Cochrane Database of Systematic Reviews Data collection and analysis Two review authors independently extracted data, assessed risk of bias and applicability using the QUADAS-2 tool. We determined pooled predicted sensitivity and specificity for TB, grouped by type of extrapulmonary specimen, and for rifampicin resistance. For TB detection, we used a bivariate random-e ects model. Recognizing that use of culture may lead to misclassification of cases of extrapulmonary TB as 'not TB' owing to the paucibacillary nature of the disease, we adjusted accuracy estimates by applying a latent class meta-analysis model. For rifampicin resistance detection, we performed univariate meta-analyses for sensitivity and specificity separately to include studies in which no rifampicin resistance was detected. We used theoretical populations with an assumed prevalence to provide illustrative numbers of patients with false positive and false negative results. Main results We included 66 unique studies that evaluated 16,213 specimens for detection of extrapulmonary TB and rifampicin resistance. We identified only one study that evaluated the newest test version, Xpert MTB/RIF Ultra (Ultra), for TB meningitis. Fi y studies (76%) took place in low-or middle-income countries. Risk of bias was low for patient selection, index test, and flow and timing domains and was high or unclear for the reference standard domain (most of these studies decontaminated sterile specimens before culture inoculation). Regarding applicability, in the patient selection domain, we scored high or unclear concern for most studies because either patients were evaluated exclusively as inpatients at tertiary care centres, or we were not sure about the clinical settings. Authors' conclusions In people presumed to have extrapulmonary TB, Xpert may be helpful in confirming the diagnosis. Xpert sensitivity varies across di erent extrapulmonary specimens, while for most specimens, specificity is high, the test rarely yielding a positive result for people without TB Xpert ® MTB/RIF assay for extrapulmonary tuberculosis and rifampicin resistance (Review)

1 47% of the global population has little to no access to diagnostics. 2 Diagnostics are central and fundamental to quality health care. This notion is underrecognised, leading to underfunding and inadequate resources at all levels. 3 The level of primary health care is the diagnostic so-called last mile and particularly affects poor, rural, and marginalised communities globally; appropriate access is essential for equity and social justice. 4 The COVID-19 pandemic has emphasised the crucial role of diagnostics in health care and that without access to diagnostics, delivery of universal health coverage, antimicrobial resistance mitigation, and pandemic preparedness cannot be achieved. 5 Innovations within the past 15 years in many areas (eg, in financing, technology, and workforce) can reduce the diagnostic gap, improve access, and democratise diagnostics to empower patients. 6 As an example of the potential impact, 1•1 million premature deaths in low-income and middle-income countries could be avoided annually by reducing the diagnostic gap for six priority conditions: diabetes, hypertension, HIV, and tuberculosis in the overall population, and hepatitis B virus infection and syphilis for pregnant women. 7 The economic case for such investment is strong. The median benefit-cost exceeds one for five of the six priority conditions in middle-income countries, and exceeds one for four of the six priority conditions in low-income countries, with a range of 1•4:1 to 24:1.Given the depth and breadth of the problems, sustained access to quality, affordable diagnostics will require multi-decade prioritisation, commitment, and investment.Incorporating diagnostics into universal health coverage packages will begin this process.

Background Xpert 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 ( ). Since the previous review, new studies have been published. We performed a review update for an upcoming WHO policy review. Objectives To 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 methods We 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 criteria Randomized 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 MTBDR plus for rifampicin resistance. Data collection and analysis Four 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 results We 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 detection Of 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 ...

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