Objective: The utility of metagenomic next-generation sequencing (mNGS) in the diagnosis of tuberculous meningitis (TBM) remains uncertain. We performed a meta-analysis to comprehensively evaluate its diagnostic accuracy for the early diagnosis of TBM. Methods: English (PubMed, Medline, Web of Science, Cochrane Library, and Embase) and Chinese (CNKI, Wanfang, and CBM) databases were searched for relevant studies assessing the diagnostic accuracy of mNGS for TBM. Review Manager was used to evaluate the quality of the included studies, and Stata was used to perform the statistical analysis. Results: Of 495 relevant articles retrieved, eight studies involving 693 participants (348 with and 345 without TBM) met the inclusion criteria and were included in the meta-analysis. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and area under the summary receiver-operating characteristic curve of mNGS for diagnosing TBM were 62% (95% confidence interval [CI]: 0.46-0.76), 99% (95% CI: 0.94-1.00), 139.08 (95% CI: 8.54-2266), 0.38 (95% CI: 0.25-0.58), 364.89 (95% CI: 18.39-7239), and 0.97 (95% CI: 0.95-0.98), respectively. Conclusions: mNGS showed good specificity but moderate sensitivity; therefore, a more sensitive test should be developed to assist in the diagnosis of TBM.
Tuberculosis, Meningeal , Humans , Tuberculosis, Meningeal/diagnosis , Sensitivity and Specificity , ROC Curve , High-Throughput Nucleotide Sequencing , Databases, Factual
Tuberculous meningitis (TBM) is the most common type of central nervous system tuberculosis (TB) and has the highest mortality and disability rate. Early diagnosis is key to improving the prognosis and survival rate of patients. However, laboratory diagnosis of TBM is often difficult due to its paucibacillary nature and sub optimal sensitivity of conventional microbiology and molecular tools which often fails to detect the pathogen. The gold standard for TBM diagnosis is the presence of MTB in the CSF. The recognised methods for the identification of MTB are acid-fast bacilli (AFB) detected under CSF smear microscopy, MTB cultured in CSF, and MTB detected by polymerase chain reaction (PCR). Currently, many studies consider that all diagnostic techniques for TBM are not perfect, and no single technique is considered simple, fast, cheap, and efficient. A definite diagnosis of TBM is still difficult in current clinical practice. In this review, we summarise the current state of microbiological and molecular biological diagnostics for TBM, the latest advances in research, and discuss the advantages of these techniques, as well as the issues and challenges faced in terms of diagnostic effectiveness, laboratory infrastructure, testing costs, and clinical expertise, for clinicians to select appropriate testing methods.
Objective: Central nervous system (CNS) infection has a high incidence and mortality worldwide. Tuberculous meningitis (TBM) accounts for approximately 5-6% of all extrapulmonary tuberculosis (TB), and is considered an extremely lethal form of CNS TB, which has become an important threat to human health. Anemia is a common symptom of TB, and its prevalence is generally higher in patients with TBM than in other meningitis patients and healthy individuals. Anemia can increase a person's susceptibility to common infectious diseases, including TB, by compromising the immune system. Information regarding anemia during the hospitalization of TBM is still scarce in China. This study aimed to describe in detail the prevalence of anemia in patients with TBM in Southern China and its association with the clinical forms of TB, as well as other characteristics of these patients. Methods: We conducted a retrospective analysis of patients diagnosed with TBM at two tertiary hospitals in southern China. The demographic characteristics, clinical characteristics, and laboratory results of 114 patients with TBM were collected. Multivariate logistic regression analysis was performed to explore the risk factors for anemia in patients with TBM. Results: Electronic medical record data of adult patients diagnosed with TBM from January 2004 to December 2019 were reviewed. Among 134 patients with TBM, 20 were excluded and 114 were analyzed, of whom 33 had anemic, the prevalence rate of anemia was 28.9%. Among patients with anemia, 51.5% had hypochromic microcytic anemia, 33.3% had normochromic normocytic anemia, and 15.2% had macrocytic anemia. Fever duration, TBM grade III and ESR were found to be independent predictors of anemia. Conclusion: Anemia was highly prevalent in patients with TBM, mainly hypochromic microcytic anemia. Besides, Fever duration, TBM grade III and ESR are predictors of anemia in patients with TBM.
Objective: Tuberculous meningitis (TBM) is a common form of central nervous system (CNS) tuberculosis (TB). Cranial nerve palsy is a serious complication of TBM. Literature regarding this subject is still limited in China. This study evaluated the incidence of cranial nerve palsy in patients with TBM in South China, its association with the clinical forms of TB, and other patient characteristics. Methods: A retrospective chart review of patients with a diagnosis of TBM between January 2004 and December 2019 was conducted, and the demographic characteristics, clinical characteristics, and laboratory results of 114 patients were collected and followed up for 3 months. A multivariate logistic regression analysis model was used to explore the risk factors of cranial nerve palsy in patients with TBM. Results: A total of 114 patients were enrolled in this study. Cranial nerve palsy was observed in approximately 38 (33.3%) of TBM patients. Among them, 13 (28.3%) had optic nerve palsy, 24 (52.2%) had oculomotor nerve palsy, 5 (10.9%) had abducens nerve palsy, 2 (4.3%) had auditory nerve palsy, 1 (2.2%) had glossopharyngeal nerve palsy, and 1 (2.2%) had vagus nerve palsy. Using logistic regression analysis, focal neurological deficit, extracranial TB and cerebrospinal fluid (CSF) total white cell count (WCC) were shown to be risk factors for cranial nerve palsy. Conclusion: The prevalence rate of cranial nerve palsy was 33.3% in patients with TBM. Focal neurological deficits, extracranial TB and CSF total WCC are important predictors of cranial nerve palsy in patients with TBM.
