Epidemiological investigation of a rifampicin-resistant tuberculosis outbreak in a middle school in Jiangsu Province
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摘要:
目的 描述江苏省某中学一起利福平耐药结核病疫情特点及流行病学调查过程，为校园结核病防控提供参考意见。 方法 本次结核病疫情采用了现场流行病学调查结合实验室检查(包括全基因组测序)。对接触者进行结核病可疑症状筛查、结核菌素皮肤试验(tuberculin skin test，TST)和胸部X光片检查。对于上述筛查异常的接触者进一步开展病原学检查，包括痰涂片、痰培养、传统药敏试验和GeneXpert结核分枝杆菌(Mycobacterium tuberculosis，MTB)/利福平(rifampin, RIF)检测，同时对培养阳性菌株进行全基因组测序。 结果 2019年6月24日―7月7日，两轮共筛查密切接触者352人。TST检测强阳性率为3.69%(13/352)，胸部X光片异常率为3.97%(14/352)。共诊断结核病患者12例，其中病原学阳性患者6例，临床诊断结核病患者6例。6例痰标本GeneXpert MTB/RIF检测检出MTB且利福平耐药。4株培养阳性菌株传统药敏实验显示均对利福平耐药，对其他检测抗结核药物敏感。全基因组测序数据显示，4株培养阳性菌株均属于L2型，突变基因和耐药位点相同。 结论 此次学校利福平耐药结核病为一起同源暴发疫情。与传统的表型药敏实验相比，全基因组测序速度快且准确，推荐用于结核病暴发调查。 Abstract:Objective To describe the characteristics and epidemiology of a rifampicin-resistant tuberculosis outbreak in a middle school of Jiangsu Province, and provide suggestions for the prevention and control of the school tuberculosis. Methods Combination of field epidemiology investigation and laboratory examinations (including whole-genome sequencing) were taken in this tuberculosis outbreak. Close contacts were screened for tuberculosis suspected symptoms, tuberculin skin test (TST), and chest X-ray. Bacteriological tests, including sputum smear, sputum culture, traditional drug susceptibility test and GeneXpert MTB/RIF test were carried out for contacts with abnormal screening results. Meanwhile, whole-genome sequencing was performed for culture-positive strains. Results From June 24, 2019 to July 7, 2019, a total of 352 close contacts were screened in two rounds contacts screening. The strongly positive rate of TST(average diameter ≥15 mm) was 3.69% (13/352) and the abnormal rate of chest X-ray was 3.97% (14/352). A total of 12 patients with pulmonary tuberculosis were diagnosed, including 6 bacteriological positive patients, and 6 bacteriological negative patients. GeneXpert MTB/RIF test detected 6 MTB positive also with rifampicin resistance. The traditional drug susceptibility test of the culture-positive strains of four tuberculosis patients showed that they were all resistant to rifampicin. Whole genome sequencing data indicated that all 4 culture-positive strains belonged to L2 type, with the same mutation and drug resistance site. Conclusions Based on the field and molecular epidemiological results, this school rifampicin-resistant tuberculosis was a homologous outbreak. Compared with traditional anti-TB drug susceptibility test, whole-genome sequencing is recommended for tuberculosis outbreak investigation due to its high-speed and accuracy. -
Key words:
- Tuberculosis /
- School outbreak /
- Whole genome sequencing /
- Rifampicin resistance
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表 1 江苏省某中学结核病病例密切接触者筛查[n(%)]
Table 1. Screening of close contacts of teachers and students in the middle school, Jiangsu Province [n(%)]
分组 学生 老师 合计 结核菌素皮肤试验(mm) ＜5 157(88.7) 20(11.3) 177(100.0) 5~＜15 159(98.1) 3(1.9) 162(100.0) ≥15 13(100.0) 0(0.0) 13(100.0) 胸部X片结果 正常 311(93.1) 23(6.9) 334(100.0) 不正常 14(100.0) 0(0.0) 14(100.0) 疑似病例 14(100.0) 0(0.0) 14(100.0) 确诊病例 12(100.0) 0(0.0) 12(100.0) 
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表 2 江苏省某中学结核病病例基本特征和实验室检查
Table 2. Characteristics and laboratory examinations of tuberculosis patients in the outbreak, Jiangsu Province
编号 性别 年龄(岁) 痰涂片 痰培养 Xpert 药敏实验 利福平 异烟肼 乙胺丁醇 链霉素 卡那霉素 氧氟沙星 患者01 女 14 阳性 阳性 MTB检出/RR 耐药 敏感 敏感 敏感 敏感 敏感 患者02 女 15 阳性 阳性 MTB检出/RR 耐药 敏感 敏感 敏感 敏感 敏感 患者03 女 15 阴性 阴性 MTB检出/RR 患者04 女 14 阳性 阳性 MTB检出/RR 耐药 敏感 敏感 敏感 敏感 敏感 患者05 男 15 阴性 阳性 MTB检出/RR 耐药 敏感 敏感 敏感 敏感 敏感 患者06 男 14 阴性 阴性 MTB检出/RR 患者07 男 14 阴性 阴性 MTB未检出 患者08 男 15 阴性 阴性 MTB未检出 患者09 男 14 阴性 阴性 MTB未检出 患者10 女 15 阴性 阴性 MTB未检出 患者11 女 15 阴性 阴性 MTB未检出 患者12 女 15 阴性 阴性 MTB未检出
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表 3 江苏省某中学结核病病例全基因组测序结果
Table 3. Whole-genome sequencing results of tuberculosis patients in a middle school, Jiangsu Province
编号 谱系 类型 密码子 标签 耐药基因 耐药性 患者01 L2 非同义突变 TCG-TTG Rv0667 rpoB 利福平 患者02 L2 非同义突变 TCG-TTG Rv0667 rpoB 利福平 患者04 L2 非同义突变 TCG-TTG Rv0667 rpoB 利福平 患者05 L2 非同义突变 TCG-TTG Rv0667 rpoB 利福平
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