Xpert MTB/RIF Ultra and Xpert MTB/RIF for diagnosis of tuberculosis in an HIV-endemic setting with a high burden of previous tuberculosis: a two-cohort diagnostic accuracy study

Mishra, Hridesh; Reeve, Byron W P; Palmer, Zaida; Caldwell, Judy; Dolby, Tania; Naidoo, C; Jackson, Jennifer G.; Schumacher, Samuel G; Denkinger, Claudia M.; Diacon, Andreas H.; Helden, Paul D. van; Marx, Florian M.; Warren, Robin M.; Theron, Grant

doi:10.1016/s2213-2600(19)30370-4

Cited by 68 publications

(69 citation statements)

References 22 publications

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“…Of the actionable results, 35/37 (95%) fell within the defined threshold (C Tmin <25) and of these all FQ results were concordant with MTBDRsl on sputum and all but one SLID result were concordant (false-susceptible). Though this percentage is slightly higher than the number of patients with C Tmin <25 in our setting, which was determined to be 86% (based on an evaluation of Ultra done in sympotmatic patients in primary care 26 ), which further show that this approach would benefit the majority of patients in our setting. Of the 2/37 (5%) results that were actionable but fell above the defined threshold, one was concordant with MTBDRsl on sputa and one was indeterminate for FQs and discordant for SLIDs (false-resistant).…”

Section: Mtbdrplus and Mtbdrsl On Extract From Cartridges Done On Dilmentioning

confidence: 58%

Extract from used Xpert MTB/RIF Ultra cartridges is useful for accurate second-line drug-resistant tuberculosis diagnosis with minimal rpoB-amplicon cross-contamination risk

Venter

Minnies

Derendinger

et al. 2020

Sci Rep

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(Ultra) detects Mycobacterium tuberculosis and rifampicin resistance. Follow-on drug susceptibility testing (DST) requires additional sputum. Extract from the diamond-shaped chamber of the cartridge (dCE) of Ultra's predecessor, Xpert MTB/RIF (Xpert), is useful for MTBDRsl-based DSt but this is unexplored with Ultra. Furthermore, whether CE from non-diamond compartments is useful, the performance of FluoroType MTBDR (FT) on CE, and rpoB cross-contamination risk associated with the extraction procedure are unknown. We tested MTBDRsl, MTBDRplus, and FT on CEs from chambers from cartridges (Ultra, Xpert) tested on bacilli dilution series. MTBDRsl on Ultra dce on tB-positive sputa (n = 40) was also evaluated and, separately, rpoB amplicon cross-contamination risk. MTBDRsl on Ultra dce from dilutions ≥10 3 cfU/ml (c tmin <25, >"low semi-quantitation") detected fluoroquinolone (FQ) and second-line injectable (SLID) susceptibility and resistance correctly (some SLIDs-indeterminate). At the same threshold (at which ~85% of Ultra-positives in our setting would be eligible), 35/35 (100%) FQ and 34/35 (97%) SLID results from Ultra dCE were concordant with sputa results. Tests on other chambers were unfeasible. No tubes open during 20 batched extractions had FT-detected rpoB cross-contamination. false-positive Ultra rpoB results was observed when dce dilutions ≤10 −3 were re-tested. MTBDRsl on Ultra dCE is concordant with isolate results. rpoB amplicon cross-contamination is unlikely. These data mitigate additional specimen collection for second-line DST and cross-contamination concerns.

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Section: Mtbdrplus and Mtbdrsl On Extract From Cartridges Done On Dilmentioning

confidence: 58%

Extract from used Xpert MTB/RIF Ultra cartridges is useful for accurate second-line drug-resistant tuberculosis diagnosis with minimal rpoB-amplicon cross-contamination risk

Venter

Minnies

Derendinger

et al. 2020

Sci Rep

Self Cite

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“…This lower specificity is proving to be an important issue in certain settings, such as areas with high numbers of HIV-TB coinfections or recurrent TB cases, like South Africa. In a recent study by Mishra and colleagues, it was shown that the Xpert Ultra assay had significantly lower specificity and positive predictive value than the Xpert MTB/RIF assay and high numbers of Ultra positive/culture negative people with previous treatment ( 23 ). The clinical consequences of treating such patients are unclear, and ongoing studies are attempting to shed light on this information.…”

Section: Developments In Test and Platforms With Who Endorsementmentioning

confidence: 99%

“…For other cases, a fresh specimen should be retested to rule out false positives ( 20 ). Trace calls may be difficult to interpret, as in the aforementioned study by Mishra et al, where it was observed that among people who were previously treated for TB, trace positives were a substantial portion of all positives, and these individuals by definition had indeterminate results for RIF resistance and were culture negative, precluding further DST ( 23 ). Trace calls may be improving Ultra’s sensitivity for extrapulmonary TB, particularly in the context of definite or probable TB meningitis, where a sensitivity of 70% (95% CI, 47% to 87%) in cerebrospinal fluid was observed ( 24 ); however, this finding is not consistent across studies, as another group observed a sensitivity of definite or probable TB of only 49% (95% CI, 35% to 63%) ( 25 ).…”

