Tuberculosis control interventions targeted to previously treated people in a high-incidence setting: a modelling study

Abstract

Summary Background In high-incidence settings, recurrent disease among previously treated individuals contributes substantially to the burden of incident and prevalent tuberculosis. The extent to which interventions targeted to this high-risk group can improve tuberculosis control has not been established. We aimed to project the population-level effect of control interventions targeted to individuals with a history of previous tuberculosis treatment in a high-incidence setting. Methods We developed a transmission-dynamic model of tuberculosis and HIV in a high-incidence setting with a population of roughly 40 000 people in suburban Cape Town, South Africa. The model was calibrated to data describing local demography, TB and HIV prevalence, TB case notifications and treatment outcomes using a Bayesian calibration approach. We projected the effect of annual targeted active case finding in all individuals who had previously completed tuberculosis treatment and targeted active case finding combined with lifelong secondary isoniazid preventive therapy. We estimated the effect of these targeted interventions on local tuberculosis incidence, prevalence, and mortality over a 10 year period (2016–25). Findings We projected that, under current control efforts in this setting, the tuberculosis epidemic will remain in slow decline for at least the next decade. Additional interventions targeted to previously treated people could greatly accelerate these declines. We projected that annual targeted active case finding combined with secondary isoniazid preventive therapy in those who previously completed tuberculosis treatment would avert 40% (95% uncertainty interval [UI] 21–56) of incident tuberculosis cases and 41% (16–55) of tuberculosis deaths occurring between 2016 and 2025. Interpretation In this high-incidence setting, the use of targeted active case finding in combination with secondary isoniazid preventive therapy in previously treated individuals could accelerate decreases in tuberculosis morbidity and mortality. Studies to measure cost and resource implications are needed to establish the feasibility of this type of targeted approach for improving tuberculosis control in settings with high tuberculosis and HIV prevalence. Funding National Institutes of Health, German Research Foundation.

Cost-effectiveness of post-treatment follow-up examinations and secondary prevention of tuberculosis in a high-incidence setting: a model-based analysis

“…6 To our knowledge, our study is the first to estimate the costeffectiveness of interventions targeted to people with a history of previous tuberculosis treatment in a highincidence setting. It extends findings of an earlier modelling study, 12 in which we found that offering tuberculosis case finding and secondary IPT to people previously treated for tuberculosis could greatly accelerate declines in tuberculosis incidence and mor tality in this setting. Both studies support the proposition that in settings with a high incidence of tuberculosis, previously treated people constitute an important group that might be especially attractive for targeted interventions given their high risk of recurrent tuberculosis and their probable role in transmission of M tuberculosis in the population.…”

“…The transmissiondynamic model is an extension of a model that we previously used to explore the impact of targeted active case finding and secondary IPT after tuberculosis treatment completion in the same study setting. 12 The tuberculosis component of the model follows the conventions of earlier models [13][14][15][16] with additional structure to distinguish between individuals who have never been treated for tuberculosis (treatment naive) and those who have previously been treated for tuberculosis (treatment experienced; figure 1). Model transitions are fully described in the appendix (pp 2-3).…”

“…[9][10][11] Using a mathematical model of tuberculosis and HIV in suburban Cape Town, South Africa, we projected that targeting tuberculosis case finding and secondary prevention to previously treated people could yield substantial populationlevel reductions in tuberculosis incidence and mortality. 12 However, it is not yet clear whether these types of targeted intervention are costeffective options for tuberculosis control in a highincidence setting.…”

Factors associated with diagnostic delay in recurrent TB

“…This was particularly true for people with recurrent TB, with almost 100% notified by PCF. It is well known that cases notified by PCF will suffer a longer diagnostic delay than those notified by active case finding (ACF) [16]. This could partly explain why people with recurrent TB have longer delays.…”

Introducing risk inequality metrics in tuberculosis policy development

“…This is a general phenomenon in infectious diseases, although there may be exceptional circumstances where the sign of the effect may be reversed as detailed below. In any case, it is a systematic error (bias) not to be confused with uncertainty in parameter estimates 19,20 .…”