One of the major challenges in tuberculosis (TB) management is to identify the different stages of Mycobacterium tuberculosis (Mtb) infection. Although a quarter of the global population is estimated to be Mtb infected, only 5-10% are estimated to progress through incipient and subclinical TB to active TB. Notably, fluctuations in immunopathology and symptoms in favour of the host, or the microbe, occurs along a continuum. Traditionally, differentiation between latent Mtb infection (LTBI) and active TB (ATB) has been emphasized due to differences in transmission risk, management, and treatment. The implications of a more refined TB disease spectrum affect TB diagnosis, management and length of treatment. Identifying subjects with incipient and subclinical TB that represent high risk of progression to active TB, provides an opportunity for early treatment to reduce transmission and sequela. However, the optimal treatment regimen, whether prophylactic or therapeutic, remains to be determined.

We would like to call upon the scientific community to provide data on diagnostic strategies in both paediatric as well as adult populations. This will help to elaborate the categorization of stages of Mtb infection and identify subjects at risk of TB progression. Furthermore, we welcome data and expert opinions on strategies for management and treatment of various stages, including stable latent Mtb infection, incipient TB, subclinical TB and active TB. Suggestions for study designs that inform these strategies are most welcome. Particular considerations should be given to the immunosuppressed host, and contributions to this theme are encouraged. Finally, every contribution should address a point-of-care approach. This is essential to clarify the feasibility of the diagnostic proposal in the field, especially in those settings where it is most needed.

This Research Topic welcomes research covering, but not limited to, the following areas:
• Immunological bases of LTBI, and the associated risk of progressing to ATB.
• Discerning the immunological spectrum of cellular and humoral responses in TB
• ”In silico” modelling to discern LTBI from ATB
• Blood RNA signatures to differentiate LTBI from ATB
• Metabolomic analysis of LTBI/ATB from blood, urine, exhaled breath
• Improving the extrapulmonary diagnosis in tissue samples and biopsies, including those that are paraffin-embedded
• Point-of-Care approaches

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Frontiers in Tuberculosis

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