Cure-screening predicts mechanism of post-antibiotic relapse in Tuberculosis

Abstract Tuberculosis (TB) remains a global health concern, as Mycobacterium tuberculosis (Mtb) currently infects a quarter of the world’s population. Though many TB patients sterilize infection with short-course treatment, regimens shorter than 4 months risk post-treatment, potentially facilitating drug resistance. Granulomas are spatially-heterogeneous hallmark immune structures that form during TB, comprising immune cells and caseum , necrotic tissue that can trap Mtb in a non-replicating state. Two mechanisms causing relapse have been hypothesized: persistence , where treatment kills all replicating Mtb, and relapse follows once Mtb trapped within caseum returns to a replicative niche; and threshold , where replicating Mtb remain alive below detectable levels. Typically, clinical relapse is described as TB recurrence