Figure 1.

The spectrum of outcomes in human tuberculosis (TB) is heterogenous. Classical clinical states are defines by the presence of detectable bacteria and host response to Mycobacterium tuberculosis antigens by interferon γ release assay (IGRA), with uninfected having neither, latent TB infection having a positive IGRA but no detectable bacteria and active TB disease diagnosed by the capture of Mtb by growth in culture, nucleic acid amplification or cell wall stain. The transition between these states is fluid and poorly captured by these criteria: a. Individuals who have received antibiotic therapy for latent TB infection cannot be differentiated from those who are treatment naïve. b. Individuals who progress subclinically from latent infection to active disease (5-10%) and those who regress or remain asymptomatic (>90%) are indistinguishable. c. After successful treatment with antibiotics for active TB disease, individuals no longer have detectable bacteria as captured by standard assays but may have residual positive IGRA. Moreover, emerging epidemiological and immune correlates data suggest that beyond these classical states, there are groups who are highly exposed to Mtb who potentially represent an alternative state to latent TB infection not yet clearly defined.