Am J Epidemiol. 2023 Nov 10;192(12):1937-1943. doi: 10.1093/aje/kwad028.
A key metric in tuberculosis epidemiology is the annual risk of infection (ARI), which is usually derived from tuberculin skin test (TST) and interferon-γ release assay (IGRA) prevalence surveys carried out in children. Derivation of the ARI assumes that immunoreactivity is persistent over time; however, reversion of immunoreactivity has long been documented. We used a deterministic, compartmental model of Mycobacterium tuberculosis (Mtb) infection to explore the impact of reversion on ARI estimation using age-specific reversion probabilities for the TST and IGRA. Using empirical data on TST reversion (22.2%/year for persons aged ≤19 years), the true ARI was 2-5 times higher than that estimated from immunoreactivity studies in children aged 8-12 years. Applying empirical reversion probabilities for the IGRA (9.9%/year for youths aged 12-18 years) showed a 1.5- to 2-fold underestimation. ARIs are increasingly underestimated in older populations, due to the cumulative impact of reversion on population reactivity over time. Declines in annual risk did not largely affect the results. Ignoring reversion leads to a stark underestimation of the true ARI in populations and our interpretation of Mtb transmission intensity. In future surveys, researchers should adjust for the reversion probability and its cumulative effect with increasing age to obtain a more accurate reflection of the burden and dynamics of Mtb infection.
在结核病流行病学中，一个关键指标是年感染率（ARI），通常通过对儿童进行结核菌素皮肤试验（TST）和干扰素-γ释放试验（IGRA）流行率调查来获得。ARI 的推导假设免疫反应是随着时间的推移而持续存在的；然而，免疫反应的逆转早已被记录在案。我们使用结核分枝杆菌（Mtb）感染的确定性、隔室模型来探讨免疫反应逆转对 ARI 估计的影响，使用 TST 和 IGRA 的年龄特异性逆转概率来估计 ARI。利用 TST 逆转的经验数据（≤19 岁者每年 22.2%），真实的 ARI 比在 8-12 岁儿童中进行的免疫反应研究估计的 ARI 高 2-5 倍。应用 IGRA 的经验逆转概率（12-18 岁青少年每年 9.9%）表明，估计值低估了 1.5-2 倍。由于免疫反应逆转对人群反应性的累积影响，ARI 在年龄较大的人群中越来越被低估。每年的风险下降并没有在很大程度上影响结果。忽略逆转会导致对人群真实 ARI 和对 Mtb 传播强度的解释明显低估。在未来的调查中，研究人员应调整逆转概率及其随年龄增长的累积效应，以更准确地反映 Mtb 感染的负担和动态。
