Rapid diagnosis of Mycobacterium tuberculosis meningitis by enumeration of cerebrospinal fluid antigen-specific T-cells.
Thomas MM., Hinks TSC., Raghuraman S., Ramalingam N., Ernst M., Nau R., Lange C., Kösters K., Gnanamuthu C., John GT., Marshall B., Lalvani A.
SettingHospital in-patients with suspected tuberculous meningitis (TBM), predominantly in India.ObjectiveTo determine whether interferon-gamma (IFN-gamma) secreting Mycobacterium tuberculosis antigen-specific T-cells are present in the cerebrospinal fluid (CSF) of patients with TBM and to evaluate the feasibility of CSF enzyme-linked immunospot (ELISpot) for the diagnosis of active TBM.DesignProspective blinded hospital-based study.ResultsThe overnight ELISpot assay detected M. tuberculosis antigen-specific IFN-gamma secreting T-cells in CSF from nine of 10 prospectively recruited patients with TBM, and zero of seven control patients with meningitis of other aetiology. This corresponds to a diagnostic sensitivity of 90% (95%CI 56-100) and specificity of 100% (95%CI 59-100).ConclusionThis pilot study demonstrates proof-of-principle for a new T-cell-based diagnostic test for TBM which is rapid, sensitive and specific.