2014—2020年广东省儿童肺结核耐药特征分析

doi:10.19982/j.issn.1000-6621.20230109

摘要/Abstract

摘要：

目的: 分析2014—2020年广东省儿童肺结核患者结核分枝杆菌(Mycobacterium tuberculosis,MTB)分离株耐药特征。方法: 从广东省32个肺结核耐药监测点收集2014年1月1日至2020年12月30日39046例肺结核患者耐药监测资料,依据入组标准从中选取1274例(3.3%)18岁及以下儿童患者耐药监测资料,分析MTB分离株对9种一线和二线抗结核药物[包括异烟肼(INH)、链霉素(Sm)、乙胺丁醇(EMB)、利福平(RFP)、卡那霉素(Km)、丙硫异烟胺(Pto)、卷曲霉素(Cm)、氧氟沙星(Ofx)和对氨基水杨酸钠(PAS)]的药物敏感性试验结果,并总结其耐药特征。结果: 儿童肺结核患者构成比从2014年的4.3%(123/2856)下降至2020年的3.1%(177/5760),呈逐年下降趋势($X_{趋势}^{2}$=25.864,P<0.001)。药物敏感性试验结果显示,1274株菌株对Sm、INH、RFP、EMB、Ofx、PAS、Pto、Km和Cm的耐药率依次为14.8%(189株)、7.7%(98株)、6.3%(80株)、6.0%(77株)、3.5%(44株)、3.5%(44株)、2.9%(37株)、2.5%(32株)和2.2%(28株),总耐药率、单耐药率、多耐药率、耐多药率和广泛耐药率分别为26.0%(331株)、15.4%(196株)、4.2%(54株)、3.1%(39株)和0.8%(10株)。其中,0~12岁年龄组和男性儿童组的MTB分离株广泛耐药率[3.0%(3/100)和1.3%(10/749)]分别明显高于13~18岁年龄组和女性儿童组[0.6%(7/1174)和0.0%(0/525)],珠江三角洲地区儿童组的MTB分离株单耐药率[28.1%(213/758)]明显高于粤东西北地区[22.9%(118/516)],差异均有统计学意义(χ²=6.837,P=0.038;χ²=10.679,P=0.007;χ²=4.370,P=0.037)。结论: 广东省儿童耐药肺结核流行形势严峻,应对珠江三角洲地区和0~12岁男性儿童肺结核的耐药情况予以足够的重视。

关键词: 儿童, 分枝杆菌,结核, 结核,抗多种药物性, 人群监测

Abstract:

Objective: To investigate the drug resistance characteristics of Mycobacterium tuberculosis (MTB) isolates from children with pulmonary tuberculosis (PTB) in Guangdong Province from 2014 to 2020. Methods: According to the enrollment standard, 1274 (3.3%) MTB isolates from children aged 0 to 18 were collected from 32 sentinel sites of PTB resistance surveillance (39046 MTB isolates) in Guangdong Province from January 1, 2014 to December 30, 2020. Analysed the data of drug resistance of MTB isolates for first- and second-line of anti-TB drugs (including isoniazid (INH), streptomycin (Sm), ethambutol (EMB), rifampicin (RFP), kanamycin (Km), propylthioisoniacin (Pto), capreomycin (Cm), ofloxacin (Ofx), and sodium p-aminosalicylate (PAS)) and summarized the drug resistance characteristics. Results: The proportion of PTB children was dropped from 4.3% (123/2856) in 2014 to 3.1% (177/5760) in 2020, showing a downward trend of year by year ($X_{trend}^{2}$=25.864, P<0.001). The resistance rates of the isolates to anti-TB drugs from high to low were Sm (14.8% (189/1274))>INH (7.7% (98/1274))>RFP (6.3% (80/1274))>EMB (6.0% (77/1274))>Ofx (3.5% (44/1274))=PAS (3.5% (44/1274))>Pto (2.9% (37/1274))>Km (2.5% (32/1274))>Cm (2.2% (28/1274)), and the drug resistance rate, mono-resistance rate, poly-resistance rate, multidrug-resistance rate (MDR) and extensively drug resistance rate (XDR) of MTB of the 1274 isolates was 26.0% (331/1274), 15.4% (196/1274), 4.2% (54/1274), 3.1% (39/1274), and 0.8% (10/1274), respectively. The XDR of MTB in children aged 0 to 12 was significantly higher than that in children aged 13 to 18 (3.0% (3/100) vs. 0.6% (7/1174); χ²=6.837, P=0.038). In addition, the XDR of MTB in boys was significantly higher than that in girls (1.3% (10/749) vs. 0.0% (0/525); χ²=10.679, P=0.007), and the resistance rate of MTB in the Pearl River Delta was significantly higher than that in eastern and northwestern Guangdong (28.1% (213/758) vs. 22.9% (118/516); χ²=4.370, P=0.037). Conclusion: The prevalence of PTB in children in Guangdong Province is serious. The drug resistance in PTB children aged 0-12 years, who were boys, and who lived in Pearl River Delta should be paid special attention.

