Background

Contacts of tuberculosis index cases are at increased risk of developing tuberculosis. Screening, preventive therapy, and surveillance for tuberculosis are underused interventions in contacts, particularly adults. We developed a score to predict risk of tuberculosis in adult contacts of tuberculosis index cases.

Methods

In 2002–06, we recruited contacts aged 15 years or older of index cases with pulmonary tuberculosis who lived in desert shanty towns in Ventanilla, Peru. We followed up contacts for tuberculosis until February, 2016. We used a Cox proportional hazards model to identify index case, contact, and household risk factors for tuberculosis from which to derive a score and classify contacts as low, medium, or high risk. We validated the score in an urban community recruited in Callao, Peru, in 2014–15.

Findings

In the derivation cohort, we identified 2017 contacts of 715 index cases, and median follow-up was 10·7 years (IQR 9·5–11·8). 178 (9%) of 2017 contacts developed tuberculosis during 19 147 person-years of follow-up (incidence 0·93 per 100 person-years, 95% CI 0·80–1·08). Risk factors for tuberculosis were body-mass index, previous tuberculosis, age, sustained exposure to the index case, the index case being in a male patient, lower community household socioeconomic position, indoor air pollution, previous tuberculosis among household members, and living in a household with a low number of windows per room. The 10-year risks of tuberculosis in the low-risk, medium-risk, and high-risk groups were, respectively, 2·8% (95% CI 1·7–4·4), 6·2% (4·8–8·1), and 20·6% (17·3–24·4). The 535 (27%) contacts classified as high risk accounted for 60% of the tuberculosis identified during follow-up. The score predicted tuberculosis independently of tuberculin skin test and index-case drug sensitivity results. In the external validation cohort, 65 (3%) of 1910 contacts developed tuberculosis during 3771 person-years of follow-up (incidence 1·7 per 100 person-years, 95% CI 1·4–2·2). The 2·5-year risks of tuberculosis in the low-risk, medium-risk, and high-risk groups were, respectively, 1·4% (95% CI 0·7–2·8), 3·9% (2·5–5·9), and 8·6%· (5·9–12·6).

Interpretation

Our externally validated risk score could predict and stratify 10-year risk of developing tuberculosis in adult contacts, and could be used to prioritise tuberculosis control interventions for people most likely to benefit.

Funding

Wellcome Trust, Department for International Development Civil Society Challenge Fund, Joint Global Health Trials consortium, Bill & Melinda Gates Foundation, Imperial College National Institutes of Health Research Biomedical Research Centre, Foundation for Innovative New Diagnostics, Sir Halley Stewart Trust, WHO, TB REACH, and Innovation for Health and Development.

中文翻译：

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预测和分层成年结核病指数成人接触者结核病风险的评分：前瞻性推导和外部验证队列研究

背景

结核病指数病例的接触者患结核病的风险增加。对接触者（尤其是成年人）的筛查，预防性治疗和结核病监测未得到充分利用。我们开发了一个得分，以预测结核病指数病例中成人接触者的结核病风险。

方法

在2002-06年，我们招募了居住在秘鲁Ventanilla沙漠棚户区中的15岁或以上的肺结核指数病例接触者。我们对结核病接触者进行了跟踪调查，直到2016年2月。我们使用Cox比例风险模型来识别结核病的指数病例，接触者和家庭危险因素，从中得出分数并将接触者分类为低，中或高风险。我们在2014-15年度在秘鲁卡亚俄（Callao）招募的一个城市社区中对该分数进行了验证。

发现

在派生队列中，我们确定了2017年有715例索引病例的接触者，中位随访时间为10·7年（IQR 9·5-11·8）。2017年有178名（9％）接触者在19 147人-年的随访期间患了肺结核（发病率每100人年0·93，95％CI 0·80-1·08）。结核病的危险因素有：身体质量指数，以前的结核病，年龄，持续暴露于该指数病例，该指数病例是男性患者，较低的社区家庭社会经济地位，室内空气污染，家庭成员中以前的结核病以及在该地区居住的人。每个房间窗户数量少的家庭。低风险，中风险和高风险组的10年结核病风险分别为2·8％（95％CI 1·7-4·4），6·2％（4· 8–8·1）和20·6％（17·3-24·4）。535名（27％）接触者被归类为高危人群，占随访期间发现的结核病的60％。该分数独立于结核菌素皮肤试验和指数病例药物敏感性结果而预测结核病。在外部验证队列中，1910年接触者中有65名（3％）在3771人年的随访期间患了肺结核（发病率每100人年1·7，95％CI 1·4-2·2）。低危，中危和高危人群的2〜5年结核病风险分别为1·4％（95％CI 0·7-2·8），3·9％（ 2·5-5·9）和8·6％·（5·9-12·6）。1910个接触者中有65个（3％）在3771人年的随访期间患了肺结核（发病率每100人年1·7，95％CI 1·4-2·2）。低危，中危和高危组的2〜5年结核病风险分别为1·4％（95％CI 0·7-2·8），3·9％（ 2·5-5·9）和8·6％·（5·9-12·6）。1910个接触者中有65个（3％）在3771人年的随访期间患了肺结核（发病率每100人年1·7，95％CI 1·4-2·2）。低危，中危和高危组的2〜5年结核病风险分别为1·4％（95％CI 0·7-2·8），3·9％（ 2·5-5·9）和8·6％·（5·9-12·6）。

解释

我们的外部验证风险评分可以预测和分层成人接触者患结核病的10年风险，并且可以用于为最有可能受益的人群确定结核病控制干预措施的优先级。

资金

惠康信托基金，国际发展部民间社会挑战基金，全球健康试验联合财团，比尔和梅琳达·盖茨基金会，帝国大学国立卫生研究院生物医学研究中心，创新新诊断基金会，哈雷·斯图尔特爵士信托基金会，世卫组织，TB REACH ，以及“健康与发展创新”。