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J Clin Microbiol. 2019 Apr 3. pii: JCM.02057-18. doi: 10.1128/JCM.02057-18. [Epub ahead of print]

Diagnostic accuracy of stool Xpert MTB/RIF for the detection of pulmonary tuberculosis in children: a systematic review and meta-analysis.

MacLean E1,2, Sulis G1,2, Denkinger CM2,3,4, Johnston JC2,5,6, Pai M1,2, Khan FA7,2,8.

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Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, Canada.
McGill International TB Centre, McGill University, Montreal, Canada.
Foundation for Innovative New Diagnostics, Geneva, Switzerland.
Department of Infectious Diseases, University of Heidelberg, Heidelberg, Germany.
Division of Respiratory Medicine, University of British Columbia, Vancouver, Canada.
BC Centre for Disease Control, Vancouver, Canada.
Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, Canada
Respiratory Epidemiology & Clinical Research Unit, Research Institute of the McGill University Health Centre & Montreal Chest Institute, Montreal, Canada.


Invasive collection methods are often required to obtain samples for the microbiologic evaluation of children with presumptive pulmonary tuberculosis (PTB). Nucleic-acid amplification testing of easier to collect stool samples could be a non-invasive method of diagnosing PTB. We conducted a systematic review and meta-analysis to evaluate the diagnostic accuracy of testing stool with the Xpert MTB/RIF assay ('stool Xpert') for childhood PTB. Four databases were searched for publications from January 2008 to June 2018. Studies assessing the diagnostic accuracy amongst children of stool Xpert compared to a microbiological reference standard of conventional specimens tested by mycobacterial culture or Xpert were eligible. Bivariate random-effects meta-analyses were performed to calculate pooled sensitivity and specificity of stool Xpert against the reference standard. From 1589 citations, 9 studies (n=1681) were included. Median participant ages ranged from 1.3 to 10.6 years. Protocols for stool processing and testing varied substantially, with differences in reagents and methods of homogenization and filtering. Against the microbiological reference standard, pooled sensitivity and specificity of stool Xpert were 67% (95%CI:52-79) and 99% (95%CI:98-99), respectively. Sensitivity was higher among children with HIV (79%; 95%CI:68-87; versus 60%; 95%CI:44-74 among HIV-uninfected). Heterogeneity was high. Data were insufficient for subgroup analyses amongst children under age 5, the most relevant target population. Stool Xpert could be a non-invasive method of ruling-in PTB in children, particularly those with HIV. However, studies focused on children under 5 are needed, and generalizability of the evidence is limited by the lack of a standardized stool preparation and testing protocol.


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