Background: In this study, we evaluated and compared the accuracy of blood and cerebrospinal fluid (CSF) interferon release tests [interferon-gamma release assays (IGRAs)] in the diagnosis of tuberculous meningitis (TBM) by a meta-analysis of the relevant literature. Methods: We searched for studies published before 2021 in Medline, Embase, the Cochrane database, and Chinese databases. All studies used the QuantiFERON-TB Gold In-Tube and/or T-SPOT.TB method. Blood and/or CSF tests that met the guidelines for the quality assessment of studies with diagnostic accuracy were included. We used the revised diagnostic accuracy study quality assessment to assess the quality of the included studies. Begg's funnel plots were used to assess publication bias in the meta-analysis of the diagnostic studies, and statistical analyses were performed by using Stata (Version 12) software. Results: A total of 12 blood and/or CSF IGRA studies were included in this meta-analysis, with 376 patients and 493 controls. The sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and area under the summary receiver operating characteristic curve (SROC) of the blood IGRAs in the pooled data from 12 studies were 74% (95% CI: 0.65-0.82), 78% (95% CI: 0.68-0.86), 3.38 (95% CI 2.26-5.06), 0.33 (95% CI: 0.23-0.46), 10.25 (95% CI: 5.46-19.25), and 0.83 (95% CI: 0.79-0.86), respectively. For CSF IGRAs, these values for the pooled data from the 10 studies included were 79% (95% CI: 0.71-0.85), 95% (95% CI: 0.88-0.98), 16.30 (95% CI 6.5-40.83), 0.22 (95% CI: 0.16-0.31), 57.93 (95% CI: 22.56-148.78), and 0.91 (95% CI: 0.88-0.93), respectively. Conclusion: CSF IGRAs exhibited a better diagnostic accuracy than blood IGRAs in diagnosing TBM.
Interferon-gamma Release Tests , Tuberculosis, Meningeal , Humans , Interferon-gamma Release Tests/methods , ROC Curve , Sensitivity and Specificity , Tuberculosis, Meningeal/diagnosis
Background: Tuberculous meningitis (TBM) is the most serious form of extrapulmonary tuberculosis caused by Mycobacterium tuberculosis, and is characterized by high morbidity and mortality. Unfortunately, it is difficult to distinguish TBM from bacterial meningitis (BM) based on clinical features alone. The latest diagnostic tests and neuroimaging methods are still not available in many developing countries. This study aimed to develop a simple diagnostic algorithm based on clinical and laboratory test results as an early predictor of TBM in South China. Methods: A retrospective study was conducted to compare the clinical and laboratory characteristics of 114 patients with TBM and 47 with BM. Multivariate logistic regression analysis was performed on the characteristics of independently predicted TBM to develop a new diagnostic rule. Results: Five characteristics were predictive of a diagnosis of TBM: duration of symptoms before admission; tuberculous symptoms; white blood cell (WBC) count, total cerebrospinal fluid WBC count, and cerebrospinal fluid chloride concentration. The sensitivity and specificity of the new scoring system developed in this study were 81.6 and 93.6%, respectively. Conclusion: The new scoring system proposed in this study can help physicians empirically diagnose TBM and can be used in countries and regions with limited microbial and radiological resources.
AIMS: In this study, we conducted a meta-analysis to systematically compare the diagnostic accuracy of IGRAs performed for extrasanguinous body fluids with that performed for blood in the diagnosis of TB. MAIN METHODS: Multiple English and Chinese databases were searched up to November 2017. Studies that complied with the guidelines for the Quality Assessment of Diagnostic Accuracy Studies and used QuantiFERON-TB Gold In-Tube and/or T-SPOT.TB (ELISPOT) assays on both blood and extrasanguinous body fluids were included. Statistical analysis was performed using Stata 12.0 software. Since publication bias is a concern in the meta-analysis of diagnostic studies, we tested for this using Begg's funnel plots. KEY FINDING: Among the 1332 articles searched from the databases, 24 articles met the inclusion criteria, which included 1040 samples in the patient group and 1044 samples in the control group. For extrasanguinous body fluids, the pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and summary receiver operating characteristic (SROC) area under the curve (AUC) were 87% (95% CI: 0.81-0.91), 89% (95% CI: 0.84-0.93), 8.22 (95% CI 5.38-12.56), 0.15 (95% CI: 0.10-0.21), 44.92 (95% CI: 25.61-78.81), and 0.94 (95% CI: 0.92-0.96), respectively. For peripheral blood, these values were 83% (95% CI: 0.79-0.87), 74% (95% CI: 0.68-0.79), 3.17 (95% CI 2.63-3.84), 0.23 (95% CI: 0.19-0.29), 12.99 (95% CI: 10.19-16.57), and 0.86 (95% CI: 0.82-0.89), respectively. SIGNIFICANCE: IGRAs performed on extrasanguinous body fluids exhibited a better diagnostic accuracy compared with IGRAs performed on peripheral blood for diagnosing TB.
Body Fluids/metabolism , Interferon-gamma/metabolism , Tuberculosis/diagnosis , Tuberculosis/metabolism , Humans
