基于全基因组测序的四川省22例复发肺结核患者感染模式及耐药情况分析

doi:10.19982/j.issn.1000-6621.20240036

摘要/Abstract

摘要：

目的: 分析复发肺结核患者感染模式和耐药信息,为结核病患者治疗及防控提供科学依据。方法: 采用前瞻性研究方法,参照入组标准从四川省峨眉山市、绵阳市涪城区和江油市3个耐药监测点收集2012—2021年肺结核患者分枝杆菌培养阳性菌株2207株,剔除286株重复菌株后与中国疾病预防控制中心结核病信息管理系统进行比对,排除18例发病间隔<12个月的患者后,对34例有2次及以上就诊情况患者菌株进行复苏、DNA提取、全基因组测序,分析复发患者结核感染模式和耐药情况。结果: 排除11例某一配对菌株传代培养失败及1例全基因组测序结果为非结核分枝杆菌的患者后,最终纳入22例复发肺结核患者进行分析。其中,14例(63.6%)患者为内源性复燃,本地患者、发病间隔、初始感染菌株为Lineage 2谱系、耐药、耐多药、异烟肼耐药患者分别为13例(92.9%)、18.00(13.50, 24.50)个月、10例(71.4%)、6例(42.9%)、2例(14.3%)、5例(35.7%),2例获得性耐药,1例乙硫异烟胺耐药性消失;8例(36.4%)患者为外源性再感染,其相应数据分别为4例(4/8)、14.50(13.25, 16.75)个月、4例(4/8)、5例(5/8)、3例(3/8)、5例(5/8),且两次感染耐药类型均不同。结论: 四川省作为结核病高负担地区,复发仍以内源性复燃为主,但耐药严重的外源性再感染也应引起重视,应积极关注这类患者的治疗情况,制定个体化用药方案,减少结核病复发。

关键词: 结核,肺, 复发, 全基因组测序, 结核,抗多种药物性, 流行病学研究

Abstract:

Objective: To analyze the infection patterns and drug resistance information of recurrent pulmonary tuberculosis patients, and to provide evidence for the treatment and prevention of tuberculosis. Methods: A prospective study was conducted. According to the inclusion criteria, 2207 strains of culture positive from pulmonary tuberculosis patients between 2012 and 2021 were collected from three drug-resistant surveillance sites in Sichuan Province (Emeishan, Fucheng and Jiangyou). After removing 286 duplicate strains, they were compared with the “Tuberculosis Information Management System” of the Chinese Center for Disease Control and Prevention to exclude 18 patients with an onset interval of less than 12 months, and the remaining 34 patients with two or more visits were selected for strain resuscitation, DNA extraction and whole genome sequencing to analyze the tuberculosis infection patterns and drug resistance of recurrent patients. Results: A total of 22 patients with recurrent tuberculosis were included in the analysis, except for 11 patients with failure of subculture of a paired strain and 1 patient with non-tuberculous by whole genome sequencing. Among them, 14 cases (63.6%) were due to relapse, 13 (92.9%) cases were local patients, onset interval was 18.00 (13.50, 24.50) months, initial infection Lineage 2, cases of drug resistance, MDR and INH resistance were 10 (71.4%), 6 (42.9%), 2 (14.3%) and 5 (35.7%), respectively. Acquired resistance occurred in 2 patients with relapse, and resistance to Eto disappeared in 1 patient. The remaining 8 (36.4%) cases were reinfection, of which 4 (4/8) were local patients, onset interval was 14.50 (13.25, 16.75) months, cases with initial infection Lineage 2, drug resistance, MDR and INH resistance were 4 (4/8), 5 (5/8), 3 (3/8), and 5 (5/8),respectively, and the drug resistance types of the two infections were different. Conclusion: As a high burden area of tuberculosis, the recurrence tuberculosis was still dominated by relapse in Sichuan Province. However, we should also focus on the serious reinfection of drug resistance, actively pay attention to the treatment of such patients, and develop individualized medication regimens to reduce the recurrence of tuberculosis.

Key words: Tuberculosis,pulmonary, Recurrence, Whole-genome sequencing, Tuberculosis, resistant to multiple drugs, Epidemiologic studies

中图分类号:

R521

雷卉, 张书, 李婷, 高媛, 刘双, 陈闯, 夏岚, 王为娜, 高文凤, 何金戈. 基于全基因组测序的四川省22例复发肺结核患者感染模式及耐药情况分析[J]. 中国防痨杂志, 2024, 46(6): 641-647. doi: 10.19982/j.issn.1000-6621.20240036

Lei Hui, Zhang Shu, Li Ting, Gao Yuan, Liu Shuang, Chen Chuang, Xia Lan, Wang Weina, Gao Wenfeng, He Jinge. Analysis of infection patterns and drug resistance of 22 recurrent pulmonary tuberculosis patients in Sichuan based on whole-genome sequencing[J]. Chinese Journal of Antituberculosis, 2024, 46(6): 641-647. doi: 10.19982/j.issn.1000-6621.20240036

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特征	内源性复燃(14例)	外源性再感染(8例)	统计检验值	P值
性别 [例(构成比,%)]			-	1.000^a
男性	13(92.9)	7(7/8)
女性	1(7.1)	1(1/8)
年龄(岁,$\bar{x}±s$)	60.57±9.08	46.00±19.50	t=1.994	0.078
民族 [例(构成比,%)]			-	0.364^a
汉族	14(100.0)	7(7/8)
彝族	0(0.0)	1(1/8)
户籍 [例(构成比,%)]			-	0.039^a
本地	13(92.9)	4(4/8)
非本地	1(7.1)	4(4/8)
糖尿病 [例(构成比,%)]			-	0.121^a
有	0(0.0)	2(2/8)
无	14(100.0)	6(6/8)
发病间隔 [月,M(Q₁,Q₃)]	18.00(13.50, 24.50)	14.50(13.25, 16.75)	Z=-1.099	0.272

菌株特征	内源性复燃(14例)			外源性再感染(8例)			P值^a	P值^b
菌株特征	初始感染	第二次感染	P值	初始感染	第二次感染	P值	P值^a	P值^b
谱系 [例(构成比,%)]			1.000			1.000	0.386	0.187
Lineage 2	10(71.4)	10(71.4)		4(4/8)	3(3/8)
Lineage 4	4(28.6)	4(28.6)		4(4/8)	5(5/8)
耐药类型 [例(构成比,%)]			1.000			0.354	0.565	0.882
药物敏感	9(64.4)	8(57.2)		4(4/8)	5(5/8)
单耐药	1(7.1)	2(14.3)		3(3/8)	0(0/8)
多耐药	1(7.1)	1(7.1)		0(0/8)	1(1/8)
耐多药	2(14.3)	2(14.3)		1(1/8)	2(2/8)
准广泛耐药	1(7.1)	1(7.1)		0(0/8)	0(0/8)