Commercial nucleic acid amplification tests in tuberculous meningitis—a meta-analysis

• Published in: Diagnostic microbiology and infectious disease 2014-04, Vol.78 (4), p.398-403
• Main Authors: Solomons, Regan S, van Elsland, Sabine L, Visser, Douwe H, Hoek, Kim G.P, Marais, Ben J, Schoeman, Johan F, van Furth, Anne M
• Format: Article
• Language: English
• Subjects: Central nervous system; Diagnostic accuracy; Humans; Infectious Disease; Internal Medicine; Molecular Diagnostic Techniques - methods; Mycobacterium tuberculosis - genetics; Mycobacterium tuberculosis - isolation & purification; Nucleic Acid Amplification Techniques - methods; Nucleic acid amplification tests; Sensitivity and Specificity; Tuberculosis; Tuberculosis, Meningeal - diagnosis
• ISSN: 0732-8893; 1879-0070
• DOI: 10.1016/j.diagmicrobio.2014.01.002

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.