Incipient tuberculosis: a comprehensive overview

Abstract

In the context of the evolving global health landscape shaped by the COVID-19 pandemic, tuberculosis (TB) is gaining renewed attention as a reemerging threat even in low-endemic countries. Immunological tests such as the tuberculin skin test (TST) and interferon-gamma release assay (IGRA) are pivotal in identifying tuberculosis infection (TBI). However, their inability to distinguish between past and ongoing infection poses a diagnostic challenge, possibly leading to the unnecessary treatment of a significant portion of the population with potential side effects. This review delves into the concept of incipient tuberculosis (ITB), a dynamic, presymptomatic stage characterized by heightened Mycobacterium tuberculosis complex (MTC) metabolic activity and replication that result in minimal radiological changes, signifying a transitional state between TBI and TB. Key focus areas include epidemiological factors, underlying pathogenesis, imaging findings, and the ongoing challenges in the identification of individuals with ITB through the development of new biomarkers and the use of whole-genome sequencing-based analyses to implement early treatment strategies.

Keywords: Incipient tuberculosis; Tuberculosis; Tuberculosis infection.

Fig. 1

Proposed algorithm in asymptomatic patients with immunoreactivity against M. tuberculosis complex (MTC) demonstrated trough tuberculin skin test (TST) or interferon-gamma release assay (IGRA). BALF bronchoalveolar lavage fluid, PET positron emission tomography. *Traces of the MTC genome detectable by high-throughput techniques on blood samples, details in the text. ^§Consider PET for monitoring response to treatment in patients with incipient tuberculosis (ITB), details in the text.