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在东帝汶进行的第一次全国抗结核药物耐药性调查(DRS)的经验。

Experience on the first national anti-TB drug resistance survey (DRS) in Timor-Leste.

机构信息

National TB Programme, Ministry of Health, Dili, Timor-Leste.

World Health Organization Country Office for Timor-Leste, Dili, Timor-Leste.

出版信息

Glob Health Res Policy. 2022 May 20;7(1):16. doi: 10.1186/s41256-022-00249-z.

Abstract

BACKGROUND

A national drug resistance survey (DRS) was implemented for the first time in Timor-Leste (TL) in 2019. The primary objective of the survey was to assess the prevalence of drug resistance among new and previously treated pulmonary TB patients in the country.

METHODS

This nation-wide cross-sectional survey was conducted in 2019 targeting all new and previously treated sputum smear-positive pulmonary TB patients. Sputum samples were submitted to the National TB Reference Laboratory for confirmation of TB and to determine resistance to rifampicin by Xpert MTB/RIF. Culture was performed on solid media, and culture isolates of confirmed TB cases were shipped to the WHO Supranational TB Reference Laboratory in Chennai, India for whole genome sequencing (WGS). Survey summary statistics, data cross-tabulations and analysis of potential risk factors of rifampicin-resistant TB (RR-TB) were conducted using R statistical software (version 3.5.2).

RESULTS

A total of 953 sputum-smear positive patients were enrolled, of which 917 were confirmed as positive for TB by either Xpert MTB/RIF or culture. An electronic web-based system was used for entry and storage of the data. Rifampicin resistance was detected among 0.6% (95% CI 0.2-1.3) of new cases and 2.7% (95% CI 0.5- 8.2) of previously treated cases. WGS was conducted for validation purposes on 65 randomly selected isolates (29% of RR-TB (2/7) and 7% of RS-TB (63/910) by Xpert MTB/RIF or pDST). The original test results agreed with the WGS validation results for 62/64 isolates (97%).

CONCLUSION

The prevalence of RR-TB in Timor-Leste is relatively low compared to the estimated proportions of RR-TB in the WHO South-East Asia Region (2.5% [95% CI 1.9-3.3] among new cases and 14% [95% CI 7.7-21] among previously treated cases). The rapid sputum collection and transportation mechanism implemented in the survey demonstrates its feasibility in low resource settings and should be replicated for routinely transporting TB specimens from microscopy labs to GeneXpert sites. Establishment of in-country capacity for rapid molecular diagnostics for both first- and second-line DST is an immediate need for achieving universal drug susceptibility testing (DST) to guide appropriate patient management.

摘要

背景

2019 年,东帝汶(TL)首次实施了全国耐药性调查(DRS)。该调查的主要目的是评估该国新的和以前治疗过的肺结核患者的耐药率。

方法

这是一项全国性的横断面调查,于 2019 年针对所有新的和以前治疗过的痰涂片阳性肺结核患者进行。将痰样提交给国家结核病参考实验室进行结核确认,并通过 Xpert MTB/RIF 确定利福平耐药性。在固体培养基上进行培养,将确诊结核病例的培养分离物运往印度钦奈的世卫组织超国家结核病参考实验室进行全基因组测序(WGS)。使用 R 统计软件(版本 3.5.2)对调查总结统计数据、数据交叉表和利福平耐药性结核(RR-TB)的潜在危险因素进行分析。

结果

共纳入 953 例痰涂片阳性患者,其中 917 例通过 Xpert MTB/RIF 或培养证实为结核阳性。一个电子网络系统用于数据的输入和存储。新病例中利福平耐药率为 0.6%(95%CI 0.2-1.3),以前治疗过的病例中为 2.7%(95%CI 0.5-8.2)。对 65 个随机选择的分离物(Xpert MTB/RIF 或 pDST 检测的 RR-TB(2/7)和 RS-TB(63/910)分别为 29%和 7%)进行了 WGS 验证。62/64 个分离物(97%)的原始检测结果与 WGS 验证结果一致。

结论

与世卫组织东南亚区域(新发病例中 RR-TB 估计比例为 2.5%[95%CI 1.9-3.3],以前治疗过的病例中为 14%[95%CI 7.7-21%])相比,东帝汶 RR-TB 的流行率相对较低。在资源有限的环境中,调查中实施的快速痰采集和运输机制证明了其可行性,应将其复制用于常规从显微镜实验室向 GeneXpert 站点运输结核标本。建立用于一线和二线 DST 的快速分子诊断的国内能力是实现普遍药物敏感性测试(DST)以指导适当的患者管理的当务之急。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d851/9121552/a91cc7d8a93e/41256_2022_249_Fig1_HTML.jpg

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