title: Commercial nucleic acid amplification tests in tuberculous meningitis--a meta-analysis.
abstract: Although nucleic acid amplification tests (NAATs) promise a rapid, definitive diagnosis of tuberculous meningitis, the performance of first-generation NAATs was suboptimal and variable. We conducted a meta-analysis of studies published between 2003 and 2013, using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool to evaluate methodological quality. The diagnostic accuracy of newer commercial NAATs was assessed. Pooled estimates of diagnostic accuracy for commercial NAATs measured against a cerebrospinal fluid Mycobacterium tuberculosis culture-positive gold standard were sensitivity 0.64, specificity 0.98, and diagnostic odds ratio 64.0. Heterogeneity was limited; P value = 0.147 and I(2) = 33.85%. The Xpert MTB/RIF® test was evaluated in 1 retrospective study and 4 prospective studies, with pooled sensitivity 0.70 and specificity 0.97. The QUADAS-2 tool revealed low risk of bias, as well as low concerns regarding applicability. Heterogeneity was pronounced among studies of in-house tests. Commercial NAATs proved to be highly specific with greatly reduced heterogeneity compared to in-house tests. Sub-optimal sensitivity remains a limitation.
authors: Department of Pediatrics and Child Health, Faculty of Health Sciences, Stellenbosch University, PO Box 19063, Tygerberg 7505, Cape, South Africa. Electronic address: regan@sun.ac.za.
authors: Regan S
authors: RS
authors: Solomons
authors: Department of Pediatrics and Child Health, Faculty of Health Sciences, Stellenbosch University, PO Box 19063, Tygerberg 7505, Cape, South Africa; Department of Pediatric Infectious Diseases and Immunology, Vrije Universiteit Medical Center, PO Box 7057, 1007 MB, Amsterdam, The Netherlands.
authors: Sabine L
authors: SL
authors: van Elsland
authors: Department of Pediatric Infectious Diseases and Immunology, Vrije Universiteit Medical Center, PO Box 7057, 1007 MB, Amsterdam, The Netherlands.
authors: Douwe H
authors: DH
authors: Visser
authors: Division of Medical Microbiology, Faculty of Health Sciences, National Health Laboratory Service and University of Stellenbosch, Tygerberg 7505, Western Cape, South Africa.
authors: Kim G P
authors: KG
authors: Hoek
authors: Sydney Emerging Infectious Diseases and Biosecurity Institute (SEIB) and the Children's Hospital, Westmead. C29 - Children's Hospital Westmead, The University of Sydney, Westmead, NSW 2006, Australia.
authors: Ben J
authors: BJ
authors: Marais
authors: Department of Pediatrics and Child Health, Faculty of Health Sciences, Stellenbosch University, PO Box 19063, Tygerberg 7505, Cape, South Africa.
authors: Johan F
authors: JF
authors: Schoeman
authors: Department of Pediatric Infectious Diseases and Immunology, Vrije Universiteit Medical Center, PO Box 7057, 1007 MB, Amsterdam, The Netherlands.
authors: Anne M
authors: AM
authors: van Furth
mesh_terms: D006801:Humans; D025202:Molecular Diagnostic Techniques / Q000379:methods*; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000302:isolation & purification*; D021141:Nucleic Acid Amplification Techniques / Q000379:methods*; D012680:Sensitivity and Specificity; D014390:Tuberculosis, Meningeal / Q000175:diagnosis*
keywords: Central nervous system; Diagnostic accuracy; Nucleic acid amplification tests; Tuberculosis