An international team of researchers has defined the series of immune system changes that occur when tuberculosis (TB) transitions from a non-infectious state to active disease. The results, published online in PLOS pathogens, highlight changes in inflammatory processes that can be detected in the blood long before clinical symptoms arise. These findings have important implications for developing diagnostics, vaccines and treatments to battle the TB epidemic.

An estimated 1.7 billion people—one quarter of the world’s population—are infected with the bacterium that causes TB, but only ~10% develop active pulmonary disease. In the article, scientists from the South African TB Vaccine Initiative, the University of Cape Town, the Center for Infectious Disease Research and SomaLogic looked for changes in various molecules in blood that together could predict the risk of TB progression. The time between the initial blood collection and TB diagnosis ranged from 1 to 894 days, so the investigators could construct a timeline of changes that occurred as the disease evolved.

The blood analyses revealed that TB progression associated with sequential modifications of immunological processes. Some of these processes, such as type I/II interferon signaling and complement cascade, were elevated as early as 18 months before TB diagnosis.

Understanding the biology of progression from infection to active pulmonary TB opens the door to blood-based tests that may determine those who are at risk of developing active disease and who need early treatment. These findings could also help development of better vaccines and host-directed therapies that accelerate eradication of TB infection.

Ref: Scriba, TJ et al. (2017) “Sequential inflammatory processes define human progression from M. tuberculosis infection to tuberculosis disease”PLOS Pathogens 13(11): e1006687.