Development of a standardized screening rule for tuberculosis in people living with HIV in resource-constrained settings: individual participant data meta-analysis of observational studies.
Development of a standardized screening rule for tuberculosis in people living with HIV in resource-constrained settings: individual participant data meta-analysis of observational studies.
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DOI：
10.1371/journal.pmed.1000391
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发表时间：
2011-01-18
期刊：
影响因子：
15.8
通讯作者：
Varma JK
中科院分区：
文献类型：
--
作者：
Getahun H;Kittikraisak W;Heilig CM;Corbett EL;Ayles H;Cain KP;Grant AD;Churchyard GJ;Kimerling M;Shah S;Lawn SD;Wood R;Maartens G;Granich R;Date AA;Varma JK
Haileyesus Getahun 及其同事报告了针对资源有限环境制定的简单、标准化结核病 (TB) 筛查规则，以识别需要进一步检查结核病的艾滋病毒感染者。世界卫生组织建议对所有艾滋病毒感染者进行结核病 (TB) 筛查，然后进行结核病治疗，或在排除结核病时进行异烟肼预防性治疗 (IPT)。然而，可靠地排除结核病的困难严重限制了资源有限环境下的结核病筛查和异烟肼治疗的采用。我们对初步研究进行了个体参与者数据荟萃分析，旨在确定敏感的结核病筛查规则。我们确定了 12 项研究，这些研究系统地收集了痰标本，无论体征或症状、至少一种分枝杆菌培养物、临床症状以及艾滋病毒和结核病状态。双变量随机效应荟萃分析和分层汇总相对操作特征曲线用于评估所有感兴趣变量组合的筛选性能。 9,626 名艾滋病毒感染者中，有 557 名 (5.8%) 被诊断出结核病。主要分析包括 8,148 名艾滋病毒感染者，可以对 12 项研究中的 9 项研究中的 5 种症状进行评估。中位年龄为 34 岁。表现最好的规则是存在以下任何一种情况：当前咳嗽（任何持续时间）、发烧、盗汗或体重减轻。该规则的总体敏感性为 78.9%（95% 置信区间 [CI] 58.3%–90.9%），特异性为 49.6%（95% CI 29.2%–70.1%）。在从临床环境中选择的参与者中，其敏感性增加至 90.1%（95% CI 76.3%–96.2%），而在之前未接受结核病筛查的参与者中，其敏感性增加至 88.0%（95% CI 76.1%–94.4%）。 HIV 感染者中结核病患病率 5% 和 20% 时，阴性预测值分别为 97.7%（95% CI 97.4%–98.0%）和 90.0%（95% CI 88.6%–91.3%）。异常的胸部X光检查结果使规则的敏感性增加了11.7%（90.6%对78.9%），而特异性降低了10.7%（49.6%对38.9%）。当前没有出现咳嗽、发烧、盗汗和体重减轻的情况，可以识别出患有结核病的可能性非常低的艾滋病毒感染者子集。在资源有限的环境中，可以使用使用上述任何一种症状的简化筛查规则来识别需要进一步进行结核病诊断评估的艾滋病毒感染者。使用该算法应能实现早期结核病诊断和治疗，并可大幅扩大 IPT 规模。 请参阅本文后面的编辑摘要 2009 年，170 万人死于结核病 (TB)，相当于每天有 4,700 人死亡，其中包括 380,000 名艾滋病毒感染者。结核病仍然是艾滋病毒感染者最常见的死亡原因，与未感染艾滋病毒的人相比，艾滋病毒感染者患结核病的可能性高出 20 倍以上。此外，结核感染可能发生在艾滋病毒疾病的任何阶段，并且通常是潜在艾滋病毒感染的最初表现。如果不进行抗逆转录病毒治疗，高达 50% 的被诊断患有结核病的艾滋病毒感染者会在 6-8 个月的结核病治疗期间死亡。尽管抗逆转录病毒治疗可以降低个人和人群层面的结核病发病率，但接受抗逆转录病毒治疗的艾滋病毒感染者的结核病发病率和死于结核病的风险仍然较高。因此，世界卫生组织建议对所有艾滋病毒感染者定期筛查活动性结核病，以便为那些被确定患有活动性结核病的人提供适当的治疗，并且可以对尚未患有活动性结核病的弱势个体进行异烟肼预防性治疗（以帮助降低结核病发病率、死亡率和传播）。目前还没有国际公认的循证工具来筛查艾滋病毒感染者中的结核病，鉴于艾滋病毒感染者中出现的结核病体征和症状与未感染艾滋病毒的人不同，因此存在严重差距。因此，研究人员旨在根据现有最佳证据，为资源有限的环境制定一种简单、标准化的结核病筛查规则，以充分区分不太可能患有结核病的艾滋病毒感染者和需要进一步检查结核病的患者。研究人员选择了 12 项符合严格标准的研究，然后向这些研究的作者询问主要数据，以便他们能够绘制个人数据，以确定大多数研究中常见的五种症状。研究人员利用统计模型，设计了源自这五种症状的 23 条筛查规则，并使用荟萃分析方法（双变量随机效应荟萃分析）以及研究水平和个体水平相关性的关联（分层总结相对操作特征曲线）来评估每项单独研究中使用的每种工具的敏感性和特异性。所选研究的作者能够提供 29,523 名参与者的数据，其中 10,057 名是艾滋病毒感染者。该数据集包括 9,626 名接受过结核病筛查和痰培养的艾滋病毒感染者，其中 8,148 名患者可以根据 12 项研究中的 9 项研究中的 5 种感兴趣的症状进行评估。 5.8% 的艾滋病毒感染者被诊断出结核病，最佳执行规则是存在以下任何一项：当前咳嗽（任何持续时间）、发烧、盗汗或体重减轻。该规则的总体敏感性为 78.9%，特异性为 49.6%。然而，在从临床环境中选择的参与者中，该规则的敏感性增加到 90.1%，在之前未进行结核病筛查的参与者中，该规则的敏感性增加到 88.0%。这项研究的结果表明，在资源有限的环境中，当前没有咳嗽、发烧、盗汗和体重减轻（全部包括在内）的情况可以识别出患有结核病的可能性较低的艾滋病毒感染者。此外，这些症状中的任何一种都可以在资源有限的环境中用于识别需要进一步诊断评估结核病的艾滋病毒感染者。尽管本研究中使用的方法存在局限性，但在有基于证据的国际推荐的艾滋病毒感染者结核病诊断和治疗指南之前，使用本研究中开发和提出的算法可能会导致艾滋病毒感染者的早期结核病诊断和治疗，并有助于大幅扩大异烟肼预防性治疗。请通过本摘要的在线版本访问这些网站：http://dx.doi.org/10.1371/journal.pmed.1000391。世界卫生组织提供有关艾滋病毒感染者结核病的信息 美国疾病控制与预防中心还提供有关结核病和艾滋病毒双重感染的信息 世界卫生组织还提供有关异烟肼预防性治疗的信息 遏制结核病伙伴关系的结核病/艾滋病毒工作组提供有关结核病和艾滋病毒双重感染的信息
