Mycobacterium tuberculosis infection and tuberculosis disease in the first decade of life: a South African birth cohort study

IF 19.9 1区医学 Q1 PEDIATRICS

Lancet Child & Adolescent Health Pub Date : 2024-11-05 DOI:10.1016/S2352-4642(24)00256-6

Fernanda Bruzadelli Paulino da Costa PhD , Prof Mark P Nicol PhD , Maresa Botha MBChB , Lesley Workman MPH , Prof Ricardo Alexandre Arcêncio PhD , Prof Heather J Zar PhD , Leonardo Martinez PhD

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引用次数: 0

Abstract

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.

查看原文本刊更多论文

生命最初十年的结核分枝杆菌感染和结核病：南非出生队列研究。

背景：小儿结核病每年导致 20 多万人死亡。德拉肯斯坦儿童健康研究（Drakenstein Child Health Study，DCHS）是南非一个结核病和艾滋病高发社区的一个队列，我们的目的是调查该研究中结核分枝杆菌感染和结核病在婴儿出生后头十年的发病率：在这项前瞻性出生队列研究中，我们在南非开普敦郊外的近郊区招募了年龄在 18 岁或 18 岁以上、妊娠期在 20 到 28 周之间的孕妇。我们对她们的孩子进行了结核病跟踪调查，直到他们 10 岁。为了测量 M 型结核病感染情况，我们在儿童 6 个月大和 12 个月大时对其进行了结核菌素皮试，然后每年对皮试呈阴性的儿童以及在下呼吸道感染时进行皮试。结核菌素皮试转阴的定义是压痕反应达到或超过 10 毫米。为了测量结核病，在整个随访过程中都进行了积极的监测。每次推测的结核病发作都要进行痰液诱导检查，并用 Xpert MTB/RIF 和液体培养法检测结核杆菌。研究人员进行了生存分析，并采用多变量考克斯回归法测定了与结核杆菌感染或疾病相关的因素：2012年3月5日至2015年3月31日期间，1137名妇女及其1143名子女（1143名子女中有248名[21-7%]暴露于HIV，2名[0-2%]感染HIV）被纳入分析。对儿童的随访时间为 8870 人年（中位数随访时间为 9-1 年 [IQR 8-2-10-2]）。在随访期间，结核菌素转阴的年风险为每 100 人年 6-6 例（95% CI 5-8-7-3），但在随访期间，每 100 人年的感染率为 4-9 例。98 名儿童患上了结核病（每 10 万人年中有 1105 例；95% CI 906-1347）。8 岁时结核菌素转阴的累积风险为 36%（95% CI 32-41），10 岁时结核病的累积风险为 10%（8-12）。在结核菌素转阴的儿童中，预防性治疗与结核病发病率的降低有关（调整后的危险比为 0-23 [95% CI 0-12-0-47]）。大多数结核病病例（98 名儿童中的 78 例 [79%；95% CI 69-86]）发生在结核菌素皮试转阴但未接受预防性治疗的儿童中：在这一前瞻性南非出生队列中，M 型结核病的传播率在儿童出生后的头十年一直居高不下，导致约 10% 的儿童罹患结核病。需要采取多管齐下的方法来减少小儿结核病的发病率，将对高危儿童的预防性治疗、减少社区间的结核病传播和积极的病例发现结合起来：比尔及梅林达-盖茨基金会、南非医学研究委员会和南非国家研究基金会。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Lancet Child & Adolescent Health Psychology-Developmental and Educational Psychology

CiteScore

40.90

自引率

0.80%

发文量

381

期刊介绍： The Lancet Child & Adolescent Health, an independent journal with a global perspective and strong clinical focus, presents influential original research, authoritative reviews, and insightful opinion pieces to promote the health of children from fetal development through young adulthood. This journal invite submissions that will directly impact clinical practice or child health across the disciplines of general paediatrics, adolescent medicine, or child development, and across all paediatric subspecialties including (but not limited to) allergy and immunology, cardiology, critical care, endocrinology, fetal and neonatal medicine, gastroenterology, haematology, hepatology and nutrition, infectious diseases, neurology, oncology, psychiatry, respiratory medicine, and surgery. Content includes articles, reviews, viewpoints, clinical pictures, comments, and correspondence, along with series and commissions aimed at driving positive change in clinical practice and health policy in child and adolescent health.