Dataset Information

Diagnostic accuracy of Xpert ultra for childhood tuberculosis: A preliminary systematic review and meta-analysis.

ABSTRACT: Diagnosis of childhood tuberculosis (TB) is challenging. Xpert MTB/RIF and the new version Xpert MTB/RIF Ultra (Ultra) are molecular tests currently used to rapidly identify the infection. We reviewed the literature for the accuracy of Ultra assay in the diagnosis of tuberculosis and rifampicin resistance in children. We conducted a full search in PubMed, Web of Science (WOS), Embase, and Scopus, up to April 2021. A bivariate random-effects model was used to determine the pooled sensitivity and specificity of Ultra, with a 95% confidence interval (CI), compared with culturing and the composite reference standard (CRS). In the ten included studies (2,427 participants), the pooled Ultra sensitivity and specificity, in diagnosing pulmonary tuberculosis (PTB), were 78% (95% CI, 73-82) and 92% (95% CI, 91-94), respectively, against culture. Since a high heterogeneity was found between studies, we created subgroups based on different samples and ages. Ultra-pooled sensitivity was consistently lower against CRS (95% CI, 35%, 32-38). Compared to Xpert MTB/RIF, Ultra sensitivity tended toward higher values (Ultra: 73%, 67%-78% vs. Xpert MTB/RIF: 66%, 60%-72%), but specificity was lower (Ultra: 95%, 94%-96% vs. Xpert MTB/RIF: 99%, 98%-99%). Ultra has improved the definitive diagnosis of PTB, particularly in subjects with paucibacillary TB, including children. The lower specificity could be due to the fact that culture is an imperfect reference standard. Further studies are needed to evaluate the accuracy of Ultra in the diagnosis of childhood TB.

SUBMITTER: Signorino C

PROVIDER: S-EPMC9306500 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Diagnostic accuracy of Xpert ultra for childhood tuberculosis: A preliminary systematic review and meta-analysis.

Signorino Claudia C Votto Martina M De Filippo Maria M Marseglia Gian Luigi GL Galli Luisa L Chiappini Elena E

Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology 20220101

Diagnosis of childhood tuberculosis (TB) is challenging. Xpert MTB/RIF and the new version Xpert MTB/RIF Ultra (Ultra) are molecular tests currently used to rapidly identify the infection. We reviewed the literature for the accuracy of Ultra assay in the diagnosis of tuberculosis and rifampicin resistance in children. We conducted a full search in PubMed, Web of Science (WOS), Embase, and Scopus, up to April 2021. A bivariate random-effects model was used to determine the pooled sensitivity and ...[more]

PMID: 35080295

Similar Datasets

Project description:IntroductionDiagnosis of childhood tuberculosis (TB) poses several challenges. Therefore, clinical signs and symptoms, radiological studies, laboratory examinations, point-based scoring systems or diagnostic algorithms have been developed to improve diagnostic yields in this population. However, there are limited data on the diagnostic test accuracy of paediatric TB scoring systems. Therefore, this systematic review and meta-analysis aims to synthesise the available evidence on the diagnostic accuracy of childhood TB diagnostic scoring systems.Methods and analysisThis protocol describes a systematic review, developed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses of Diagnostic Test Accuracy. We will conduct a comprehensive literature search for relevant articles in the following databases: PubMed, CINAHL, Embase, Scopus and Cochrane Databases. The eligibility criteria for studies will be formulated based on the Participants (Population), Index Test, Comparator Test and Target Condition criteria for the review question. The index test will be defined as any attempt to diagnose childhood TB using either a scoring system or a diagnostic algorithm, whereas a composite reference standard will be used as a reference standard. This will include any attempt to confirm diagnosis of TB. Where bacteriological confirmation is not obtained and there are at least two of the following features: chest radiograph consistent with TB, immunological evidence of Mycobacterium tuberculosis infection and/or positive response to TB treatment will also be considered. The QUADAS-2 Tool will be used to assess the quality of the studies. The diagnostic accuracy measures (ie, sensitivity, specificity, negative predictive and positive predictive values) will be pooled with the random-effects or fixed-effects models, as appropriate. All statistical analyses will be performed using the Review Manager V.5.4.Ethics and disseminationThis research is exempt from ethics approval given that this is a protocol for a systematic review, which uses published data. The findings from this review will be disseminated through peer-reviewed publications and scientific conferences.Prospero registration numberCRD42022367049.

