Center for TB Research, Division of Infectious Diseases, School of Medicine, Johns Hopkins University, Baltimore, Maryland, United States of America.
Division of Tuberculosis, Delek Hospital, Department of Health, Central Tibetan Administration, Dharamsala, India.
PLoS Med. 2021 Jan 19;18(1):e1003502. doi: 10.1371/journal.pmed.1003502. eCollection 2021 Jan.
Tuberculosis (TB) rates among Tibetan refugee children and adolescents attending boarding schools in India are extremely high. We undertook a comprehensive case finding and TB preventive treatment (TPT) program in 7 schools in the Zero TB Kids project. We aimed to measure the TB infection and disease burden and investigate the risk of TB disease in children and adults who did and did not receive TPT in the schools.
A mobile team annually screened children and staff for TB at the 7 boarding schools in Himachal Pradesh, India, using symptom criteria, radiography, molecular diagnostics, and tuberculin skin tests. TB infection (TBI) was treated with short-course regimens of isoniazid and rifampin or rifampin. TB disease was treated according to Tibetan and Indian guidelines. Between April 2017 and December 2019, 6,582 schoolchildren (median age 14 [IQR 11-16] years) and 807 staff (median age 40 [IQR 33-48] years) were enrolled. Fifty-one percent of the students and 58% of the staff were females. Over 13,161 person-years of follow-up in schoolchildren (median follow-up 2.3 years) and 1,800 person-years of follow-up in staff (median follow-up 2.5 years), 69 TB episodes occurred in schoolchildren and 4 TB episodes occurred in staff, yielding annual incidence rates of 524/100,000 (95% CI 414-663/100,000) person-years and 256/100,000 (95% CI 96-683/100,000) person-years, respectively. Of 1,412 schoolchildren diagnosed with TBI, 1,192 received TPT. Schoolchildren who received TPT had 79% lower risk of TB disease (adjusted hazard ratio [aHR] 0.21; 95% CI 0.07-0.69; p = 0.010) compared to non-recipients, the primary study outcome. Protection was greater in recent contacts (aHR 0.07; 95% CI 0.01-0.42; p = 0.004), the secondary study outcome. The prevalence of recent contacts was 28% (1,843/6,582). Two different TPT regimens were used (3HR and 4R), and both were apparently effective. No staff receiving TPT developed TB. Overall, between 2017 and 2019, TB disease incidence decreased by 87%, from 837/100,000 (95% CI 604-1,129/100,000) person-years to 110/100,000 (95% CI 36-255/100,000) person-years (p < 0.001), and TBI prevalence decreased by 42% from 19% (95% CI 18%-20%) to 11% (95% CI 10%-12%) (p < 0.001). A limitation of our study is that TB incidence could be influenced by secular trends during the study period.
In this study, following implementation of a school-wide TB screening and preventive treatment program, we observed a significant reduction in the burden of TB disease and TBI in children and adolescents. The benefit of TPT was particularly marked for recent TB contacts. This initiative may serve as a model for TB detection and prevention in children and adolescents in other communities affected by TB.
在印度的寄宿学校中，藏族难民儿童和青少年的结核病（TB）发病率极高。我们在 Zero TB Kids 项目的 7 所学校中开展了全面的病例发现和结核预防治疗（TPT）计划。我们旨在衡量 TB 感染和疾病负担，并调查在学校中接受和未接受 TPT 的儿童和成人患 TB 病的风险。
一个移动小组每年在印度喜马偕尔邦的 7 所寄宿学校对儿童和工作人员进行 TB 筛查，使用症状标准、放射学、分子诊断和结核菌素皮肤试验。使用异烟肼和利福平或利福平的短程方案治疗 TB 感染（TBI）。根据藏族和印度的指南治疗 TB 病。2017 年 4 月至 2019 年 12 月期间，共有 6582 名学生（中位数年龄 14 [IQR 11-16] 岁）和 807 名工作人员（中位数年龄 40 [IQR 33-48] 岁）入组。51%的学生和 58%的工作人员为女性。在学生中进行了超过 13161 人年的随访（中位数随访 2.3 年），在工作人员中进行了 1800 人年的随访（中位数随访 2.5 年），发生了 69 例 TB 发作，4 例工作人员发生了 TB 发作，导致儿童的年发病率为 524/100000（95%CI 414-663/100000），工作人员的年发病率为 256/100000（95%CI 96-683/100000）。在 1412 名诊断为 TBI 的学生中，有 1192 名接受了 TPT。接受 TPT 的学生患 TB 病的风险降低了 79%（调整后的危险比[aHR]0.21；95%CI 0.07-0.69；p=0.010），这是主要的研究结果。在近期接触者中，保护作用更大（aHR 0.07；95%CI 0.01-0.42；p=0.004），这是次要的研究结果。近期接触者的患病率为 28%（1843/6582）。使用了两种不同的 TPT 方案（3HR 和 4R），两种方案都显然有效。没有接受 TPT 的工作人员患上了 TB。总的来说，2017 年至 2019 年间，TB 病的发病率下降了 87%，从 837/100000（95%CI 604-1129/100000）人年降至 110/100000（95%CI 36-255/100000）人年（p<0.001），TBI 的患病率从 19%（95%CI 18%-20%）下降至 11%（95%CI 10%-12%）（p<0.001）。我们研究的一个限制是，TB 发病率可能受到研究期间的季节性趋势的影响。
在这项研究中，在实施了全校范围的 TB 筛查和预防治疗计划后，我们观察到儿童和青少年的 TB 病和 TBI 负担显著减轻。TPT 的益处对近期 TB 接触者尤为明显。这一举措可能成为其他受 TB 影响社区中儿童和青少年 TB 检测和预防的典范。
