Sensitivity Of Xpert Ultra Research Articles

Performance of stool-based molecular tests and processing methods for paediatric tuberculosis diagnosis: a systematic review and meta-analysis

There has been a global pursuit to improve the diagnosis of tuberculosis in young children by applying diagnostic methods on accessible biospecimens such as stool. We aimed to conduct a systematic review on the accuracy of stool-based molecular tests for tuberculosis diagnosis in children and to assess the impact of the available pre-processing methods and other design characteristics. In this systematic review and meta-analysis, we evaluated studies in children younger than 16years with presumptive tuberculosis that were published in English, Spanish, French, and Portuguese from Jan 1, 2000, to May3, 2024, in MEDLINE, Embase, and Embase Classic, comparing the molecular detection of Mycobacterium tuberculosis DNA in stool with microbiological tests on other samples or a clinical diagnosis. We did not exclude studies based on geographical location, sample size, or study design if they were reporting primary data. Two independent reviewers (LC-C and SM) screened titles, abstracts, and full-text articles for eligibility and extracted data on study characteristics, study population, and diagnostic performance. If information relevant to the main analysis was not reported in the article, the corresponding authors were contacted. Point estimates and 95% CIs were calculated for sensitivity and specificity for each study and for the different molecular tests (Xpert MTB/RIF, Xpert Ultra MTB/RIF [Cepheid, Sunnyvale, CA, USA], and other tests) versus a reference standard (culture only, any bacteriological confirmation, and tuberculosis case definition). Sensitivity and specificity were stratified by the stool processing method. We also quantified the additionality of stool Xpert Ultra tests for tuberculosis bacteriological confirmation. The protocol was registered with PROSPERO, CRD42022341514. A total of 4521records were identified through the database search, one record was identified from an article bibliography, and 67studies were retained for full-text reading. 39studies were included in the qualitative synthesis, 35of which were included in the meta-analyses. When using any bacteriological confirmation from a respiratory sample as the reference standard, stool Xpert sensitivity was 0·60 (95% CI 0·48-0·71), stool Xpert Ultra sensitivity was 0·73 (0·63-0·81), and sensitivity was 0·44 (0·29-0·60) for other in-house molecular methods combined. When using tuberculosis case definition as the reference standard, stool Xpert sensitivity was 0·23 (0·11-0·41), stool Xpert Ultra sensitivity was 0·38 (0·22-0·56), and sensitivity was 0·17 (0·09-0·23) for other in-house molecular methods. The addition of stool Xpert Ultra increased bacteriological confirmation of tuberculosis by 38·6% overall. Further, the utilisation of centrifuge-free simplified methods improved the sensitivity of stool Xpert Ultra when using any bacteriological confirmation as a reference standard (0·77 [0·66-0·85] for centrifuge-free methods vs 0·61[0·41-0·78] for non-centrifuge-free methods). This systematic review and meta-analysis supports the use of Xpert Ultra in stool samples as a diagnostic tool for paediatric tuberculosis diagnosis. Stool-based Xpert Ultra can contribute to increase the bacteriological confirmation in this population, even when respiratory specimens are also tested. The EDCTP2 programme supported by the EU via Stool4TB Project and the European Society of Pediatric Infectious Diseases.

Usefulness of Xpert MTB/RIF Ultra for rapid diagnosis of extrapulmonary tuberculosis in Tunisia

Extrapulmonary tuberculosis (EPTB) remains a challenging diagnosis. The purpose of this study was to assess the accuracy of Xpert MTB/RIF Ultra (Cepheid, USA) for rapid diagnosis of EPTB in Tunisia. Eight hundred and forty-seven extrapulmonary samples collected from 2017 to 2021, were subjected to Xpert MTB/RIF Ultra. Microscopy and culture were performed for all the specimens. The accuracy of Xpert Ultra was evaluated in comparison to the culture. Xpert Ultra diagnosed EPTB with a global sensitivity of 80.66% (74.3–85.75) and specificity of 70.87% (67.31–74.20). The molecular test was most accurate when performed in cerebrospinal fluids, bones and joints and cutaneous specimens showing a sensitivity of 100% and a specificity ranging from 70.60 to 91.11%. In lymph node samples comprising aspirates and biopsies, the sensitivity of Xpert Ultra was high 87.50% (77.23–93.53), however, the specificity was 51.08% (44.67–57.46). For pleural samples, the Xpert Ultra sensitivity was 77.50% (68.34–84.68) ranging from 71.43 to 80% in pleural biopsies and fluids respectively. The specificity in all pleural specimens was 79.56% (74.40–83.91). Xpert Ultra showed promise in the diagnosis of EPTB. The performances varied according to the site of the disease. The test may be more valuable if used in combination with other diagnostic modalities.

