Modeling the impact of case finding for tuberculosis: The role of infection dynamics

BackgroundOur understanding of Mycobacterium tuberculosis (Mtb) natural history and infection dynamics is evolving, including recognition that many individuals previously infected with Mtb may clear their infections or experience substantially reduced progression risks with time since infection. Such dynamics suggest that recent transmission is more important in driving TB incidence in high-burden settings than previously estimated; thus, the impact of interventions to reduce transmission (e.g., community-based active case-finding) may also be greater than previously thought. MethodsWe constructed two models of Mtb transmission that differed only in that one model included a clearance mechanism while the other did not. We then calibrated these models independently to the same set of epidemiological data representative of a high-TB-burden setting (India). Finally, we used the calibrated models to project the impact of illustrative biennial active case-finding campaigns (achieving 75% population coverage with 65% screening sensitivity). ResultsThe model that included a clearance mechanism projected a greater impact of case-finding on the incidence of TB disease: 45% [95% uncertainty interval 28-57%] reduction versus no intervention after 10 years, versus 11% [6-18%] in the model without a clearance mechanism. The estimated annual risk of Mtb infection and prevalence of recent infection were both substantially higher in the model that allowed for Mtb clearance, despite being fit to the same data. ConclusionsModels that allow for Mtb clearance are supported by biological and epidemiological evidence and project greater impact from active case-finding than models that do not include these dynamics.