Rapid diagnosis of tuberculous meningitis by polymerase chain reaction

doi:10.1016/0140-6736(91)93328-7

The Lancet

Volume 337, Issue 8732, 5 January 1991, Pages 5-7

https://doi.org/10.1016/0140-6736(91)93328-7 Get rights and content

Abstract

The polymerase chain reaction (PCR) in cerebrospinal fluid was compared with conventional bacteriology and an enzyme—linked immunosorbent assay (ELISA) for cerebrospinal fluid antibodies in the diagnosis of tuberculous meningitis (TBM). PCR was the most sensitive technique; it detected 15 (75%) of 20 cases of highly probable TBM (based on clinical features), 4 (57%) of 7 probable cases, and 3 (43%) of 7 possible cases. ELISA detected 11 (55%) of the highly probable cases and 2 each of the probable and possible cases. Culture was positive in only 4 of the highly probable cases. Among the controls (14 pyogenic meningitis, 3 aseptic meningitis, 34 other neurological disorders), 6 subjects tested early in the study (2 pyogenic meningitis, 4 other disorders) were PCR positive. Second DNA preparations from their stored cerebrospinal fluid samples were all PCR negative, suggesting that the false-positive results were due to cross-contamination. 18 PCR-positive TBM samples retested were all still PCR positive. The antibody ELISA was positive in 3 controls despite the use of a high cutoff value.

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Cited by (218)

