      high annual risk of M. tb infection (ARI). Active contact investigation of children exposed
      to newly diagnosed adult TB index cases in the household allows for the creation of a
      standardized M. tb exposure gradient to serve as a surrogate measure of M. tb infection in
      the absence of an existing gold standard. After determination of household membership,
      researchers will administer a standard questionnaire, assess M. tb exposure, TB disease and
      HIV status, collect approximately 6-8 ml of blood for IGRAs, place a TST (after phlebotomy)
      and read the TST at 48-72 hours. In sub-groups of children enrolled during the first 18
      months, the TST, IGRAs and measures of cellular immunity will be repeated at 3, 6, 12 and
      24-months post enrollment. This study has been designed to meet guidelines for complete and
      accurate reporting of studies on diagnostic accuracy. There will be one study site (The
      Desmond Tutu TB Center, Stellenbosch University, Tygerberg, Cape Town, South Africa). Study
      enrollment will occur over 3 years. The expected duration of subject participation will range
      from 2 days to 24 months. The primary (dependent) outcome is M. tb infection as defined by
      TST, T. Spot Tb, and Quantiferon-Gold In-tube (QTF) completed at baseline. The secondary
      (dependent) outcome is M. tb infection as defined by TST, T. Spot Tb, and QTF completed at 3,
      6, 12, and 24 months. The primary independent outcome is M. tb infection as defined by M. tb
      contact score. The secondary independent outcome is HIV status, age, nutritional status, and
      cellular immunity (CD4 count).
    

Intervention name(s): Interferon-Gamma Release Assay; RT-23
Intervention type(s): Procedure; Drug
Intervention description(s): IGRAs; TST - tuberculin skin test
Intervention MeSH terms: Interferons; Interferon-gamma
Observational model: Ecologic or Community
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Study participants will include 300 HIV-infected (HIV infection is a viral infection that
        causes disease which destroys the body's ability to protect itself from infection and
        disease.) children and 500 HIV-uninfected children, ages 3 months to 5 years, residing in
        the Khayelitsha and Ravensmead/Uitsig Communities of the Western Cape Province, South
        Africa.
      
Keywords: Mycobacterium tuberculosis; Tuberculin Test; South Africa