Dynamics of sputum conversion during effective tuberculosis treatment: A systematic review and meta-analysis.
Dynamics of sputum conversion during effective tuberculosis treatment: A systematic review and meta-analysis.
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DOI：
10.1371/journal.pmed.1003566
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发表时间：
2021-04
期刊：
影响因子：
15.8
通讯作者：
Moore DAJ
中科院分区：
文献类型：
--
作者：
Calderwood CJ;Wilson JP;Fielding KL;Harris RC;Karat AS;Mansukhani R;Falconer J;Bergstrom M;Johnson SM;McCreesh N;Monk EJM;Odayar J;Scott PJ;Stokes SA;Theodorou H;Moore DAJ
广泛建议开始接受肺结核治疗的患者隔离两周。这与清除痰中潜在传染性结核分枝杆菌有关的证据尚未得到很好的证实。世界卫生组织委托进行的这项审查调查了结核病治疗期间的痰消毒动态。为了进行主要分析，对OvidSP MEDLINE、Embase和Global Health以及EBSCO CINAHL Plus进行了2次系统文献检索，以确定具有结核病传染性数据的研究（所有研究检索日期为2017年12月1日）和所有药物敏感结核病的随机对照试验（rct）（从1990年1月1日至检索日期为2018年2月20日）。纳入了对经培养证实的药物敏感肺结核患者接受有效治疗的报道。感兴趣的结果是痰细菌转化：通过涂片或培养评估，在规定的时间点或时间的汇总测量中转化的患者比例。任何有10个或更多参与者的研究设计都被考虑在内。记录筛选和数据提取一式两份。进行随机效应荟萃分析。叙述性摘要还描述了系统搜索评估人类对实验动物传染性的数据的结果（PubMed，截至2018年3月27日的所有研究）。其他关于感染持续时间的证据——包括咳嗽动力学、人结核菌素皮肤试验转换或结核病治疗的早期杀菌活性的研究报告——不在本综述的范围之内。应编辑的要求，于2020年11月22日再次进行文献检索，以确定在前一个审查日期之后发表的研究。四项小型研究报告了三种不同的结果测量方法，其中没有数据可以改变综述的结果；他们不包括在meta分析中。在5290个已确定的记录中，有44个被包括在内。27项（61%）为随机对照试验，17项（39%）为队列研究。13项研究（30%）报告了来自非洲的数据，12项（27%）来自亚洲，6项（14%）来自南美，5项（11%）来自北美，4项（9%）来自欧洲。四项研究报告了来自多个大洲的数据。总结估计表明，9%的患者在治疗2周时（95% CI 3%-24%， 1项单一研究[N = 1]）， 82%的患者在治疗2个月时（95% CI 78%-86%, N = 10）。在基线涂片阳性患者中，固体培养转化在2周内发生的比例为5% (95% CI 0%-14%, N = 2)，在2个月时增加到88% （95% CI 84%-92%, N = 20）。在等效时间点，液体培养转化率分别为3% （95% CI 1%-16%, N = 1）和59% （95% CI 47%-70%, N = 8）。观察到显著的异质性。由于缺乏对结果的分类，包括艾滋病毒状况、基线涂片状况和肺空化的存在与否等因素，对解释这种异质性的数据的进一步调查受到限制。该系统综述发现，大多数患者在结核病治疗2周后仍保持培养阳性，这挑战了个体在此间隔后不具有传染性的观点。然而，培养阳性仅是传染性的一个组成部分，在结核治疗开始后减少咳嗽频率和气溶胶产生可能也很重要。将我们的研究结果与咳嗽动力学数据相结合的研究可以提供一个更完整的视角，了解接受治疗的个体对结核分枝杆菌的潜在传播。系统评价注册：PROSPERO 85226。尽管在许多国家的国家指南中都有引用，但结核病患者在接受有效结核病治疗两周后不再具有传染性的证据受到质疑。这项系统审查是由世界卫生组织委托进行的，目的是为结核病感染预防和控制指南提供证据。我们试图综合有关开始有效治疗后患者痰中潜在传染性结核细菌清除的现有数据。我们使用预定的纳入标准对文献数据库进行系统检索以确定相关文章。提取的数据采用叙述性总结和荟萃分析进行综合。通过痰涂片或培养评估，少数患者在有效治疗2周后痰中结核细菌清除。正如预期的那样，从痰中清除结核细菌的比例随着时间的推移而增加；然而，在治疗2个月时，分别通过固体和液体培养评估，12%和41%的患者仍然存在活结核菌。有效治疗超过2周的肺结核患者痰中存在活结核菌表明个体的传染性可能超过这一时间间隔。结核病传播需要痰中存在活的分枝杆菌，并有气溶胶或飞沫传播的机制。了解咳嗽等其他因素在治疗期间如何变化，对结核病感染的预防和控制也很重要。
Two weeks’ isolation is widely recommended for people commencing treatment for pulmonary tuberculosis (TB). The evidence that this corresponds to clearance of potentially infectious tuberculous mycobacteria in sputum is not well established. This World Health Organization–commissioned review investigated sputum sterilisation dynamics during TB treatment. For the main analysis, 2 systematic literature searches of OvidSP MEDLINE, Embase, and Global Health, and EBSCO CINAHL Plus were conducted to identify studies with data on TB infectiousness (all studies to search date, 1 December 2017) and all randomised controlled trials (RCTs) for drug-susceptible TB (from 1 January 1990 to search date, 20 February 2018). Included articles reported on patients receiving effective treatment for culture-confirmed drug-susceptible pulmonary TB. The outcome of interest was sputum bacteriological conversion: the proportion of patients having converted by a defined time point or a summary measure of time to conversion, assessed by smear or culture. Any study design with 10 or more particpants was considered. Record sifting and data extraction were performed in duplicate. Random effects meta-analyses were performed. A narrative summary additionally describes the results of a systematic search for data evaluating infectiousness from humans to experimental animals (PubMed, all studies to 27 March 2018). Other evidence on duration of infectiousness—including studies reporting on cough dynamics, human tuberculin skin test conversion, or early bactericidal activity of TB treatments—was outside the scope of this review. The literature search was repeated on 22 November 2020, at the request of the editors, to identify studies published after the previous censor date. Four small studies