Haileyesus Getahun and colleagues report the development of a simple, standardized tuberculosis (TB) screening rule for resource-constrained settings, to identify people living with HIV who need further investigation for TB disease. The World Health Organization recommends the screening of all people living with HIV for tuberculosis (TB) disease, followed by TB treatment, or isoniazid preventive therapy (IPT) when TB is excluded. However, the difficulty of reliably excluding TB disease has severely limited TB screening and IPT uptake in resource-limited settings. We conducted an individual participant data meta-analysis of primary studies, aiming to identify a sensitive TB screening rule. We identified 12 studies that had systematically collected sputum specimens regardless of signs or symptoms, at least one mycobacterial culture, clinical symptoms, and HIV and TB disease status. Bivariate random-effects meta-analysis and the hierarchical summary relative operating characteristic curves were used to evaluate the screening performance of all combinations of variables of interest. TB disease was diagnosed in 557 (5.8%) of 9,626 people living with HIV. The primary analysis included 8,148 people living with HIV who could be evaluated on five symptoms from nine of the 12 studies. The median age was 34 years. The best performing rule was the presence of any one of: current cough (any duration), fever, night sweats, or weight loss. The overall sensitivity of this rule was 78.9% (95% confidence interval [CI] 58.3%–90.9%) and specificity was 49.6% (95% CI 29.2%–70.1%). Its sensitivity increased to 90.1% (95% CI 76.3%–96.2%) among participants selected from clinical settings and to 88.0% (95% CI 76.1%–94.4%) among those who were not previously screened for TB. Negative predictive value was 97.7% (95% CI 97.4%–98.0%) and 90.0% (95% CI 88.6%–91.3%) at 5% and 20% prevalence of TB among people living with HIV, respectively. Abnormal chest radiographic findings increased the sensitivity of the rule by 11.7% (90.6% versus 78.9%) with a reduction of specificity by 10.7% (49.6% versus 38.9%). Absence of all of current cough, fever, night sweats, and weight loss can identify a subset of people living with HIV who have a very low probability of having TB disease. A simplified screening rule using any one of these symptoms can be used in resource-constrained settings to identify people living with HIV in need of further diagnostic assessment for TB. Use of this algorithm should result in earlier TB diagnosis and treatment, and should allow for substantial scale-up of IPT. Please see later in the article for the Editors' Summary In 2009, 1.7 million people died from tuberculosis (TB)—equating to 4,700 deaths a day—including 380,000 people living with HIV. TB remains the most common cause of death in people living with HIV and compared to people without HIV, people living with HIV are more than 20 times more likely to develop TB. Furthermore, TB infection may occur at any stage of HIV disease and is often the initial presentation of underlying HIV infection. Without antiretroviral treatment, up to 50% of people living with HIV who are diagnosed with TB die during the 6–8 months of TB treatment. Although antiretroviral treatment can reduce the incidence of TB both at the individual and population level, people living with HIV on antiretroviral treatment still have higher TB incidence rates and a higher risk of dying from TB. Therefore, the World Health Organization recommends regular screening for active TB disease in all people living with HIV, so those identified as having active TB disease can be provided with appropriate treatment, and isoniazid preventive therapy (to help mitigate TB morbidity, mortality, and transmission) can be given to vulnerable individuals who do not yet have active TB. There is currently no internationally accepted evidence-based tool to screen for TB in people living with HIV—a serious gap given that the presenting signs and symptoms of TB in people living with HIV are different