耐多药肺结核家庭内传播情况分析

doi:10.19982/j.issn.1000-6621.20220355

摘要/Abstract

摘要：

目的: 探索耐多药肺结核(multidrug-resistant pulmonary tuberculosis, MDR-PTB)家庭内传播特征。方法: 对2018年7月至2020年6月武汉市肺科医院登记的全部166例MDR-PTB患者(一代病例)的282名家庭密切接触者(在其中发现的MDR-PTB患者为二代病例)进行结核菌素皮肤试验(TST)、胸部X线检查、分枝杆菌培养和表型药物敏感性试验,采用DTM-PCR和24位点MIRU-VNTR分型方法对一、二代病例分离菌株进行基因分型。计算家庭密切接触者结核分枝杆菌感染率和MDR-PTB发病例数,比较一、二代病例的耐药表型,绘制分离菌株MIRU最小生成树。结果: 282名家庭密切接触者中,TST检测阴性率、一般阳性率、中度阳性率和强阳性率分别为53.90%(152名)、8.51%(24名)、10.64%(30名)和26.95%(76名),结核感染率为37.59%(106例)。282名密切接触者中有疑似症状者9例(3.19%);274名行胸部X线检查者中异常者8例(2.92%);106例行痰结核分枝杆菌细菌学检查者中病原学阳性者4例(3.77%),且全部为二代MDR-PTB,发病率为1.42%。二代病例中有3例表型耐药谱与一代病例相同,1例不同;对来自3个家庭的6株菌株进行24位点MIRU-VNTR基因分型,发现其中2个家庭的MIRU基因分型24位点完全相同,1个家庭仅1个位点有差异;DTM-PCR分型显示6株菌株均为北京株。结论: MDR-PTB患者家庭密切接触存在较高结核感染传播风险,家庭二代MDR-PTB发病率高于一般人群,应对家庭密切接触者做好宣传教育、筛查及随访,减少MDR-PTB的家庭内传播。

关键词: 分枝杆菌,结核, 抗多种药物性, 接触者追踪, 家庭, 人群监测

Abstract:

Objective: To explore transmission characteristics of multidrug-resistant pulmonary tuberculosis (MDR-PTB) in family. Methods: A total of 282 household contacts of 166 MDR-PTB patients (first generation cases) registered in Wuhan Pulmonary Hospital from July 2018 to June 2020 (MDR-PTB patients found in them were second generation cases) were enrolled. All the subjects were treated with tuberculin skin test (TST), chest X-ray, mycobacterium culture and phenotypic drug sensitivity test. Genotypes of strains from the first and second generation patients were tested by DTM-PCR and standard 24-loci MIRU-VNTR. The infection rate of Mycobacterium tuberculosis and the number of cases of MDR-PTB in close family contacts were calculated. The drug-resistant phenotype of first and second generation cases were compared, and the MIRU minimum spanning tree of the isolated strain was drawn. Results: Among 282 family contacts, the negative rate, general positive rate, moderate positive rate and strong positive rate of TST were 53.90% (n=152), 8.51% (n=24), 10.64% (n=30) and 26.95% (n=76), respectively, the infection rate of Mycobacterium tuberculosis was 37.59% (n=106). Of the 282 subjects, 9 (3.19%) had suspected symptoms, and 8 (2.92%) had abnormal chest films among 274 subjects who underwent chest X-ray. Among 106 subjects who had performed bacteriological examination of sputum Mycobacterium tuberculosis, 4 (3.77%) were positive in etiology, and all of them were second generation MDR-PTB, with a incidence rate of 1.42%. In the second generation cases, 3 cases had the same drug resistance phenotype as the indicator case, and 1 case was different. The 24 locus MIRU-VNTR genotyping of 6 strains from 3 families showed that the 24 loci of MIRU genotyping of 2 families were identical, and only 1 locus of 1 family was different. DTM-PCR genotyping showed that all 6 strains were Beijing strains. Conclusion: Close family contacts of MDR-PTB patients are at risk of infection. The incidence rate of second generation MDR-PTB in families is higher than that of the general population. Therefore, publicity, education, screening and follow-up should be coducted for close family contacts to reduce the spread of MDR-PTB within families.