The diagnostic performance of Xpert MTB/RIF Ultra on Pericardial, Pleural and Ascitic cohort study fluids for diagnosis of extra-pulmonary Tuberculosis at a referral hospital in Malawi.

Extra-pulmonary tuberculosis (EPTB) accounts for 15% of the 1.4 million patients with TB notified in 2019. EPTB carries a high risk of mortality and so early diagnosis and treatment are important to reduce this risk. Diagnosis of EPTB in low- and middle-income countries is challenging. This study investigated the diagnostic performance of Xpert MTB Ultra for the diagnosis of EPTB (pericardial, pleural, and ascitic fluid) in adults at a referral hospital in Malawi. Adults with suspected extra-pulmonary TB were screened for evidence of extra-pulmonary fluid and tested for TB using Xpert MTB Ultra, mycobacterial culture, and a Focused Abdominal Sonography in HIV-associated TB (FASH scan). The diagnostic performance of the Xpert MTB Ultra was compared to mycobacterial culture and a composite reference standard defined as a positive FASH scan or a positive mycobacterial culture or a clinical TB diagnosis (constitutional symptoms not otherwise explained with response to empirical TB treatment). There were 174 patients recruited: 99/174 (57%) pleural, 70/174 (40%) ascitic and 5/174 (3%) pericardial. Overall, 10/174 (6%) had bacteriologically confirmed TB and 30/174 (17%) were started on TB treatment based on a positive FASH scan or a clinical TB diagnosis. The sensitivity and specificity of Xpert ultra compared to culture was 83% (95%CI:36%-100%) and 98% (95%CI:94%-99%), respectively. Compared to the composite reference standard, the sensitivity of Xpert Ultra was 17% (95%CI:7%-34%) and specificity was 98% (95%CI:94%-100%). Xpert MTB Ultra provides good diagnostic performance on pleural, pericardial and ascitic fluid with reference to mycobacterial culture. Improved EPTB diagnostic tests are required to improve patient outcomes. We recommend larger multi-centre studies to corroborate our findings.

Xpert MTB/RIF Ultra assay for tuberculosis disease and rifampicin resistance in children.

Xpert MTB/RIF Ultra assay for tuberculosis disease and rifampicin resistance in children.

Xpert MTB/RIF Ultra outperformed the Xpert assay in tuberculosis lymphadenitis diagnosis: a prospective head-to-head cohort study

ObjectivesXpert Mycobacterium tuberculosis/rifampin (MTB/RIF) Ultra (Xpert-Ultra) has shown better sensitivity in comparison with Xpert MTB/RIF (Xpert) in extrapulmonary tuberculosis (TB), whereas the head-to-head comparison of these methods in TB lymphadenitis had barely been performed. MethodsPatients with undiagnosed lymphadenopathy were recruited prospectively and consecutively, and fine-needle aspiration (FNA) biopsy or lymph node tissue was collected. The specimen was subjected to smear, culture, Xpert, and Xpert-Ultra assays. Culture and/or smear for acid-fast bacilli (AFB) or AFB observed on histopathology were performed as a reference. ResultsA total of 106 participants were recruited, including 41 confirmed TB, 33 probable TB, and 32 non-TB lymphadenopathies. The head-to-head comparison for MTB detection showed that Xpert-Ultra produced the highest sensitivity when compared with smear, culture, and Xpert (75.7% vs 5.4 %, 13.5%, and 48.7%). When Xpert-Ultra outcomes were integrated for diagnosis, the percentage of confirmed TB lymphadenitis cases increased from 55.4% (41/74) to 85.1% (63/74). The sensitivities of Xpert-Ultra and Xpert on tissue were 73.6% (95% CI: 59.4-84.3) and 39.6% (95% CI: 26.8-54.0), respectively. The sensitivity of Xpert-Ultra on FNA samples (81.0%, 95% CI: 57.4-93.7) was higher than that of Xpert (71.4%, 95% CI: 47.7-87.8). ConclusionXpert-Ultra detected significantly more TB lymphadenitis cases than Xpert or culture. This superiority was particularly distinct using lymph node tissue than FNA detection.

