Latent tuberculosis testing through the ages: the search for a sleeping killer

Tuberculosis has been present in the world’s population for as long as there has been written language. It is a disease known to the ancient Egyptians, Greeks, Romans, and Hebrews, but its etiology eluded the world for thousands of years. Even after the germ theory was accepted and early scientists hypothesized a pathogen as the cause, the identity of the sleeping killer in society remained a mystery. That is until Robert Koch was able to grow and visualize Mycobacterium tuberculosis. Koch introduced his Old Tuberculin solution as a diagnostic therapy of tuberculosis (TB), with the intent to reduce the number of infected persons and stop its spread. Old Tuberculin’s ability to treat TB proved minimal, but its diagnostic potential paved the way for more effective tests from von Pirquet, Calmette, Wolff-Eisner, and Mantoux. Florence Seibert set out to identify and purify the active principle in Koch’s Old Tuberculin and ended up creating purified protein derivative (PPD) tuberculin which is still used as the standard for the tuberculin skin test (TST). Interferon-γ release assays (IGRAs) are a more modern diagnostic tool for detecting latent TB infection that offer some benefits (and some disadvantages) to TST. TSTs and IGRAs can determine if an individual has been infected with M. tuberculosis but are equally unable to predict progression to active tuberculosis, the diagnosis of which relies on assessment of clinical symptoms, radiographic imaging, and sample culture.