Diagnostic accuracy of nucleic acid amplification based assays for tuberculous meningitis: A meta-analysis
2018, Journal of Infection
Numerous in-house and commercial nucleic acid amplification tests (NAAT) have been evaluated using variable reference standards for diagnosis of TBM but their diagnostic potential is still not very clear.
We conducted a meta-analysis to assess the diagnostic accuracy of different NAAT based assays for diagnosing TBM against 43 data sets of confirmed TBM (n = 1066) and 61 data sets of suspected TBM (n = 3721) as two reference standards. The summary estimate of the sensitivity and the specificity were obtained using the bivariate model. QUADAS-2 tool was used to perform the Quality assessment for bias and applicability. Publication bias was assessed with Deeks' funnel plot.
Studies with confirmed TBM had better summary estimates as compared to studies with clinically suspected TBM irrespective of NAAT and index tests used. Among in-house assays, MPB as the gene target had best summary estimates in both confirmed [sensitivity:90%(83–95), specificity:97-%(87–99), DOR:247 (50–1221), AUC:99%(97–100), PLR:38.8-(6.6–133), NLR:0.11(0.05–0.18), I²= 15%] and clinically suspected [sensitivity:69%(47–85), specificity:96%(90–98), DOR:62(16.8–232), AUC:94%(92–97), PLR:16.9(6.5–36.8), NLR:0.33(0.16–0.56), I²:15.3%] groups. GeneXpert revealed good diagnostic accuracy only in confirmed TBM group [sensitivity = 57%(38–74), specificity = 98%(89–100), DOR = 62(7–589), AUC = 87%(79–96), PLR = 33.2(3.8–128), NLR = 0.45(0.26–0.68), I²= 0%].
This meta-analysis identified potential role of MPB gene among in-house assays and GeneXpert as commercial assay for diagnosing TBM.
Adenosine deaminase activity in cerebrospinal fluid and serum for the diagnosis of tuberculous meningitis
2013, Clinical Neurology and Neurosurgery
Citation Excerpt :
The supportive criteria included (1) CSF cell count (more than 0.02 × 109 cells/L with lymphocytic predominance), protein more than 1 g/L, sterile routine bacterial and fungal culture; (2) CT or MRI evidences of exudates, infarctions, hydrocephalus and tuberculoma in various combinations; (3) evidence of tuberculosis outside the central nervous system; and (4) a clinical response to antitubercular therapy. All our patients had definitive evidence of TBM or suggestive TBM with the presence of clinical essential and three of four supportive criteria [13–15]. Patients were included after discharge if having definitive evidence of TBM, or excluded if another diagnosis was confirmed by microbiologic or histopathologic evaluation such as fungal and carcinomatous meningitides.
To evaluate the usefulness of serum and CSF adenosine deaminase (ADA) activity for the diagnosis of tuberculous meningitis (TBM) from other meningitis.
We studied CSF and serum ADA activity for 83 cases of TBM, 148 of bacterial meningitis (BM), and 262 of viral or aseptic meningitis.
The mean ADA activities (IU/L) in CSF and serum were higher in TBM (11.80 ± 2.50, 30.28 ± 7.30) than in other types of meningitis (8.52 ± 3.60, 17.90 ± 9.20 in BM; 5.26 ± 1.90, 8.56 ± 5.9 in viral or aseptic meningitis). When we accepted a serum ADA activity cut-off value of 15 IU/L for the differential diagnosis of TBM and non-TBM with ROC analysis, the sensitivity was 84% and specificity was 82%. Combining CSF (≥10) and serum (≥15) ADA activity significantly increased overall specificity from 92% to 97% for the diagnosis of TBM.
The determination of CSF and serum ADA activity is a simple and reliable test for differentiating TBM from other types of meningitis.
Diagnostic appraisal of simultaneous application of two nested PCRs targeting MPB64 gene and IS6110 region for rapid detection of M. tuberculosis genome in culture proven clinical specimens
2013, Indian Journal of Medical Microbiology
Background: Early diagnosis of tuberculosis is critical for its effective management and prevention. Several gene amplification methods are used in the detection of tubercle bacilli from clinical specimens. MPB64 gene and IS6110 region have been identified as potential gene targets for the specific detection of Mycobacterium tuberculosis from direct clinical specimens. Objective: The present study was conducted to evaluate the diagnostic utility of simultaneous application of two nested polymerase chain reaction (nPCRs) targeting MPB64 and IS6110 region for the detection of M. tuberculosis genome. Materials and Methods: A total of 100 and 354 clinical specimens from the control group and clinically suspected tuberculosis patients, respectively, were included in the study. nPCRs targeting MPB64 and IS6110 region were performed. Results and Conclusion: All of the 100 clinical specimens from the control group were negative for both nPCRs. Out of the 354 clinical specimens, 339 were positive for both culture and nPCRs, 10 and 5 were positive for culture, and nPCR targeting IS6110 and MPB64 regions, respectively. To conclude, nPCRs targeting MPB64 and IS6110 region are reliable and specific targets when applied simultaneously on clinical specimens to attain 100% sensitivity for the detection of M. tuberculosis genome.
Childhood tubercular meningitis: An institutional experience and analysis of predictors of outcome
2013, Pediatric Neurology
Tubercular meningitis constitutes an important cause of morbidity and mortality in developing countries, and various factors determine its outcome. We studied demographic and clinical profiles of childhood tubercular meningitis, and identified predictors of outcome. This prospective study was performed in 65 children aged ≤18 years, hospitalized with a diagnosis of tubercular meningitis. Boys outnumbered girls. Most patients presented with a poor clinical grade. Headache and vomiting comprised common features. Cerebrospinal fluid was characterized by predominant lymphocytosis. Many patients were diagnosed for Mycobacterium tuberculosis via polymerase chain reaction. Hydrocephalus comprises a common finding via computed tomography. Low Glasgow Coma Scores, seizures, basal exudates, and infarcts predict outcomes. Children with headaches, fevers, and altered sensorium should be investigated promptly for tubercular meningitis. Timely intervention may lead to early diagnoses and reductions in morbidity and mortality.
Management of Tuberculous Infections of the Nervous System
2012, Schmidek and Sweet Operative Neurosurgical Techniques: Indications, Methods, and Results: Sixth Edition
Tuberculous meningitis: a uniform case definition for use in clinical research
2010, The Lancet Infectious Diseases
Tuberculous meningitis causes substantial mortality and morbidity in children and adults. More research is urgently needed to better understand the pathogenesis of disease and to improve its clinical management and outcome. A major stumbling block is the absence of standardised diagnostic criteria. The different case definitions used in various studies makes comparison of research findings difficult, prevents the best use of existing data, and limits the management of disease. To address this problem, a 3-day tuberculous meningitis workshop took place in Cape Town, South Africa, and was attended by 41 international participants experienced in the research or management of tuberculous meningitis. During the meeting, diagnostic criteria were assessed and discussed, after which a writing committee was appointed to finalise a consensus case definition for tuberculous meningitis for use in future clinical research. We present the consensus case definition together with the rationale behind the recommendations. This case definition is applicable irrespective of the patient's age, HIV infection status, or the resources available in the research setting. Consistent use of the proposed case definition will aid comparison of studies, improve scientific communication, and ultimately improve care.

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ORIGINAL ARTICLESRapid diagnosis of tuberculous meningitis by polymerase chain reaction

Abstract

Lancet

Tubercle

Lancet

Tuberculous meningitis

Tuberculous meningitis

Med Clin North Am

New approaches to the rapid diagnosis of tuberculous meningitis

J Infect Dis

ORIGINAL ARTICLES
Rapid diagnosis of tuberculous meningitis by polymerase chain reaction