In 1890, at a World Congress of Medicine in Berlin, Robert Koch announced a substance that he claimed would both cure and prevent tuberculosis. Although this substance, a glycerin extract of tubercle bacilli, subsequently failed as a therapy, it has become an important diagnostic tool for tuberculosis. Referred to eventually as “old tuberculin”, this tubercle protein soup was later refined to create the current diagnostic material we now know as purified protein derivative or PPD.

Over the last century, the tuberculin skin test (TST) has become the established screening method for diagnosing latent TB infection (LTBI) in adults and children. The TST exploits the fact that LTBI induces a strong cell-mediated immune response to intradermal inoculation of tuberculin PPD, a crude mixture of >200 Mycobacterium tuberculosis proteins. However, the TST suffers from poor specificity (false positive tests due to prior BCG vaccination or previous exposure to environmental mycobacteria) and poor sensitivity (false negative tests particularly in children and immunocompromised individuals). Furthermore, the TST does not differentiate active disease from LTBI, so additional microbiological, radiological and molecular investigations are used to establish a diagnosis of TB disease. The diagnosis of active disease in children remains difficult with much lower “culture confirmed” disease than in adults. However, in children up to 50% of infants and 15% of older children with LTBI who do not receive chemoprophylaxis, will develop disease within 2 years of being infected, highlighting the importance of identifying children through contact tracing. …