Detjen, A

Eisenhut, M

Fernández, L

Kay, A

Mandalakas, A

Steingart, Karen

Takwoingi, Y

LSTM Online Archive

Xpert MTB/RIF and Xpert MTB/RIF Ultra assays for active tuberculosis and rifampicin resistance in childrenAlexander Kay, MDXpert MTB/RIF and Xpert MTB/RIF Ultra assays for active tuberculosis and rifampicin resistance in childrenKay AW1,2, González Fernández L1, Takwoingi Y3, Eisenhut M4, Detjen AK5, Steingart KR6, Mandalakas AM1,2.1The Global Tuberculosis Program, Texas Children’s Hospital, Section of Global and Immigrant Health, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA. 2Department of Paediatrics, Baylor College of Medicine, Houston, Texas, USA. 3Test Evaluation Research Group, Institute of Applied Health Research, University of Birmingham, Birmingham, UK. 4Paediatric Department, Luton & Dunstable University Hospital NHS Foundation Trust, Luton, UK. 5Health Section, 5UNICEF, New York, New York, USA. 6Honorary Research Fellow, Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UK.CONFLICT OF INTEREST DISCLOSURE X  I have no Conflict of Interest to report. ☐ I have the following Conflict of Interest(s) to report: Please tick the type of affiliation / financial interest and specify the name of the organisation:☐ Receipt of grants/research supports: _______________________________☐ Receipt of honoraria or consultation fees: ___________________________☐ Participation in a company sponsored speaker’s bureau: _______________☐ Tobacco-industry and tobacco corporate affiliate: _____________________☐ Stock shareholder: _____________________________________________☐ Spouse/partner: _______________________________________________☐ Other:  ______________________________________________________BACKGROUND• Child TB accounts for 11% of the 10 million global cases• Children shoulder a disproportionate share of TB mortality (14%)• 96% of child TB deaths occur in the undiagnosed (Dodd et al, Lancet Global Health, 2017) • Previous Xpert MTB/RIF Review (Detjen et al, Lancet Resp Med, 2015)• sensitivity (62% sputum, 66% gastric specimen) • specificity (98% sputum and gastric specimens)• Updated the systematic review as additional Xpert MTB/RIF studies have been published and Xpert Ultra was introduced in order to inform 2020 WHO TB molecular diagnostic guidelinesMETHODS: SEARCH• Searched multiple databases without language restriction to 29 Apr 2019• Covidence systematic review software to manage selection of studies• Reviewed reference lists of articles and review articles• Reviewed included studies from prior review• Data obtained directly from manuscripts and through author inquiriesMETHODS: APPROACH• Types of Studies: Diagnostic accuracy cross-sectional studies, cohort studies, and randomized controlled trials from all settings• Participants: Studies that evaluated the index tests for pulmonary TB in HIV-positive and HIV-negative children aged 0 to 14 years with presumptive TB• Index Test: Xpert MTB/RIF and Xpert Ultra• Specimens: sputum, gastric aspirate, stool or nasopharyngeal specimens • Target Condition: Pulmonary TBMETHODS: REFERENCE STANDARDS• Microbiologic Reference Standard: A positive culture on liquid or solid media from the same specimen type as the index test • The reference test for stool was a positive culture or Xpert test on a respiratory specimen• Composite Reference Standard: A positive culture or a clinical decision to treat for TB based on clinical features• If treatment decisions could not be abstracted then study specific definitions were usedMETHODS: ANALYSIS• Methodological quality assessed by QUADAS-2: patient selection, index test, reference standard, and flow & timing domains• Performed meta-analyses using bivariate random-effects models when data were sufficient to estimate pooled results• Investigated sources of heterogeneity by subgroup analysis: age groups, smear status, HIV status• Sensitivity analyses were based on methodological qualityRESULTS• 49 studies, which provided 