DIAGNOSIS OF TUBERCULOUS MENINGITIS - A COMPARATIVE-ANALYSIS OF 3 IMMUNOASSAYS, AN IMMUNE-COMPLEX ASSAY AND THE POLYMERASE CHAIN-REACTION

Objective: To compare 3 immunoassays, an immune complex assay, and an application of the polymerase chain reaction (PCR) for the diagnosis of tuberculous meningitis (TBM). Material: Cerebrospinal fluid (CSF) from 33 patients with TBM and from 34 control patients with infectious and non-infectious CNS diseases was analysed. Results: The antibody immunoassays were either nonspecific or insensitive. However, detection of mycobacterial IgG immune complexes correlated strongly with infection, as they were detected in the CSF from 64% of the patients with TBM compared to only 3 (9%) of the control samples. PCR analysis, using Mycobacterium tuberculosis-specific oligonucleotide primers, also strongly correlated with infection, as DNA was amplified from 54% of the samples from patients with TBM, but from only 2 (6%) of the control samples. Both 'false positive' samples were also positive in the immune complex assay and came from 2 patients with otogenic brain abscesses. It is conceivable that these patients suffered from otogenic tuberculosis with secondary non-mycobacterial meningitis. When combining the immune complex assay with DNA-detection by PCR, 100% of the culture positive and 74% of culture negative samples were found to be positive, while maintaining a high specificity. Conclusion: Parallel analysis to detect mycobacterial immune complexes and M. tuberculosis-specific DNA by PCR from the CSF of patients may offer a sensitive and specific tool for the diagnosis of TBM.