Optimising Xpert-Ultra and culture testing to reliably measure tuberculosis prevalence in the community: findings from surveys in Zambia and South Africa

ObjectivesPrevalence surveys remain the best way to assess the national tuberculosis (TB) burden in many countries. Challenges with using culture (the reference standard) for TB diagnosis in prevalence surveys have...

Head-to-head comparison of the efficacy of Xpert MTB/RIF Ultra and Xpert MTB/RIF for the diagnosis of tuberculous pleurisy: A systematic review and meta-analysis.

Background:The aim of this study was to evaluate the diagnostic accuracy of Xpert MTB/RIF Ultra (Xpert Ultra) and Xpert MTB/RIF (Xpert) for the diagnosis of tuberculous pleurisy (TBP) head-to-head using meta-analysis method.Methods:On May 12, 2021, we searched multiple databases for reports that used Xpert Ultra and Xpert for TBP diagnosis head-to-head and screened eligible studies for inclusion. Accuracy of Xpert Ultra and Xpert were compared to that of the composite reference standard (CRS) and culture. When heterogeneity was evident, sources of heterogeneity were explored using subgroup analyses, sensitivity analysis, and meta-regression analyses.Results:Five articles met the inclusion criteria for meta-analysis. When results from different specimens or different reference standards were reported in the same article, we analyzed them as separate studies. Thus, 6 studies compared Xpert Ultra and Xpert with CRS, 5 studies compared Xpert Ultra and Xpert with culture. Pooled sensitivity and specificity of Xpert Ultra were 52% and 98% compared to CRS, and 82% and 77% compared to culture. Pooled sensitivity and specificity of Xpert were 22% and 99% compared to CRS, and 48% and 94% compared to culture. Significant heterogeneity in sensitivity was observed compared to CRS.Conclusion:The sensitivity of Xpert Ultra was moderate but better than that of the Xpert; however, its specificity was lower. The role of Xpert Ultra and Xpert in the early and rapid diagnosis of TBP was limited.

Efficacy of Xpert MTB/RIF Ultra in diagnosing tuberculosis meningitis: A systematic review and meta-analysis.

Background:This study aimed to assess whether Xpert MTB/RIF Ultra (Xpert Ultra) can effectively diagnose tuberculosis meningitis (TBM) and to simultaneously compare its effectiveness with Xpert in diagnosing TBM in the same population.Methods:On August 12, 2020, Wanfang Database, China National Knowledge Infrastructure, Embase, Cochrane Library, and PubMed were searched for studies evaluating the diagnostic accuracy of Xpert Ultra for TBM. Then, we assessed the efficacy of Xpert Ultra against a composite reference standard and culture. If applicable, we also examined the diagnostic efficacy of Xpert in the same population. Heterogeneity was then explored by meta-regression, subgroup, and sensitivity analyses.Results:Six studies containing 601 specimens reported the diagnostic efficacy of Xpert Ultra for TBM, with a composite reference standard. No study had compared the efficacy between Xpert Ultra and culture. The pooled sensitivity of Xpert Ultra was 64% (95% confidence interval [CI]: 45–80), and the I2 value was 86% (95% CI: 76–96); its specificity for TBM was consistently 100%. In the same population, 5 studies compared the diagnostic efficacy between Xpert Ultra and Xpert for TBM. The pooled sensitivity of Xpert Ultra and Xpert was 68% (95% CI: 46–84; I2 = 87%) and 37% (95% CI: 25–50; I2 = 72%), respectively. The studies were significantly heterogeneous in terms of sensitivity but not heterogeneous in specificity.Conclusions:Xpert Ultra was more sensitive than Xpert, but both were specific (100%). Therefore, Xpert Ultra had an excellent diagnostic efficacy for TBM, and it could be the preferred initial test for TBM.