Key words: Child, Mycobacterium tuberculosis, Tuberculosis, multidrug-resistant, Population surveillance

中图分类号:

R181.2
R52

卓文基, 张晨晨, 陈珣珣, 魏文静, 余美玲, 彭柯皓, 徐镠粤, 陈燕梅. 2014—2020年广东省儿童肺结核耐药特征分析[J]. 中国防痨杂志, 2023, 45(7): 687-692. doi: 10.19982/j.issn.1000-6621.20230109

Zhuo Wenji, Zhang Chenchen, Chen Xunxun, Wei Wenjing, Yu Meiling, Peng Kehao, Xu Liuyue, Chen Yanmei. Analysis of drug resistance characteristics of pulmonary tuberculosis in children in Guangdong, 2014—2020[J]. Chinese Journal of Antituberculosis, 2023, 45(7): 687-692. doi: 10.19982/j.issn.1000-6621.20230109

图/表 5

表1

2014—2020年广东省儿童肺结核患者结核分枝杆菌分离株耐药情况

年份	全年龄段人群分离菌株数	儿童患者分离菌株
年份	全年龄段人群分离菌株数	合计	耐药	单耐药	多耐药	耐多药	广泛耐药
2014	2856	123(4.3)	28(22.8)	15(12.2)	5(4.1)	4(3.3)	0(0.0)
2015	4943	146(3.0)	32(21.9)	19(13.0)	4(2.7)	4(2.7)	1(0.7)
2016	6087	156(2.6)	37(23.7)	22(14.1)	5(3.2)	5(3.2)	1(0.6)
2017	7045	228(3.2)	63(27.6)	39(17.1)	9(3.9)	10(4.4)	4(1.8)
2018	5930	210(3.5)	57(27.1)	36(17.1)	8(3.8)	3(1.4)	0(0.0)
2019	6425	234(3.6)	59(25.2)	28(12.0)	16(6.8)	7(3.0)	1(0.4)
2020	5760	177(3.1)	55(31.1)	37(20.9)	7(4.0)	6(3.4)	3(1.7)
合计	39046	1274(3.3)	331(26.0)	196(15.4)	54(4.2)	39(3.1)	10(0.8)
$χ 趋势 2$ 值		25.864	5.260	9.049	5.300	3.380	9.220
P值		<0.001	0.511	0.171	0.506	0.760	0.162