Project description:BackgroundXpert MTB/RIF Ultra (Ultra) is a widely used rapid front-line tuberculosis and rifampicin-susceptibility testing. Mycobacterium Growth Indicator Tube (MGIT) 960 liquid culture is used as an adjunct but is vulnerable to contamination. We aimed to assess whether Ultra can be used on to-be-discarded contaminated cultures.MethodsWe stored contaminated MGIT960 tubes (growth-positive, acid-fast bacilli [AFB]-negative) originally inoculated at a high-volume laboratory in Cape Town, South Africa, to diagnose patients with presumptive pulmonary tuberculosis. Patients who had no positive tuberculosis results (smear, Ultra, or culture) at contamination detection and had another, later specimen submitted within 3 months of the contaminated specimen were selected. We evaluated the sensitivity and specificity of Ultra on contaminated growth from the first culture for tuberculosis (next-available non-contaminated culture result reference standard) and rifampicin resistance (vs MTBDRplus on a later isolate). We calculated potential time-to-diagnosis improvements and also evaluated the immunochromatographic MPT64 TBc assay.FindingsBetween June 1 and Aug 31, 2019, 36 684 specimens from 26 929 patients were processed for diagnostic culture. 2402 (7%) cultures from 2186 patients were contaminated. 1068 (49%) of 2186 patients had no other specimen submitted. After 319 exclusions, there were 799 people with at least one repeat specimen submitted; of these, we included in our study 246 patients (31%) with a culture-positive repeat specimen and 429 patients (54%) with a culture-negative repeat specimen. 124 patients (16%) with a culture-contaminated repeat specimen were excluded. When Ultra was done on the initial contaminated growth, sensitivity was 89% (95% CI 84-94) for tuberculosis and 95% (75-100) for rifampicin-resistance detection, and specificity was 95% (90-98) for tuberculosis and 98% (93-100) for rifampicin-resistance detection. If our approach were used the day after contamination detection, the time to tuberculosis detection would improve by a median of 23 days (IQR 13-45) and provide a result in many patients who had none. MPT64 TBc had a sensitivity of 5% (95% CI 0-25).InterpretationUltra on AFB-negative growth from contaminated MGIT960 tubes had high sensitivity and specificity, approximating WHO criteria for sputum test target product performance and exceeding drug susceptibility testing. Our approach could mitigate negative effects of culture contamination, especially when repeat specimens are not submitted.FundingThe European & Developing Countries Clinical Trials Partnership, National Institutes of Health.

Project description:BackgroundThe Xpert MTB/RIF assay is an automated molecular test that has improved the detection of tuberculosis and rifampicin resistance, but its sensitivity is inadequate in patients with paucibacillary disease or HIV. Xpert MTB/RIF Ultra (Xpert Ultra) was developed to overcome this limitation. We compared the diagnostic performance of Xpert Ultra with that of Xpert for detection of tuberculosis and rifampicin resistance.MethodsIn this prospective, multicentre, diagnostic accuracy study, we recruited adults with pulmonary tuberculosis symptoms presenting at primary health-care centres and hospitals in eight countries (South Africa, Uganda, Kenya, India, China, Georgia, Belarus, and Brazil). Participants were allocated to the case detection group if no drugs had been taken for tuberculosis in the past 6 months or to the multidrug-resistance risk group if drugs for tuberculosis had been taken in the past 6 months, but drug resistance was suspected. Demographic information, medical history, chest imaging results, and HIV test results were recorded at enrolment, and each participant gave at least three sputum specimen on 2 separate days. Xpert and Xpert Ultra diagnostic performance in the same sputum specimen was compared with culture tests and drug susceptibility testing as reference standards. The primary objectives were to estimate and compare the sensitivity of Xpert Ultra test with that of Xpert for detection of smear-negative tuberculosis and rifampicin resistance and to estimate and compare Xpert Ultra and Xpert specificities for detection of rifampicin resistance. Study participants in the case detection group were included in all analyses, whereas participants in the multidrug-resistance risk group were only included in analyses of rifampicin-resistance detection.FindingsBetween Feb 18, and Dec 24, 2016, we enrolled 2368 participants for sputum sampling. 248 participants were excluded from the analysis, and 1753 participants were distributed to the case detection group (n=1439) and the multidrug-resistance risk group (n=314). Sensitivities of Xpert Ultra and Xpert were 63% and 46%, respectively, for the 137 participants with smear-negative and culture-positive sputum (difference of 17%, 95% CI 10 to 24); 90% and 77%, respectively, for the 115 HIV-positive participants with culture-positive sputum (13%, 6·4 to 21); and 88% and 83%, respectively, across all 462 participants with culture-positive sputum (5·4%, 3·3 to 8·0). Specificities of Xpert Ultra and Xpert for case detection were 96% and 98% (-2·7%, -3·9 to -1·7) overall, and 93% and 98% for patients with a history of tuberculosis. Xpert Ultra and Xpert performed similarly in detecting rifampicin resistance.InterpretationFor tuberculosis case detection, sensitivity of Xpert Ultra was superior to that of Xpert in patients with paucibacillary disease and in patients with HIV. However, this increase in sensitivity came at the expense of a decrease in specificity.FundingGovernment of Netherlands, Government of Australia, Bill & Melinda Gates Foundation, Government of the UK, and the National Institute of Allergy and Infectious Diseases.

Dataset Information

Diagnostic accuracy of Xpert ultra for childhood tuberculosis: A preliminary systematic review and meta-analysis.

Publications

Diagnostic accuracy of Xpert ultra for childhood tuberculosis: A preliminary systematic review and meta-analysis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets