Researchers at the University of Cape Town in South Africa have identified a sequence of biological processes that occur as tuberculosis infection progresses to active pulmonary tuberculosis disease. The findings, which demonstrate a clear timeline of biological events that occur between infection and disease, hold important implications for the development of new diagnostics, treatments, and vaccines.
In the longitudinal study, published in PLOS Pathogens Journal, researchers followed 150 adolescents infected with latent TB for several years, and found that while 106 adolescents remained healthy, 44 developed active tuberculosis disease. After comparing immune activity between those who developed active disease and those who remained healthy, they found several key differences, some detectable as early as one to two years before diagnosis, while most were detectable right before active disease began.
Researchers found that 18 months before diagnosis, participants who developed active disease had elevated activity of interferons — immune system signaling molecules which aid in fighting infection. Closer to diagnosis, they found additional immune changes, including increased activity of white blood cells. They also found that certain genes associated with white blood cell response were suppressed in participants who went on to develop active disease, but not in those who remained healthy.
“These data suggest that TB progression is a slow but steady transition from an immunologically quiescent state…to the highly inflammatory, clinical manifestations (fever, cough, hemoptysis and weight loss) of microbiologically confirmed, active TB disease,” study authors noted.
Study authors note the findings highlight the importance of developing new vaccination and drug treatment strategies to prevent the progression from latent to active TB infection.