Protection from Mycobacterium tuberculosis infection : learning from exposed but uninfected children

Background: Children are more susceptible than adults to progression from infection to tuberculosis and development of severe forms of disease. However, most children exposed to Mycobacterium tuberculosis are able to effectively control the pathogen without becoming infected. A better understanding of effective paediatric immunity to tuberculosis infection and discovery of correlates of protection could help to develop a novel vaccine as part of the End TB Strategy. Methods: A matched case-control study was conducted in The Gambia recruiting pairs of children with discordant tuberculin skin test infection status but the same sleeping proximity to the same adult with sputum smear positive tuberculosis (Highly Exposed Infected [HEI] and Highly Exposed Uninfected [HEU] children). Whole blood samples were used in a novel assay with an autoluminescent strain of Bacillus Calmette-Guérin (BCG). Serial luminescence measurements were recorded and supernatants from baseline, 24 hours and 96 hours were analysed with a multiplex assay to detect cytokines and targeted mass spectrometry to detect eicosanoids. Results: 29 pairs of HEI and HEU children aged between 5 and 15 years old were enrolled. HEU children had higher ... (continues)