Xpert MTB/RIF and Xpert Ultra assays for screening for pulmonary tuberculosis and rifampicin resistance in adults, irrespective of signs or symptoms.

Xpert MTB/RIF and Xpert Ultra assays for screening for pulmonary tuberculosis and rifampicin resistance in adults, irrespective of signs or symptoms.

Xpert MTB/RIF Ultra and Xpert MTB/RIF assays for extrapulmonary tuberculosis and rifampicin resistance in adults.

Xpert MTB/RIF Ultra and Xpert MTB/RIF assays for extrapulmonary tuberculosis and rifampicin resistance in adults.

A Prospective Evaluation of Xpert MTB/RIF Ultra for Childhood Pulmonary Tuberculosis in Uganda

Xpert MTB/RIF Ultra (Xpert Ultra) has improved the sensitivity to detect pulmonary tuberculosis (TB) in adults. However, there have been limited prospective evaluations of its diagnostic accuracy in children. We enrolled children undergoing assessment for pulmonary TB in Kampala, Uganda, over a 12-month period. Children received a complete TB evaluation and were classified as Confirmed, Unconfirmed, or Unlikely TB. We calculated the sensitivity and specificity of Xpert Ultra among children with Confirmed vs Unlikely TB. We also determined the diagnostic accuracy with clinical, microbiological, and extended microbiological reference standards (MRSs). Of the 213 children included, 23 (10.8%) had Confirmed TB, 88 (41.3%) had Unconfirmed TB, and 102 (47.9%) had Unlikely TB. The median age was 3.9 years, 13% were HIV-positive, and 61.5% were underweight. Xpert Ultra sensitivity was 69.6% (95% confidence interval [CI]: 47.1-86.8) among children with Confirmed TB and decreased to 23.4% (95% CI: 15.9-32.4) with the clinical reference standard. Specificity was 100% (95% CI: 96.4-100) among children with Unlikely TB and decreased to 94.7% (95% CI: 90.5-97.4) with a MRS. Sensitivity was 52.9% (95% CI: 35.1-70.2) and specificity 95.5% (95% CI: 91.4-98.1) with the extended MRS. Of the 26 positive Xpert Ultra results, 6 (23.1%) were "Trace-positive," with most (5/6) occurring in children with Unconfirmed TB. Xpert Ultra is a useful tool for diagnosing pulmonary TB in children, but there remains a need for more sensitive tests to detect culture-negative TB.

Usefulness of Xpert MTB/RIF Ultra to Rapidly Diagnose Sputum Smear-Negative Pulmonary Tuberculosis Using Bronchial Washing Fluid.

This study evaluated the performance of the Xpert MTB/RIF Ultra assay (Xpert Ultra) to detect smear-negative pulmonary tuberculosis (PTB). Xpert Ultra assay was prospectively performed using bronchial washing fluid (BWF) in comparison to COBAS TaqMan MTB (COBAS) assay and mycobacterial culture. Of the 165 enrolled participants, 27 (16.4%) had PTB based on composite reference standard and 16 (9.7%) had culture-confirmed PTB. By the composite reference standard of PTB, the sensitivity of Xpert Ultra (63.0, 95% confidence interval, CI, 42.4–80.6%) was higher than the COBAS assay (25.9%, P = 0.006), BWF-culture (33.3%, P = 0.029) and sputum-culture (37.0%, P = 0.057). Meanwhile, the specificity of Xpert Ultra was 99.3% which was slightly lower than the 100.0% specificity of the COBAS assay (P = 1.000) and cultures (P = 1.000). Against the reference standard of culture-confirmed PTB, Xpert Ultra also had a higher sensitivity (62.5, 95% CI, 35.4–84.8%) than the COBAS assay (31.3%, P = 0.077) and was similar to BWF-culture (56.3%, P = 0.719) and sputum-culture (62.5%, P = 1.000). However, one subject with previously treated old PTB had a false-positive result on the Xpert Ultra assay. This prospective study showed Xpert Ultra assay using BWF had better sensitivity than COBAS assay and mycobacterial cultures but could represent a false positive in patients with inactive old PTB.

