Infant BCG vaccination and risk of pulmonary and extrapulmonary tuberculosis throughout the life course: a systematic review and individual participant data meta-analysis.
Infant BCG vaccination and risk of pulmonary and extrapulmonary tuberculosis throughout the life course: a systematic review and individual participant data meta-analysis.
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DOI：
10.1016/s2214-109x(22)00283-2
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发表时间：
2022-09
影响因子：
34.3
通讯作者：
Andrews, Jason R.
中科院分区：
文献类型：
--
作者：
Martinez, Leonardo;Cords, Olivia;Liu, Qiao;Acuna-Villaorduna, Carlos;Bonnet, Maryline;Fox, Greg J.;Carvalho, Anna Cristina C.;Chan, Pei-Chun;Croda, Julio;Hill, Philip C.;Lopez-Varela, Elisa;Donkor, Simon;Fielding, Katherine;Graham, Stephen M.;Espinal, Marcos A.;Kampmann, Beate;Reingold, Arthur;Huerga, Helena;Villalba, Julian A.;Grandjean, Louis;Sotgiu, Giovanni;Egere, Uzochukwu;Singh, Sarman;Zhu, Limei;Lienhardt, Christian;Denholm, Justin T.;Seddon, James A.;Whalen, Christopher C.;Garcia-Basteiro, Alberto L.;Triasih, Rina;Chen, Cheng;Singh, Jitendra;Huang, Li-Min;Sharma, Surendra;Hannoun, Djohar;Del Corral, Helena;Mandalakas, Anna M.;Malone, LaShaunda L.;Ling, Du-Lin;Kritski, Afranio;Stein, Catherine M.;Vashishtha, Richa;Boulahbal, Fadila;Fang, Chi-Tai;Boom, W. Henry;Netto, Eduardo Martins;Lemos, Antonio Carlos;Hesseling, Anneke C.;Kay, Alexander;Jones-Lopez, Edward C.;Horsburgh, C. Robert;Lange, Christoph;Andrews, Jason R.
每年有1亿多儿童接种卡介苗，但关于卡介苗接种在预防结核病和死亡方面的有效性，特别是在年龄较大的儿童和成人中，存在相当大的争论。因此，我们的目的是调查婴儿卡介苗接种对结核病（肺和肺外）发展和死亡率的年龄特异性影响。在这项系统性综述和个体受试者数据荟萃分析中，我们在MEDLINE、Web of Science、BIOSIS和Embase中无语言限制地检索了1998年1月1日至2018年4月7日期间发表的结核病接触者病例接触队列研究。检索词包括“结核分枝杆菌”、“TB”、“结核病”和“接触”。我们排除了没有提供卡介苗接种信息的队列研究，或者在不推荐出生时接种卡介苗的国家进行的队列研究。要求所有合格研究的作者提供预先指定变量列表的个体水平参与者数据，包括暴露参与者（接触者）的特征、索引病例和环境。我们的主要结果是暴露于结核病的接触者中的流行（在基线或基线后90天内诊断）和事件（基线后90天以上诊断）结核病的复合。次要结局为肺结核、肺外结核和死亡率。我们采用混合效应、二元、多变量logistic回归分析和研究水平随机效应，调整了相关变量、基线年龄、性别、既往结核病史以及数据是前瞻性还是回顾性收集，得出了调整后的比值比（aOR）。我们根据接触年龄和结核分枝杆菌感染状况对结果进行分层。本研究在PROSPERO注册，CRD 42020180512。我们从数据库检索中确定了14927条原始记录。在我们的荟萃分析中，我们纳入了来自17个国家的26项队列研究的参与者水平数据。在68552名参与者中，1782名（2.6%）患上了结核病（49686名接种BCG的参与者中有1309名[2.6%]，而18866名未接种疫苗的参与者中有473名[2.5%]）。卡介苗接种对所有结核病的总有效率为18%（aOR 0.82，95%CI 0.74 - 0.91）。当按年龄分层时，卡介苗接种仅对5岁以下儿童的所有结核病具有显著保护作用（aOR 0.63，95%CI 0.49 - 0.81）。在结核菌素皮试或IFNγ释放试验阳性的接触者中，卡介苗接种在所有参与者（aOR 0·81，95% CI 0·69-0·96）、5岁以下参与者（0·68，0·47-0·97）和5-9岁参与者（0·62，0·38-0·99）中对结核病具有显著保护作用。在阴性试验者中没有保护作用，除非他们小于5岁（0.54，0.32 - 0.90）。14个队列报告了肺结核或肺外结核（n=57 421）。卡介苗接种对所有参与者的肺结核具有显著保护作用（41119名接种疫苗的参与者中有916名[2.2%]，而16161名未接种疫苗的参与者中有334名[2.1%]; aOR 0.81，0.70 ~ 0.94），但对肺外结核无明显影响（40318名接种疫苗的参与者中有106名[0.3%]，而15865名未接种疫苗的参与者中有38名[0.2%]; 0.96，0.65 - 1.41）。在有死亡率数据的四项研究中，卡介苗接种对死亡具有显著的保护作用（0.25，0.13 - 0.49）。我们的研究结果表明，出生时接种卡介苗对预防幼儿结核病有效，但对青少年和成人无效。因此，需要在老年人群中加强免疫保护。国立卫生研究院。
