Modelling heterogeneity in host susceptibility to tuberculosis and its effect on public health interventions

A tuberculosis (TB) model that accounts for heterogeneity in host susceptibility to tuberculosis is proposed, with the aim of investigating the implications this may have for the effectiveness of public health interventions. The model examines the possibility that recovered individuals treated from active TB and individuals treated with preventive therapy acquire different levels of immunity. This contrasts with recent studies that assume the two cohorts acquire the same level of immunity, and therefore both groups are reinfected at the same rate. The analysis presented here examines the impact of this assumption when designing intervention strategies. Comparison of reinfection rates between cohorts treated with preventive therapy and recovered individuals who were previously treated for active TB provides important epidemiological insights. It is found that the reinfection rate of the cohort treated with preventive therapy is the one that plays the key role in qualitative changes in TB dynamics. By contrast, the reinfection rate of recovered individuals (previously treated from active TB) plays a minor role. Moreover, the study shows that preventive treatment of individuals during early latency is always beneficial regardless of the level of susceptibility to reinfection. Further, if patients have greater immunity following treatment for late latent infection, then treatment is again beneficial. However, if susceptibility increases following treatment for late latent infection, the effect of treatment depends on the epidemiological setting. That is: (i) in (very) low burden settings, the effect on reactivation predominates and the burden declines with treatment; (ii) in moderate to high burden settings the effect of reinfection predominates and burden increases with treatment. The effect is most dominant between the two reinfection thresholds, RT2 and RT1, respectively associated with individuals being treated with preventive therapy and individuals with untreated late latent TB infection.

本研究提出了一种考虑宿主对结核病（TB）易感性异质性的结核病模型，旨在探究其对公共卫生干预措施有效性的潜在影响。该模型探讨了曾接受活动性结核病治疗后康复的个体，与接受预防性治疗的个体所获得的免疫水平存在差异的可能性。这与近期相关研究的假设相悖——后者认为这两类人群可获得同等水平的免疫力，因此二者的再感染速率相同。本文开展的分析旨在探究，在设计干预策略时，该假设会产生何种影响。对比接受预防性治疗的人群与曾接受活动性结核病治疗后康复人群的再感染速率，可获得重要的流行病学见解。研究发现，接受预防性治疗人群的再感染速率是驱动结核病动力学发生定性变化的关键因素；相比之下，曾接受活动性结核病治疗后康复人群的再感染速率仅发挥次要作用。此外，本研究表明，无论对再感染的易感性水平如何，对处于潜伏期早期的个体实施预防性治疗始终是有益的。进一步而言，若患者在接受晚期潜伏感染治疗后免疫力增强，则此类治疗同样具有益处。然而，若患者在接受晚期潜伏感染治疗后易感性升高，则治疗效果将取决于流行病学场景：（i）在（极）低负担场景中，再激活效应占据主导地位，治疗可降低疾病负担；（ii）在中至高负担场景中，再感染效应占据主导地位，治疗反而会增加疾病负担。该效应在两个再感染阈值之间最为显著，其中阈值RT2、RT1分别对应接受预防性治疗的个体与未接受治疗的晚期潜伏性结核感染个体。