Abstract
BackgroundIn Africa, tuberculous meningitis (TBM) is an important opportunistic infection in HIV-positive patients. Current diagnostic tools for TBM perform sub-optimally. In particular, the rapid diagnosis of TBM is challenging because smear microscopy has a low yield and PCR is not widely available in resource-poor settings.MethodsWe evaluated the performance outcome of a novel standardized lipoarabinomannan (LAM) antigen-detection assay, using archived cerebrospinal fluid samples, in 50 African TBM suspects of whom 68% were HIV-positive.ResultsOf the 50 participants 14, 23 and 13 patients had definite, probable and non-TBM, respectively. In the non-TB group there were 5 HIV positive patients who were lost to follow-up and in whom concomitant infection with Mycobacterium tuberculosis could not be definitively excluded. The test sensitivities and specificities were as follows: LAM assay 64% and 69% (cut-point 0.22), smear microscopy 0% and 100% and PCR 93% and 77%, respectively.ConclusionIn this preliminary proof-of-concept study, a rapid diagnosis of TBM could be achieved using LAM antigen detection. Although specificity was sub-optimal, the estimates provided here may be unreliable because of a classification bias inherent in the study design where it was not possible to exclude TBM in the presumed non-TBM cases owing to a lack of clinical follow-up. As PCR is largely unavailable, the LAM assay may well prove to be a useful adjunct for the rapid diagnosis of TBM in high HIV-incidence settings. These preliminary results justify further enquiry and prospective studies are now required to definitively establish the place of this technology for the diagnosis of TBM.
Highlights
In Africa, tuberculous meningitis (TBM) is an important opportunistic infection in HIV-positive patients
Tuberculosis is increasing in Africa [1], where HIV infection has fuelled an increasing prevalence of pulmonary and extra-pulmonary tuberculosis (TB) including tuberculous meningitis (TBM) [2,3]
Biochemistry and cell counts are unreliable in HIV+ve patients, PCR is not widely available, smear microscopy of the cerebrospinal fluid (CSF) has a poor sensitivity (~5%) and culture results are delayed for several weeks [4]
Summary
In Africa, tuberculous meningitis (TBM) is an important opportunistic infection in HIV-positive patients. The rapid diagnosis of TBM is challenging because smear microscopy has a low yield and PCR is not widely available in resource-poor settings. PCR is a useful rule-in test (60% sensitivity and 98% specificity); it is expensive, technically demanding and it not widely available in resource-poor settings. Alternative methods such as liquid-based culture provide results only after several weeks [5,6,7] and gas chromatography for tuberculostearic acid is expensive and has limited availability even in resourcerich settings [8]. The utility of quantitative antigen-specific T cell responses though recently described [9] has not been validated in clinical trials and is untested in TBM
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