Victorian Tuberculosis Program, Royal Melbourne Hospital, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC, Australia; Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC, Australia.
Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC, Australia; Baker Heart and Diabetes Institute, Melbourne, VIC, Australia.
Lancet Infect Dis. 2021 Oct;21(10):e303-e317. doi: 10.1016/S1473-3099(20)30728-3. Epub 2021 Apr 20.
The risk of tuberculosis is greatest soon after infection, but Mycobacterium tuberculosis can remain in the body latently, and individuals can develop disease in the future, sometimes years later. However, there is uncertainty about how often reactivation of latent tuberculosis infection (LTBI) occurs. We searched eight databases (inception to June 25, 2019) to identify studies that quantified tuberculosis reactivation rates occurring more than 2 years after infection (late reactivation), with a focus on identifying untreated study cohorts with defined timing of LTBI acquisition (PROSPERO registered: CRD42017070594). We included 110 studies, divided into four methodological groups. Group 1 included studies that documented late reactivation rates from conversion (n=14) and group 2 documented late reactivation rates in LTBI cohorts from exposure (n=11). Group 3 included 86 studies in LTBI cohorts with an unknown exposure history, and group 4 included seven ecological studies. Since antibiotics have been used to treat tuberculosis, only 11 studies have documented late reactivation rates in infected, untreated cohorts from either conversion (group 1) or exposure (group 2); six of these studies lasted at least 4 years and none lasted longer than 10 years. These studies found that tuberculosis rates declined over time, reaching approximately 200 cases per 100 000 person-years or less by the fifth year, and possibly declining further after 5 years but interpretation was limited by decreasing or unspecified cohort sizes. In cohorts with latent tuberculosis and an unknown exposure history (group 3), tuberculosis rates were generally lower than those seen in groups 1 and 2, and beyond 10 years after screening, rates had declined to less than 100 per 100 000 person-years. Reinfection risks limit interpretation in all studies and the effect of age is unclear. Late reactivation rates are commonly estimated or modelled to prioritise tuberculosis control strategies towards tubuculosis elimination, but significant gaps remain in our understanding that must be acknowledged; the relative importance of late reactivation versus early progression to the global burden of tuberculosis remains unknown.
结核分枝杆菌感染后不久，结核病的风险最大，但结核分枝杆菌可能潜伏在体内，个体可能在未来患病，有时甚至在感染多年后。然而，潜伏性结核感染（LTBI）再激活的频率尚不确定。我们检索了 8 个数据库（从建库至 2019 年 6 月 25 日），以确定定量研究 LTBI 感染后 2 年以上（晚期再激活）结核分枝杆菌再激活率的研究，重点是确定具有 LTBI 获得明确时间的未治疗研究队列（PROSPERO 注册号：CRD42017070594）。我们纳入了 110 项研究，分为 4 个方法学组。第 1 组包括通过转化（n=14）记录晚期再激活率的研究，第 2 组包括通过 LTBI 队列的暴露（n=11）记录晚期再激活率的研究。第 3 组包括 86 项 LTBI 队列的研究，这些研究的暴露史未知，第 4 组包括 7 项生态学研究。由于抗生素已被用于治疗结核病，只有 11 项研究记录了从转化（第 1 组）或暴露（第 2 组）中未经治疗的感染队列的晚期再激活率；其中 6 项研究的持续时间至少为 4 年，没有一项研究的持续时间超过 10 年。这些研究发现，结核病的发病率随着时间的推移而下降，在第 5 年时，每 100000 人年约有 200 例病例，在第 5 年之后可能会进一步下降，但由于队列规模减少或未指定，解释受到限制。在潜伏性结核病和暴露史未知的队列（第 3 组）中，结核病的发病率通常低于第 1 组和第 2 组，在筛查后 10 年以上，发病率已降至每 100000 人年 100 例以下。在所有研究中，再感染风险限制了对研究结果的解释，年龄的影响尚不清楚。晚期再激活率通常用于估计或建模，以确定结核病控制策略的优先次序，以实现结核病消除，但我们对这方面的理解仍存在重大差距，必须加以承认；晚期再激活与向结核病全球负担进展的相对重要性仍不清楚。
