Abstract
Despite current control efforts, global tuberculosis (TB) incidence is decreasing slowly. New regimens that can shorten treatment hold promise for improving treatment completion and success, but their impact on population-level transmission remains unclear. Earlier models projected that a four-month regimen could reduce TB incidence by 10% but assumed that an entire course of therapy must be completed to derive any benefit. We constructed a dynamic transmission model of TB disease calibrated to global estimates of incidence, prevalence, mortality, and treatment success. To account for the efficacy of partial treatment, we used data from clinical trials of early short-course regimens to estimate relapse rates among TB patients who completed one-third, one-half, two-thirds, and all of their first-line treatment regimens. We projected population-level incidence and mortality over 10 years, comparing standard six-month therapy to hypothetical shorter-course regimens with equivalent treatment success but fewer defaults. The impact of hypothetical four-month regimens on TB incidence after 10 years was smaller than estimated in previous modeling analyses (1.9% [95% uncertainty range 0.6–3.1%] vs. 10%). Impact on TB mortality was larger (3.5% at 10 years) but still modest. Transmission impact was most sensitive to the proportion of patients completing therapy: four-month therapy led to greater incidence reductions in settings where 25% of patients leave care (“default”) over six months. Our findings remained robust under one-way variation of model parameters. These findings suggest that novel regimens that shorten treatment duration may have only a modest effect on TB transmission except in settings of very low treatment completion.
Highlights
Tuberculosis (TB) is the second leading cause of death from a single infectious agent: it is estimated that one-third of the world population is infected with TB, with 8.7 million developing active disease and 1.4 million dying each year [1]
Starting from a steady-state ‘‘global reference’’ rate of 125 new cases per 100,000 population, introducing a four-month treatment regimen reduced incidence by only 1.9% [95% uncertainty range 0.6–3.1%] over 10 years; the shorter two-month and two-week regimens reduced incidence by 4.3% [1.8–7.0%] and 6.7% [3.0–10.2%], respectively
Even in the high-burden scenario, the uncertainty analysis yielded incidence reductions of $10% in only 8.5% of simulations. This mathematical model of TB treatment and transmission suggests that novel treatment regimens are unlikely to have the dramatic impact on global TB incidence projected by earlier models; we found that immediate implementation of a four-month treatment regimen could reduce TB incidence by 1.9% and mortality by 3.5% over 10 years compared to a sixmonth regimen of equal efficacy, suggesting that previous analyses significantly overestimated the impact of shortened treatment duration
Summary
Tuberculosis (TB) is the second leading cause of death from a single infectious agent: it is estimated that one-third of the world population is infected with TB, with 8.7 million developing active disease and 1.4 million dying each year [1]. For the first time in decades, novel treatment regimens hold the realistic promise of shortening the standard six-month first-line TB treatment course [8,9,10]. If their efficacy is confirmed in ongoing trials, these novel regimens could reduce healthcare costs [11] and improve both patient satisfaction and treatment outcomes [12,13]. The expectation that shorter treatment will help control transmission has been a key driver of ongoing efforts by global organizations to develop new drugs and regimens for TB [14,15]
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