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新型抗结核药物贝达喹啉治疗非洲耐药结核病的有效性:文献系统评价

Effectiveness of the Novel Anti-TB Bedaquiline against Drug-Resistant TB in Africa: A Systematic Review of the Literature.

作者信息

Traoré Afsatou Ndama, Rikhotso Mpumelelo Casper, Banda Ntshuxeko Thelma, Mashilo Maphepele Sara, Ngandu Jean Pierre Kabue, Mavumengwana Vuyo, Loxton Andre G, Kinnear Craig, Potgieter Natasha, Heysell Scott, Warren Rob

机构信息

Department of Biochemistry and Microbiology, Faculty of Sciences, Engineering & Agriculture, University of Venda, Thohoyandou 0950, South Africa.

DSI-NRF Centre of Excellence for Biomedical Tuberculosis Research, South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town 7505, South Africa.

出版信息

Pathogens. 2022 Jun 1;11(6):636. doi: 10.3390/pathogens11060636.

Abstract

BACKGROUND

In 2018, an estimated 10.0 million people contracted tuberculosis (TB), and 1.5 million died from it, including 1.25 million HIV-negative persons and 251,000 HIV-associated TB fatalities. Drug-resistant tuberculosis (DR-TB) is an important contributor to global TB mortality. Multi-drug-resistant TB (MDR-TB) is defined as TB resistant to at least isoniazid (INH) and rifampin (RMP), which are recommended by the WHO as essential drugs for treatment.

OBJECTIVE

To investigate the effectiveness of bedaquiline addition to the treatment of drug-resistant TB infections on the African continent.

METHODOLOGY

The search engine databases Medline, PubMed, Google Scholar, and Embase were used to obtain published data pertaining to DR-TB between 2012 and 2021 in Africa. Included studies had to document clinical characteristics at treatment initiation and outcomes at the end of treatment (i.e., success, failure, recurrence, loss to follow-up, and death). The included studies were used to conduct a meta-analysis. All data analysis and visualization were performed using the R programming environment. The log risk ratios and sample variances were calculated for DR-TB patients treated with BBQ monotherapy vs. BDQ and other drug therapy. To quantify heterogeneity among the included studies, random effect sizes were calculated.

RESULTS

A total of 16 studies in Africa from Mozambique (N = 1 study), Eswatini (N = 1 study), Democratic Republic of the Congo (N = 1 study), South Africa (N = 12 studies), and a multicenter study undertaken across Africa (N = 1 study) were included. In total, 22,368 individuals participated in the research studies. Among the patients, (55.2%; 12,350/22,368) were male while 9723/22,368 (44%) were female. Overall, (9%; 2033/22,368) of patients received BDQ monotherapy, while (88%; 19,630/22,368) patients received bedaquiline combined with other antibiotics. In total, (42%; 9465/22,368) of the patients were successfully treated. About (39%; 8653/22,368) of participants finished their therapy, meanwhile (5%; 1166/22,368) did not finish their therapy, while people (0.4%; 99/22,368) were lost to follow up. A total of (42%; 9265/22,368) patients died.

CONCLUSION

Very few studies on bedaquiline usage in DR-TB in Africa have been published to date. Bedaquiline has been shown to enhance DR-TB results in clinical studies and programmatic settings. Hence, the World Health Organization (WHO) has recommended that it be included in DR-TB regimens. However, in the current study limited improvement to DR-TB treatment results were observed using BDQ on the continent. Better in-country monitoring and reporting, as well as multi-country collaborative cohort studies of DR-TB, can expand the knowledge of bedaquiline usage and clinical impact, as well as the risks and benefits throughout the continent.

摘要

背景

2018年,估计有1000万人感染结核病(TB),150万人死于该病,其中包括125万HIV阴性者和25.1万例与HIV相关的结核病死亡病例。耐多药结核病(DR-TB)是全球结核病死亡率的一个重要促成因素。耐多药结核病(MDR-TB)被定义为对至少异烟肼(INH)和利福平(RMP)耐药的结核病,而异烟肼和利福平是世界卫生组织推荐的治疗必需药物。

目的

研究在非洲大陆,加用贝达喹啉治疗耐多药结核感染的有效性。

方法

使用搜索引擎数据库Medline、PubMed、谷歌学术和Embase获取2012年至2021年期间非洲有关耐多药结核病公布的数据。纳入的研究必须记录治疗开始时的临床特征以及治疗结束时的结果(即成功、失败、复发、失访和死亡)。纳入的研究用于进行荟萃分析。所有数据分析和可视化均使用R编程环境进行。计算接受贝达喹啉单药治疗与接受贝达喹啉联合其他药物治疗的耐多药结核病患者的对数风险比和样本方差。为了量化纳入研究之间的异质性,计算随机效应量。

结果

总共纳入了非洲的16项研究,分别来自莫桑比克(1项研究)、斯威士兰(1项研究)、刚果民主共和国(1项研究)、南非(12项研究)以及一项在非洲开展的多中心研究(1项研究)。共有22368人参与了这些研究。在这些患者中,男性占(55.2%;12350/22368),而女性占9723/22368(44%)。总体而言,(9%;2033/22368)的患者接受了贝达喹啉单药治疗,而(88%;19630/22368)的患者接受了贝达喹啉联合其他抗生素治疗。总共有(42%;9465/22368)的患者得到成功治疗。约(39%;8653/22368)的参与者完成了治疗,同时(5%;1166/22368)未完成治疗,而(0.4%;99/22368)的人失访。共有(42%;9265/22368)的患者死亡。

结论

迄今为止,非洲关于贝达喹啉用于耐多药结核病治疗的研究发表得很少。在临床研究和项目实施环境中,贝达喹啉已被证明能改善耐多药结核病的治疗效果。因此,世界卫生组织(WHO)已建议将其纳入耐多药结核病治疗方案。然而,在本研究中,在非洲大陆使用贝达喹啉观察到耐多药结核病治疗效果的改善有限。更好的国内监测和报告,以及耐多药结核病的多国协作队列研究,可以扩大对贝达喹啉使用情况和临床影响以及整个非洲大陆的风险和益处的了解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a79/9229213/85c771a9c12c/pathogens-11-00636-g001.jpg

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