Impact of the diagnostic test Xpert MTB/RIF on patient outcomes for tuberculosis

Abstract

Background The World Health Organization (WHO) recommends Xpert MTB/RIF in place of smear microscopy to diagnose tuberculosis (TB), and many countries have adopted it into their diagnostic algorithms. However, it is not clear whether the greater accuracy of the test translates into improved health outcomes. Objectives To assess the impact of Xpert MTB/RIF on patient outcomes in people being investigated for tuberculosis. Search methods We searched the following databases, without language restriction, from 2007 to 24 July 2020: Cochrane Infectious Disease Group (CIDG) Specialized Register; CENTRAL; MEDLINE OVID; Embase OVID; CINAHL EBSCO; LILACS BIREME; Science Citation Index Expanded (Web of Science), Social Sciences citation index (Web of Science), and Conference Proceedings Citation Index ‐ Social Science & Humanities (Web of Science). We also searched the WHO International Clinical Trials Registry Platform, ClinicalTrials.gov, and the Pan African Clinical Trials Registry for ongoing trials. Selection criteria We included individual‐ and cluster‐randomized trials, and before‐after studies, in participants being investigated for tuberculosis. We analysed the randomized and non‐randomized studies separately. Data collection and analysis For each study, two review authors independently extracted data, using a piloted data extraction tool. We assessed the risk of bias using Cochrane and Effective Practice and Organisation of Care (EPOC) tools. We used random effects meta‐analysis to allow for heterogeneity between studies in setting and design. The certainty of the evidence in the randomized trials was assessed by GRADE. Main results We included 12 studies: eight were randomized controlled trials (RCTs), and four were before‐and‐after studies. Most included RCTs had a low risk of bias in most domains of the Cochrane 'Risk of bias' tool. There was inconclusive evidence of an effect of Xpert MTB/RIF on all‐cause mortality, both overall (risk ratio (RR) 0.89, 95% confidence interval (CI) 0.75 to 1.05; 5 RCTs, 9932 participants, moderate‐certainty evidence), and restricted to studies with six‐month follow‐up (RR 0.98, 95% CI 0.78 to 1.22; 3 RCTs, 8143 participants; moderate‐certainty evidence). There was probably a reduction in mortality in participants known to be infected with HIV (odds ratio (OR) 0.80, 95% CI 0.67 to 0.96; 5 RCTs, 5855 participants; moderate‐certainty evidence). It is uncertain whether Xpert MTB/RIF has no or a modest effect on the proportion of participants starting tuberculosis treatment who had a successful treatment outcome (OR) 1.10, 95% CI 0.96 to 1.26; 3RCTs, 4802 participants; moderate‐certainty evidence). There was also inconclusive evidence of an effect on the proportion of participants who were treated for tuberculosis (RR 1.10, 95% CI 0.98 to 1.23; 5 RCTs, 8793 partic...

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

“…Systematic reviews evaluating the effect of Xpert MTB/RIF and LAM on patient-important outcomes like mortality demonstrate the challenges of moving from diagnostic test accuracy assessment to proving impact. 53 , 86 Careful evaluation of intended and actual test placement and use within the wider TB care cascade is needed to understand potential implementation barriers, 87 , 88 such as gaps in linkage and engagement with care. The global roll-out of Xpert MTB/RIF has provided key lessons for policy makers and program implementers, 89 which include recognising that high costs and unfulfilled quality assurance and maintenance needs in chronically underfunded programmes will continue to result in underutilisation.…”

GeneXpert rollout in three high-burden tuberculosis countries in Africa: A review of pulmonary tuberculosis diagnosis and outcomes from 2001 to 2019

“…Xpert performance in other tuberculosis high-burden countries reflects similar trends for case detection and treatment success. 15 , 36 …”

Addressing TB-related mortality in adults living with HIV: a review of the challenges and potential solutions

“…A recent Cochrane Review from 2021 analyzing data from five RCTs with 9932 participants judged to represent moderate-certainty evidence reported that it was not possible to determine the impact of the use of Xpert MTB/RIF compared with smear microscopy on all-cause mortality (RR: 0.9, 95% CI: 0.8–1.1). 61 They did, however, report that there was probably a reduction in mortality in PLHIV (OR: 0.8, 95% CI: 0.67–0.96), which emphasizes the importance of access to Xpert and other mWRDs in PLHIV being evaluated for TB. 61 Given the increased sensitivity of Xpert Ultra, including on CSF samples, wider scale-up of Xpert Ultra can facilitate TB diagnosis in PLHIV.…”

“… 61 They did, however, report that there was probably a reduction in mortality in PLHIV (OR: 0.8, 95% CI: 0.67–0.96), which emphasizes the importance of access to Xpert and other mWRDs in PLHIV being evaluated for TB. 61 Given the increased sensitivity of Xpert Ultra, including on CSF samples, wider scale-up of Xpert Ultra can facilitate TB diagnosis in PLHIV. 41 …”