表1

表2

表3

表4

表5

参考文献 24

[1]	World Health Organization. Global tuberculosis report 2022. Geneva: World Health Organization, 2022.
[2]	Reuter A, Hughes J, Furin J, et al. Challenges and controversies in childhood tuberculosis. Lancet, 2019, 394(10202):967-978. doi:10.1016/S0140-6736(19)32045-8. doi: S0140-6736(19)32045-8 pmid: 31526740
[3]	Igbokwe V, Ruby LC, Sultanli A, et al. Post-tuberculosis sequelae in children and adolescents: a systematic review. Lancet Infect Dis, 2023, 23(4):e138-e150. doi:10.1016/S1473-3099(23)00004-X. doi: 10.1016/S1473-3099(23)00004-X pmid: 36963920
[4]	Martinez L, Gray DM, Botha M, et al. The Long-Term Impact of Early-Life Tuberculosis Disease on Child Health: A Prospective Birth Cohort Study. Am J Respir Crit Care Med, 2023, 207(8):1080-1088. doi:10.1164/rccm.202208-1543OC. doi: 10.1164/rccm.202208-1543OC URL
[5]	Cohen KA, Manson AL, Abeel T, et al. Extensive global movement of multidrug-resistant M.tuberculosis strains revealed by whole-genome analysis. Thorax, 2019, 74(9):882-889. doi:10.1136/thoraxjnl-2018-211616. doi: 10.1136/thoraxjnl-2018-211616 URL
[6]	赵雁林, 逄宇. 结核病实验室检验规程. 北京: 人民卫生出版社, 2015:18-65.
[7]	中华人民共和国国家卫生和计划生育委员会. WS 196—2017结核病分类. 2017-11-09.
[8]	Furin J, Cox H, Pai M. Tuberculosis. Lancet, 2019, 393(10181):1642-1656. doi:10.1016/S0140-6736(19)30308-3. doi: S0140-6736(19)30308-3 pmid: 30904262
[9]	刘志辉, 钟球. 全面应对耐多药结核病的挑战——问题困惑、行动和希望. 实用医学杂志, 2022, 38(13):1573-1577. doi:10.3969/j.issn.1006-5725.2022.13.001. doi: 10.3969/j.issn.1006-5725.2022.13.001
[10]	Dodd PJ, Gardiner E, Coghlan R, et al. Burden of childhood tuberculosis in 22 high-burden countries: a mathematical modelling study. Lancet Glob Health, 2014, 2(8):e453-459. doi:10.1016/S2214-109X(14)70245-1. doi: 10.1016/S2214-109X(14)70245-1 URL
[11]	焦伟伟, 孙琳, 肖婧, 等. 国家结核病规划指南——儿童结核病管理. 2版. 中国循证儿科杂志, 2016, 11(1):65-74. doi:10.3969/j.issn.1673-5501.2016.01.016.
[12]	Tao NN, He XC, Zhang XX, et al. Drug-Resistant Tuberculosis among Children, China, 2006—2015. Emerg Infect Dis, 2017, 23(11):1800-1805. doi:10.3201/eid2311.170234. doi: 10.3201/eid2311.170234 URL
[13]	Song WM, Li YF, Liu YX, et al. Drug-Resistant Tuberculosis Among Children: A Systematic Review and Meta-Analysis. Front Public Health, 2021, 9:721817. doi:10.3389/fpubh.2021.721817. doi: 10.3389/fpubh.2021.721817 URL
[14]	Xu Y, Li Q, Zhu M, et al. The epidemiological characteristics and profile of drug-resistant tuberculosis among children with tuberculosis in Sichuan, China, 2015—2018: A retrospective study. Medicine (Baltimore), 2020, 99(43):e22608. doi:10.1097/MD.0000000000022608. doi: 10.1097/MD.0000000000022608 URL
[15]	Wang G, Jiang G, Jing W, et al. Prevalence and molecular characterizations of seven additional drug resistance among multidrug-resistant tuberculosis in China: A subsequent study of a national survey. J Infect, 2021, 82(3):371-377. doi:10.1016/j.jinf.2021.02.004. doi: 10.1016/j.jinf.2021.02.004 pmid: 33556430
[16]	Diriba G, Alemu A, Yenew B, et al. Epidemiology of extensively drug-resistant tuberculosis among patients with multidrug-resistant tuberculosis: A systematic review and meta-analysis. Int J Infect Dis, 2023, 132:50-63. doi:10.1016/j.ijid.2023.04.392. doi: 10.1016/j.ijid.2023.04.392 URL
[17]	Akalu TY, Clements ACA, Wolde HF, et al. Prevalence of long-term physical sequelae among patients treated with multi-drug and extensively drug-resistant tuberculosis: a systematic review and meta-analysis. EClinicalMedicine, 2023, 57:101900. doi:10.1016/j.eclinm.2023.101900. doi: 10.1016/j.eclinm.2023.101900 URL
[18]	Martinez L, Lo NC, Cords O, et al. Paediatric tuberculosis transmission outside the household: challenging historical paradigms to inform future public health strategies. Lancet Respir Med, 2019, 7(6):544-552. doi:10.1016/S2213-2600(19)30137-7. doi: 10.1016/S2213-2600(19)30137-7 pmid: 31078497
[19]	Zhou XL, Chen QP, Wang MS. Prevalence of multidrug-resistant tuberculosis in suspected childhood tuberculosis in Shandong, China: a laboratory-based study. J Int Med Res, 2020, 48(1):300060519869715. doi:10.1177/0300060519869715. doi: 10.1177/0300060519869715
[20]	Weldegebreal F, Teklemariam Z, Mitiku H, et al. Treatment outcome of pediatric tuberculosis in eastern Ethiopia. Front Pediatr, 2022, 10:966237. doi:10.3389/fped.2022.966237. doi: 10.3389/fped.2022.966237 URL
[21]	郭雪丽, 马晓雪, 陈慧娟, 等. 2011—2020年贵州省儿童青少年肺结核流行病学分析. 现代预防医学, 2021, 48(16):2892-2896, 2904.
[22]	陈燕梅, 温文沛, 吴惠忠, 等. 2016—2020年广东省结核病耐药监测结果分析. 中国防痨杂志, 2022, 44(7):685-689. doi:10.19982/j.issn.1000-6621.20220028. doi: 10.19982/j.issn.1000-6621.20220028
[23]	Sun YX, Zhu L, Lu ZH, et al. Notification Rate of Tuberculosis among Migrants in China 2005—2014: A Systematic Review and Meta-analysis. Chin Med J (Engl), 2016, 129(15):1856-1860. doi:10.4103/0366-6999.186650. doi: 10.4103/0366-6999.186650
[24]	Viney K, Linh NN, Gegia M, et al. New definitions of pre-extensively and extensively drug-resistant tuberculosis: update from the World Health Organization. Eur Respir J, 2021, 57(4):2100361. doi:10.1183/13993003.00361-2021. doi: 10.1183/13993003.00361-2021 URL

