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).


METHODS
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.


CONCLUSIONS
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.
D000293:Adolescent; D000328:Adult; D000918:Antibody Specificity; D000936:Antigen-Antibody Complex / Q000134:cerebrospinal fluid*; D001483:Base Sequence; D002493:Central Nervous System Diseases / Q000175:diagnosis; D002648:Child; D002675:Child, Preschool; D003937:Diagnosis, Differential; D004797:Enzyme-Linked Immunosorbent Assay; D005189:False Positive Reactions; D006801:Humans; D007118:Immunoassay; D007223:Infant; D008875:Middle Aged; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D014390:Tuberculosis, Meningeal / Q000134:cerebrospinal fluid / Q000175:diagnosis* / Q000276:immunology
D000936:Antigen-Antibody Complex