Sponsor - U.S. National Institutes of Health (HHSN272200900053C)
Principal Investigator - David Lewinsohn, M.D., Oregon Health and Sciences University
ADULT SUB-STUDY: CD8+ T Cell Responses in Latent TB Infection and Pulmonary TB in HIV Infected
and Un-infected Ugandan Adults (AC80)
DMID Protocol Number: 10-0042
|Type of Study||Observational|
|Design||Cross-Sectional w/2 month follow-up|
|Sample Size||385 active TB/HIV-; up to 385 latent TB/HIV-; 55 active TB/HIV+|
|Population||Adults with a culture confirmed , initial case of clinically active tuberculosis or latent TB infection|
|Study Period||September 2011 - 2014|
Detection of novel CD8+ T cell receptors directed towards MTB antigens may distinguish LTBI from pulmonary TB.
- To determine novel epitopes/antigens common and dominant in MTB-infected Uganda adults with LTBI and PTB.
- To determine epitopes/antigens associated specifically with pulmonary TB versus LTBI.
- To determine epitopes/antigens associated with pulmonary TB in HIV infected Uganda adults (CD4 T cell count >150).
PEDIATRIC SUB-STUDY: Novel Cd8+ T Cell Diagnostics For Childhood Tuberculosis (PC08)
DMID Protocol Number: 09-0109
|Type of Study||Observational|
|Sample Size||Proposed 92 subjects with intrathoracic TB HIV uninfected, 18-19 subjects with intrathoracic TB HIV infected and 50 subjects with LRTI not due to TB HIV uninfected, final enrollment was 323|
|Population||Hospitalized Ugandan children greater than 2 months and less than 5 years of age|
|Study Period||Nov 2011 - 2014|
Goal of Study:
Our goal is to answer: Is detection of CD8+ T cells directed towards Mtb proteins can be utilized to distinguish young children with intrathoracic TB from those with pneumonia or lower respiratory infection (LRTI) from etiologies other than TB?
To do this, we have designed a cross sectional, observational study to define the presence and magnitude of a CD8+ T cells responses among these distinct clinical groups (intrathoracic TB vs. pneumonia or LRTI not TB).
Objectives of Study:
- To determine if measurement of CD8+ T cells specific for two-Mtb antigen combinations distinguishes between intrathoracic TB and LRTI not due to TB (LRTInotTB) in children less than 5 years old.
- To determine if measurement of CD8+ T cells specific for three-Mtb antigens distinguishes between intrathoracic TB and LRTInotTB in children less than 5 years old.
- To determine if measurement of CD8+ T cells specific for Mtb antigens distinguishes between intrathoracic TB (HIV infected and uninfected) and LRTInotTB (HIV uninfected) in children less than 5 years old.
Lancioni C, Swarbrick GM, Park B, Nyendak M, Nsereko M, Mayanja-Kizza H, Null MD, Cansler ME, Duncan RB, Baseke J, Chervenak K, Malone L, Heaphy EG, Boom WH, Lewinsohn DM, Lewinsohn DA. Recognition of CD8+ T-cell epitopes to identify adults with pulmonary tuberculosis. Eur Respir J. 2019 May 30;53(5):1802053. doi: 10.1183/13993003.02053-2018. PMID: 30923183; PMCID: PMC7055653.
Lewinsohn DA, Swarbrick GM, Park B, Cansler ME, Null MD, Toren KG, Baseke J, Zalwango S, Mayanja-Kizza H, Malone LL, Nyendak M, Wu G, Guinn K, McWeeney S, Mori T, Chervenak KA, Sherman DR, Boom WH, Lewinsohn DM. Comprehensive definition of human immunodominant CD8 antigens in tuberculosis. NPJ Vaccines. 2017;2:8. doi: 10.1038/s41541-017-0008-6. Epub 2017 Apr 3. PMID: 28775896; PMCID: PMC5538316.