reporting 3 different outcome measures were identified, which included no data that would alter the findings of the review; they are not included in the meta-analyses. Of 5,290 identified records, 44 were included. Twenty-seven (61%) were RCTs and 17 (39%) were cohort studies. Thirteen studies (30%) reported data from Africa, 12 (27%) from Asia, 6 (14%) from South America, 5 (11%) from North America, and 4 (9%) from Europe. Four studies reported data from multiple continents. Summary estimates suggested smear conversion in 9% of patients at 2 weeks (95% CI 3%–24%, 1 single study [N = 1]), and 82% of patients at 2 months of treatment (95% CI 78%–86%, N = 10). Among baseline smear-positive patients, solid culture conversion occurred by 2 weeks in 5% (95% CI 0%–14%, N = 2), increasing to 88% at 2 months (95% CI 84%–92%, N = 20). At equivalent time points, liquid culture conversion was achieved in 3% (95% CI 1%–16%, N = 1) and 59% (95% CI 47%–70%, N = 8). Significant heterogeneity was observed. Further interrogation of the data to explain this heterogeneity was limited by the lack of disaggregation of results, including by factors such as HIV status, baseline smear status, and the presence or absence of lung cavitation. This systematic review found that most patients remained culture positive at 2 weeks of TB treatment, challenging the view that individuals are not infectious after this interval. Culture positivity is, however, only 1 component of infectiousness, with reduced cough frequency and aerosol generation after TB treatment initiation likely to also be important. Studies that integrate our findings with data on cough dynamics could provide a more complete perspective on potential transmission of Mycobacterium tuberculosis by individuals on treatment. Systematic review registration: PROSPERO 85226. Though cited in many countries’ national guidance, the evidence that individuals with pulmonary tuberculosis (TB) are rendered non-infectious by 2 weeks of effective TB treatment is challenged. This systematic review was commissioned by the World Health Organization to provide evidence to inform TB infection prevention and control guidelines. We sought to synthesise the available data on the clearance of potentially infectious TB bacteria from the sputum of patients after starting effective treatment. We performed systematic searches of literature databases to identify relevant articles, using predetermined inclusion criteria. Extracted data were synthesised using narrative summaries and meta-analyses. A minority of patients had clearance of TB bacteria from sputum at 2 weeks of effective treatment, as assessed by either sputum smear or culture. As expected, the proportion having cleared TB bacteria from sputum increased over time; however, at 2 months of treatment 12% and 41% of patients still had viable TB bacteria present, as assessed by solid and liquid culture, respectively. The presence of viable TB bacteria in the sputum of pulmonary TB patients beyond 2 weeks of effective treatment suggests individuals may be infectious for longer than this interval. TB transmission requires the presence of viable mycobacteria in sputum and a mechanism for aerosol or droplet spread. Understanding how other factors, such as the presence of cough, change during treatment is also important for TB infection prevention and control.
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DOI：
10.1086/655127
发表时间：
2010-08-15
期刊：
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
影响因子：
--
作者：
Fitzwater SP;Caviedes L;Gilman RH;Coronel J;LaChira D;Salazar C;Saravia JC;Reddy K;Friedland JS;Moore DA
通讯作者：
Moore DA
影响因子：
4.3
作者：
Abal, AT;Jayakrishnan, B;Sharma, PN
通讯作者：
Sharma, PN
DOI：
10.5588/ijtld.12.0732
发表时间：
2013-07-01
影响因子：
4
作者：
Click, E. S.;Winston, C. A.;Mac Kenzie, W. R.
通讯作者：
Mac Kenzie, W. R.
影响因子：
3.7
作者：
Al-Shaer MH;Elewa H;Alkabab Y;Nazer LH;Heysell SK
通讯作者：
Heysell SK
影响因子：
3.7
作者：
Conde, Marcus B.;Mello, Fernanda C. Q.;Dorman, Susan E.
通讯作者：
Dorman, Susan E.