Key words: Mycobacterium tuberculosis, Multidrug-resistant tuberculosis, Contact tracing, Family, Population surveillance

中图分类号:

周燕, 周萌, 彭军, 段琼红, 陈军, 周美兰, 张云侠, 梁军. 耐多药肺结核家庭内传播情况分析[J]. 中国防痨杂志, 2023, 45(2): 195-199. doi: 10.19982/j.issn.1000-6621.20220355

Zhou Yan, Zhou Meng, Peng Jun, Duan Qionghong, Chen Jun, Zhou Meilan, Zhang Yunxia, Liang Jun. Analysis on transmission of multidrug-resistant pulmonary tuberculosis in family[J]. Chinese Journal of Antituberculosis, 2023, 45(2): 195-199. doi: 10.19982/j.issn.1000-6621.20220355

图/表 4

表1

表2

表3

图1

参考文献 17

[1]	World Health Organization. Global tuberculosis report 2022. Geneva: World Health Organization, 2022.
[2]	Javaid A, Khan MA, Khan MA, et al. Screening outcomes of household contacts of multidrug-resistant tuberculosis patients in Peshawar, Pakistan. Asian Pac J Trop Med, 2016, 9(9): 909-912. doi:10.1016/j.apjtm.2016.07.017. doi: S1995-7645(16)30154-7 pmid: 27633308
[3]	李婕, 王黎霞, 成君, 等. 活动性肺结核患者家庭密切接触者结核病防治核心信息知晓情况调查. 中国防痨杂志, 2015, 37(10): 1035-1041. doi:10.3969/j.issn.1000-6621.2015.10.007. doi: 10.3969/j.issn.1000-6621.2015.10.007
[4]	Lu P, Ding X, Liu Q, et al. Mediating Effect of Repeated Tuberculosis Exposure on the Risk of Transmission to Household Contacts of Multidrug-Resistant Tuberculosis Patients. Am J Trop Med Hyg, 2018, 98(2): 364-371. doi:10.4269/ajtmh.17-0325. doi: 10.4269/ajtmh.17-0325 URL
[5]	中华人民共和国国家卫生和计划生育委员会. WS 288—2017肺结核诊断. 2017-11-09.
[6]	Khosravi AD, Goodarzi H, Alavi SM, et al. Application of Deletion-Targeted Multiplex PCR technique for detection of Mycobacterium tuberculosis Beijing strains in samples from tuberculosis patients. Iran J Microbiol, 2014, 6(5): 330-334.
[7]	Chizimu JY, Solo ES, Bwalya P, et al. Genetic Diversity and Transmission of Multidrug-Resistant Mycobacterium tuberculosis strains in Lusaka, Zambia. Int J Infect Dis, 2021, 114: 142-150. doi:10.1016/j.ijid.2021.10.044. doi: 10.1016/j.ijid.2021.10.044 URL
[8]	姚芳, 袁保东, 陈国玺, 等. 武汉市635例初治涂阳肺结核患者家庭接触者肺结核发病情况分析. 中国防痨杂志, 2020, 42(2): 164-167. doi:10.3969/j.issn.1000-6621.2020.02.015. doi: 10.3969/j.issn.1000-6621.2020.02.015
[9]	杜雨华, 江坤洪, 梁成双, 等. 对广州市涂阳肺结核患者家庭密切接触者筛查的情况分析. 中国防痨杂志, 2014, 36(10): 897-900. doi:10.3969/j.issn.1000-6621.2014.10.008. doi: 10.3969/j.issn.1000-6621.2014.10.008
[10]	韩志英, 张怀庆, 顾凯侃. 耐多药结核病患者密切接触者感染状况分析. 中国初级卫生保健, 2020, 34(7): 75-78. doi:10.3969/j.issn.1001-568X.2020.07.0021. doi: 10.3969/j.issn.1001-568X.2020.07.0021
[11]	成诗明, 王国治, 王黎霞, 等. 结核菌素皮肤试验使用指导手册. 北京: 人民卫生出版社, 2014.
[12]	Vella V, Racalbuto V, Guerra R, et al. Household contact investigation of multidrug-resistant and extensively drug-resistant tuberculosis in a high HIV prevalence setting. Int J Tuberc Lung Dis, 2011, 15(9): 1170-1175, i. doi:10.5588/ijtld.10.0781. doi: 10.5588/ijtld.10.0781 pmid: 21943840
[13]	Iliaz S, Caglar E, Koksalan OK, et al. An outbreak of multidrug-resistant tuberculosis among a family. Indian J Tuberc, 2016, 63(2): 130-132. doi:10.1016/j.ijtb.2015.07.009. doi: 10.1016/j.ijtb.2015.07.009 URL
[14]	彭城, 项莉. 武汉市初治涂阳肺结核患者规范化隔离治疗住院费用及治疗效果分析. 医学与社会, 2020, 33(6): 69-72. doi:10.13723/j.yxysh.2020.06.017. doi: 10.13723/j.yxysh.2020.06.017
[15]	Moore DA. What can we offer to 3 million MDRTB household contacts in 2016? BMC Med, 2016, 14: 64. doi:10.1186/s12916-016-0610-x. doi: 10.1186/s12916-016-0610-x
[16]	段琼红, 陈军, 王卫华. MIRU-VNTR在耐多药结核病分子流行病学中的应用进展. 公共卫生与预防医学, 2018, 29(5): 85-88. doi:10.3969/j.issn.1006-2483.2018.05.023. doi: 10.3969/j.issn.1006-2483.2018.05.023
[17]	Cavany SM, Vynnycky E, Sumner T, et al. Transmission events revealed in tuberculosis contact investigations in London. Sci Rep, 2018, 8(1): 6676. doi:10.1038/s41598-018-25149-6. doi: 10.1038/s41598-018-25149-6 pmid: 29703981

