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. 1. Introduction Central nervous system (CNS) disease caused by Mycobacterium tuberculosis (M.Tb), particularly tuberculous meningitis (TBM), is uncommon and accounts for approximately 1% of all tuberculosis cases in the United States [1, 2]. CNS tuberculosis is the severest form of M.Tb infection, causing death or severe neurological defects in more than half of those affected, in spite of recent advancements in available antituberculosis treatment (ATT) [1–5]. In addition, owing to an increasing number of immunocompromised hosts caused by the prevalence of AIDS, increasing numbers of older people, the wider use of immunosuppressive agents, and other factors, TBM remains a serious clinical and social problem [1–5]. Owing to its relative rarity and the wide spectrum of its neurological symptoms, CNS tuberculosis remains a formidable diagnostic challenge [1–5]. In TBM, accurate and rapid diagnosis and early treatment for tuberculosis are the most important factors with regard to the prognosis and the prevention of long-term neurological sequelae [1–5]. However, the conventional “gold standard” based on bacteriological detection methods of M.Tb, including the direct smear examination for acid-fast bacilli (AFB) and culture
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