某高级中学一起结核病聚集性疫情传播的时空序列与分子流行病学分析

Spatial-temporal sequence and molecular epidemiology analysis on a tuberculosis cluster in a high school

目的探讨本起学校结核病聚集性疫情传播的原因、特点和规律,为持续改进学校结核病控制策略的有效实施提供科学依据。方法遵照广东省汕头市卫生健康局对本起疫情处置工作的具体要求,以指示病例为中心、以学习生活空间要素为重点、以人际交往活动要素为辅助进行密切接触者筛查,对纳入者进行结核病可疑症状检查、X线胸部检查和结核菌素(PPD)皮肤试验;对其中任何1项异常者进行IFN-γ释放试验、CT影像检查、痰涂片抗酸染色检查、分枝杆菌培养与菌种鉴定和Xpert MTB/RIF分子检测,以综合诊断结核病例;对分离培养获得的结核分枝杆菌,分析其ETRA、ETRB、ETRC、ETRE、ETRF、MIRU10、MIRU20、MIRU26、MIRU39、MIRU40、Mtub04、Mtub21、Mtub38、Oub11b、Qub26等15个基因位点的串联重复拷贝数,分析其成簇性以判断病例间的传播关系。结果(1)指示病例首次结核可疑症状出现并一直在校学习5个月后,出现双肺上叶斑片状、斑点状、条索状密度增高影和左肺上叶多发空洞(最大者约2.1 cm×1.7 cm)等病变,培养与分子检测阳性;(2)指示病例发现的3个月内,在该校相继发现其他15例学生肺结核患者,其中3例有临床症状、3例痰涂片镜检可疑阳性、9例培养阳性、7例分子检测阳性,10例与指示病例有同班上课、同舍住宿和同室晚自习等空间性密切接触,4例与指示病例有直接或间接的人际密切交往,1例则未找到明确的密切交往线索;(3)对9例患者分离培养的结核分枝杆菌进行基因分型,8例得到成功结果,15个VNTR-MIRU分型位点的拷贝数模式完全相同;(4)依据PPD皮肤试验≥5 mm判断结核感染,409例受检者中252例阳性,潜伏感染率为61.61%,潜伏感染率在指示病例班级与后续发现病例班级学生间差异有统计学意义(100%vs.56.58%,χ^(2)=30.781,P<0.001),而在男-女、学生-教职工、寄宿生-走读生、不同楼层学生、同层同侧-同层对侧学生等多组人群间则差异无统计学意义(P>0.05)。结论该起结核聚集性疫情为同一传染源传播所致,且导致了远高于一般人群的结核潜伏感染率,学校结核病控制管理缺失为其主要原因,强化学校结核病控制措施的有效执行力刻不容缓。

Objective To investigate clearly the causes,characteristics and patterns of the clustered epidemic of tuberculosis in this high school and provide scientific basis for improving continuously implementation of tuberculosis control strategies in schools.Methods Complying with the specific requirements of Shantou Health Bureau of Guangdong Province on handling this affair,close contacts who were deemed to be in close contact with index case in terms of study,living space and interpersonal interaction were screened.Suspicious symptom examination,chest x-ray examination and skin test of tuberculin(PPD)were performed among these close con-tacts.For diagnosing comprehensively to tuberculosis,interferon gamma release assay(IGRA),CT image examination,sputum smear acid-fast staining microscopic examination,isolation and species identification of mycobacteria and Xpert MTB/RIF molecular detection were performed for any patients with any abnormal results from the abovementioned screening process.In order that the transmission relationships were established correctly bases on genic cluster patterns of MIRU-VNTR,15-loci MIRU-VNTR(ETRA,ETRB,ETRC,ETRE,ETRF,MIRU10,MIRU20,MIRU26,MIRU39,MIRU40,Mtub04,Mtub21,Mtub38,Oub11b,and Qub26)of Mycobacterium tuberculosis from cases with tuberculosis were detected and analyzed.Results The first,the index case had presented these lesions such as patchy,speckled and streak-like increased density images in the upper lobe of both lungs and multiple cavities of which the largest was about 2.1 cm×1.7 cm in the upper lobe of left lung,and his laboratorial results of isolation and molecular detection of pathogen were positive.The second,15 other cases with pulmonary tuberculosis were found following three months after the discovery of the index case in this school.Among these cases,there were clinical symptoms in 3 cases,sputum-smear suspicious positive in 3 cases,pathogen isolation culture positive in 9 cases and molecular detection positive in 7 cases respectively.As to close contact with index case,10 cases had close spatial contact cluding the same classroom,dormitory or evening selfstudy classroom and 4 cases direct or indirect interpersonal contact while one case had no clear clues of close contact.The third,genotyping laboratory results demonstrated that the copy number patterns of 15-loci MIRU-VNTR were identical in eight isolates among nine isolates,of which one isolate was not obtained genotyping result.Finally,assuming“PPD skin test≥5 mm”was regard as the criterion of latent tuberculosis infection,252 out of 409 patients were positive and the latent infection rate was 61.61%.There was a significant difference in latent infection rate between the students from class of the index case and the students from classes of other cases(100%vs.56.58%,χ^(2)=30.781,P<0.001).However,there is no significant difference between the following population groups:male vs.female,resident students vs.day students,students from different floors and students from the same side of same vs.students from the opposite side of same(P>0.05).Conclusions This clustered epidemic of tuberculosis was caused by the same infectious source,which caused much higher latent tuberculosis infection rate than that of the general population.It is urgent to strengthen the effective implementation of school tuberculosis control measures because the main reason causing this affair is serious lack of management of school tuberculosis control.