Evaluating systematic targeted universal testing for tuberculosis in primary care clinics of South Africa: A cluster-randomized trial (The TUTT Trial).
Evaluating systematic targeted universal testing for tuberculosis in primary care clinics of South Africa: A cluster-randomized trial (The TUTT Trial).
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DOI：
10.1371/journal.pmed.1004237
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发表时间：
2023-05
期刊：
影响因子：
15.8
通讯作者：
中科院分区：
文献类型：
--
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世界卫生组织（WHO）建议对结核病（TB）进行系统的症状筛查。然而，结核病流行率调查表明，这一战略并没有确定全球数百万结核病患者。未确诊或延误诊断的结核病助长了结核病的传播，并使发病率和死亡率恶化。我们在南非3个省的大型城市和农村初级卫生保健诊所进行了一项群集随机试验，以评估与目前的标准护理（SoC）结核病导向的结核病检测相比，在高危人群中进行靶向结核病通用检测（TUTT）的新干预措施是否每月诊断出更多的结核病患者。对62家诊所进行了随机化;自2019年3月起，在6个月内启动了干预诊所。由于诊所限制接触患者，该研究于2020年3月提前停止，一周后又由于2019冠状病毒病（COVID-19）全国封锁;到那时，我们已累计了与功效估计相似的结核病诊断数量，并永久停止了试验。在干预诊所，艾滋病毒感染者，那些自我报告最近与结核病密切接触的人，或以前的结核病发作都提供了结核病的痰液检测，无论他们是否报告了结核病症状。我们使用泊松回归模型分析了从国家公共部门实验室数据库中提取的数据，并比较了研究组之间每个诊所每月诊断的结核病患者的平均数量。在研究期间，干预诊所诊断出6，777例TB患者，每个诊所月20.7例TB患者（95% CI 16.7，24.8），而对照诊所每个诊所月6，750例，18.8例TB患者（95% CI 15.3，22.2）。直接比较，调整省和诊所结核病例量分层，未显示两组之间结核病例数的显著差异，发病率比（IRR）为1.14（95% CI 0.94，1.38，p = 0.46）。然而，预先设定的差异中差异分析显示，虽然对照诊所的结核病诊断率随时间推移而下降，但与前一年相比，干预诊所每月诊断的结核病患者相对增加17%，交互作用IRR为1.17（95% CI 1.14，1.19，p < 0.001）。试验的局限性是由于COVID-19封锁而提前停止，以及缺乏对诊断为结核病的患者的结核病治疗开始和结果的组间比较。我们的试验表明，TUTT在这3组极高风险的结核病患者中的实施比SoC识别出更多的结核病患者，并有助于减少结核病高发环境中未确诊的结核病患者。南非国家临床试验注册处DOH-27-092021-4901。在南非初级保健诊所的一项群集随机试验中，Neil Martinson及其同事研究了结核病靶向检测在高危人群中的价值。结核病（TB）的诊断是通过实验室痰液检测，通常提示存在至少一种结核病症状（咳嗽，发烧或盗汗，体重减轻）。世界卫生组织提倡对所有结核病高危人群进行筛查，不论其症状如何。在南非，高风险群体包括艾滋病毒感染者、报告与结核病患者密切接触的人以及最近患过结核病的人。关于诊断试验作为筛查试验的有用性的数据很少。我们的试验评估了对没有结核病症状的高危人群进行有针对性的痰液检测是否有助于识别未确诊的结核病。南非共有62家大型初级保健诊所被随机分配到我们的干预组（对高危人群中的所有人进行痰结核检测）或我们的对照组（继续进行结核病症状导向检测（标准治疗））。记录了所有诊所每月诊断的结核病病例总数。干预和控制诊所之间进行了比较。在试验性干预诊所中，6，777人被诊断患有结核病，平均每个诊所月有20.7名患者，而在对照诊所中，6，750人被诊断患有结核病，平均每个诊所月有18.8名患者。在对2017年最后一个季度每月诊断的结核病患者的平均人数进行聚类、省份和分层调整后，干预诊所诊断的结核病患者比对照诊所多14%，但这并没有达到统计学意义。二次分析，包括干预前一年的数据，表明每月结核病诊断有统计学显著增加，报告为17%的相对增加。一项针对高危人群的结核病普遍检测战略（TUTT）可能有助于提高结核病高发地区的诊断率。如果检测费用得到解决，可以在资源匮乏的环境中实施普遍检测战略，并可以针对其他与当地有关的结核病高危群体。
The World Health Organization (WHO) recommends systematic symptom screening for tuberculosis (TB). However, TB prevalence surveys suggest that this strategy does not identify millions of TB patients, globally. Undiagnosed or delayed diagnosis of TB contribute to TB transmission and exacerbate morbidity and mortality. We conducted a cluster-randomized trial of large urban and rural primary healthcare clinics in 3 provinces of South Africa to evaluate whether a novel intervention of targeted universal testing for TB (TUTT) in high-risk groups diagnosed more patients with TB per month compared to current standard of care (SoC) symptom-directed TB testing. Sixty-two clinics were randomized; with initiation of the intervention clinics over 6 months from March 2019. The study was prematurely stopped in March 2020 due to clinics restricting access to patients, and then a week later due to the Coronavirus Disease 2019 (COVID-19) national lockdown; by then, we had accrued a similar number of TB diagnoses to that of the power estimates and permanently stopped the trial. In intervention clinics, attendees living with HIV, those self-reporting a recent close contact with TB, or a prior episode of TB were all offered a sputum test for TB, irrespective of whether they reported symptoms of TB. We analyzed data abstracted from the national public sector laboratory database using Poisson regression models and compared the mean number of TB patients diagnosed per clinic per month between the study arms. Intervention clinics diagnosed 6,777 patients with TB, 20.7 patients with TB per clinic month (95% CI 16.7, 24.8) versus 6,750, 18.8 patients with TB per clinic month (95% CI 15.3, 