Abstract

BackgroundTuberculosis (TB) burden shows wide disparities across ages in Taiwan. In 2016, the age-specific notification rate in those older than 65 years old was about 100 times as much as in those younger than 15 years old (185.0 vs 1.6 per 100,000 population). Similar patterns are observed in other intermediate TB burden settings. However, driving mechanisms for such age disparities are not clear and may have importance for TB control efforts.MethodsWe hypothesised three mechanisms for the age disparity in TB burden: (i) older age groups bear a higher risk of TB progression due to immune senescence, (ii) elderly cases acquired TB infection during a past period of high transmission, which has since rapidly declined and thus contributes to little recent infections, and (iii) assortative mixing by age allows elders to maintain a higher risk of TB infection, while limiting spillover transmission to younger age groups. We developed a series of dynamic compartmental models to incorporate these mechanisms, individually and in combination. The models were calibrated to the TB notification rates in Taiwan over 1997–2016 and evaluated by goodness-of-fit to the age disparities and the temporal trend in the TB burden, as well as the deviance information criterion (DIC). According to the model performance, we compared contributions of the hypothesised mechanisms.ResultsThe ‘full’ model including all the three hypothesised mechanisms best captured the age disparities and temporal trend of the TB notification rates. However, dropping individual mechanisms from the full model in turn, we found that excluding the mechanism of assortative mixing yielded the least change in goodness-of-fit. In terms of their influence on the TB dynamics, the major contribution of the ‘immune senescence’ and ‘assortative mixing’ mechanisms was to create disparate burden among age groups, while the ‘declining transmission’ mechanism served to capture the temporal trend of notification rates.ConclusionsIn settings such as Taiwan, the current TB burden in the elderly may be impacted more by prevention of active disease following latent infection, than by case-finding for blocking transmission. Further studies on these mechanisms are needed to disentangle their impacts on the TB epidemic and develop corresponding control strategies.

Highlights

  • Global tuberculosis (TB) incidence and mortality have been declining in recent decades, with continuous efforts in improving case detection and treatment outcomes [1]

  • If concentrated TB burden in older age groups is due to a high risk of disease progression from remote infection, this suggests that measures to prevent reactivation, such as treating latent TB infection in the elderly, could be important

  • The ‘full’ model with all the three mechanisms (m123) best captured the age-specific notification rates over time, but we found that the two-mechanism model which incorporates the mechanisms of immune senescence and declining transmission (m12), demonstrated a good fit to the adult-child and elder-child ratios of the notification rates

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Summary

Introduction

Global tuberculosis (TB) incidence and mortality have been declining in recent decades, with continuous efforts in improving case detection and treatment outcomes [1]. A similar age disparity is reported in Hong Kong, where the age-specific TB notification rate is as large as 100 times among people older than 85 years old, compared to children less than 15 years old [3]. If concentrated TB burden in older age groups is due to a high risk of disease progression from remote infection, this suggests that measures to prevent reactivation, such as treating latent TB infection in the elderly, could be important. If, these disparities could be explained by preferential mixing between the elderly, measures to early diagnose and treat TB could be more impactful. Driving mechanisms for such age disparities are not clear and may have importance for TB control efforts

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