Xpert MTB/RIF ultra for the diagnosis of tuberculous meningitis: A diagnostic accuracy study from India

SettingStudies evaluating Xpert MTB/RIF Ultra assay (Xpert Ultra) for diagnosing tuberculous meningitis (TBM) are scarce and have reported contrasting results in comparison to Xpert MTB/RIF assay (Xpert). ObjectiveTo evaluate the performance of Xpert Ultra in diagnosing TBM and compare it with Xpert and multiplex polymerase chain reaction (MPCR). DesignXpert Ultra was performed on 244 cerebrospinal fluid (CSF) samples: 56 definite TBM, 148 probable TBM and 40 non-TBM controls. 105/244 CSF samples were also subjected to Xpert and MPCR (IS6110, MPB64, protein B). ResultsThe overall sensitivity of Xpert Ultra in diagnosing TBM from 244 CSF samples was 72.05% (96.42% - definite TBM, 62.83% - probable TBM) with a specificity of 100%. 18 (12.24%) cases [8 definite TBM, 10 probable TBM] were reported rifampicin resistant (RifR) by Xpert Ultra and confirmed by rpoB sequencing. 60 (40.81%) cases [9 definite TBM, 51 probable TBM] were reported rifampicin indeterminate (RifI) by Xpert Ultra (all trace category), out of which 45 [8 definite, 37 probable) were rifampicin susceptible (RifS) and 5 probable cases were RifR on rpoB sequencing. Out of 105 CSF samples subjected to all three techniques, TBM was diagnosed in 70.66%, 28% and 88% by Xpert Ultra, Xpert and MPCR, respectively. ConclusionXpert Ultra detected TBM with higher sensitivity than Xpert. Among trace category, constituting 40% of TBM cases, rpoB gene sequencing confirmed 5 RifR cases.

Xpert MTB/RIF and Xpert MTB/RIF Ultra assays for active tuberculosis and rifampicin resistance in children

Xpert MTB/RIF and Xpert MTB/RIF Ultra assays for active tuberculosis and rifampicin resistance in children

Comparison of diagnostic accuracy of the GeneXpert Ultra and cell-free nucleic acid assay for tuberculous meningitis: A multicentre prospective study

DesignA prospective multicentre study was conducted to compare the diagnostic accuracy of the GeneXpert MTB/RIF Ultra (Xpert Ultra) and cell-free DNA (cfDNA) assay for tuberculous meningitis (TBM) in China. MethodsA prospective cohort study was conducted among individuals with symptoms suggestive of TBM registered in three TB specialised hospitals in China between June 2018 and January 2019. ResultsOverall, 84 patients suggestive of TBM were included in this analysis between June 2018 and January 2019. Using microbiological evidence as reference, the sensitivity/specificity for the diagnostic tests were Xpert Ultra 93.3%/100%, cfDNA 93.3%/92.6% and mycobacteria growth indicator tube (MGIT) culture 13.3%/100%. In addition, the sensitivity of culture was 6.7% when using clinical diagnosis criteria as the gold standard. Xpert Ultra correctly identified 28 cases as TBM, indicating a sensitivity of 46.7%. Notably, four additional TBM cases were detected by cfDNA compared with Xpert Ultra, yielding an overall sensitivity of 53.3%. Statistical analysis revealed that the sensitivity of Xpert Ultra and cfDNA was significantly higher than that of culture. ConclusionsThe data demonstrate that Xpert Ultra and cfDNA assay showed optimal sensitivity compared with MGIT culture. In addition, there was no significant correlation between bacterial load and TBM severity in the participants.

Xpert MTB/RIF Ultra for the Diagnosis of Tuberculous Meningitis: A Small Step Forward.

The delayed diagnosis of tuberculous meningitis (TBM) leads to poor outcomes, yet the current diagnostic methods for identifying Mycobacterium tuberculosis in cerebrospinal fluid (CSF) are inadequate. The first comparative study of the new GeneXpert MTB/RIF Ultra (Xpert Ultra) for TBM diagnosis suggested increased sensitivity of Xpert Ultra. Two subsequent studies have shown Xpert Ultra has improved sensitivity, but has insufficient negative predictive value to exclude TBM. Collecting and processing large volumes of CSF for mycobacterial testing are important for optimal diagnostic test performance. But clinical, radiological, and laboratory parameters remain essential for TBM diagnosis and empiric therapy is often needed. We therefore caution against the use of Xpert Ultra as a single diagnostic test for TBM; it cannot be used to “rule out” TBM.

