Reevaluating progression and pathways following Mycobacterium tuberculosis infection within the spectrum of tuberculosis.
Reevaluating progression and pathways following Mycobacterium tuberculosis infection within the spectrum of tuberculosis.
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重新评估结核谱系内结核分枝杆菌感染后的进展和途径。
DOI：
10.1073/pnas.2221186120
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发表时间：
2023-11-21
影响因子：
11.1
通讯作者：
Houben, Rein M. G. J.
中科院分区：
文献类型：
--
作者：
Horton, Katherine C.;Richards, Alexandra S.;Emery, Jon C.;Esmail, Hanif;Houben, Rein M. G. J.
对结核分枝杆菌（Mtb）感染后进展为结核病（TB）的风险的理解传统上依赖于感染和感染性症状性疾病之间的二元区分。然而，这种晚期疾病状态只是一系列疾病表现中的一种。我们利用数学建模告知结核病自然史的广泛系统性审查，以重新评估结核分枝杆菌感染后的进展和途径。我们显示了不同疾病阈值的影响，并通过疾病谱突出了异质性途径。这些结果更新了我们对结核病进展风险和时间表的理解，以指导更有效的预防，检测和治疗工作，并避免发病和传播，以结束结核病。对结核分枝杆菌（Mtb）感染进展为结核病（TB）风险的传统理解忽略了疾病谱中的不同表现。我们开发了结核分枝杆菌感染和最小（病理损伤，但没有传染性），亚临床（传染性，但没有报告的症状），和临床（传染性和症状）结核病的确定性模型，通过严格的评估数据从结核病自然史的系统性审查。使用贝叶斯方法，我们校准模型的数据，从历史队列，结核菌素阴性的个人结核菌素转换和结核病，以及队列的数据，疾病状态，疾病状态患病率，疾病持续时间和死亡率之间的进展和回归。我们估计了模拟队列中结核分枝杆菌感染后的发病率、途径和10年结局。然后，92.0%（95%不确定性区间，UI，91.4至92.5）的个体在感染后10年内自我清除，而7.9%（95% UI 7.4至8.5）进展为TB。其中，68.6%（95%UI 65.4至72.0）发展为感染性疾病，33.2%（95%UI 29.9至36.4）进展为临床疾病。虽然98%的进展为轻微疾病发生在感染后2年内，但在此期间分别仅71%和44%的亚临床和临床疾病发生。感染的多个进展途径是校准模型所必需的，49.5%（95%UI 45.6至53.7）的感染性疾病患者在疾病状态之间波动。我们确定了结核分枝杆菌感染后疾病状态的异质性途径，强调需要明确定义的疾病阈值，以提供更有效的预防和治疗工作，以结束结核病。
Understanding of the risk of progression to tuberculosis (TB) after infection with Mycobacterium tuberculosis (Mtb) has traditionally relied on a binary distinction between infection and infectious, symptomatic disease. However, this advanced disease state is only one of many across a spectrum of disease presentations. We utilized mathematical modeling informed by an extensive systematic review of TB natural history to reevaluate progression and pathways following Mtb infection. We show the impact of different disease thresholds and highlight heterogeneous pathways through the spectrum of disease. These results update our understanding of progression risks and timelines in line with the spectrum of TB to guide more effective prevention, detection, and treatment efforts and avert morbidity and transmission to end TB. Traditional understanding of the risk of progression from Mycobacterium tuberculosis (Mtb) infection to tuberculosis (TB) overlooks diverse presentations across a spectrum of disease. We developed a deterministic model of Mtb infection and minimal (pathological damage but not infectious), subclinical (infectious but no reported symptoms), and clinical (infectious and symptomatic) TB, informed by a rigorous evaluation of data from a systematic review of TB natural history. Using a Bayesian approach, we calibrated the model to data from historical cohorts that followed tuberculin-negative individuals to tuberculin conversion and TB, as well as data from cohorts that followed progression and regression between disease states, disease state prevalence ratios, disease duration, and mortality. We estimated incidence, pathways, and 10-y outcomes following Mtb infection for a simulated cohort. Then, 92.0% (95% uncertainty interval, UI, 91.4 to 92.5) of individuals self-cleared within 10 y of infection, while 7.9% (95% UI 7.4 to 8.5) progressed to TB. Of those, 68.6% (95% UI 65.4 to 72.0) developed infectious disease, and 33.2% (95% UI 29.9 to 36.4) progressed to clinical disease. While 98% of progression to minimal disease occurred within 2 y of infection, only 71% and 44% of subclinical and clinical disease, respectively, occurred within this period. Multiple progression pathways from infection were necessary to calibrate the model and 49.5% (95% UI 45.6 to 53.7) of those who developed infectious disease undulated between disease states. We identified heterogeneous pathways across disease states after Mtb infection, highlighting the need for clearly defined disease thresholds to inform more effective prevention and treatment efforts to end TB.
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DOI：
10.1007/bf02148098
发表时间：
1954-01-01
期刊：
Beitrage zur Klinik der Tuberkulose und spezifischen Tuberkulose-Forschung
影响因子：
--
作者：
BREU, K
通讯作者：
BREU, K
DOI：
10.1136/bmj.k2738
发表时间：
2018-08-23
期刊：
BMJ (Clinical research ed.)
影响因子：
--
作者：
Behr MA;Edelstein PH;Ramakrishnan L
通讯作者：
Ramakrishnan L
影响因子：
19.7
作者：
BOBROWITZ, ID;HURST, A
通讯作者：
HURST, A
DOI：
10.2307/3347663
发表时间：
1938-07-01
期刊：
MILBANK MEMORIAL FUND QUARTERLY
影响因子：
--
作者：
Downes, Jean
通讯作者：
Downes, Jean
DOI：
10.1038/nrmicro2236
发表时间：
2009-12
期刊：
Nature reviews. Microbiology
影响因子：
--
作者：
通讯作者：
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