Diagnosis of Active Tuberculosis in HIV-infected and Uninfected Young Children in India

Tuberculosis (TB) is the most common cause of morbidity/mortality in HIV-infected individuals in India. India has the world's highest burden of HIV and TB, and since children acquire HIV/TB from their caregivers, active TB is highly prevalent (14-67.5%) among HIV-infected young children in India. Children are a vulnerable population where lack of early detection and prevention of TB often has fatal consequences, and TB Diagnosis is particularly challenging in young children. Due to a similar clinical presentation, active TB cannot be reliably distinguished from HIV (or co-infections). Tuberculin skin test (TST) is often unreliable, and bacterial confirmation (culture), when available, is difficult and does not provide a diagnosis for weeks to months. IFN-gamma-release assays (IGRA) measure T-cells in response to two antigens, ESAT-6 and CFP-10, which are strong targets of T-helper cells that are encoded by Mycobacterium tuberculosis, but not by BCG or most nontuberculous mycobacteria (NTB). IGRAs such as ELISpot are significantly more sensitive/specific than TST for the diagnosis of active TB in young children with high rates of HIV, malnutrition, BCG vaccination and NTB. They are also especially useful for diagnosing extra-pulmonary TB, which is prevalent in young children but often difficult to diagnose, particularly because specimen collection and yield is limited. In collaboration with BJGMC, NARI and the Imperial College of London, we are conducting a prospective observational cohort study to test novel ELISpot assays for the diagnosis of TB in young children (under age 5 years). We are also assessing potentially modifiable risk factors (e.g. Vitamin D and indoor air pollution exposure) along with TB in young children.