TB Centre, London School of Hygiene & Tropical Medicine, London, United Kingdom.
Library & Archives Service, London School of Hygiene & Tropical Medicine, London, United Kingdom.
PLoS Med. 2021 Apr 26;18(4):e1003566. doi: 10.1371/journal.pmed.1003566. eCollection 2021 Apr.
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.
对于开始接受肺结核（TB）治疗的人，建议进行两周的隔离。但目前尚不清楚这是否能对应清除痰液中潜在传染性结核分枝杆菌。本项由世界卫生组织委托的综述调查了 TB 治疗过程中痰液杀菌动力学。
在主要分析中，我们进行了 2 次系统文献检索，检索数据库包括 OvidSP MEDLINE、Embase、Global Health 和 EBSCO CINAHL Plus，以确定具有 TB 传染性数据的研究（所有研究截止日期为 2017 年 12 月 1 日）和所有药物敏感性结核的随机对照试验（RCTs）（从 1990 年 1 月 1 日至检索日期 2018 年 2 月 20 日）。纳入的文章报告了接受培养证实的药物敏感性肺结核有效治疗的患者。感兴趣的结局是痰液细菌学转换：通过特定时间点或通过痰液或培养评估的转换时间的综合测量来评估患者转换的比例。考虑了具有 10 个或更多参与者的任何研究设计。记录筛选和数据提取均由两人独立进行。进行了随机效应荟萃分析。此外，还对系统搜索从人类到实验动物评估传染性的数据（PubMed，所有研究截止日期为 2018 年 3 月 27 日）进行了系统性搜索结果的描述性总结。其他关于传染性持续时间的证据——包括报告咳嗽动力学、人类结核菌素皮肤试验转换或结核治疗早期杀菌活性的研究——不在本综述范围内。应编辑要求，于 2020 年 11 月 22 日再次进行文献检索，以确定之前截止日期后发表的研究。确定了 4 项报告了 3 种不同结局指标的小型研究，其中没有数据会改变综述的发现；它们不包括在荟萃分析中。在确定的 5290 份记录中，有 44 份被纳入。其中 27 项（61%）为 RCTs，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%）来自南美洲，5 项（11%）来自北美洲，4 项（9%）来自欧洲。有 4 项研究报告了来自多个大陆的数据。汇总估计表明，在治疗 2 周时，有 9%的患者（95%CI，3%24%，1 项研究[N=1]）和 82%的患者（95%CI，78%86%，N=10）出现痰液涂片阳性。在基线痰液涂片阳性的患者中，2 周时固体培养阳性的比例为 5%（95%CI，0%14%，N=2），2 个月时增至 88%（95%CI，84%92%，N=20）。在等效时间点，液体培养阳性的比例分别为 3%（95%CI，1%16%，N=1）和 59%（95%CI，47%70%，N=8）。观察到显著的异质性。由于缺乏结果的细分，包括按 HIV 状态、基线痰液状态以及有无肺空洞等因素进行细分，我们对数据进行了进一步分析以解释这种异质性，但受到限制。
本系统综述发现，大多数患者在接受 TB 治疗 2 周时仍为培养阳性，这对治疗后个体无传染性的观点提出了挑战。然而，培养阳性只是传染性的一个组成部分，治疗开始后咳嗽频率降低和气溶胶生成减少也可能很重要。将我们的发现与咳嗽动力学数据相结合的研究可能会提供对个体治疗期间传播结核分枝杆菌的潜在途径的更全面的看法。
系统综述注册：PROSPERO 85226。
