Comparative evaluation of early diagnosis of tuberculous meningitis by different assays

Cerebrospinal fluid (CSF) and peripheral blood (PBL) were sampled multiple times from 25 patients with a clinical diagnosis of tuberculous meningitis (TBM) and 49 controls, including 27 patients with other infectious diseases of the central nervous system and 22 patients with other noninfectious neurological diseases. We used an enzyme-linked immunospot assay (ELISPOT) to detect anti-Mycobacterium bovis BCG antibody-secreting cells in CSF and PBL, PCR to detect a repeated insertion sequence (IS6110) specific for Mycobacterium tuberculosis in CSF, and an enzyme-linked immunosorbent assay (ELISA) to detect anti-BCG antibodies in CSF and PBL. In the meantime, culture of CSF from every TBM and control patient was done on Lowenstein-Jensen medium. ELISPOT proved to be the most valuable test, with a sensitivity of 84.0% and a specificity of 91.8%, and showed a sensitivity of 100.0% with the CSF specimens obtained within 4 weeks after the onset of TBM. The numbers of CSF anti-BCG immunoglobulin-secreting cells tested by ELISPOT were even higher in the early phase of TBM and declined while the disease was going on (P = 0.008), which allowed an early diagnosis to be made. The sensitivities of PCR and ELISA were only 75.0% and 52.3%, respectively; and the specificities were 93.7% and 91.6%, respectively. Culture of CSF on Lowenstein-Jensen medium was the least sensitive (16%) compared to the sensitivities of the other three assays. Our results demonstrate that the ELISPOT technique is worthy for routine use in the laboratory to support the clinical diagnosis of TBM.