Section: Developments In Test and Platforms With Who Endorsementmentioning

confidence: 99%

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Advances in Molecular Diagnosis of Tuberculosis

et al. 2020

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Molecular tests for tuberculosis (TB) have the potential to help reach the three million people with TB who are undiagnosed or not reported each year, and to improve the quality of care TB patients receive by providing accurate, quick results, including rapid drug-susceptibility. The World Health Organization (WHO) has recommended the use of molecular nucleic acid amplification tests (NAATs) tests for TB detection instead of smear microscopy, as they are able to detect TB more accurately, particularly in patients with paucibacillary disease and in people living with HIV. Importantly, some of these WHO-endorsed tests can detect Mycobacterial gene mutations associated with anti-TB drug resistance, allowing for tailoring of effective TB treatment. Currently, a wide array of molecular tests for TB detection is being developed and evaluated, and while some are intended for reference laboratory use, others are being aimed at the point-of-care and peripheral healthcare settings. Notably, there is an emergence of molecular tests designed, manufactured, and rolled out in high TB burden countries, some of which are explicitly aimed for near-patient placement. These developments should increase access to molecular TB testing for larger patient populations. With respect to drug susceptibility testing, NAATs and next generation sequencing can provide results substantially faster than traditional phenotypic culture. Here, we review recent advances and developments in molecular tests for detecting TB as well as anti-TB drug resistance.

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“…We identified 50 articles: 17 [7,[24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39] in the adult BAL group, 14 [35,[40][41][42][43][44][45][46][47][48][49][50][51][52] in the adult ES group, 7 [35,45,50,[53][54][55][56] in the adult IS group, 2 [57,58] in the pediatric ES group, 6 [57,[59][60][61][62][63] in the pediatric GA group, and 9 [59,[64][65][66][67]…”

Section: Studies' Characteristicsmentioning

confidence: 99%

Which sample type is better for Xpert MTB/RIF to diagnose adult and pediatric pulmonary tuberculosis?

et al. 2020

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Objective: This review aimed to identify proper respiratory-related sample types for adult and pediatric pulmonary tuberculosis (PTB), respectively, by comparing performance of Xpert MTB/RIF when using bronchoalveolar lavage (BAL), induced sputum (IS), expectorated sputum (ES), nasopharyngeal aspirates (NPA) and gastric aspiration (GA) as sample. Methods: Articles were searched in Web of Science, PubMed, and Ovid from inception up to June 29, 2020. Pooled sensitivity and specificity were calculated, each with a 95% confidence interval (CI). Quality assessment and heterogeneity evaluation across included studies were performed. Results: Fifteen articles were included. The respective sensitivity and specificity were 87% (95% CI: 0.84–0.89), 91% (95% CI: 0.90–0.92) and 95% (95% CI: 0.93–0.97) in the adult BAL group, 90% (95% CI: 0.88–0.91), 98% (95% CI: 0.97–0.98) and 97% (95% CI: 0.95–0.99) in the adult ES group, 86% (95% CI: 0.84–0.89) and 97% (95% CI: 0.96–0.98) in the adult IS group, 14% (95% CI: 0.10–0.19) and 99% (95% CI: 0.97–1.00) in the pediatric ES group, 80% (95% CI: 0.72–0.87) and 94% (95% CI: 0.92–0.95) in the pediatric GA group, 67% (95% CI: 0.62–0.72) and 99% (95% CI: 0.98–0.99) in the pediatric IS group, and 54% (95% CI: 0.43–0.64) and 99% (95% CI: 0.97–0.99) in the pediatric NPA group. The heterogeneity across included studies was deemed acceptable. Conclusion: Considering diagnostic accuracy, cost and sampling process, ES was a proper choice for adult PTB. GA might be more suitable than others for pediatric PTB. The actual choice of sample types should consider the needs of specific situations.

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Xpert MTB/RIF Ultra and Xpert MTB/RIF for diagnosis of tuberculosis in an HIV-endemic setting with a high burden of previous tuberculosis: a two-cohort diagnostic accuracy study

Cited by 68 publications

References 22 publications

Extract from used Xpert MTB/RIF Ultra cartridges is useful for accurate second-line drug-resistant tuberculosis diagnosis with minimal rpoB-amplicon cross-contamination risk

Extract from used Xpert MTB/RIF Ultra cartridges is useful for accurate second-line drug-resistant tuberculosis diagnosis with minimal rpoB-amplicon cross-contamination risk

Advances in Molecular Diagnosis of Tuberculosis

Which sample type is better for Xpert MTB/RIF to diagnose adult and pediatric pulmonary tuberculosis?

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