基于全基因组测序的昌平区高校结核病传播链确定研究  

Identification of tuberculosis transmission chain in universities in Changping District Based on whole genome sequencing

作　　者：张治国[1] 杨震[1] 孙倩[1] 包城 赵飞 Zhang Zhiguo;Yang Zhen;Sun Qian;Bao Cheng;Zhao Fei(Changping Institute for Tuberculosis Control and Treatment,Beijing 102200,China;Pharmacy Department.Beijing Hospital,National Center of Gerontology,Institute of Geriatric Medicine,Chinese Academy of Medical Sciences,Beijing 100730,China)

机构地区：[1]北京市昌平区结核病防治所,北京102200 [2]北京医院药学部,国家老年医学中心,中国医学科学院老年医学研究院,药物临床风险与个体化应用评价北京市重点实验室,北京100730

出　　处：《中国医学前沿杂志（电子版）》2023年第4期50-54,共5页Chinese Journal of the Frontiers of Medical Science(Electronic Version)

基　　金：北京市自然科学基金(7174323);首都卫生发展科研专项(2022-1G-3012)。

摘　　要：目的 对北京市昌平区高校内出现的结核分枝杆菌培养阳性患者进行调查,以期从流行病学角度和分子生物学角度评价病例之间是否存在传播关系。方法 纳入2018年1月1日至2019年12月31日北京市昌平区27所高校出现的结核病患者为指示病例,通过密切接触者调查尽量筛查出密切接触者中的结核病患者。对发现的结核分枝杆菌培养阳性患者提取细菌的DNA并进行全基因组测序,通过与标准菌株比对,以评价菌株之间是否同源。结果在101例指示病例中,有44例细菌学阳性的患者,但仅有29例培养阳性,且其中1例被诊断为非结核分枝杆菌感染。在29例培养阳性指示病例的64例密切接触者中,并未发现结核病患者。而72例培养阴性指示病例的250例密切接触者中,有3例被诊断为结核病,且其中2例培养阳性。因此,提取培养阳性的28例指示病例和2例密切接触者中的结核分枝杆菌DNA并进行全基因组测序。全基因组测序结果显示30例菌株核心基因组SNP的差异均≥100SNPs,按照本研究分子生物学鉴定标准,30例菌株被认为非相同菌株传播,不存在同源性。结论本研究未找到指示病例和密切接触者具有相同细菌的证据,因此无法从分子生物学角度鉴定其存在传播关系的可能。Objective To investigate the patients with positive cultures of Mycobacterium tuberculosis(TB)in universities in Changping District,Beijing,in order to evaluate whether there is a transmission relationship between cases from the perspective of epidemiology and molecular biology.Methods Tuberculosis patients from 27 colleges and universities in Changping District of Beijing from January 1,2018 to December 31,2019 were included as indicator cases,the close contacts of the index cases were screened as much as possible through close contact survey.Bacterial DNA was extracted from patients with positive culture of Mycobacterium tuberculosis and whole genome sequencing(WGS)was performed to evaluate whether the strains were homologous by comparison with standard strains.Results Of the 101 indicated cases,44 were bacteriologically positive,but only 29 were culture-positive including 1 non-tuberculosis mycobacterium infection.However,among the 64 close contacts of 29 culture-positive index cases,no TB patients were found.Of the 250 close contacts from the 72 culture-negative index cases,3 were diagnosed with TB and 2 of them were culture-positive.Therefore,Mycobacterium tuberculosis DNA from the 28 positive index cases and 2 close contacts with positive-culture was extracted and WGS was performed.The results of WGS showed that the differences in the core genomic SNPs of the 30 strains were≥100 SNPs,and according to the molecular biology identification criteria of this study,30 strains were considered non-identical strain propagation and not homologous.Conclusions In this study,no evidence was found that the index cases and the close contacts had the same bacteria in terms of molecular biology identification,so the possibility of a transmission relationship could not be identified from the molecular biology point of view.

关 键 词：结核分枝杆菌 全基因组测序 传播 学生 高校 

分 类 号：R52[医药卫生—内科学] R181.3[医药卫生—临床医学]