299 data sets (68,544 participants) for pulmonary TB• 80% of studies were performed in TB high-burden settings•Median TB prevalence in the included studies was similar across specimen types ranging from 7-11%RESULTS: SPUTUMXpert MTB/RIF against Culture (23 studies, 6612 participants)• Sensitivity: 64.6% (95% CI 55.3 to 72.9) • Specificity: 99.0% (95% CI 98.1 to 99.5)Xpert MTB/RIF against Composite (16 studies, 4379 participants)• Sensitivity: 19.7% (95% CI 12.1 to 30.4) • Specificity: 100% (95% CI 100 to 100) Xpert Ultra against Culture (3 studies, 697 participants)• Sensitivity: 72.8%(95% CI 64.7 to 79.6)• Specificity: 97.5% (95% CI 95.8 to 98.5) Xpert Ultra against Composite (3 studies, 753 participants)• Sensitivity: 23.5% (95% CI 20.0 to 27.4) • Specificity: 99.2% (95% CI 96.9 to 99.8) RESULTS: GASTRIC ASPIRATIONXpert MTB/RIF against Culture (14 studies, 3482 participants):• Sensitivity: 73.0% (95% CI 52.9 to 86.7) • Specificity: 98.1% (95% CI 95.5 to 99.2) Xpert MTB/RIF against Composite (6 studies, 933 participants): • Sensitivity: 31.7% (95% CI 20.2 to 46.0) • Specificity: 99.7% (95% CI 97.1 to 100) * No studies evaluated Xpert Ultra on gastric aspirationRESULTS: NASOPHARYNGEAL ASPIRATIONXpert MTB/RIF against Culture (4 studies, 1125 participants): • Sensitivity 45.7% (95% CI 27.6% to 65.1%) • Specificity: (4 studies, 981 participants): 99.6% (95% CI 98.9 to 99.8) Xpert Ultra against Culture (1 study, 195 participants): • Sensitivity 45.7% (95% CI 28.9 to 63.3)• Specificity 97.5% (95% CI 93.7 to 99.3) *Composite reference standard was not assessed due to limited dataRESULTS: STOOLXpert MTB/RIF against Culture (11 studies, 1512 participants):• Sensitivity: 61.5% (95% CI 44.1 to 76.4)• Specificity: 98.5% (95% CI 97.0 to 99.2)Xpert MTB/RIF against Composite (10 studies, 1739 participants): • Sensitivity: 16.3% (95% CI 8.4 to 29.2)• Specificity: 99.7% (95% CI 97.8 to 100) *No studies evaluated Xpert Ultra on stoolRESULTS: RIFAMPICIN RESISTANCE• Xpert MTB/RIF pooled sensitivity against culture or LPA DST was: 90.0% (95% CI 67.6% to 97.5%) and specificity was 98.3% (95% CI 87.7% to 99.8%) *No studies evaluated Xpert Ultra rifampicin resistance detectionCONCLUSIONS• Xpert MTB/RIF sensitivity varied by specimen type but 95% CIs overlapped• Gastric aspirate specimens had the highest sensitivity followed by sputum and stool, and nasopharyngeal specimens the lowest; specificity in all specimens was > 98%• Compared with Xpert MTB/RIF, Xpert Ultra sensitivity in sputum was higher (overlapping 95% CIs) and specificity was slightly lower• The small number of studies and reliance on stored specimens limits our confidence in the precision of the accuracy estimates for Xpert Ultra• Test sensitivity remains poor against a composite reference standard. Treatment decisions should be based on the entirety of clinical information and treatment not withheld based solely on an Xpert MTB/RIF or Xpert Ultra result. ACKNOWLEDGEMENTS• Vittoria Lutje (CIDG) for developing the search strategy.• Ryan Vu (Rice University) who contributed to development of the protocol• Mikashmi Kohli (McGill University) for providing technical expertise• Emily Maclean (McGill University) for providing data on stool analysis• Andrew DiNardo (Baylor College of Medicine) for technical assistance• Gemma Villanueva and Hanna Bergman (Cochrane Response) for assisting with data entry • Aakshi Kalra (FIND), provided data from a large-scale Xpert MTB/RIF demonstration project conducted in IndiaThank you

OA-41-751-24 A systematic review of Xpert MTB/RIF and Xpert Ultra diagnostic accuracy for detection of active pulmonary tuberculosis and rifampicin resistance in children

https://archive.lstmed.ac.uk/16242/1/Kay_PTB_Slides_Union%20Conf%202020.pdf

OA-41-751-24 A systematic review of Xpert MTB/RIF and Xpert Ultra diagnostic accuracy for detection of active pulmonary tuberculosis and rifampicin resistance in children

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