Tuberculosis control in South African gold mines: mathematical modeling of a trial of community-wide isoniazid preventive therapy.
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.
- Antitubercular Agents/therapeutic use*
- Isoniazid/therapeutic use*
- Models, Theoretical*
- Public Health Practice/statistics & numerical data*
- Tuberculosis/complications/prevention & control*
- HIV Infections/complications
- Middle Aged
- South Africa
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KWU320F6: Impact of different interventions implemented individually (A–C) or in combination (D) predicted for the Thibela TB randomized controlled trial among South African gold miners, 2006–2011. Summary of the predicted impact of different interventions on the number of cases/100,000/year (the true TB incidence rate), after the treatment delay has been reduced. Each panel shows the impact of reduced treatment delay plus in A) preventive treatment, with 1) IPT provided community-wide in an initial round for 9 months of IPT, with coverage at the highest levels seen in Thibela, and 2) IPT provided community-wide in an initial round for 9 months, with coverage at the highest levels seen in Thibela, followed by continuous community-wide IPT with 50% coverage. This is achieved through keeping those who are still on IPT at the end of the initial round on IPT thereafter and providing IPT to 50% of new mining employees, and 3) a single round with a 3-month fully curing regimen provided community-wide (without 9 months of IPT), with coverage at the highest levels seen in Thibela. B) Scale-up of ART, with ART coverage increasing to reach 80% in 2009 in the HIV-positive groups specified in the figure legend; C) improved diagnosis using Xpert MTB/RIF, with 1) radiographs being used to screen at routine medical examinations and for newly employed miners and Xpert MTB/RIF being used to diagnose people with suspected TB, and 2) Xpert MTB/RIF being used to screen and diagnose at routine medical examinations for newly employed miners and on passive presentation; D) combined interventions. Combined impact of introducing reduced treatment delay, screening with Xpert MTB/RIF, ART for 80% of HIV-positive people, and IPT for those on ART. The shaded areas show the incremental impact of adding each intervention, so that the white area reflects the impact of having all interventions in place simultaneously. For the scenario involving Xpert MTB/RIF, Xpert MTB/RIF is used in routine medical examinations, for newly employed miners, and on passive presentation. For both the ART and ART/IPT scenarios, the coverage is increased to reach 80% by 2009. ART, antiretroviral therapy; HIV+, human immunodeficiency virus–positive; IPT, isoniazid preventive therapy; PT, preventive therapy; TB, tuberculosis.
Without additional interventions, the average predicted true tuberculosis incidence declined from about 5,000 to 4,000/100,000/year during 2008–2017 (Figure 6), reflecting increasing ART uptake in some clusters. Reducing initial loss to follow-up to 5% and the average treatment delay to 3 and 2 weeks for all smear-negative and smear-positive cases, respectively, detected by the health services (Table 2) reduced this further to 3,000/100,000/year by 2017 (Figure 6A). Implementing interventions individually resulted in <30% reductions in the predicted long-term true incidence compared with that without interventions (Figure 6). The greatest reductions resulted from scaling-up ART to levels in Table 2, providing continuous IPT or tuberculosis screening (routine medical examination, new employees, and self-presenting miners) with Xpert MTB/RIF.Figure 6.