Characterizing the spectrum of latent Mtb infection in the cynomolgus macaque model: Clinical, immunologic, and PET CT features of evolution.

Mycobacterium tuberculosis (Mtb) infection outcomes have been described as active tuberculosis (TB) or latent infection but a spectrum of outcomes is now recognized. We used a non-human primate model which recapitulates human infection to characterize the clinical, microbiologic, and radiographic patterns associated with developing latent Mtb infection. Four patterns were identified. "Controller" had normal erythrocyte sedimentation rate (ESR) without Mtb growth in bronchoalveolar lavage or gastric aspirate. "Early subclinicals" showed transient ESR elevation and/or Mtb growth on BAL/GA for 60 days post-infection, "mid subclinicals" were positive for 90 days, and "late subclinicals" were positive intermittently, despite the absence of clinical disease. Variability was noted regarding granuloma formation, lung/lymph node metabolic activity, lung/lymph node bacterial burden, gross pathology, and extrapulmonary disease. Like human Mtb infection, this highlights the heterogeneity associated with the establishment of latent infection underscoring the need to understand the clinical spectrum and risk factors associated with severe disease.