Subclinical tuberculosis: a paradigm shift from a binary to a continuous disease spectrum

Progress in tuberculosis (TB) control has long been constrained by a limited understanding of the continuous disease spectrum. Traditionally, TB has been simplistically dichotomized into latent infection and active disease; however, recent research has provided compelling evidence that the disease actually constitutes a spectrum encompassing continuous changes in bacterial metabolic activity and host immune responses, thereby establishing subclinical tuberculosis as a crucial clinical state within this continuum. Subclinical TB is characterized by the absence of typical clinical symptoms but the presence of bacteriological or radiological evidence, accounting for 36–80% of bacteriologically confirmed TB cases and constituting a substantial hidden reservoir of disease. Critically, this population has been shown to pose a potential transmission risk, with modeling studies indicating that subclinical disease could be a major driver of ongoing Mycobacterium tuberculosis spread, thereby fundamentally challenging traditional control strategies reliant on passive case detection. Given its concealed nature and the low sensitivity of conventional diagnostic methods, the prevention and management of subclinical TB present immense challenges. Consequently, elucidating its immunopathological mechanisms, developing novel diagnostic approaches, and identifying new therapeutic targets have become paramount. This review aims to systematically outline the current landscape and challenges of subclinical TB, providing a comprehensive exposition of its pathogenesis, immunological features, epidemiology, diagnosis, and control strategies, with the goal of offering key insights to advance scientific progress and innovate control policies in this field.