临床资料	人数(名)	构成比(%)	临床资料	人数(名)	构成比(%)
性别			年龄组(岁)
男性	122	43.26	3~25	62	21.99
女性	160	56.74	26~64	203	71.98
与一代病例关系			65~71	17	6.03
夫妻	103	36.52	结核菌素皮肤试验
子女	97	34.40	阴性	152	53.90
父母	55	19.50	一般阳性	24	8.51
兄弟姐妹	12	4.26	中度阳性	30	10.64
其他亲人	15	5.32	强阳性	76	26.95

特征	接触者人数 (名)	非结核感染				结核感染
		阴性		一般阳性		中度阳性		强阳性		合计		χ²值	P值
		人数 (名)	构成比 (%)	人数 (名)	构成比 (%)	例数	构成比 (%)	例数	构成比 (%)	例数	构成比 (%)	χ²值	P值
性别												3.803	0.051
男性	122	73	59.84	11	9.02	17	13.93	21	17.21	38	31.14
女性	160	79	49.38	13	8.12	13	8.12	55	34.38	68	42.50
年龄组(岁)												1.654	0.437
3~25	62	37	59.68	6	9.68	10	16.13	9	14.51	19	30.64
26~64	203	105	51.72	18	8.87	20	9.85	60	29.56	80	39.41
65~71	17	10	58.82	-	-	-	-	7	41.18	7	41.18
合计	282	152	53.90	24	8.51	30	10.64	76	26.95	106	37.59

病例编号	类别	家庭关系	性别	年龄 (岁)	诊断耐药间隔时间(月)	临床症状	耐药谱
B1-1	一代病例	父亲	男	72	0.0	咳嗽、喘气15年	H、R、E、Sm、Ofx
B1-2	二代病例	儿子	男	40	0.5	咳嗽、咳痰9个月	H、R、E、Sm、Ofx
B2-1	一代病例	父亲	男	62	0.0	咳嗽、间断咳血4个月	H、R
B2-2	二代病例	儿子	男	35	3.0	无	H、R、Sm
B2-3	二代病例	儿媳	女	31	8.0	无	H、R
B3-1	一代病例	姐姐	女	29	0.0	肾透析,行CT检查	H、R、E、Ofx、Lfx、Mfx、Rfb
B3-2	二代病例	妹妹	女	26	12.0	咳嗽3个月	H、R、E、Ofx、Lfx、Mfx、Rfb