Incipient and Subclinical Tuberculosis: a Clinical Review of Early Stages and Progression of Infection

Abstract

Tuberculosis (TB) is the leading infectious cause of mortality worldwide, due in part to a limited understanding of its clinical pathogenic spectrum of infection and disease. Historically, scientific research, diagnostic testing, and drug treatment have focused on addressing one of two disease states: latent TB infection or active TB disease. Recent research has clearly demonstrated that human TB infection, from latent infection to active disease, exists within a continuous spectrum of metabolic bacterial activity and antagonistic immunological responses. This revised understanding leads us to propose two additional clinical states: incipient and subclinical TB. The recognition of incipient and subclinical TB, which helps divide latent and active TB along the clinical disease spectrum, provides opportunities for the development of diagnostic and therapeutic interventions to prevent progression to active TB disease and transmission of TB bacilli. In this report, we review the current understanding of the pathogenesis, immunology, clinical epidemiology, diagnosis, treatment, and prevention of both incipient and subclinical TB, two emerging clinical states of an ancient bacterium.

Keywords: Mycobacterium tuberculosis; tuberculosis.

Copyright © 2018 American Society for Microbiology.

Figures

FIG 1

Pathways of tuberculosis disease progression. After initial exposure, M. tuberculosis may be eliminated by the host immune response, persist as a latent infection, or progress to primary active disease. Following the establishment of latent infection, disease may persist in a latent form, naturally progress in a slow or rapid fashion to active tuberculosis, or cycle through incipient and subclinical states before developing into symptomatic disease or eventual disease resolution. Although not all possibilities for regression of disease burden are depicted, spontaneous recovery may occur in any of these clinical trajectories.

FIG 2

Primary and secondary disease states for the five categorical states of TB. Clinical outcomes following treatment are variable and depend on the respective pathophysiological outcomes. MTB, M. tuberculosis.