Xpert MTB/RIF Ultra versus Xpert MTB/RIF for the diagnosis of tuberculous meningitis: a prospective, randomised, diagnostic accuracy study

SummaryBackgroundXpert MTB/RIF Ultra (Xpert Ultra) might have higher sensitivity than its predecessor, Xpert MTB/RIF (Xpert), but its role in tuberculous meningitis diagnosis is uncertain. We aimed to compare Xpert Ultra with Xpert for the diagnosis of tuberculous meningitis in HIV-uninfected and HIV-infected adults.MethodsIn this prospective, randomised, diagnostic accuracy study, adults (≥16 years) with suspected tuberculous meningitis from a single centre in Vietnam were randomly assigned to cerebrospinal fluid testing by either Xpert Ultra or Xpert at baseline and, if treated for tuberculous meningitis, after 3–4 weeks of treatment. Test performance (sensitivity, specificity, and positive and negative predictive values) was calculated for Xpert Ultra and Xpert and compared against clinical and mycobacterial culture reference standards. Analyses were done for all patients and by HIV status.FindingsBetween Oct 16, 2017, and Feb 10, 2019, 205 patients were randomly assigned to Xpert Ultra (n=103) or Xpert (n=102). The sensitivities of Xpert Ultra and Xpert for tuberculous meningitis diagnosis against a reference standard of definite, probable, and possible tuberculous meningitis were 47·2% (95% CI 34·4–60·3; 25 of 53 patients) for Xpert Ultra and 39·6% (27·6–53·1; 21 of 53) for Xpert (p=0·56); specificities were 100·0% (95% CI 92·0–100·0; 44 of 44) and 100·0% (92·6–100·0; 48 of 48), respectively. In HIV-negative patients, the sensitivity of Xpert Ultra was 38·9% (24·8–55·1; 14 of 36) versus 22·9% (12·1–39·0; eight of 35) by Xpert (p=0·23). In HIV co-infected patients, the sensitivities were 64·3% (38·8–83·7; nine of 14) for Xpert Ultra and 76·9% (49·7–91·8; ten of 13) for Xpert (p=0·77). Negative predictive values were 61·1% (49·6–71·5) for Xpert Ultra and 60·0% (49·0–70·0) for Xpert. Against a reference standard of mycobacterial culture, sensitivities were 90·9% (72·2–97·5; 20 of 22 patients) for Xpert Ultra and 81·8% (61·5–92·7; 18 of 22) for Xpert (p=0·66); specificities were 93·9% (85·4–97·6; 62 of 66) and 96·9% (89·5–91·2; 63 of 65), respectively. Six (22%) of 27 patients had a positive test by Xpert Ultra after 4 weeks of treatment versus two (9%) of 22 patients by Xpert.InterpretationXpert Ultra was not statistically superior to Xpert for the diagnosis of tuberculous meningitis in HIV-uninfected and HIV-infected adults. A negative Xpert Ultra or Xpert test does not rule out tuberculous meningitis. New diagnostic strategies are urgently required.FundingWellcome Trust and the Foundation for Innovative New Diagnostics.

Xpert MTB/RIF and Xpert MTB/RIF Ultra for pulmonary tuberculosis and rifampicin resistance in adults.

