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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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General structure of the dynamic transmission model for an intervention cluster in the Thibela TB randomized controlled trial among South African gold miners, 2006–2011. Because of high levels of transmission in the miners, all gold miners were assumed to have been infected at least once in their lifetime, which accounts for the absence of an uninfected compartment. The dashed lines reflect activities relating to case finding or isoniazid preventive therapy. The arrows out of the compartments, which have no destination, reflect out-migration or death. The small arrows into the compartments, which do not start from any destination, reflect in-migration. The shaded boxes reflect people who are taking IPT. IPT, isoniazid preventive therapy; s−c+, smear-negative, culture-positive; s+c+, smear-positive, culture-positive; TB, tuberculosis.
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KWU320F2: General structure of the dynamic transmission model for an intervention cluster in the Thibela TB randomized controlled trial among South African gold miners, 2006–2011. Because of high levels of transmission in the miners, all gold miners were assumed to have been infected at least once in their lifetime, which accounts for the absence of an uninfected compartment. The dashed lines reflect activities relating to case finding or isoniazid preventive therapy. The arrows out of the compartments, which have no destination, reflect out-migration or death. The small arrows into the compartments, which do not start from any destination, reflect in-migration. The shaded boxes reflect people who are taking IPT. IPT, isoniazid preventive therapy; s−c+, smear-negative, culture-positive; s+c+, smear-positive, culture-positive; TB, tuberculosis.

Mentions: We developed an age-structured deterministic compartmental model (Figure 2) describing M. tuberculosis transmission dynamics for each intervention cluster and its control, matching identically, except for the intervention. The model considers culture-positive tuberculosis (“active disease”), extending previous work (7, 8). Cluster populations comprise 4 age strata (<30, 30–39, 40–49, and ≥50 years) because of age-dependent population mobility and 2 human immunodeficiency virus (HIV) strata (HIV-positive or HIV-negative). Model output is aggregated into 2 age strata (<40 and ≥40 years) or all ages, given insufficient data to further stratify the incidence and prevalence. Clusters are considered independent, because little movement occurred between intervention and control arms.Figure 2.


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)

General structure of the dynamic transmission model for an intervention cluster in the Thibela TB randomized controlled trial among South African gold miners, 2006–2011. Because of high levels of transmission in the miners, all gold miners were assumed to have been infected at least once in their lifetime, which accounts for the absence of an uninfected compartment. The dashed lines reflect activities relating to case finding or isoniazid preventive therapy. The arrows out of the compartments, which have no destination, reflect out-migration or death. The small arrows into the compartments, which do not start from any destination, reflect in-migration. The shaded boxes reflect people who are taking IPT. IPT, isoniazid preventive therapy; s−c+, smear-negative, culture-positive; s+c+, smear-positive, culture-positive; TB, tuberculosis.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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

KWU320F2: General structure of the dynamic transmission model for an intervention cluster in the Thibela TB randomized controlled trial among South African gold miners, 2006–2011. Because of high levels of transmission in the miners, all gold miners were assumed to have been infected at least once in their lifetime, which accounts for the absence of an uninfected compartment. The dashed lines reflect activities relating to case finding or isoniazid preventive therapy. The arrows out of the compartments, which have no destination, reflect out-migration or death. The small arrows into the compartments, which do not start from any destination, reflect in-migration. The shaded boxes reflect people who are taking IPT. IPT, isoniazid preventive therapy; s−c+, smear-negative, culture-positive; s+c+, smear-positive, culture-positive; TB, tuberculosis.
Mentions: We developed an age-structured deterministic compartmental model (Figure 2) describing M. tuberculosis transmission dynamics for each intervention cluster and its control, matching identically, except for the intervention. The model considers culture-positive tuberculosis (“active disease”), extending previous work (7, 8). Cluster populations comprise 4 age strata (<30, 30–39, 40–49, and ≥50 years) because of age-dependent population mobility and 2 human immunodeficiency virus (HIV) strata (HIV-positive or HIV-negative). Model output is aggregated into 2 age strata (<40 and ≥40 years) or all ages, given insufficient data to further stratify the incidence and prevalence. Clusters are considered independent, because little movement occurred between intervention and control arms.Figure 2.

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