BCG vaccines are given to more than 100 million children every year, but there is considerable debate regarding the effectiveness of BCG vaccination in preventing tuberculosis and death, particularly among older children and adults. We therefore aimed to investigate the age-specific impact of infant BCG vaccination on tuberculosis (pulmonary and extrapulmonary) development and mortality. In this systematic review and individual participant data meta-analysis, we searched MEDLINE, Web of Science, BIOSIS, and Embase without language restrictions for case-contact cohort studies of tuberculosis contacts published between Jan 1, 1998, and April 7, 2018. Search terms included “mycobacterium tuberculosis”, “TB”, “tuberculosis”, and “contact”. We excluded cohort studies that did not provide information on BCG vaccination or were done in countries that did not recommend BCG vaccination at birth. Individual-level participant data for a prespecified list of variables, including the characteristics of the exposed participant (contact), the index case, and the environment, were requested from authors of all eligible studies. Our primary outcome was a composite of prevalent (diagnosed at or within 90 days of baseline) and incident (diagnosed more than 90 days after baseline) tuberculosis in contacts exposed to tuberculosis. Secondary outcomes were pulmonary tuberculosis, extrapulmonary tuberculosis, and mortality. We derived adjusted odds ratios (aORs) using mixed-effects, binary, multivariable logistic regression analyses with study-level random effects, adjusting for the variable of interest, baseline age, sex, previous tuberculosis, and whether data were collected prospectively or retrospectively. We stratified our results by contact age and Mycobacterium tuberculosis infection status. This study is registered with PROSPERO, CRD42020180512. We identified 14 927 original records from our database searches. We included participant-level data from 26 cohort studies done in 17 countries in our meta-analysis. Among 68 552 participants, 1782 (2·6%) developed tuberculosis (1309 [2·6%] of 49 686 BCG-vaccinated participants vs 473 [2·5%] of 18 866 unvaccinated participants). The overall effectiveness of BCG vaccination against all tuberculosis was 18% (aOR 0·82, 95% CI 0·74–0·91). When stratified by age, BCG vaccination only significantly protected against all tuberculosis in children younger than 5 years (aOR 0·63, 95% CI 0·49–0·81). Among contacts with a positive tuberculin skin test or IFNγ release assay, BCG vaccination significantly protected against tuberculosis among all participants (aOR 0·81, 95% CI 0·69–0·96), participants younger than 5 years (0·68, 0·47–0·97), and participants aged 5–9 years (0·62, 0·38–0·99). There was no protective effect among those with negative tests, unless they were younger than 5 years (0·54, 0·32–0·90). 14 cohorts reported on whether tuberculosis was pulmonary or extrapulmonary (n=57 421). BCG vaccination significantly protected against pulmonary tuberculosis among all participants (916 [2·2%] in 41 119 vaccinated participants vs 334 [2·1%] in 16 161 unvaccinated participants; aOR 0·81, 0·70–0·94) but not against extrapulmonary tuberculosis (106 [0·3%] in 40 318 vaccinated participants vs 38 [0·2%] in 15 865 unvaccinated participants; 0·96, 0·65–1·41). In the four studies with mortality data, BCG vaccination was significantly protective against death (0·25, 0·13–0·49). Our results suggest that BCG vaccination at birth is effective at preventing tuberculosis in young children but is ineffective in adolescents and adults. Immunoprotection therefore needs to be boosted in older populations. National Institutes of Health.