22.2) in control clinics during study months. A direct comparison, adjusting for province and clinic TB case volume strata, did not show a significant difference in the number of TB cases between the 2 arms, incidence rate ratio (IRR) 1.14 (95% CI 0.94, 1.38, p = 0.46). However, prespecified difference-in-differences analyses showed that while the rate of TB diagnoses in control clinics decreased over time, intervention clinics had a 17% relative increase in TB patients diagnosed per month compared to the prior year, interaction IRR 1.17 (95% CI 1.14, 1.19, p < 0.001). Trial limitations were the premature stop due to COVID-19 lockdowns and the absence of between-arm comparisons of initiation and outcomes of TB treatment in those diagnosed with TB. Our trial suggests that the implementation of TUTT in these 3 groups at extreme risk of TB identified more TB patients than SoC and could assist in reducing undiagnosed TB patients in settings of high TB prevalence. South African National Clinical Trials Registry DOH-27-092021-4901. In a cluster randomised trial of primary care clinics in South Africa, Neil Martinson and colleagues, investigate the value of targeted testing for Tuberculosis in those at highest risk. Tuberculosis (TB) diagnosis is made by laboratory sputum testing usually prompted by the presence of at least 1 symptom of TB (cough, fever or night sweats, loss of weight). The World Health Organization promotes screening of entire groups of people at high risk of TB irrespective of symptoms. In South Africa, high-risk groups include people living with HIV, those who report being a close contact of someone with TB, and those who have had a recent episode of TB. There is little data on the usefulness of diagnostic assays as screening tests. Our trial assessed if targeted sputum testing of people at high risk without TB symptoms helped to identify undiagnosed TB. A total of 62 large primary care clinics in South Africa were randomized to either our intervention—TB testing of sputum of all people in high-risk groups, or our control—to continue symptom directed testing for TB (the standard of care). The total number of TB cases diagnosed each month in all clinics was recorded. Comparisons were made between intervention and control clinics. In trial intervention clinics, 6,777 people were diagnosed with TB, an average of 20.7 patients per clinic month versus 6,750 in control clinics, an average of 18.8 patients with TB per clinic month. After adjusting for clustering, province, and the strata of average number of TB patients diagnosed per month in the last quarter of 2017, intervention clinics diagnosed 14% more patients with TB than control clinics, but this did not reach statistical significance. Secondary analyses, including data from the year prior to the intervention, demonstrated a statistically significant increase in TB diagnoses per month, reported as a 17% relative increase. A strategy targeting high-risk groups for universal testing for TB (TUTT) may help to improve diagnostic rates of TB in areas where prevalence is high. Universal testing strategies could be be implemented in low-resource settings provided costs of testing were addressed, and other locally relevant high-risk groups for TB could be targeted.
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影响因子：
8.4
作者：
Osman, Muhammad;Welte, Alex;Marx, Florian M.
通讯作者：
Marx, Florian M.
影响因子：
1.7
作者：
Myburgh, Hanlie;Peters, Remco P.H.;Hoddinott, Graeme
通讯作者：
Hoddinott, Graeme
DOI：
10.1183/09031936.00070812
发表时间：
2013-01
期刊：
The European respiratory journal
影响因子：
--
作者：
Fox GJ;Barry SE;Britton WJ;Marks GB
通讯作者：
Marks GB
影响因子：
3.7
作者：
Alsdurf H;Empringham B;Miller C;Zwerling A
通讯作者：
Zwerling A
影响因子：
3.7
作者：
Hoffmann, Christopher J.;Variava, Ebrahim;Martinson, Neil A.
通讯作者：
Martinson, Neil A.