Commercial nucleic acid amplification tests in tuberculous meningitis—a meta-analysis |
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Authors: | Regan S. Solomons Sabine L. van Elsland Douwe H. Visser Kim G.P. Hoek Ben J. Marais Johan F. Schoeman Anne M. van Furth |
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Affiliation: | 1. Department of Pediatrics and Child Health, Faculty of Health Sciences, Stellenbosch University, PO Box 19063, Tygerberg 7505, Cape, South Africa;2. Department of Pediatric Infectious Diseases and Immunology, Vrije Universiteit Medical Center, PO Box 7057, 1007 MB, Amsterdam, The Netherlands;3. Division of Medical Microbiology, Faculty of Health Sciences, National Health Laboratory Service and University of Stellenbosch, Tygerberg 7505, Western Cape, South Africa;4. 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 |
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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 I2 = 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. |
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Keywords: | Central nervous system Tuberculosis Nucleic acid amplification tests Diagnostic accuracy |
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