特征	分离株	单耐药	χ²值	P值	多耐药	χ²值	P值	耐多药	χ²值	P值	广泛耐药	χ²值	P值
性别			3.591	0.058		0.602	0.438		0.094	0.759		10.679	0.007
男性	749(58.8)	180(24.0)			29(3.9)			22(2.9)			10(1.3)
女性	525(41.2)	151(28.8)			25(4.8)			17(3.2)			0(0.0)
年龄组(岁)			0.911	0.340		0.829	0.362		1.375	0.241		6.837	0.038
0~12	100(7.8)	30(30.0)			6(6.0)			5(5.0)			3(3.0)
13~18	1174(92.2)	301(25.6)			48(4.1)			34(2.9)			7(0.6)
地区			4.370	0.037		0.662	0.416		1.582	0.209		1.758	0.216
粤东西北	516(40.5)	118(22.9)			19(3.7)			12(2.3)			2(0.4)
珠江三角洲	758(59.5)	213(28.1)			35(4.6)			27(3.6)			8(1.1)
居住地			0.231	0.631		0.105	0.746		0.920	0.338		1.038	0.308
城市	688(54.0)	175(25.4)			28(4.1)			24(3.5)			7(1.0)
农村	586(46.0)	156(26.6)			26(4.4)			15(2.6)			3(0.5)
民族			1.024	0.311		0.768	0.381		0.997	0.318		0.218	0.641
汉族	1184(92.9)	305(25.8)			49(4.1)			35(3.0)			9(0.8)
少数民族	90(7.1)	25(27.8)			5(5.6)			4(4.4)			1(1.1)

年份	分离株数	耐INH	耐Sm	耐EMB	耐RFP	耐Km	耐Pto	耐Cm	耐Ofx	耐PAS
2014	123	11(8.9)	19(15.4)	9(7.3)	5(4.1)	4(3.3)	1(0.8)	1(0.8)	5(4.1)	2(1.6)
2015	146	10(6.8)	19(13.0)	7(4.8)	6(4.6)	3(2.1)	3(2.1)	1(0.7)	5(3.4)	2(1.4)
2016	156	9(5.8)	25(16.0)	6(3.8)	7(4.5)	3(1.9)	5(3.2)	3(1.9)	7(4.5)	4(2.6)
2017	228	23(10.1)	41(18.0)	10(4.4)	17(7.5)	2(0.9)	9(3.9)	5(2.2)	10(4.4)	9(3.9)
2018	210	9(4.3)	21(10.0)	13(6.2)	17(8.1)	9(4.3)	5(2.4)	7(3.3)	5(2.4)	12(5.7)
2019	234	23(9.8)	39(16.7)	15(6.4)	11(4.7)	5(2.1)	6(2.6)	5(2.1)	7(3.0)	8(3.4)
2020	177	13(7.3)	25(14.1)	17(9.6)	17(9.6)	6(3.4)	8(4.5)	6(3.4)	5(2.8)	7(4.0)
合计	1274	98(7.7)	189(14.8)	77(6.0)	80(6.3)	32(2.5)	37(2.9)	28(2.2)	44(3.5)	44(3.5)
χ²值		8.039	6.960	7.198	9.073	6.499	5.149	5.141	2.317	7.023
P值		0.235	0.325	0.303	0.169	0.370	0.525	0.526	0.888	0.319

分类	菌株	耐INH	耐Sm	耐EMB	耐RFP	耐Km	耐Pto	耐Cm	耐Ofx	耐PAS
初治	1255(98.5)	97(7.7)	184(14.7)	76(6.1)	78(6.2)	31(2.5)	37(2.9)	27(2.2)	43(3.4)	43(3.4)
复治	19(1.5)	1(5.3)	5(26.3)	1(5.3)	2(10.5)	1(5.3)	0(0.0)	1(5.3)	1(5.3)	1(5.3)
合计	1274(100.0)	98(7.7)	189(14.8)	77(6.0)	80(6.3)	32(2.5)	37(2.9)	28(2.2)	44(3.5)	44(3.5)
χ²值		0.160	2.012	0.021	0.591	0.596	0.005	0.843	0.189	0.189
P值		0.689	0.156	0.886	0.337	0.385	1.000	0.346	0.490	0.490

分类	菌株	耐药	单耐药	多耐药	耐多药	广泛耐药
初治	1255(98.5)	325(25.9)	192(15.3)	53(4.2)	38(3.0)	10(0.8)
复治	19(1.5)	6(31.6)	4(21.1)	1(5.3)	1(5.3)	0(0.0)
合计	1274(100.0)	331(26.0)	196(15.4)	54(4.2)	39(3.1)	10(0.8)
χ²值		0.314	0.476	0.050	0.315	0.153
P值		0.575	0.517	0.563	0.448	1.000