from those in people without HIV. Therefore, the researchers aimed to develop a simple, standardized TB screening rule for resource-constrained settings, on the basis of the best available evidence that would adequately distinguish between people living with HIV who are very unlikely to have TB from those who require further investigation for TB disease. The researchers selected 12 studies that met their strict criteria, then asked the authors of these studies for primary data so that they could map individual-level data to identify five symptoms common to most studies. Using a statistical model, the researchers devised 23 screening rules derived from these five symptoms and used meta-analysis methods (bivariate random-effects meta-analysis) and the association of study-level and individual-level correlates (hierarchical summary relative operating characteristic curves) to evaluate the sensitivity and specificity of each tool used in each individual study. The authors of the selected studies were able to provide data for 29,523 participants, of whom 10,057 were people living with HIV. The dataset included 9,626 people living with HIV who had TB screening and sputum culture performed, of which 8,148 individuals could be evaluated on the five symptoms of interest from nine of 12 studies. TB disease was diagnosed in 5.8% of people living with HIV and the best performing rule was the presence of any one of the following: current cough (any duration), fever, night sweats, or weight loss. The overall sensitivity of the rule was 78.9% and the specificity was 49.6%. However, the sensitivity of the rule increased to 90.1% among participants selected from clinical settings and to 88.0% among those who were not previously screened for TB. The results of this study suggest that in resource-constrained settings, the absence of current cough, fever, night sweats, and weight loss (all inclusive) can identify those people living with HIV who have a low probability of having TB disease. Furthermore, any one of these symptoms can be used in resource-constrained settings to identify people living with HIV who are in need of further diagnostic assessment for TB. Despite the limitations of the methodology used in this study, until there are evidence-based and internationally recommended guidelines for the diagnosis and treatment of TB in people living with HIV, use of the algorithm developed and presented in this study could result in earlier TB diagnosis and treatment for people living with HIV and could help to substantially scale-up isoniazid preventive therapy. Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000391. The World Health Organization has information about TB in people living with HIV The US Centers for Disease Control and Prevention also provide information about TB and HIV coinfection The World Health Organization also has information about isoniazid preventative therapy The Stop TB Partnership's TB/HIV Working Group provide information about TB and HIV co-infection
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高艾滋病毒患病率的结核病流行病学和症状疾病的诊断增加。
影响因子：
15.8
作者：
Corbett, Elizabeth L.;Bandason, Tsitsi;Cheung, Yin Bun;Munyati, Shungu;Godfrey-Faussett, Peter;Hayes, Richard;Churchyard, Gavin;Butterworth, Anthony;Mason, Peter
通讯作者：
Mason, Peter
影响因子：
9.4
作者：
Cruciani, M;Scarparo, C;Mengoli, C
通讯作者：
Mengoli, C
影响因子：
120.7
作者：
Havlir, Diane V.;Getahun, Haileyesus;Nunn, Paul
通讯作者：
Nunn, Paul
影响因子：
3.7
作者：
Ayles, Helen;Schaap, Albertus;Godfrey-Faussett, Peter
通讯作者：
Godfrey-Faussett, Peter
影响因子：
3.8
作者：
Burgess, AL;Fitzgerald, DW;Pape, JW
通讯作者：
Pape, JW