Recently, Behr et al. posit a more nuanced understanding of tuberculosis infection.92 In an analysis of studies spanning 5 decades, they concluded that the majority of TB-immunoreactive individuals have cleared their infection while retaining immunologic memory of it.93 As a result, such patients would not benefit from preventive therapy. Unfortunately, there is no currently available test to identify patients who still harbor viable M. tuberculosis and so would benefit from tuberculosis preventive treatment (see also Chapter 4: Diagnosis of Tuberculosis Infection and Chapter 6: Tuberculosis Preventive Treatment in Adults).
Added to this conceptualization of infection is a more nuanced understanding of disease with 2 additional states of infection: incipient TB (an intermediate state that is likely to progress to active disease but does not cause detectable abnormalities) and a subclinical state of active TB due to viable M. tuberculosis that does not cause clinical TB-related symptoms, but causes other abnormalities that can be detected using radiologic and microbiologic assays.94,95 These newly described states are conceivably determined by the host’s immunological response and the virulence of the pathogen, with the capacity of the host to shift between states. In the future, biomarkers may permit the early diagnosis and treatment of these intermediate states. This more nuanced pathogenesis of infection and disease is summarized in Figure 1.

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