Tumor necrosis factor α level in cerebrospinal fluid for bacterial and aseptic meningitis: a diagnostic meta-analysis.
OBJECTIVE
In our previous study, tumor necrosis factor α (TNF-α) was identified as an effective target for sepsis patients (Int J Clin Pract, 68, 2014, 520). TNF-α in cerebrospinal fluid (CSF) was also investigated for its utility in the differential diagnosis of bacterial and aseptic meningitis. However, there has been neither definite nor convincing evidence so far. Here the overall diagnostic accuracy of TNF-α in differentiation between bacterial and aseptic meningitis was evaluated through the meta-analysis of diagnostic tests.


METHODS
The sensitivity, specificity and other measures of accuracy were pooled using random effect models. Summary receiver operating characteristic curves were used to assess overall test performance. Publication bias was evaluated using funnel plots, and sensitivity analysis was also introduced.


RESULTS
A total of 21 studies involving bacterial meningitis (678) and aseptic meningitis (694) involved a total of 1372 patients. The pooled sensitivity and specificity for the TNF-α test were 0.83 [95% confidence interval (CI) 0.80-0.86, I(2)  = 65.1] and 0.92 (95% CI 0.89-0.94, I(2)  = 61.8), respectively. The positive likelihood ratio was 12.05 (95% CI 7.41-19.60, I(2)  = 36.5), the negative likelihood ratio was 0.17 (95% CI 0.13-0.24, I(2)  = 59.4), and TNF-α was significantly associated with bacterial meningitis, with a diagnostic odds ratio of 49.84 (95% CI 28.53-87.06, I(2)  = 47.9). The overall accuracy of the TNF-α test was very high with the area under the curve 0.9317. Publication bias was absent, and sensitivity analysis suggested that our results were highly stable.


CONCLUSIONS
Our meta-analysis suggested that TNF-α could be recommended as a useful marker for diagnosis of bacterial meningitis and differential diagnosis between bacterial and aseptic meningitis with high sensitivity and specificity. Thus, hospitals should be encouraged to conduct TNF-α tests in CSF after lumbar puncture.
Department of Endocrinology, Key Laboratory of Endocrinology of the Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
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S
Lv
Department of Endocrinology, Key Laboratory of Endocrinology of the Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
J
J
Zhao
Department of Endocrinology, Key Laboratory of Endocrinology of the Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.|First Clinical College of Nanjing Medical University, Nanjing, Jiangsu, China.
J
J
Zhang
University of Toronto, Toronto, ON, Canada.
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S
Kwon
Shandong University School of Medicine, Jinan, Shandong, China.
M
M
Han
Shandong University School of Medicine, Jinan, Shandong, China.
R
R
Bian
Shandong University School of Medicine, Jinan, Shandong, China.
H
H
Fu
Shandong University School of Medicine, Jinan, Shandong, China.
Y
Y
Zhang
Department of Endocrinology, Key Laboratory of Endocrinology of the Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
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H
Pan
D015415:Biomarkers / Q000134:cerebrospinal fluid*; D006801:Humans; D008582:Meningitis, Aseptic / Q000134:cerebrospinal fluid*; D016920:Meningitis, Bacterial / Q000134:cerebrospinal fluid*; D012680:Sensitivity and Specificity; D014409:Tumor Necrosis Factor-alpha / Q000134:cerebrospinal fluid*
D015415:Biomarkers; D014409:Tumor Necrosis Factor-alpha
TNF-α; aseptic meningitis; bacterial meningitis; cerebrospinal fluid; diagnostic meta-analysis