Explaining age disparities in tuberculosis burden in Taiwan: a modelling study

Tuberculosis (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.

We 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.

The '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.

In 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.