Performance of Xpert MTB/RIF Ultra for tuberculosis diagnosis in the context of passive and active case finding

Saavedra, Belén; Mambuque, Edson; Nguenha, Dinis; Gomes, Neide; Munguane, Shilzia; García, Juan Ignacio García; Izco, Santiago; Acácio, Sozinho; Murias-Closas, Adrià; Cossa, Marta; Losada, Irene; Pernas, Hadrián; Oliveras, Laura; Theron, Grant; García‐Basteiro, Alberto L.

doi:10.1183/13993003.00257-2021

Cited by 12 publications

(11 citation statements)

References 23 publications

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“…While ultra-sensitive tests are still needed to detect early disease (especially in the context of active case finding), 36 , 82 as tests slowly increase in sensitivity, diagnostic accuracy assessments may be compromised by reference standard limitations, especially as bacteriological tests like liquid culture are often only applied to sputum. 83 Thus, positive results from highly sensitive tests could be classified as false positives, representing potentially missed treatment opportunities. This false-positivity issue may be of less concern for tests that use antigens or DNA rather than host biosignatures such as mRNA, however, challenges remain: for example, sputum Ultra trace semi-quantitation results are often culture-negative, especially in settings where patients have high rates of previous TB or a where there is a high background intensity of TB transmissiont.…”

Section: Overview Of Diagnostic Technologies and Tests By Specimen Typementioning

confidence: 99%

Reimagining the status quo: How close are we to rapid sputum-free tuberculosis diagnostics for all?

et al. 2022

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Section: Overview Of Diagnostic Technologies and Tests By Specimen Typementioning

confidence: 99%

Reimagining the status quo: How close are we to rapid sputum-free tuberculosis diagnostics for all?

et al. 2022

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“…Xpert MTB/RIF (Xpert) and its successor Ultra revolutionized diagnosis (Ultra has 88% sensitivity and 96% specificity) [ 74 ]. Small improvements in the performance (and POC suitability) of sputum-based diagnostic technologies continue [ 75 , 76 , 77 , 78 ]. For example, GeneXpert Edge is a portable battery-powered solution operated by a tablet able to do Ultra onsite in difficult-to-reach populations [ 79 ].…”

Section: Confirmatory Toolsmentioning

confidence: 99%

Diagnosing Tuberculosis: What Do New Technologies Allow Us to (Not) Do?

Abdulgader¹,

Ojo-Okunola²,

Ndlangalavu³

et al. 2022

Respiration

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New tuberculosis (TB) diagnostics are at a crossroads: their development, evaluation, and implementation is severely damaged by resource diversion due to COVID-19. Yet several technologies, especially those with potential for non-invasive non-sputum-based testing, hold promise for efficiently triaging and rapidly confirming TB near point-of-care. Such tests are, however, progressing through the pipeline slowly and will take years to reach patients and health workers. Compellingly, such tests will create new opportunities for difficult-to-diagnose populations, including primary care attendees (all-comers in high burden settings irrespective of reason for presentation) and community members (with early stage disease or risk factors like HIV), many of whom cannot easily produce sputum. Critically, all upcoming technologies have limitations that implementers and health workers need to be cognizant of to ensure optimal deployment without undermining confidence in a technology that still offers improvements over the status quo. In this state-of-the-art review, we critically appraise such technologies for active pulmonary TB diagnosis. We highlight strengths, limitations, outstanding research questions, and how current and future tests could be used in the presence of these limitations and uncertainties. Among triage tests, CRP (for which commercial near point-of-care devices exist) and computer-aided detection software with digital chest X-ray hold promise, together with late-stage blood-based assays that detect host and/or microbial biomarkers; however, aside from a handful of prototypes, the latter category has a shortage of promising late-stage alternatives. Furthermore, positive results from new triage tests may have utility in people without TB; however, their utility for informing diagnostic pathways for other diseases is under-researched (most sick people tested for TB do not have TB). For confirmatory tests, few true point-of-care options will be available soon; however, combining novel approaches like tongue swabs with established tests like Ultra have short-term promise but first require optimizations to specimen collection and processing procedures. Concerningly, no technologies yet have compelling evidence of meeting the World Health Organization optimal target product profile performance criteria, especially for important operational criteria crucial for field deployment. This is alarming as the target product profile criteria are themselves almost a decade old and require urgent revision, especially to cater for technologies made prominent by the COVID-19 diagnostic response (e.g., at-home testing and connectivity solutions). Throughout the review, we underscore the importance of how target populations and settings affect test performance and how the criteria by which these tests should be judged vary by use case, including in active case finding. Lastly, we advocate for health workers and researchers to themselves be vocal proponents of the uptake of both new tests and those – already available tests that remain suboptimally utilized.

