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Tuberculosis control in South African gold mines: mathematical modeling of a trial of community-wide isoniazid preventive therapy.

Vynnycky E, Sumner T, Fielding KL, Lewis JJ, Cox AP, Hayes RJ, Corbett EL, Churchyard GJ, Grant AD, White RG - Am. J. Epidemiol. (2015)

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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Summary of the best-fitting impact on the weekly measured tuberculosis disease incidence rate (per 100,000 person-years) during the Thibela TB randomized controlled trial among South African gold miners, 2006–2011. The incidence rate is defined as the incidence that would be observed if it were measured weekly. A) Model predictions obtained by assuming that IPT fully cures all infections and protects against reinfection (IPT assumption 1: 100% cure, 100% protection); B) model is permitted to estimate that 6 months of IPT does not cure all infections and also does not give 100% protection against reinfection during IPT (IPT assumption 3: estimated percentage cured, estimated percentage protection). Note that, for all IPT models, the best-fitting values for the disease rates differed slightly (Web Figure 10), leading to differences in the predicted measured incidence before the introduction of IPT. For each plot, the predicted measured incidence increases in the intervention clusters after the start of the trial because of increased case detection, resulting from screening miners on recruitment into the trial. The cross shows the observed incidence in the intervention arm, aggregated for all intervention clusters; the empty square shows the “observed” incidence in the control arm, taken to equal the incidence in the intervention clusters, divided by 0.98 (the point estimate of the trial impact on incidence). Bars, 95% confidence intervals. IPT, isoniazid preventive therapy; TB, tuberculosis.
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KWU320F4: Summary of the best-fitting impact on the weekly measured tuberculosis disease incidence rate (per 100,000 person-years) during the Thibela TB randomized controlled trial among South African gold miners, 2006–2011. The incidence rate is defined as the incidence that would be observed if it were measured weekly. A) Model predictions obtained by assuming that IPT fully cures all infections and protects against reinfection (IPT assumption 1: 100% cure, 100% protection); B) model is permitted to estimate that 6 months of IPT does not cure all infections and also does not give 100% protection against reinfection during IPT (IPT assumption 3: estimated percentage cured, estimated percentage protection). Note that, for all IPT models, the best-fitting values for the disease rates differed slightly (Web Figure 10), leading to differences in the predicted measured incidence before the introduction of IPT. For each plot, the predicted measured incidence increases in the intervention clusters after the start of the trial because of increased case detection, resulting from screening miners on recruitment into the trial. The cross shows the observed incidence in the intervention arm, aggregated for all intervention clusters; the empty square shows the “observed” incidence in the control arm, taken to equal the incidence in the intervention clusters, divided by 0.98 (the point estimate of the trial impact on incidence). Bars, 95% confidence intervals. IPT, isoniazid preventive therapy; TB, tuberculosis.

Mentions: After incorporating all known data and factors (migration, ART uptake, silicosis, IPT uptake and retention, treatment delay, and initial loss to follow-up) and fitting to the observed outcomes, we found that the model based on IPT assumptions 1 (100% cure, 100% protection) fitted the data poorly. The best-fitting impact of 24.5% (95% CI: 24.2, 25.0) and 17.8% (95% CI: 15.0, 21.0) on the measured incidence for IPT assumptions 1 and 2, respectively, exceeded that observed but was inside the latter's 95% confidence interval (−48, 27) (Figure 4A). Findings for the best-fitting impact on prevalence were similar. Web Appendix 5, Web Table 12, and Web Figures 10–14 include further details.Figure 4.


Tuberculosis control in South African gold mines: mathematical modeling of a trial of community-wide isoniazid preventive therapy.

Vynnycky E, Sumner T, Fielding KL, Lewis JJ, Cox AP, Hayes RJ, Corbett EL, Churchyard GJ, Grant AD, White RG - Am. J. Epidemiol. (2015)

Summary of the best-fitting impact on the weekly measured tuberculosis disease incidence rate (per 100,000 person-years) during the Thibela TB randomized controlled trial among South African gold miners, 2006–2011. The incidence rate is defined as the incidence that would be observed if it were measured weekly. A) Model predictions obtained by assuming that IPT fully cures all infections and protects against reinfection (IPT assumption 1: 100% cure, 100% protection); B) model is permitted to estimate that 6 months of IPT does not cure all infections and also does not give 100% protection against reinfection during IPT (IPT assumption 3: estimated percentage cured, estimated percentage protection). Note that, for all IPT models, the best-fitting values for the disease rates differed slightly (Web Figure 10), leading to differences in the predicted measured incidence before the introduction of IPT. For each plot, the predicted measured incidence increases in the intervention clusters after the start of the trial because of increased case detection, resulting from screening miners on recruitment into the trial. The cross shows the observed incidence in the intervention arm, aggregated for all intervention clusters; the empty square shows the “observed” incidence in the control arm, taken to equal the incidence in the intervention clusters, divided by 0.98 (the point estimate of the trial impact on incidence). Bars, 95% confidence intervals. IPT, isoniazid preventive therapy; TB, tuberculosis.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4388015&req=5

KWU320F4: Summary of the best-fitting impact on the weekly measured tuberculosis disease incidence rate (per 100,000 person-years) during the Thibela TB randomized controlled trial among South African gold miners, 2006–2011. The incidence rate is defined as the incidence that would be observed if it were measured weekly. A) Model predictions obtained by assuming that IPT fully cures all infections and protects against reinfection (IPT assumption 1: 100% cure, 100% protection); B) model is permitted to estimate that 6 months of IPT does not cure all infections and also does not give 100% protection against reinfection during IPT (IPT assumption 3: estimated percentage cured, estimated percentage protection). Note that, for all IPT models, the best-fitting values for the disease rates differed slightly (Web Figure 10), leading to differences in the predicted measured incidence before the introduction of IPT. For each plot, the predicted measured incidence increases in the intervention clusters after the start of the trial because of increased case detection, resulting from screening miners on recruitment into the trial. The cross shows the observed incidence in the intervention arm, aggregated for all intervention clusters; the empty square shows the “observed” incidence in the control arm, taken to equal the incidence in the intervention clusters, divided by 0.98 (the point estimate of the trial impact on incidence). Bars, 95% confidence intervals. IPT, isoniazid preventive therapy; TB, tuberculosis.
Mentions: After incorporating all known data and factors (migration, ART uptake, silicosis, IPT uptake and retention, treatment delay, and initial loss to follow-up) and fitting to the observed outcomes, we found that the model based on IPT assumptions 1 (100% cure, 100% protection) fitted the data poorly. The best-fitting impact of 24.5% (95% CI: 24.2, 25.0) and 17.8% (95% CI: 15.0, 21.0) on the measured incidence for IPT assumptions 1 and 2, respectively, exceeded that observed but was inside the latter's 95% confidence interval (−48, 27) (Figure 4A). Findings for the best-fitting impact on prevalence were similar. Web Appendix 5, Web Table 12, and Web Figures 10–14 include further details.Figure 4.

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.

View Article: PubMed Central - PubMed

Show MeSH
Related in: MedlinePlus