Analysis of infection patterns and drug resistance of 22 recurrent pulmonary tuberculosis patients in Sichuan based on whole-genome sequencing

doi:10.19982/j.issn.1000-6621.20240036

Abstract

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

CLC Number:

R521

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

Figures/Tables 5

References 28

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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)

患者编号	耐药谱		感染类型
患者编号	初始感染	第2次感染	感染类型
5	-	INH	内源性
8	INH	INH+RFP+ EMB+PZA	外源性
9	INH	-	外源性
10	-	INH+RFP+ EMB+PZA	外源性
11	INH	-	外源性
12	Sm+Mfx+Ofx	Sm+Mfx+Ofx	内源性
13	INH+RFP+EMB+ PZA+Sm	INH+RFP+EMB+ PZA+Sm	内源性
14	INH+RFP+PZA+ Sm+Mfx+Ofx+Eto	INH+RFP+PZA+ Sm+Mfx+Ofx	内源性
17	INH+RFP+EMB+ Sm	INH+Sm	外源性
19	INH+Sm	INH+Sm	内源性
20	INH+RFP	INH+RFP+EMB	内源性