Experimental versus clinical studies capture distinct types of relapse in tuberculosis.

Experimental models and clinical studies reveal distinct relapse mechanisms in tuberculosis, with clinical relapse driven by non-replicating bacteria and experimental relapse by residual replicating bacteria.

• Why it matters: Understanding these differences is crucial because relapse causes prolonged treatment and ongoing transmission, yet current definitions and models do not fully capture the underlying biology, hindering effective interventions.
• What they did: Using the HostSim computational model, the study simulated TB relapse scenarios, analyzing how study design and diagnostic criteria influence observed relapse rates and mechanisms across 2,000 virtual hosts.
• The result: Findings indicate clinical relapse mainly results from reactivation of non-replicating bacteria in granulomas, suggesting treatment should include caseum-penetrating antibiotics, while experimental relapse often stems from incomplete sterilization of replicating bacteria.