In this letter, we propose a novel method for diagnosis of tuberculous meningitis using Raman spectroscopy. The silicate Raman signature obtained from Mycobacterium tuberculosis positive cases enables specific and sensitive detection of tuberculous meningitis from acquired cerebrospinal fluid samples. The association of silicates with the tuberculosis mycobacterium is discussed. We envision that this new method will facilitate rapid diagnosis of tuberculous meningitis without application of exogenous reagents or dyes and can be aptly used as a complementary screening tool to the existing gold standard methods.
Given that the newer generation fluoroquinolones (FQN), for example, levofloxacin and moxifloxacin, have strong activity against most strains of M. tuberculosis and have excellent CSF penetration and safety profiles, FQN would appear to have great potential as part of first-line therapy for TBM. In a randomized controlled study for TBM treatment, addition of an FQN to standard regimen enhanced anti-TB performance as measured by various clinical parameters. Although there was no significant difference in mortality, the study was likely not adequately powered to demonstrate such an effect [ 38 ]. It is important to note that serum FQN concentrations are lowered by concurrent RIF use; furthermore, the optimal area-under-the-curve to minimum inhibitory concentration ratio for FQN as anti-TB agents has not been well described. Another randomized controlled study is currently underway to evaluate treatment of TBM with high-dose RIF and levofloxacin compared to standard treatment [ 42 ]; if they have positive results, the recommended standard treatment may change in the near future.
The findings reported above challenged previous assumptions about anti-inflammatory effects of corticosteroids in this disease. A potential explanation for this came from studies of mycobacterial infections in a zebrafish model. 43 A polymorphism in the leukotriene A4 hydrolase (LTA4H) gene, which controls the balance of pro-inflammatory and anti-inflammatory eicosanoids, was found to influence susceptibility of zebrafish to Mycobacterium marinum infection and humans to tuberculosis. 44 Furthermore, in humans with TBM, the polymorphism was associated with inflammatory cell recruitment, patient survival and response to adjunctive corticosteroids. These findings provide a possible explanation for the failure to find a mechanism by which corticosteroids improved survival in TBM and suggest the possibility of using host-directed therapies tailored to patient LTA4H genotypes.