Tuberculosis control in South African gold mines: mathematical modeling of a trial of community-wide isoniazid preventive therapy.
Bottom Line: A recent major cluster randomized trial of screening, active disease treatment, and mass isoniazid preventive therapy for 9 months during 2006-2011 among South African gold miners showed reduced individual-level tuberculosis incidence but no detectable population-level impact.We found the following: 1) The model suggests that a small proportion of latent infections among human immunodeficiency virus-positive people were cured, which could have been a key factor explaining the lack of detectable population-level impact. 2) The optimized implementation increased impact by only 10%. 3) Implementing additional interventions individually and in combination led to up to 30% and 75% reductions, respectively, in tuberculosis incidence after 10 years.Tuberculosis control requires a combination prevention approach, including health systems strengthening to minimize treatment delay, improving diagnostics, increased antiretroviral treatment coverage, and effective preventive treatment regimens.
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Mentions: Multiple competing hypotheses exist for why the trial detected no population-level impact, including suboptimal IPT uptake and/or retention or high population mobility (5). To robustly explore this question, we included in the model all known factors (age, HIV, silicosis, ART, in- and out-migration, case detection, initial loss to follow-up after detection, treatment delay, IPT uptake, and retention), at levels supported by detailed data collected during the study or by mine health services (Figure 3; Web Figure 1 (available at http://aje.oxfordjournals.org/)). Parameters (Table 1) were also drawn from publications or estimated by fitting model predictions to trial outcomes. Web Appendixes 1 and 2, Web Tables 1–7, and Web Figures 1–7 provide further details, including the model equations.Table 1.