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Adaptive Immunity to Mtb

Adaptive Immunity to Mtb-infection and TB Disease Among Young Ugandan Children (PA21)

Information:

Sponsor - U. S. National Institutes of Health
Principal Investigators – Christine Lancioni, MD, OHSU; Catherine Stein, PhD, CWRU; Ezekiel Mupere, MBChB, PhD, Uganda-CWRU Research Collaboration

Gutierrez J, Malone LL, Mohammadi M, Mukisa J, Atuhairwe M, Mwesigwa SPG, Athieno S, Buwule S, Ameda F, Kiyingi S, Mupere E, Stein CM, Lancioni CL. Immune-sensitization to Mycobacterium tuberculosis Among Young Children With and Without Tuberculosis. medRxiv [Preprint]. 2025 Jan 17:2025.01.16.25320625. doi: 10.1101/2025.01.16.25320625. PMID: 39867405; PMCID: PMC11759604.

Morrow E, Liu Q, Kiguli S, Swarbrick G, Nsereko M, Null MD, Cansler M, Mayanja-Kizza H, Boom WH, Chheng P, Nyendak MR, Lewinsohn DM, Lewinsohn DA, Lancioni CL. Production of Proinflammatory Cytokines by CD4+ and CD8+ T Cells in Response to Mycobacterial Antigens among Children and Adults with Tuberculosis. Pathogens. 2023 Nov 14;12(11):1353. doi: 10.3390/pathogens12111353. PMID: 38003817; PMCID: PMC10675744

 

Type of Study Non-Interventional, Prospective Observational Study Household Contact
Design Household Contact
Project Site Kampala, Uganda
Population  
Sample Size 300 children less than 5 years old (less than 60 months) who are household contacts of an index case with active TB

Children will be grouped into two baseline cohorts:

Cohort 1:Asymptomatic, TB exposed and no signs and symptoms of Active TB PedAS)

Cohort2: Signs and symptoms of Active TB and/or diagnosed with TB Disease (PedTB)
Study Period

2021 - Present

Overall study duration:

It may take up to 4 years to enroll cohorts

Follow up duration:

Household Contacts without active TB: 12 Months

Household Contacts with active TB: 12 months

Goal of Study:

The goal of this study is to define the spectrum of adaptive immune responses to primary MTB exposure, and create immune biosignatures that reflect pediatric TB disease, and asymptomatic MTB-exposure with and without evidence of immune sensitization.  This study will also determine if HIV-exposure or infection impact a young child’s MTB-specific immune response.

Objectives of Study:

  1. To recruit Ugandan children 5 years and younger (60 months), with and without perinatal HIV-exposure and/or infection, who are household contacts of an adult

  2. To identify immunologic phenotypes that correlate with TB disease, versus >remaining asymptomatic following TB household contact, in young children with and without perinatal HIV-exposure and/or infection

  3. To determine if MTB-specific T cell and/or antibody profiles can be used to distinguish TB disease from asymptomatic MTB infection, in young children with and without perinatal HIV-exposure and/or infection

  4. To determine how perinatal HIV exposure/infection alters MTB-specific adaptive immune profiles

 

Research Activities:

Immunology