Background

Shorter regimens for tuberculosis prevention can improve completion rates and protection against developing active tuberculosis disease after tuberculosis exposure. We aimed to assess the safety and feasibility of 1 month of daily isoniazid and rifapentine (1HP) in children and adolescents in a low-resource setting in south Asia with low prevalence of HIV.

Methods

This prospective cohort study was done in eight tuberculosis facilities in Karachi, Pakistan. Eligible participants were aged 2–19 years and were household contacts of patients with drug-susceptible tuberculosis infection. After clinical, radiological, and laboratory evaluation to rule out tuberculosis disease, participants were prescribed 1HP as a preventive regimen. Isoniazid was administered as 100 mg or 300 mg oral tablets and rifapentine was administered as 150 mg oral tablets. Dosing was according to participant bodyweight. The primary endpoints were the cumulative probability of a household contact completing all stages of the preventive care cascade, assessed in all eligible participants, and the proportion of household contacts completing 1HP, assessed among all those who initiated the regimen. Safety was assessed in all household contacts who initiated the 1HP regimen.

Findings

Between Dec 21, 2019, and March 20, 2020, 1395 household contacts of 253 patients with tuberculosis were identified, including 678 household contacts who were eligible to participate. 628 (93%) completed evaluation, of whom ten (2%) had active tuberculosis disease. Of the 618 individuals eligible for tuberculosis prevention, 408 (66%) initiated 1HP, 385 (94%) of whom completed the regimen. The median duration of 1HP was 31 days (IQR 30–32) in those who completed the regimen. The cumulative probability of completing all steps of the tuberculosis prevention cascade was 58%. A girl aged 11 years developed tuberculosis disease within 6 months of completing 1HP. A boy aged 14 years developed a burning sensation during 1HP therapy and discontinued the regimen. No other adverse events were observed.

Interpretation

1HP can be safely and feasibly implemented as tuberculosis prevention in children and adolescents in programmatic settings.

Funding

The Global Fund to Fight AIDS, Tuberculosis and Malaria.

中文翻译：

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每日1个月的利福喷汀加异烟肼预防儿童和青少年结核病的安全性和可行性：一项前瞻性队列研究

背景

较短的结核病预防方案可以提高完成率，并防止在暴露于结核病后发展为活动性结核病。我们旨在评估在资源匮乏，艾滋病毒感染率较低的南亚地区，儿童和青少年每日使用异烟肼和利福喷丁（1HP）1个月的安全性和可行性。

方法

这项前瞻性队列研究是在巴基斯坦卡拉奇的八个结核病设施中进行的。符合条件的参与者年龄在2-19岁之间，并且是药物敏感性结核感染患者的家属。在经过临床，放射学和实验室评估以排除结核病之后，为参加者开出1HP作为预防方案。异烟肼以100 mg或300 mg口服片剂的形式给药，利福喷丁以150 mg口服片剂的形式给药。剂量根据参与者的体重而定。主要终点是在所有符合条件的参与者中进行评估的家庭接触完成预防保健工作的所有阶段的累积概率，以及在发起该方案的所有参与者中评估的完成1HP的家庭接触的比例。

发现

在2019年12月21日至2020年3月20日之间，确定了253名结核病患者的1395户家庭接触者，其中678户有资格参加。评估完成628例（93％），其中活动性结核病10例（2％）。在618名符合结核病预防标准的人中，有408名（66％）发起了1HP，其中385名（94％）完成了该方案。在完成该方案的患者中，1HP的中位持续时间为31天（IQR 30–32）。完成结核预防级联所有步骤的累积概率为58％。一个11岁的女孩在完成1HP后的6个月内患上了结核病。一个14岁的男孩在1HP治疗期间出现烧灼感，并中止了该疗程。没有观察到其他不良事件。

解释

1HP可在编程环境中安全，可行地实施，以预防儿童和青少年的肺结核。

资金

全球抗击艾滋病，结核病和疟疾基金。