粪便Gene Xpert MTB/RIF检测对HIV阴性肠结核的早期快速诊断价值

目的:评价Gene Xpert结核分枝杆菌/利福平(MTB/RIF,简称"Xpert")在人类免疫缺陷病毒(HIV)阴性肠结核患者早期快速诊断中的价值。方法:选取2018年1月至2019年6月在山东省胸科医院、北京胸科医院、苏州市第五人民医院3家医院就诊的254例HIV阴性疑似肠结核患者。采集所有患者的粪便标本,每份标本分别进行Xpert检测、涂片查抗酸杆菌、BACTEC MGIT 960(简称"MGIT 960")分枝杆菌培养。以临床诊断为标准,评价Xpert检测粪便标本的敏感度和特异度,若培养结果为阳性,则对菌株进行利福平药物敏感性检测,并对Xpert检测结果与MGIT 960药敏检测结果一致性进行分析。结果:254例患者中139例(54.7%)临床诊断为肠结核,115例(45.3%)临床诊断为非肠结核。139例肠结核患者中,60例(43.2%)MGIT 960分枝杆菌培养阳性;79例(56.8%)按临床表现、肠镜检查结果、抗结核治疗效果等临床诊断为肠结核。以临床诊断为标准,Xpert检测粪便标本的敏感度[60.4%(84/139)]优于抗酸杆菌涂片敏感度[13.2%(17/139)],两者敏感度比较有统计学差异(P0.001),Xpert检测特异度为100.0%(84/84);MGIT 960分枝杆菌培养敏感度为43.2%(60/139),与Xpert检测比较有统计学差异(P=0.004)。结核分枝杆菌(MTB)培养阳性患者中,Xpert检测的敏感度为98.3%(59/60)。在涂片和培养均为阴性的肠结核患者中,Xpert检测的阳性率为31.6%(25/79)。结论:Xpert检测粪便标本中MTB较抗酸杆菌涂片和MGIT 960分枝杆菌培养敏感度更高,并且可以同时检测利福平耐药性,为早期快速诊断肠结核提供细菌学依据。     

Consequence of enhanced LC3-trafficking for a live,attenuated M. tuberculosis vaccine

Development of a new vaccine against tuberculosis is urgently needed. Recent work has demonstrated that two related LC3-associated trafficking pathways, autophagy and LC3-associated phagocytosis (LAP), enhance antigen presentation and might play a role in vaccine efficacy. Mycobacterium tuberculosis inhibits both LC3-trafficking pathways. Moreover, the vaccine strain, BCG, induces even less LC3-trafficking than M. tuberculosis, which may help explain its limited efficacy. To determine whether enhanced LC3-trafficking can improve efficacy of a live, attenuated M. tuberculosis vaccine, we took advantage of our recent finding that the bacterial virulence factor CpsA inhibits LAP. When we deleted cpsA in the mc²6206 vaccine strain, it dramatically increased LC3-trafficking. We compared the protective efficacy of the strain lacking cpsA to the parent strain and to BCG in mice challenged with M. tuberculosis. We found that the strain lacking cpsA generated modestly enhanced protection in the spleen, but overall did not outperform BCG.