Estimating the contribution of subclinical tuberculosis disease to transmission: An individual patient data analysis from prevalence surveys.
Estimating the contribution of subclinical tuberculosis disease to transmission: An individual patient data analysis from prevalence surveys.
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DOI：
10.7554/elife.82469
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发表时间：
2023-12-18
期刊：
影响因子：
7.7
通讯作者：
Houben RMGJ
中科院分区：
文献类型：
--
作者：
Emery JC;Dodd PJ;Banu S;Frascella B;Garden FL;Horton KC;Hossain S;Law I;van Leth F;Marks GB;Nguyen HB;Nguyen HV;Onozaki I;Quelapio MID;Richards AS;Shaikh N;Tiemersma EW;White RG;Zaman K;Cobelens F;Houben RMGJ
未报告症状的细菌学确诊肺结核（TB）患者（亚临床TB）约占所有结核病流行病例的一半，但其对结核分枝杆菌（Mtb）传播的贡献尚不清楚，特别是与诊断时报告症状的患者（临床TB）相比。相对传染性可以通过家庭接触者的累积感染来估算，但这种数据很少。我们回顾了文献，以确定结核分枝杆菌感染调查与结核病人口调查相关的研究。我们整理了代表性人群的个体水平数据进行分析，并使用关于亚临床和临床结核病相对持续时间的文献，通过累积风险模型估计相对传染性，说明了结核病涂片状态。亚临床和临床疾病在高负担环境中的相对流行率被用来估计亚临床结核病对全球结核病传播的贡献。我们整理了来自三项流行率调查（孟加拉国、菲律宾和越南）和一项越南病例发现试验的414例指数病例和789例家庭接触者的数据。临床与亚临床指标病例（不考虑痰涂片状态）家庭感染的比值比为1.2（0.6-2.3，95%置信区间）。调整疾病持续时间后，我们发现亚临床结核相对于临床结核的单位时间传染性为1.93（0.62-6.18，95%预测区间[PrI]）。亚洲和非洲的14个国家提供了亚临床和临床结核病相对流行率的数据，表明估计68%（27- 92%，95% PrI）的全球传播来自亚临床结核病。我们的研究结果表明，亚临床结核病在很大程度上有助于传播，需要进行诊断和治疗，以有效地实现消除结核病的进展。JCE、KCH、ASR、NS和RH已获得欧洲研究理事会（ERC）在地平线2020研究和创新计划下的资助（ERC启动资助编号757699）KCH还得到英国FCDO的支持（不让任何人掉队：将性别化途径转变为结核病健康途径）。这项研究部分由英国政府（对KCH）的英国援助资助;然而，所表达的观点并不一定反映英国政府的官方政策。PJD由英国医学研究理事会（MR/P022081/1）的奖学金支持;这个英国资助的奖项是由欧盟支持的EDCTP 2计划的一部分。RGW由Wellcome Trust提供资金（218261/Z/19/Z）、NIH（1R01AI147321-01）、EDTCP（RIA208D-2505B）、UK MRC（CCF 17 -7779 via SET Bloomsbury）、ESRC（ES/P008011/1）、BMGF（OPP1084276、OPP1135288和INV-001754）和WHO（2020/985800-0）。
Individuals with bacteriologically confirmed pulmonary tuberculosis (TB) disease who do not report symptoms (subclinical TB) represent around half of all prevalent cases of TB, yet their contribution to Mycobacterium tuberculosis (Mtb) transmission is unknown, especially compared to individuals who report symptoms at the time of diagnosis (clinical TB). Relative infectiousness can be approximated by cumulative infections in household contacts, but such data are rare. We reviewed the literature to identify studies where surveys of Mtb infection were linked to population surveys of TB disease. We collated individual-level data on representative populations for analysis and used literature on the relative durations of subclinical and clinical TB to estimate relative infectiousness through a cumulative hazard model, accounting for sputum-smear status. Relative prevalence of subclinical and clinical disease in high-burden settings was used to estimate the contribution of subclinical TB to global Mtb transmission. We collated data on 414 index cases and 789 household contacts from three prevalence surveys (Bangladesh, the Philippines, and Viet Nam) and one case-finding trial in Viet Nam. The odds ratio for infection in a household with a clinical versus subclinical index case (irrespective of sputum smear status) was 1.2 (0.6–2.3, 95% confidence interval). Adjusting for duration of disease, we found a per-unit-time infectiousness of subclinical TB relative to clinical TB of 1.93 (0.62–6.18, 95% prediction interval [PrI]). Fourteen countries across Asia and Africa provided data on relative prevalence of subclinical and clinical TB, suggesting an estimated 68% (27–92%, 95% PrI) of global transmission is from subclinical TB. Our results suggest that subclinical TB contributes substantially to transmission and needs to be diagnosed and treated for effective progress towards TB elimination. JCE, KCH, ASR, NS, and RH have received funding from the European Research Council (ERC) under the Horizon 2020 research and innovation programme (ERC Starting Grant No. 757699) KCH is also supported by UK FCDO (Leaving no-one behind: transforming gendered pathways to health for TB). This research has been partially funded by UK aid from the UK government (to KCH); however, the views expressed do not necessarily reflect the UK government’s official policies. PJD was supported by a fellowship from the UK Medical Research Council (MR/P022081/1); this UK-funded award is part of the EDCTP2 programme supported by the European Union. RGW is funded by the Wellcome Trust (218261/Z/19/Z), NIH (1R01AI147321-01), EDTCP (RIA208D-2505B), UK MRC (CCF17-7779 via SET Bloomsbury), ESRC (ES/P008011/1), BMGF (OPP1084276, OPP1135288 and INV-001754), and the WHO (2020/985800-0).