scholarly journals Efficient diagnosis of tuberculous meningitis by detection of Mycobacterium tuberculosis DNA in cerebrospinal fluid filtrates using PCR

2009 ◽  
Vol 58 (5) ◽  
pp. 616-624 ◽  
Author(s):  
Sagarika Haldar ◽  
Neera Sharma ◽  
V. K. Gupta ◽  
Jaya Sivaswami Tyagi

Tuberculous meningitis (TBM) is the most devastating form of meningitis and prompt diagnosis holds the key to its management. Conventional microbiology has limited utility and nucleic acid-based methods have not been widely accepted for various reasons. In view of the paucibacillary nature of cerebrospinal fluid (CSF) and the recent demonstration of free Mycobacterium tuberculosis DNA in clinical specimens, the present study was designed to evaluate the utility of CSF ‘filtrates’ for the diagnosis of TBM using PCR. One hundred and sixty-seven CSF samples were analysed from patients with ‘suspected’ TBM (n=81) and a control group including other cases of meningitis or neurological disorders (n=86). CSF ‘sediments’ and ‘filtrates’ were analysed individually for M. tuberculosis DNA by quantitative real-time PCR (qRT-PCR) and conventional PCR. Receiver-operating characteristic curves were generated from qRT-PCR data and cut-off values of 84 and 30 were selected for calling a ‘filtrate’ or ‘sediment’ sample positive, respectively. Based on these, TBM was diagnosed with 87.6 % and 53.1 % sensitivity (P <0.001) in ‘filtrates’ and ‘sediments’, respectively, and with 92 % specificity each. Conventional devR and IS6110 PCR were also significantly more sensitive in ‘filtrates’ versus ‘sediments’ (sensitivity of 87.6 % and 85.2 % vs 31 % and 39.5 %, respectively; P <0.001). The qRT-PCR test yielded a positive likelihood ratio of 11 and 6.6 by analysing ‘filtrate’ and ‘sediment’ fractions, respectively, which establishes the superiority of the ‘filtrate’-based assay over the ‘sediment’ assay. PCR findings were separately verified in 10 confirmed cases of TBM, where M. tuberculosis DNA was detected using devR PCR assays in ‘sediment’ and ‘filtrate’ fractions of all samples. From this study, we conclude that (i) CSF ‘filtrates’ contain a substantial amount of M. tuberculosis DNA and (ii) ‘filtrates’ and not ‘sediments’ are likely to reliably provide a PCR-based diagnosis in ‘suspected’ TBM patients.

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Zhaoqiang Jiang ◽  
Shibo Ying ◽  
Wei Shen ◽  
Xianglei He ◽  
Junqiang Chen ◽  
...  

Fibulin-3 has been reported as a potential biomarker for mesothelioma. However, little is known about the diagnostic efficacies of fibulin-3 for asbestos-related diseases (ARDs) in China. This study was to investigate the utility of fibulin-3 for asbestos exposure and ARDs. A total of 430 subjects were recruited from Southeast China, including healthy individuals, asbestos-exposed (AE) individuals, and patients with pleural plaques (PP), asbestosis, and malignant pleural mesothelioma (MPM). Plasma fibulin-3 was measured using the enzyme-linked immunosorbent assay. Linear regression analyses were applied to explore the influencing factors of fibulin-3. Receiver operating characteristic curves were used to determine the cutoff values. The median fibulin-3 level of subjects in the mesothelioma group was higher than that in other groups. Subjects in the asbestosis group had higher median fibulin-3 level than those in the control group. A higher fibulin-3 level was found in the group with ≥10 years of asbestos exposure as compared with control groups. The AUCs of fibulin-3 for distinguishing MPM subjects from control, AE, PP, and asbestosis subjects were 0.92, 0.88, 0.90, and 0.81, respectively. Our study provided evidence that fibulin-3 could be a potential biomarker for the early screening of MPM, but not of other nonmalignant ARDs in Chinese populations.


