Updating age-specific contact structures to match evolving demography in a dynamic mathematical model of tuberculosis vaccination

摘要

We investigated the effects of updating age-specific social contact matrices to match evolving demography on vaccine impact estimates. We used a dynamic transmission model of tuberculosis in India as a case study. We modelled four incremental methods to update contact matrices over time, where each method incorporated its predecessor: fixed contact matrix (M0), preserved contact reciprocity (M1), preserved contact assortativity (M2), and preserved average contacts per individual (M3). We updated the contact matrices of a deterministic compartmental model of tuberculosis transmission, calibrated to epidemiologic data between 2000 and 2019 derived from India. We additionally calibrated the M0, M2, and M3 models to the 2050 TB incidence rate projected by the calibrated M1 model. We stratified age into three groups, children (= 15y, = 65y), using World Population Prospects demographic data, between which we applied POLYMOD-derived social contact matrices. We simulated an M72-AS01(E)-like tuberculosis vaccine delivered from 2027 and estimated the per cent TB incidence rate reduction (IRR) in 2050 under each update method. We found that vaccine impact estimates in all age groups remained relatively stable between the M0-M3 models, irrespective of vaccine-targeting by age group. The maximum difference in impact, observed following adult-targeted vaccination, was 7 in the elderly, in whom we observed IRRs of 19 (uncertainty range 13-32), 20 (UR 13-31), 22 (UR 14-37), and 26 (UR 18-38) following M0, M1, M2 and M3 updates, respectively. We found that model-based TB vaccine impact estimates were relatively insensitive to demography-matched contact matrix updates in an India-like demographic and epidemiologic scenario. Current model-based TB vaccine impact estimates may be reasonably robust to the lack of contact matrix updates, but further research is needed to confirm and generalise this finding. Author summaryMathematical models are increasingly used to predict the impact of new and existing tools, e.g., vaccines, that aim to control the transmission of infectious diseases. Within these models, investigators often assume that individuals contact each other according to specific patterns, particularly between and within different age groups. These patterns are typically derived from surveys of social contact or other models and reflect the particular age composition of their source population. However, when models are set over long time scales, e.g., decades, population age composition is likely to change. Despite this reality, few models update their contact patterns to match changing age composition. Furthermore, none have assessed whether their final estimates of disease-control intervention impact are affected by updating contact patterns. We measured whether different techniques to update social contact patterns to match evolving demography produce different vaccine impact estimates, using a mathematical model of tuberculosis set in an India-like scenario between 2025-2050. We found that vaccine impact was stable across a range of different update methods. Thus, existing model-based vaccine impact estimates may be stable to a lack of these updates, but further work is required to confirm these findings.