BACKGROUND Paediatric tuberculosis leads to more than 200 000 deaths annually. We aimed to investigate the incidence of Mycobacterium tuberculosis infection and tuberculosis disease in the first decade of life in the Drakenstein Child Health Study (DCHS), a South African cohort in a community with high tuberculosis and HIV incidence. METHODS In this prospective birth cohort study, we enrolled pregnant women aged 18 years or older who were between 20 and 28 weeks' of gestation in a peri-urban setting outside of Cape Town, South Africa. We followed up their children for tuberculosis until age 10 years. To measure M tuberculosis infection tuberculin skin tests were administered to children at age 6 months, 12 months, and then annually in children with a negative test, and at the time of a lower respiratory tract infection. Tuberculin skin test conversion was defined by an induration reaction of 10 mm or more. To measure tuberculosis disease, active surveillance was done throughout follow-up. Each episode of presumed tuberculosis disease was investigated using sputum induction, tested with Xpert MTB/RIF and liquid culture for M tuberculosis. Survival analyses were performed and multivariable Cox regression was used to measure factors associated with M tuberculosis infection or disease. FINDINGS Between March 5, 2012, and March 31, 2015, 1137 women and their 1143 children (248 [21·7%] of 1143 children were HIV-exposed, two [0·2%] children with HIV) were included in the analysis. Children were followed up for 8870 person-years (median follow-up 9·1 years [IQR 8·2-10·2]). The annual risk of tuberculin conversion during follow-up was 6·6 infections per 100 person-years (95% CI 5·8-7·3) but ranged from 4-9 infections per 100 person-years over the follow-up period. 98 children developed tuberculosis (1105 cases per 100 000 person-years; 95% CI 906-1347). The cumulative hazard of tuberculin conversion was 36% (95% CI 32-41) at age 8 years and the cumulative hazard of tuberculosis disease was 10% (8-12) at age 10 years. Preventive treatment was associated with a reduction in tuberculosis disease among children who had tuberculin conversion (adjusted hazard ratio 0·23 [95% CI 0·12-0·47]). Most cases of tuberculosis disease (78 [79%; 95% CI 69-86] of 98 children) occurred among children who had tuberculin skin test conversion but were not administered preventive treatment. INTERPRETATION In this prospective South African birth cohort, M tuberculosis transmission was consistently high throughout the first decade of life leading to approximately 10% of children developing tuberculosis disease. A multipronged approach to decrease paediatric tuberculosis is needed that combines preventive treatment for children at risk, reducing community M tuberculosis transmission, and active case finding. FUNDING Bill & Melinda Gates Foundation, Medical Research Council South Africa, and National Research Foundation South Africa.

中文翻译：

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结核分枝杆菌感染和生命最初十年的结核病：南非出生队列研究。


背景 儿童结核病每年导致超过 200 000 人死亡。我们旨在调查 Drakenstein 儿童健康研究 （DCHS） 中结核分枝杆菌感染和结核病在生命最初十年的发病率，该研究是南非结核病和 HIV 发病率高的社区的队列。方法 在这项前瞻性出生队列研究中，我们在南非开普敦郊外的城郊环境中招募了 18 岁或以上的妊娠 20 至 28 周的孕妇。我们对他们的孩子进行肺结核随访，直到 10 岁。为了测量结核分枝杆菌感染，在 6 个月、12 月龄时对儿童进行结核菌素皮肤试验，然后每年对检测阴性的儿童和下呼吸道感染时进行一次。结核菌素皮肤试验转换定义为 10 毫米或更大的硬结反应。为了测量结核病，在整个随访过程中进行了主动监测。使用痰液诱导检查推定结核病的每次发作，用 Xpert MTB/RIF 和结核分枝杆菌液体培养物检测。进行生存分析，并使用多变量 Cox 回归来测量与结核分枝杆菌感染或疾病相关的因素。结果在 2012 年 3 月 5 日至 2015 年 3 月 31 日期间，1137 名妇女及其 1143 名儿童（1143 名儿童中有 248 名 [21·7%] 感染了 HIV，两名 [0·2%] 儿童感染了 HIV）被纳入分析。儿童随访 8870 人年 （中位随访 9·1 年 [IQR 8·2-10·2]）。随访期间结核菌素转化的年风险为每 100 人年 6·6 例感染 （95% CI 5·8-7·3），但在随访期间为每 100 人年 4-9 例感染。 98 名儿童发展为结核病 （1105 例/100 000 人年;95% CI 906-1347）。8 岁时结核菌素转化的累积风险为 36% （95% CI 32-41），10 岁时结核病的累积风险为 10% （8-12）。预防性治疗与结核菌素转换儿童结核病的减少有关 （校正风险比 0·23 [95% CI 0·12-0·47]）。大多数结核病病例（98 名儿童中有 78 例 [79%;95% CI 69-86]）发生在结核菌素皮肤试验转换但未接受预防性治疗的儿童中。解释 在这个前瞻性的南非出生队列中，结核分枝杆菌的传播率在生命的前十年一直很高，导致大约 10% 的儿童患上结核病。需要一种多管齐下的方法来减少儿科结核病，将对高危儿童的预防性治疗、减少社区结核分枝杆菌传播和积极发现病例相结合。资金 比尔和梅琳达·盖茨基金会，南非医学研究委员会和南非国家研究基金会。