BackgroundXpert MTB/RIF (Xpert MTB/RIF) and Xpert MTB/RIF Ultra (Xpert Ultra), the newest version, are the only World Health Organization (WHO)‐recommended rapid tests that simultaneously detect tuberculosis and rifampicin resistance in persons with signs and symptoms of tuberculosis, at lower health system levels. A previous Cochrane Review found Xpert MTB/RIF sensitive and specific for tuberculosis (Steingart 2014). Since the previous review, new studies have been published. We performed a review update for an upcoming WHO policy review.ObjectivesTo determine diagnostic accuracy of Xpert MTB/RIF and Xpert Ultra for tuberculosis in adults with presumptive pulmonary tuberculosis (PTB) and for rifampicin resistance in adults with presumptive rifampicin‐resistant tuberculosis.Search methodsWe searched the Cochrane Infectious Diseases Group Specialized Register, MEDLINE, Embase, Science Citation Index, Web of Science, Latin American Caribbean Health Sciences Literature, Scopus, the WHO International Clinical Trials Registry Platform, the International Standard Randomized Controlled Trial Number Registry, and ProQuest, to 11 October 2018, without language restriction.Selection criteriaRandomized trials, cross‐sectional, and cohort studies using respiratory specimens that evaluated Xpert MTB/RIF, Xpert Ultra, or both against the reference standard, culture for tuberculosis and culture‐based drug susceptibility testing or MTBDRplus for rifampicin resistance.Data collection and analysisFour review authors independently extracted data using a standardized form. When possible, we also extracted data by smear and HIV status. We assessed study quality using QUADAS‐2 and performed meta‐analyses to estimate pooled sensitivity and specificity separately for tuberculosis and rifampicin resistance. We investigated potential sources of heterogeneity. Most analyses used a bivariate random‐effects model. For tuberculosis detection, we first estimated accuracy using all included studies and then only the subset of studies where participants were unselected, i.e. not selected based on prior microscopy testing.Main resultsWe identified in total 95 studies (77 new studies since the previous review): 86 studies (42,091 participants) evaluated Xpert MTB/RIF for tuberculosis and 57 studies (8287 participants) for rifampicin resistance. One study compared Xpert MTB/RIF and Xpert Ultra on the same participant specimen.Tuberculosis detectionOf the total 86 studies, 45 took place in high tuberculosis burden and 50 in high TB/HIV burden countries. Most studies had low risk of bias.Xpert MTB/RIF pooled sensitivity and specificity (95% credible Interval (CrI)) were 85% (82% to 88%) and 98% (97% to 98%), (70 studies, 37,237 unselected participants; high‐certainty evidence). We found similar accuracy when we included all studies.For a population of 1000 people where 100 have tuberculosis on culture, 103 would be Xpert MTB/RIF‐positive and 18 (17%) would not have tuberculosis (false‐positives); 897 would be Xpert MTB/RIF‐negative and 15 (2%) would have tuberculosis (false‐negatives).Xpert Ultra sensitivity (95% confidence interval (CI)) was 88% (85% to 91%) versus Xpert MTB/RIF 83% (79% to 86%); Xpert Ultra specificity was 96% (94% to 97%) versus Xpert MTB/RIF 98% (97% to 99%), (1 study, 1439 participants; moderate‐certainty evidence).Xpert MTB/RIF pooled sensitivity was 98% (97% to 98%) in smear‐positive and 67% (62% to 72%) in smear‐negative, culture‐positive participants, (45 studies). Xpert MTB/RIF pooled sensitivity was 88% (83% to 92%) in HIV‐negative and 81% (75% to 86%) in HIV‐positive participants; specificities were similar 98% (97% to 99%), (14 studies).Rifampicin resistance detectionXpert MTB/RIF pooled sensitivity and specificity (95% Crl) were 96% (94% to 97%) and 98% (98% to 99%), (48 studies, 8020 participants; high‐certainty evidence).For a population of 1000 people where 100 have rifampicin‐resistant tuberculosis, 114 would be positive for rifampicin‐resistant tuberculosis and 18 (16%) would not have rifampicin resistance (false‐positives); 886 would be would be negative for rifampicin‐resistant tuberculosis and four (0.4%) would have rifampicin resistance (false‐negatives).Xpert Ultra sensitivity (95% CI) was 95% (90% to 98%) versus Xpert MTB/RIF 95% (91% to 98%); Xpert Ultra specificity was 98% (97% to 99%) versus Xpert MTB/RIF 98% (96% to 99%), (1 study, 551 participants; moderate‐certainty evidence).Authors' conclusionsWe found Xpert MTB/RIF to be sensitive and specific for diagnosing PTB and rifampicin resistance, consistent with findings reported previously. Xpert MTB/RIF was more sensitive for tuberculosis in smear‐positive than smear‐negative participants and HIV‐negative than HIV‐positive participants. Compared with Xpert MTB/RIF, Xpert Ultra had higher sensitivity and lower specificity for tuberculosis and similar sensitivity and specificity for rifampicin resistance (1 study). Xpert MTB/RIF and Xpert Ultra provide accurate results and can allow rapid initiation of treatment for multidrug‐resistant tuberculosis.

