Incipient and subclinical tuberculosis: defining early disease states in the context of host immune response

Abstract

Latent Mycobacterium tuberculosis infection (LTBI) and active tuberculosis (TB) are 2 ends of a spectrum of states ranging from asymptomatic infection to overt disease. While progressing from LTBI to TB, patients often undergo asymptomatic states with detectable manifestations indicative of disease. Such asymptomatic disease states frequently remain undiagnosed, and their manifestations and duration are mostly dependent on host immune response. Various terms referring to such states are used in the literature, often interchangeably and without explicit definitions. Defining these intermediate states in concrete terms is important for pragmatic reasons, as they might impact upon the diagnostic performance of TB biomarkers and could also present targets for therapeutic interventions. We here propose definitions for 2 commonly used terms, "incipient" and "subclinical" TB, to describe asymptomatic disease states occurring at opposite ends of the host response spectrum. We propose using the term "incipient TB" when referring to early, contained disease in asymptomatic, relatively immunocompetent persons. In contrast, we propose using the term "subclinical TB" to refer to disease in asymptomatic, immunocompromised individuals in whom it is largely associated with loss of effective containment. The rationale for this article is to facilitate the discussion of such early disease states, especially in relation to their impact on TB biomarker discovery and assessment of new diagnostics, and with regard to treatment decisions and ultimately outcome.

Figure 1.

A, Adaptation from Casadevall and Pirofski [8] reflecting the damage-response framework of microbial pathogenesis; B, Conceptual view of early TB disease states based on host response