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

Detjen, Anne; DiNardo, Andrew; Leyden, Jacinta; Steingart, Karen R; Menzies, Dick; Schiller, Ian; Dendukuri, Nandini; Mandalakas, Anna M.

doi:10.1016/s2213-2600(15)00095-8

Cited by 279 publications

(266 citation statements)

References 34 publications

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“…In its 2013 policy update, the WHO reported a pooled sensitivity of 66% for Xpert compared to culture with a pooled specificity of 98% (30). A second comprehensive metaanalysis through December of 2014 reported a pooled sensitivity of 62% (95% confidence interval [CI], 44% to 80%) for Xpert compared to culture of sputum specimens and a pooled specificity of 99% (95% CI, 97% to 99%) ( Table 3) (33). The same analysis reported that the odds of a positive Xpert result were four times greater in smear-positive pediatric samples than in smear-negative samples.…”

Section: Molecular Detection Methodsmentioning

confidence: 99%

Laboratory Diagnosis of Mycobacterium tuberculosis Infection and Disease in Children

2016

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Diagnosis of tuberculosis in children is challenging; even with advanced technologies, the diagnosis is often difficult to confirm microbiologically in part due to the paucibacillary nature of the disease. Clinical diagnosis lacks standardization, and traditional and molecular microbiologic methods lack sensitivity, particularly in children. Immunodiagnostic tests may improve sensitivity, but these tests cannot distinguish tuberculosis disease from latent infection and some lack specificity. While molecular tools like Xpert MTB/RIF have advanced our ability to detectMycobacterium tuberculosisand to determine antimicrobial resistance, decades old technologies remain the standard in most locales. Today, the battle against this ancient disease still poses one of the primary diagnostic challenges in pediatric laboratory medicine.

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Section: Molecular Detection Methodsmentioning

confidence: 99%

Laboratory Diagnosis of Mycobacterium tuberculosis Infection and Disease in Children

2016

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“…Although culture is currently considered the best available reference standard, its sensitivity for detecting CPTB is acknowledged to be imperfect (3,4,10). The culture reference standard thus inevitably leads to true CPTB case patients being misclassified as being negative for CPTB.…”

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confidence: 99%

Diagnostic Test Accuracy in Childhood Pulmonary Tuberculosis: A Bayesian Latent Class Analysis

Schumacher¹,

Smeden²,

Dendukuri³

et al. 2016

American Journal of Epidemiology

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Evaluation of tests for the diagnosis of childhood pulmonary tuberculosis (CPTB) is complicated by the absence of an accurate reference test. We present a Bayesian latent class analysis in which we evaluated the accuracy of 5 diagnostic tests for CPTB. We used data from a study of 749 hospitalized South African children suspected to have CPTB from 2009 to 2014. The following tests were used: mycobacterial culture, smear microscopy, Xpert MTB/RIF (Cepheid Inc.), tuberculin skin test (TST), and chest radiography. We estimated the prevalence of CPTB to be 27% (95% credible interval (CrI): 21, 35). The sensitivities of culture, Xpert, and smear microscopy were estimated to be 60% (95% CrI: 46, 76), 49% (95% CrI: 38, 62), and 22% (95% CrI: 16, 30), respectively; specificities of these tests were estimated in accordance with prior information and were close to 100%. Chest radiography was estimated to have a sensitivity of 64% (95% CrI: 55, 73) and a specificity of 78% (95% CrI: 73, 83). Sensitivity of the TST was estimated to be 75% (95% CrI: 61, 84), and it decreased substantially among children who were malnourished and infected with human immunodeficiency virus (56%). The specificity of the TST was 69% (95% CrI: 63%, 76%). Furthermore, it was estimated that 46% (95% CrI: 42, 49) of CPTB-negative cases and 93% (95% CrI: 82; 98) of CPTB-positive cases received antituberculosis treatment, which indicates substantial overtreatment and limited undertreatment. childhood pulmonary tuberculosis; diagnosis; latent class analysis; overtreatment; sensitivity; specificity Abbreviations: CPTB, childhood pulmonary tuberculosis; CrI, credible interval; HIV, human immunodeficiency virus; PTB, pulmonary tuberculosis; TST, tuberculin skin test.Tuberculosis in children is an important global health problem. There are an estimated 0.5 to 1 million new cases each year (1, 2), with childhood pulmonary tuberculosis (CPTB) being the most common form. One of the major challenges in diagnosing CPTB is the lack of sensitive diagnostic tests (3-6). In clinical practice, the diagnosis of CPTB therefore relies on a combination of imperfect tests, which gives rise to unknown degrees of under-or overtreatment (7,8).In recent years, new tests for CPTB have been developed, and their accuracy has been evaluated using mycobacterial culture as a reference standard (4, 9). Although culture is currently considered the best available reference standard, its sensitivity for detecting CPTB is acknowledged to be imperfect (3,4,10). The culture reference standard thus inevitably leads to true CPTB case patients being misclassified as being negative for CPTB. If these misclassifications by the reference standard are ignored, then the assessment of the test accuracy can be biased (11)(12)(13)(14).To address the problem of the lack of an accurate reference standard, multivariable diagnostic algorithms for CPTB have been proposed to combine information from multiple imperfect diagnostic tests (including tests for tuberculosis infection and clinical data) in a sy...

