Rios-Sarabia Nora, Hernández-González Olivia, González-Y-Merchand Jorge, Gordillo Guadalupe, Vázquez-Rosales Guillermo, Muñoz-Pérez Leopoldo, Torres Javier, Maldonado-Bernal Carmen
Medical Research Unit on Infectious Diseases, Hospital of Pediatrics, XXI Century National Medical Center, Mexican Social Security Institute, Mexico City 06720, Mexico.
Laboratory of Molecular Microbiology, Department of Microbiology, National School of Biological Sciences, National Polytechnic Institute, Mexico City 11340, Mexico.
Int J Mol Med. 2016 Oct;38(4):1289-95. doi: 10.3892/ijmm.2016.2698. Epub 2016 Aug 4.
Tuberculous meningitis (TBM) is the most severe form of tuberculosis. It is caused by Mycobacterium tuberculosis (M. tuberculosis; MT) and it is very difficult to diagnose. The symptoms are similar to other infectious neurological diseases, such as neurocysticercosis, neuroborreliosis, or herpes viral infection. The aim of this study was to identify tuberculosis (TB) in cases of meningitis with clinical and laboratory evidence suggestive of TBM, and to confirm our findings with molecular tests for TB infection. We recruited patients with neurological symptoms who were examined at the neurology services of Hospitals of Instituto Mexicano del Seguro Social (IMSS) in Mexico City. A total of 144 consecutive patients with suggestive infectious meningitis were initially included; 94 cases of meningitis with clinical and laboratory evidence suggestive of TBM were included, but only 50 of these cases fulfilled the criteria for probable TBM. As the controls, we included 50 cases of meningitis with clinical and laboratory evidence suggestive of non-TBM. Cerebrospinal fluid (CSF) was collected from all 100 patients (cases and controls) and tested for TB by multiplex and nested PCR analyses. Nested PCR detected 0.1 fg of M. tuberculosis DNA. TB infection was confirmed with molecular tests in 49 patients from the 50 cases suggestive of TBM and in 1 of the 50 non-TBM cases. The analysis exhibited a sensitivity of 98.0%, a specificity of 92.0%, a positive predictive value of 88.0% and a negative predictive value of 98.0%. The use CSF for the analyses proved to be effective for the rapid diagnosis of TBM using a developed system of multiplex and nested PCR analyses in patients presenting neurological symptoms.
结核性脑膜炎(TBM)是结核病最严重的形式。它由结核分枝杆菌(M. tuberculosis;MT)引起,诊断非常困难。其症状与其他传染性神经系统疾病相似,如神经囊尾蚴病、神经莱姆病或疱疹病毒感染。本研究的目的是在具有临床和实验室证据提示为TBM的脑膜炎病例中识别结核病(TB),并通过结核感染的分子检测来证实我们的发现。我们招募了在墨西哥城墨西哥社会保障局(IMSS)医院神经科接受检查的有神经症状的患者。最初共纳入144例连续的提示为感染性脑膜炎的患者;其中94例脑膜炎患者具有临床和实验室证据提示为TBM,但只有50例符合可能的TBM标准。作为对照,我们纳入了50例具有临床和实验室证据提示为非TBM的脑膜炎病例。从所有100例患者(病例和对照)中采集脑脊液(CSF),并通过多重和巢式PCR分析检测结核。巢式PCR可检测到0.1 fg的结核分枝杆菌DNA。在50例提示为TBM的病例中有49例以及50例非TBM病例中有1例通过分子检测确诊为结核感染。分析显示敏感性为98.0%,特异性为92.0%,阳性预测值为88.0%,阴性预测值为98.0%。在出现神经症状的患者中,使用脑脊液进行分析经证明对于使用开发的多重和巢式PCR分析系统快速诊断TBM是有效的。