Tuberculosis Immunity in Children

Tuberculosis (TB) is the number one cause of infectious morbidity and mortality worldwide accounting for 8 million cases and 3 million deaths annually. The impact of TB on children is particularly devastating in that children are more likely than adults to develop active TB following exposure to the bacterium, M. tuberculosis (Mtb) and once infected, children are much more likely than adults to develop disseminated disease, including miliary disease, bone and joint disease, and meningitis. These clinical differences likely reflect fundamental differences of the immune system of children and adults. The first specific aim of this study is to determine if severity of disease following Mtb infection in young children is associated with TH2-type immunity; and conversely, if absence of disease following Mtb infection is associated with TH1-type immunity by comparison of the magnitude and phenotype of Mtb-specific T cell responses in children less than or equal to 10 years old with: disseminated TB including miliary disease and meningitis; localized disease as defined by disease contained in the thoracic cavity (pulmonary, pleural, and cardiac), extrapulmonary lymph nodes (lymphadenitis), gastrointestinal tract, or bone (osteomyelitis); and latent Mtb infection (LTBI) defined as individuals with a positive Tuberculin Skin Test (TST) and without radiographic or clinical evidence of active tuberculosis. The second specific aim of this study is to determine if immunologic immaturity is associated with the development of TH2-type immunity following Mtb infection, and conversely if immunologic maturity is associated with the development of TH1-type immunity following Mtb infection by characterizing the magnitude and phenotype of Mtb-specific T cell responses in individuals with: localized disease; comparing 0-1 year olds, 2-4 year olds, 5-10 year olds, and adults; and LTBI; comparing 0-1 year olds, 2-4 year olds, 5-10 year olds, and adults. The data obtained from the present study may contribute to an improved understanding of TB immunity in children, which in turn may help in the development of a more effective TB vaccine for infants and young children. The number of participants is estimated to be 260 subjects to be enrolled over the course of 5 years.