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“…5 In a recent systematic review, Detjen et al reported sub-optimal sensitivity (51-81%) of Xpert in expectorated/induced sputum and gastric lavage samples in children, calling for further research to improve pediatric TB diagnostics. 35 However, none of the studies in this review were conducted in children. There are ongoing studies evaluating urine samples in TB patients including children; however, data from these studies are not yet available.…”

Section: Discussionmentioning

confidence: 99%

Diagnostic accuracy of nucleic acid amplification tests in urine for pulmonary tuberculosis: A meta-analysis

2015

Indian Journal of Tuberculosis

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OBJECTIVE-To determine the diagnostic accuracy of tuberculosis (TB) nucleic acid amplification tests (NAATs) in urine samples for individuals with active pulmonary tuberculosis (PTB).DESIGN-Systematic review and meta-analysis. Electronic databases and reference lists were searched without age or setting restrictions up to May 2015. Eligible articles examined Mycobacterium tuberculosis NAATs in urine samples for PTB diagnosis in patients with sputum culture as the reference standard, and reported sufficient data to separately calculate sensitivity or specificity.RESULTS-Eight studies, including 1212 participants from seven countries with a mean age ranging from 28 to 48 years, were included. Polymerase chain reaction (PCR) with insertion sequence (IS) 6110, rpoB or cfp32/hf6 as gene targets was used for NAATs. The pooled sensitivity and specificity was respectively 0.55 (95%CI 0.36-0.72) and 0.94 (95%CI 0.78-0.99), with slightly higher sensitivity in human immunodeficiency virus positive individuals, at 0.59 (95%CI 0.20-0.89). Sensitivity was higher in sputum microscopy-positive than -negative individuals. Storage temperatures below −70°C, centrifuge speed <5000 rpm and IS6110 increased sensitivity on meta-regression.Correspondence to: Diana Marangu, Department of Paediatrics and Child Health, University of Nairobi, P O Box 19676 -0202, Nairobi, Kenya. marangud@gmail.com. Conflicts of interest: none declared. HHS Public Access KeywordsNAAT; PCR; systematic review; meta-regression In 2013, it was estimated that there were 9 million incident tuberculosis (TB) cases globally, 3.3 million of whom were not diagnosed. 1 Urine nucleic acid amplification tests (NAATs) have potential for use in the diagnosis of pulmonary tuberculosis (PTB), the most common form of TB worldwide. [2][3][4] The relative simplicity of urine collection could be ideal to address diagnostic challenges of active PTB, 5 and could be exploited in point-of-care (POC) testing of active PTB at all levels of health care, and potentially in households and the community. 6,7 In addition to being safer to handle, normal urine production yields frequent and relatively large amounts, making urine specimens convenient to obtain and easier to test in comparison to sputum. Children could benefit the most from urine NAATs for PTB diagnosis due to challenges in obtaining sputum samples, particularly from young children who cannot expectorate, and the paucibacillary nature of their disease. 5,8 With the advancement of molecular techniques and wider use of the NAAT Xpert ® MTB/RIF assay (Cepheid, Sunnyvale, CA, USA) in many high TB endemic countries, exploration of alternative samples such as urine for TB diagnosis is increasing due to its ease of collection and potential for decentralized implementation. 9,10 Cell-free nucleic acids released from dying human cells and Mycobacterium tuberculosis microorganisms may be filtered through the kidneys, resulting in the detection of trans-renal DNA fragments in urine. 6 Although the exact pathophysiological mech...

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

Cited by 279 publications

References 34 publications

Laboratory Diagnosis of Mycobacterium tuberculosis Infection and Disease in Children

Laboratory Diagnosis of Mycobacterium tuberculosis Infection and Disease in Children

Diagnostic Test Accuracy in Childhood Pulmonary Tuberculosis: A Bayesian Latent Class Analysis

Diagnostic accuracy of nucleic acid amplification tests in urine for pulmonary tuberculosis: A meta-analysis

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