Antibody detection tests for early diagnosis in tuberculous meningitis

• A systematic review was performed to assess the diagnostic accuracy of antibody detection tests for tuberculous meningitis (TBM).
• For the diagnosis of patients thought to have TBM based on antibodies in the cerebrospinal fluid (CSF), the detection of anti-M37Ra, anti-antigen 5, or anti-M37Rv provides the greatest sensitivity and specificity.
• Antibody detection tests could be translated into rapid point-of-care tests; research to improve their performance is urgently needed.

SummaryBackgroundTuberculous meningitis (TBM) is the most severe form of tuberculosis. Microbiological confirmation is rare and treatment is often delayed. Early diagnosis and immediate initiation of treatment are essential for effective TBM control. A systematic review was performed in this study to assess the diagnostic accuracy of detecting antibodies against Mycobacterium tuberculosis in the cerebrospinal fluid (CSF), according to standard methods. Test performance was summarized using a bivariate random-effects meta-analysis.MethodsStudies were identified by a search of the literature, up to July 25, 2015, in the EMBASE and MEDLINE databases via Ovid SP and PubMed. The Cochrane Library was also searched for original, peer-reviewed molecular epidemiology studies that reported the diagnosis of TBM based on antibody detection in the CSF.ResultsThirty-six articles (58 studies) were identified. The sensitivity of antibody detection was 0.75 (95% confidence interval (CI) 0.66–0.82), specificity was 0.98 (95% CI 0.96–0.99), and the area under the receiver operating characteristic curve (AUROC) was 0.97 (95% CI 0.95–0.98). By subgroup analysis, the detection of anti-M37Ra was the highest (AUROC 0.99, 95% CI 0.98–1.00), followed by anti-antigen 5 (AUROC 0.99, 95% CI 0.97–0.99) and anti-M37Rv (AUROC 0.97, 95% CI 0.95–0.98).ConclusionsFor the early diagnosis of TBM based on antibodies in the CSF, the detection of anti-M37Ra, anti-antigen 5, or anti-M37Rv provides the greatest sensitivity and specificity.