Microbiological diagnosis of tuberculous meningitis: Phenotype to genotype

Abstract

Tuberculous meningitis (TBM) is a commonly encountered central nervous system infection. Characteristic clinical, imaging and cerebrospinal fluid parameters help clinicians to make a prompt presumptive diagnosis that enables them to start empirical anti-tuberculosis treatment. There are several close mimic to TBM, such as partially treated pyogenic meningitis, fungal meningitis, sarcoidosis, meningeal metastases and meningeal lymphomatosis. Microbiological confirmation instils a sense of confidence amongst treating physicians. With conventional phenotypic methods (cerebrospinal fluid microscopy and culture), in more than 50 per cent patients, microbiological confirmation is not achieved. Moreover, these methods take a long time before providing conclusive results. Negative result does not rule out Mycobacterium tuberculosis infection of the brain. Genotypic methods, such as IS 6110 polymerase chain reaction and automated Xpert M. tuberculosis/rifampicin (MTB/RIF) assay system improved the TBM diagnostics, as results are rapidly available. Xpert MTB/RIF assay, in addition, detects rifampicin resistance. Xpert MTB/RIF Ultra is advanced technology which has higher (60-70%) sensitivity and is being considered a game-changer in the diagnostics of TBM. A large number of TBM cases remain unconfirmed. The situation of TBM diagnostics will remain grim, if low-cost technologies are not widely available. Till then, physicians continue to rely on their clinical acumen to start empirical anti-tuberculosis treatment.