What will it take to achieve the End TB targets in South Africa? A mathematical modelling analysis

Background: The WHO End TB strategy targets 80% and 90% reductions in TB incidence and mortality, respectively, between 2015 and 2030. Objective: We assess which epidemiologic factors, including existing and new interventions, are most critical to reducing future TB in South Africa. Methods: We adapted an existing mathematical model of TB and HIV in South Africa. Prior distributions were specified to represent uncertainty ranges for 27 model parameters that are highly uncertain and potentially important in driving future TB dynamics. Latin Hypercube Sampling was used to sample 1000 parameter combinations from these distributions, and the model was projected to 2040 for each. Partial rank correlation coefficients (PRCCs) were calculated to assess correlation between each parameter and average adult TB incidence and mortality rates over 2025-2040. Results: Adult TB incidence and mortality rates in South Africa are projected to decline by 46% (95% CI: 17-69%) and 54% (95% CI: 21-84%) respectively by 2030, relative to 2015. The parameters most strongly associated with future TB incidence are the increase in microbiological testing in symptomatic individuals due to near-point-of-care/tongue swab (NPOC/TS) testing (PRCC=-0.67), reductions in social contact rates post-COVID (PRCC=-0.61), the probability of sputum testing in symptomatic individuals in the absence of NPOC/TS testing (PRCC=-0.39), and the efficacy of TB preventive therapy (PRCC=-0.35). TB mortality predictors are similar. Conclusions: Increasing testing among people with TB symptoms, including through new NPOC/TS technologies, is likely to have the largest impact on progress towards End TB goals in South Africa, though attainment by 2030 is unlikely.