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

Regan S Solomons; Sabine L van Elsland; Douwe H Visser; Kim G P Hoek; Ben J Marais; Johan F Schoeman; Anne M van Furth

doi:10.1016/j.diagmicrobio.2014.01.002

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

Diagn Microbiol Infect Dis. 2014 Apr;78(4):398-403. doi: 10.1016/j.diagmicrobio.2014.01.002. Epub 2014 Jan 10.

Authors

Regan S Solomons¹, Sabine L van Elsland², Douwe H Visser³, Kim G P Hoek⁴, Ben J Marais⁵, Johan F Schoeman⁶, Anne M van Furth³

Affiliations

¹ 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.
² 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.
³ Department of Pediatric Infectious Diseases and Immunology, Vrije Universiteit Medical Center, PO Box 7057, 1007 MB, Amsterdam, The Netherlands.
⁴ Division of Medical Microbiology, Faculty of Health Sciences, National Health Laboratory Service and University of Stellenbosch, Tygerberg 7505, Western Cape, South Africa.
⁵ 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.
⁶ Department of Pediatrics and Child Health, Faculty of Health Sciences, Stellenbosch University, PO Box 19063, Tygerberg 7505, Cape, South Africa.

PMID: 24503504
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 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.

Keywords: Central nervous system; Diagnostic accuracy; Nucleic acid amplification tests; Tuberculosis.

Publication types

Comparative Study
Evaluation Study
Meta-Analysis

MeSH terms

Humans
Molecular Diagnostic Techniques / methods*
Mycobacterium tuberculosis / genetics
Mycobacterium tuberculosis / isolation & purification*
Nucleic Acid Amplification Techniques / methods*
Sensitivity and Specificity
Tuberculosis, Meningeal / diagnosis*