OC 8215 DIAGNOSTIC ACCURACY OF XPERT MTB/RIF ULTRA FOR PULMONARY TUBERCULOSIS IN CHILDREN: A MULTICENTRE COMPARATIVE STUDY

BackgroundXpert® MTB/RIF (Xpert) has suboptimal sensitivity for the diagnosis of pulmonary tuberculosis in children. The next-generation Xpert MTB/RIF Ultra assay (Xpert Ultra) is substantially more sensitive than Xpert and may allow improved detection of paediatric tuberculosis. We evaluated the diagnostic accuracy of Xpert Ultra versus Xpert in the detection of pulmonary tuberculosis in children.MethodsFrom May 2011 to September 2012, children with presumptive pulmonary tuberculosis were enrolled at two „Tanzanian research sites in the EDCTP-funded TB CHILD project. Sputum samples were collected and examined for tuberculosis using sputum smear, Xpert and culture. Xpert Ultra analysis was performed between January and June 2017 at both sites using decontaminated sputum pellets which had been stored at −80°C. The diagnostic accuracy of Xpert and Xpert Ultra was determined using well-defined case definitions as reference standard.ResultsIn total, 215 children were included in the analysis. The median age was 5.4 years (IQR, 1.5 to 9.9), the HIV prevalence was 52%, and 28 children (13%) had culture-confirmed pulmonary tuberculosis. When only the first available sample of each patient was considered, the sensitivity of Xpert Ultra was 64.3% (95% CI: 44.1 to 81.4) while that of Xpert was 53.6% (95% CI: 33.9 to 72.5). The specificity of Xpert Ultra based on the analysis of all available samples was 98.1% (95% CI: 93.4 to 99.7), whereas that of Xpert was 100%.ConclusionIn settings with a high burden of tuberculosis and HIV, Xpert Ultra had a better sensitivity than Xpert in children. However, the specificity was slightly lower than that of Xpert. Thus, Xpert Ultra has the potential to increase the reliability and the speed of tuberculosis diagnosis in children.

Xpert MTB/RIF Ultra improved the diagnosis of paucibacillary tuberculosis: A prospective cohort study

We assessed the diagnostic performance of Xpert MTB/RIF Ultra (Xpert Ultra) in comparison to Xpert MTB/RIF (Xpert) for the detectionof paucibacillary tuberculosis (TB). Smear-negative sputum, pleural fluid and cerebrospinal fluid (CSF) were collected from TB suspects at Beijing Chest Hospital (Beijing, China) and were examined using smear, Xpert and culture. Xpert Ultra was tested using specimens stored at -80°C. Drug susceptibility testing (DST) was conducted for all of the isolates recovered. The performances of Xpert Ultra and Xpert were evaluated using composite reference standard (CRS) as gold standard, which included clinical, laboratory, histopathological, radiological and follow-up features. Totally 689 cases were included. The direct head-to-head diagnostic performance comparison showed higher sensitivity of Xpert Ultra in contrast with Xpert among 292 smear-negative pulmonary TB (PTB) (70.89% vs 57.88%, P = 0.001), 108 tuberculous pleurisy (61.11% vs 34.26%, P<0.001), and 43 tuberculous meningitis (44.19% vs 18.60%, P = 0.011). The percentage of definite PTB, tuberculous pleurisy and tuberculous meningitis increased from 67.12% to 78.77%, 61.11% to 69.44% and 23.26% to 51.16%, respectively after integrating Xpert Ultra outcomes. The specificity of Xpert Ultra and Xpert was 96.75% (238/246) and 98.37% (242/246), respectively. Xpert Ultra and Xpert performed similarly in detecting rifampicin resistance. Xpert Ultra has higher sensitivity but relatively reduced specificity compared with Xpert in diagnosis of paucibacillary TB. Performing Xpert Ultra would improve the definite diagnosis of smear-negative pulmonary tuberculosis, tuberculous pleurisy and tuberculous meningitis.