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“…Up to three attempts (visits) were made within 90 days of IC enrolment in order to recruit identified contacts. After providing informed consent, contacts were systematically screened following a 3-step approach: 1) HIV status verification: All participants with unknown or negative HIV status were offered HIV testing; 2) TB symptom screening (22) (cough, hemoptysis, fever, weight loss and night sweats); and 3) sputum collection for microbiological testing for HIV negative participants who reported TB symptoms and HIV positive participants irrespective of symptoms (Figure 1). If participants were not able to provide spontaneous sputum, field sputum inductions were performed using portable nebulizers.…”

Section: Methodsmentioning

confidence: 99%

“…During the study period, the novel Xpert MTB/RIF Ultra assay (Cepheid, Sunnyvale, CA, USA, hereinafter Xpert Ultra) was used as the frontline test for active TB diagnosis in the entire district, as it has been described elsewhere (22). New and relapse TB patients who started treatment from January 1st to December 31st of 2018 in Manhiça district were invited to participate in this study.…”

Section: Xpatial Strategymentioning

confidence: 99%

“…Following our predefined algorithm, ICs with low, medium or high Xpert Ultra results, generated both household (HCs) and community contacts (CCs). Those ICs with a very low, trace or negative result, only generated HCs (based on studies relating infectiveness and bacillary burden 21,22). The area around which neighboring contacts were screened depended on predefined radii from the ICs' household.…”

Section: Xpatial Strategymentioning

confidence: 99%

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Improving case detection through TB contact risk stratification by Xpert MTB/RIF Ultra and spatial parameters. Evaluation of an innovative ACF strategy in Mozambique

Saavedra

Nguenha

Torre-Perez

et al. 2022

Preprint

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Prompt diagnosis is critical for tuberculosis (TB) control, as it enables early treatment which in turn, reduces transmission and improves treatment outcomes. We aimed to determine the impact of the scale-up of Xpert Ultra as frontline test for TB diagnosis, and an innovative active-case finding (ACF) strategy (based on Xpert Ultra semi quantitative results and spatial parameters) on new TB cases diagnosed in a semi-rural district of Southern Mozambique. From January-December 2018 we recruited all incident TB-cases (index cases, ICs) and their household contacts (HCs). Community contacts (CCs) recruitment depended on the semi-quantitative results of Xpert Ultra of the IC and the population density of the area where the IC lived in. TB-contacts, either symptomatic or people living with HIV (regardless of symptoms), were asked for providing a spot sputum for lab-testing. Trends on TB case notification in the intervention area were compared to the previous years and to those of two districts in the south of the Maputo province (control area) using an interrupted time series analysis with and without control (CITS/ITS). A total of 1010 TB ICs (37.2% laboratory-confirmed) were recruited; 3165 HC and 4730 CC were screened for TB. Eighty-nine additional TB cases were identified through the ACF intervention (52.8% laboratory-confirmed). The ACF intervention increased by 8.2% all forms of TB cases detected in 2018. CITS model showed an increase of laboratory confirmed TB cases in the intervention district, compared to the control area. Xpert Ultra trace positive results accounted for a high proportion of laboratory confirmations in the ACF cohort (51.1% vs 13.7% of those passively diagnosed). Number needed to screen (NNS) to find a TB case differed widely among HCs (NNS:55) and CCs (153). The intervention resulted in an overall increase in TB diagnoses and higher proportion of laboratory confirmation.

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Performance of Xpert MTB/RIF Ultra for tuberculosis diagnosis in the context of passive and active case finding

Cited by 12 publications

References 23 publications

Reimagining the status quo: How close are we to rapid sputum-free tuberculosis diagnostics for all?

Reimagining the status quo: How close are we to rapid sputum-free tuberculosis diagnostics for all?

Diagnosing Tuberculosis: What Do New Technologies Allow Us to (Not) Do?

Improving case detection through TB contact risk stratification by Xpert MTB/RIF Ultra and spatial parameters. Evaluation of an innovative ACF strategy in Mozambique

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