2007 ◽  
Vol 156 (5) ◽  
pp. 569-575 ◽  
Author(s):  
Michèle d’Herbomez ◽  
Gérard Forzy ◽  
Catherine Bauters ◽  
Catherine Tierny ◽  
Pascal Pigny ◽  
...  

Objectives: The aims of this study were to determine the performance of each variable, to define the optimal diagnostic thresholds and to determine the relative value of assaying chromogranin A (CgA). Design: Prospective study. Methods: Two groups of patients were studied: a control group of 71 patients and a group of 63 patients with a histologically-proven pheochromocytoma (52 pheochromocytomas and 14 paragangliomas). Fourteen of the patients had a family history of the disease. Eleven variables were assayed in each patient, i.e. the plasma and urinary concentrations of amines and their derivatives, and the CgA serum concentration. Results: The study of the control group showed that all the serum assays gave false positive results (from 6 to 23%), as did four of the six urinary assays (from 2.9 to 12.3%). The areas under the receiver operating characteristic curves varied from 0.689 to 0.992. The variables relating to the epinephrine pathway were significantly less expressed in the hereditary diseases than in the sporadic cases. The diagnostic thresholds of the three most efficient variables have been raised. Conclusions: Plasma determinations of metanephrines are now an easy and convenient tool for the diagnosis of pheochromocytoma. However, in our study the best specificity was obtained with the urinary tests rather than with the plasma assays while the highest sensitivities were for the normetanephrine assays. The assay of CgA was highly efficient in diagnosing pheochromocytomas in the absence of renal insufficiency. By combining it with fractionated metanephrine assays, the sensitivities of the latter were increased.


2020 ◽  
Vol 73 (12) ◽  
pp. 800-802
Author(s):  
Toby Chun Hei Chan ◽  
Sammy Pak Lam Chen ◽  
Chloe Miu Mak ◽  
Chor Kwan Ching ◽  
Kristine Shik Luk ◽  
...  

AimsTuberculous meningitis (TBM) is a severe infection which may lead to serious complication and mortality. Prompt diagnosis and treatment are essential. There is a need for a simple and fast laboratory test to differentiate TBM from other causes.MethodsRetrospective review was conducted for cerebrospinal fluid adenosine deaminase (CSF-ADA) activity which was measured at the Chemical Pathology Laboratory of Princess Margaret Hospital, the sole centre providing such service in Hong Kong, for 51 patients with suspected meningitis from nine local hospitals between June 2014 and July 2017. TBM diagnosis was defined by positive culture and/or nucleic acid amplification test result of Mycobacterium tuberculosis complex in CSF.ResultsCSF-ADA activity was significantly higher in the TBM group (8.6±2.1 IU/L, n=8) than that of the non-TBM group (2.8±5.9 IU/L, n=43). The optimal clinical cut-off of 5.1 U/L for TBM diagnosis in our laboratory yielded 100% sensitivity, 91% specificity, positive likelihood ratio of 10.8 and negative likelihood ratio of 0. In rare circumstance, false elevation may be seen in non-tuberculous cause, such as central nervous system lymphoma and fungal infection.ConclusionsWe recommend the use of CSF-ADA activity, which is a simple, fast and robust test for early differentiation of TBM from other causes, to facilitate timely initiation of antituberculous treatment and potentially improve patients’ outcome.


2019 ◽  
Vol 70 (11) ◽  
pp. 3981-3983
Author(s):  
Ioana Florina Mihai ◽  
Alexandra Largu ◽  
V. Dorobat ◽  
Carmen Manciuc

Tuberculous meningitis is the most lethal form of Mycobacterium tuberculosis infection, with a high rate of neurological complications and sequelae. We present the case of a 6 years old child diagnosed with tuberculous meningitis based on epidemiological, clinical and biological data and who has rapidly developed neurological complications with persistent fever and headache for a long time. Under tuberculostatic, depletion and corticosteroid treatment, the evolution of the disease was slowly favorable.


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