TB Immunity in Children


Sponsor \x96 U.S. National Institutes of Health (R01-AI48090)
Principal Investigator - Deborah Lewinsohn, M.D., Oregon Health and Science University

Type of Study Observational Study
Design Cross-Sectional
Project Site Uganda
Sample Size 385 subjects
Population Children < 11 years old, HIV infected/uninfected, with suspected active tuberculosis
Study Period July 2007-November 2009
Interactions Collaborating investigators and staff, utilizing shared project management infrastructure, utilizing shared JCRC laboratory infrastructure

Goal of Study:

Children are more likely than adults to develop active TB following exposure to M. tuberculosis (Mtb). Children are also much more likely than adults to develop severe disease, including disseminated/miliary disease and meningitis, which are associated with significant morbidity and mortality. These clinical differences may represent differences between the immune system of children and adults. Young children are thought to be deficient in their ability to generate the TH1 cell responses necessary to contain Mtb infection. Also, HIV-coinfection in children may promote TH2 cell immunity, which is non-protective for Mtb infection. The central hypothesis is that young children who develop disseminated disease and/or who are HIV co-infected develop excessive Mtb-specific TH2 cell and deficient Mtb-specific TH1 cell immunity compared to and young children with localized disease or healthy children.

Objectives of Study:

  1. To compare the magnitude and phenotype of Mtb-specific CD4+ TH1 and TH2 cell and CD8+ T cell responses in children < 11 years old with disseminated TB disease (including miliary disease and meningitis) to children with localized disease (including disease contained in pulmonary, pleural, cardiac cavities, extrapulmonary lymph nodes, gastrointestinal tract or bone), and healthy child household contacts of adults with infectious pulmonary TB in the Kawempe community
  2. To characterize the magnitude and phenotype of Mtb-specific T cell immunity in children with localized disease by comparing < 2 year olds, 2-5 year olds, and 5-10 year olds
  3. To compare the magnitude and phenotype of Mtb-specific CD4+ TH1 and TH2 cell and CD8+ T cell responses in HIV-infected children ≤ 10 years old with TB to those without HIV co-infection

The results of this completed study can be found in:

Lancioni C, Nyendak M, Kiguli S, Zalwango S, Mori T, Mayanja-Kizza H, Balyejusa S, Null M, Baseke J, Mulindwa D, Byrd L, Swarbrick G, Scott C, Johnson DF, Malone L, Mudido-Musoke P, Boom WH, Lewinsohn DM, Lewinsohn DA; for the Tuberculosis Research Unit. CD8+ T Cells Provide an Immunologic Signature of Tuberculosis in Young Children. Am J Respir Crit Care Med. 2012; 185:206-212.