Rapid Diagnosis of Tuberculous Meningitis by Using an Enzyme-Linked Immunosorbent Assay to Detect Mycobacterial Antigen and Antibody in Cerebrospinal Fluid

Abstract

Rapid diagnostic tests for tuberculous meningitis are urgently needed because delayed treatment increases the already high mortality rate of this disease. Direct acid-fast staining of cerebrospinal fluid is the only quick method generally available, but it lacks sensitivity. Therefore, we evaluated the use of an enzyme-linked immunosorbent assay (ELISA) to mycobacterial antigen and antibody in the cerebrospinal fluid of 29 patients with proven tuberculous meningitis, 83 patients with nontuberculous central nervous system infections, and 15 normal controls. The specificity of the test was 96%; the four false-positive results all occurred in patients with bacterial meningitis. Fifteen (52%) of 29 patients with tuberculous meningitis had either a positive antigen or antibody ELISA test, which was significantly more than the number of patients testing positive by direct staining (two of 29 positive; P less than .01). We therefore recommend using an ELISA to detect antigen and antibody but caution that because of limited sensitivity a negative test result does not exclude the diagnosis of tuberculous meningitis.

Central Nervous System Tuberculosis: Pathogenesis and Clinical Aspects

“…Antibody detection. While the detection of antibodies in the CSF to diagnose TBM is rapid, earlier studies evaluating the utility of measuring M. tuberculosis-specific antibodies in the CSF have shown that these techniques are limited by the inability to differentiate acute infection from previous infection and problems with cross-reactivity (91, 94) in addition to variable and often poor sensitivity and specificity (13,33,130,149,159,239) (Table 3). An example of a more recent study shows that measuring antibodies against a 30-kDa protein that is a specific antigen of M. tuberculosis (88) yielded a more promising sensitivity of 92% (89).…”

Antibodies to antigen A60 in cerebrospinal fluid from patients with tuberculous meningitis

“…Two additional groups have reported the detection of specific IgM antibodies in the CSF of patients with tuberculous meningitis, but their data were integrated with results of assays for IgG (5,32).…”

Rapid diagnosis of tuberculous meningitis with a dot enzyme immunoassay to detect antibody in cerebrospinal fluid

“…Isolation of Mycobacterium tuberculosis' in CSF by a culture technique is not only a time-consuming process but also lacks sensitivity. The development of EIA techniques (1)(2)(3)(4)(5) as an aid in the diagnosis of TBM has evoked considerable interest during the past decade. However, interpretation of the results and reliability of the EIAs have been affected by variability in the amount of antigen absorbed onto the surface of individual wells in the polystyrene or polyvinylchloride microtitre plates (6, 7).…”