The PCR-Based Diagnosis of Central Nervous System Tuberculosis: Up to Date

Abstract

Central nervous system (CNS) tuberculosis, particularly tuberculous meningitis (TBM), is the severest form of Mycobacterium tuberculosis (M.Tb) infection, causing death or severe neurological defects in more than half of those affected, in spite of recent advancements in available anti-tuberculosis treatment. The definitive diagnosis of CNS tuberculosis depends upon the detection of M.Tb bacilli in the cerebrospinal fluid (CSF). At present, the diagnosis of CNS tuberculosis remains a complex issue because the most widely used conventional “gold standard” based on bacteriological detection methods, such as direct smear and culture identification, cannot rapidly detect M.Tb in CSF specimens with sufficient sensitivity in the acute phase of TBM. Recently, instead of the conventional “gold standard”, the various molecular-based methods including nucleic acid amplification (NAA) assay technique, particularly polymerase chain reaction (PCR) assay, has emerged as a promising new method for the diagnosis of CNS tuberculosis because of its rapidity, sensitivity and specificity. In addition, the innovation of nested PCR assay technique is worthy of note given its contribution to improve the diagnosis of CNS tuberculosis. In this review, an overview of recent progress of the NAA methods, mainly highlighting the PCR assay technique, was presented.

An 11-Year-Old Boy with Headache, Fever, and Neck Pain

“…Recently, molecular-based methods, particularly polymerase chain reaction (PCR) assay, have emerged as new methods for the diagnosis of central nervous system tuberculosis because of their rapidity, sensitivity, and specificity. 7 Identification of M. tuberculosis by PCR assay in our case led us to start antituberculous therapy promptly. On the other hand, absence of respiratory symptoms and a normal chest radiograph does not exclude lung involvement, so a chest CT scan is highly recommended.…”

Cerebro-Meningeal Tuberculosis in HIV-Negative Adults

“…Although the wide use of nested PCR assay in clinical practice is expected, regrettably, it has rarely been performed for tuberculous meningitis diagnosis. A recent systematic review and metaanalysis calculated that the sensitivity and specificity of commercial nucleic-acid-amplification assays for the diagnosis of tuberculous meningitis was 56% (95% CI 46-66) and 98% (97-99) respectively [38,39]. In view of this low sensitivity, the negativity of PCR should not be used to exclude the diagnosis of cerebro-meningeal tuberculosis.…”

Chronic Infectious Inflammatory Diseases of the Central Nervous System

“…Molecular methods may be useful even in partially treated patients as mycobacterial DNA in CSF can be detected for 1 month after the initiation of the treatment (Solomons et al 2014 ;Nhu et al 2014 ;Garg et al 2013 ). Quantitative RT-PCR for M. tuberculosis DNA and multiplex PCR using different primers have been introduced as possible useful methods for a rapid diagnosis (Takahashi et al 2012 ;Kusum et al 2011 ). CSF Infl ammatory Parameters For the diagnosis of CNS tuberculosis, examination of CSF is mandatory; the volume of CSF is important, and repeated lumbar punctures may be needed.…”