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Meta-Analysis
. 2015 Jun;3(6):451-61.
doi: 10.1016/S2213-2600(15)00095-8. Epub 2015 Mar 24.

Xpert MTB/RIF assay for the diagnosis of pulmonary tuberculosis in children: a systematic review and meta-analysis

Anne K Detjen  1 , Andrew R DiNardo  2 , Jacinta Leyden  3 , Karen R Steingart  4 , Dick Menzies  5 , Ian Schiller  6 , Nandini Dendukuri  6 , Anna M Mandalakas  7
Affiliations
Meta-Analysis

Xpert MTB/RIF assay for the diagnosis of pulmonary tuberculosis in children: a systematic review and meta-analysis

Anne K Detjen et al. Lancet Respir Med. 2015 Jun.

Abstract

Background: Microbiological confirmation of childhood tuberculosis is rare because of the difficulty of collection of specimens, low sensitivity of smear microscopy, and poor access to culture. We aimed to establish summary estimates for sensitivity and specificity of of the Xpert MTB/RIF assay compared with microscopy in the diagnosis of pulmonary tuberculosis in children.

Methods: We searched for studies published up to Jan 6, 2015, that used Xpert in any setting in children with and without HIV infection. We systematically reviewed studies that compared the diagnostic accuracy of Xpert MTB/RIF (Xpert) with microscopy for detection of pulmonary tuberculosis and rifampicin resistance in children younger than 16 years against two reference standards-culture results and culture-negative children who were started on anti-tuberculosis therapy. We did meta-analyses using a bivariate random-effects model.

Findings: We identified 15 studies including 4768 respiratory specimens in 3640 children investigated for pulmonary tuberculosis. Culture tests were positive for tuberculosis in 12% (420 of 3640) of all children assessed and Xpert was positive in 11% (406 of 3640). Compared with culture, the pooled sensitivities and specificities of Xpert for tuberculosis detection were 62% (95% credible interval 51-73) and 98% (97-99), respectively, with use of expectorated or induced sputum samples and 66% (51-81) and 98% (96-99), respectively, with use of samples from gastric lavage. Xpert sensitivity was 36-44% higher than was sensitivity for microscopy. Xpert sensitivity in culture-negative children started on antituberculosis therapy was 2% (1-3) for expectorated or induced sputum. Xpert's pooled sensitivity and specificity to detect rifampicin resistance was 86% (95% credible interval 53-98) and 98% (94-100), respectively.

Interpretation: Compared with microscopy, Xpert offers better sensitivity for the diagnosis of pulmonary tuberculosis in children and its scale-up will improve access to tuberculosis diagnostics for children. Although Xpert helps to provide rapid confirmation of disease, its sensitivity remains suboptimum compared with culture tests. A negative Xpert result does not rule out tuberculosis. Good clinical acumen is still needed to decide when to start antituberculosis therapy and continued research for better diagnostics is crucial.

Funding: WHO, Global TB Program of Texas Children's Hospital.

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Conflict of interest statement

Declaration of interests

We declare no competing interests.

Figures

Figure 1
Figure 1. Study selection
TB=tuberculosis.
Figure 2
Figure 2. Sensitivity and specificity of Xpert against culture reference standard by study and specimen type
TP=true positive. FP=false positive. FN=false negative. TN=true negative. *Walters E, Desmond Tutu TB Centre, personal communication.
Figure 3
Figure 3. Sensitivity and specificity of smear microscopy against culture reference standard by study and specimen type
TP=true positive. FP=false positive. FN=false negative. TN=true negative. *Walters E, Desmond Tutu TB Centre, personal communication.
Figure 4
Figure 4. Sensitivity and specificity of Xpert against a culture reference standard by smear status
TP=true positive. FP=false positive. FN=false negative. TN=true negative. *Walters E, Desmond Tutu TB Centre, personal communication.
See this image and copyright information in PMC

Comment in

References

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