Abstract:Xpert CT values and smear status were strongly associated. However, diagnostic accuracy at set cut-off CT values of 27.7 or 31.8 would not replace smear microscopy. How CT values compare with smear microscopy in predicting infectiousness remains to be seen.
“…These are also presented according to different CT cut-offs between 25 and 30 in Table 5 and Supplementary Table S4 . Cut-offs of 31.8 and 27.7 (sensitivity of 95%, specificity of 35% and sensitivity 85%, specificity 67%) identified by the recent meta-analysis of C T predictors of smear positivity 20 , resulted in sensitivity of 98.8%, specificity 22.0% with a cut-off of 31.8 and sensitivity of 94.2% and specificity of 58.3% in this study. Figure 2 ROC curve analysis showing sensitivity for differing mean cycle threshold (C T ) – (average of positive Xpert MTB/RIF probes) values as a test for smear positivity.…”
Section: Resultssupporting
confidence: 48%
“…demonstrated that the correlation of TTP and C T is less strong among HIV positive individuals comparted to HIV negative individuals 18 . A recent meta-analysis identified cut-of C T values of 27.7 and 31.8 to predict smear positivity with 85% and 95% sensitivity respectively 20 .…”
Traditionally, smear microscopy has been used as a point-of-care measure of bacillary burden in tuberculosis patients to inform infection control and contact tracing. Xpert MTB/RIF has the potential to replace smear. However, data to support the use of its quantitative output [cycle threshold (CT)] as an alternate point-of-care measure of bacillary burden are limited. This study assessed the correlation (Spearman’s) between CT, smear, culture time-to-positivity (TTP), and clinical factors in patients with Xpert-positive sputum from Mozambique (n = 238) and South Africa (n = 462). Mean CT and smear grade correlated well (ρ0.72); compared to TTP and smear (ρ0.61); and mean CT and TTP (ρ0.50). In multivariate analyses, lower CT (higher bacillary load) was associated with negative HIV serostatus and low BMI. A smear positivity rule-out (95% sensitivity) CT cut-off of 28.0 was identified, with 54.1% specificity, 2.07 positive likelihood ratio, 0.09 negative likelihood ratio and 79.0% correctly classified. Cut-offs were higher for HIV positive compared to HIV negative individuals for any set sensitivity level. This study suggests Xpert CT values correlate well with smear, both in HIV positive and negative individuals, and that CT cut-offs might be broadly applicable to multiple settings. Studies to directly assess the association of CT with infectiousness are needed.
“…These are also presented according to different CT cut-offs between 25 and 30 in Table 5 and Supplementary Table S4 . Cut-offs of 31.8 and 27.7 (sensitivity of 95%, specificity of 35% and sensitivity 85%, specificity 67%) identified by the recent meta-analysis of C T predictors of smear positivity 20 , resulted in sensitivity of 98.8%, specificity 22.0% with a cut-off of 31.8 and sensitivity of 94.2% and specificity of 58.3% in this study. Figure 2 ROC curve analysis showing sensitivity for differing mean cycle threshold (C T ) – (average of positive Xpert MTB/RIF probes) values as a test for smear positivity.…”
Section: Resultssupporting
confidence: 48%
“…demonstrated that the correlation of TTP and C T is less strong among HIV positive individuals comparted to HIV negative individuals 18 . A recent meta-analysis identified cut-of C T values of 27.7 and 31.8 to predict smear positivity with 85% and 95% sensitivity respectively 20 .…”
Traditionally, smear microscopy has been used as a point-of-care measure of bacillary burden in tuberculosis patients to inform infection control and contact tracing. Xpert MTB/RIF has the potential to replace smear. However, data to support the use of its quantitative output [cycle threshold (CT)] as an alternate point-of-care measure of bacillary burden are limited. This study assessed the correlation (Spearman’s) between CT, smear, culture time-to-positivity (TTP), and clinical factors in patients with Xpert-positive sputum from Mozambique (n = 238) and South Africa (n = 462). Mean CT and smear grade correlated well (ρ0.72); compared to TTP and smear (ρ0.61); and mean CT and TTP (ρ0.50). In multivariate analyses, lower CT (higher bacillary load) was associated with negative HIV serostatus and low BMI. A smear positivity rule-out (95% sensitivity) CT cut-off of 28.0 was identified, with 54.1% specificity, 2.07 positive likelihood ratio, 0.09 negative likelihood ratio and 79.0% correctly classified. Cut-offs were higher for HIV positive compared to HIV negative individuals for any set sensitivity level. This study suggests Xpert CT values correlate well with smear, both in HIV positive and negative individuals, and that CT cut-offs might be broadly applicable to multiple settings. Studies to directly assess the association of CT with infectiousness are needed.
“…Several publications have reported on the correlation between the semi-quantitative results of Xpert and smear microscopy [35]. This positive correlation made Xpert semi-quantitative results useful to estimate patients' infectious potential and to guide airborne isolation strategies when integrated with other clinical features in smear independent algorithms [36e38] (Fig.…”
Section: Correlation Between the Semi-quantitative Results Of Ultra Anmentioning
“…The cycle threshold value (C T ) is the number of PCR cycles after which Xpert MTB/RIF probes successfully detect M tuberculosis DNA in a given sample. Xpert MTB/RIF C T values are strongly correlated with AFB smear status ( Lange 2017 ). The lower sensitivity of Xpert MTB/RIF in individuals with AFB smear‐negative PTB is related to the lower bacillary burden and higher associated C T value compared to individuals with AFB smear‐positive PTB.…”
Section: Discussionmentioning
confidence: 99%
“…The lower sensitivity of Xpert MTB/RIF in individuals with AFB smear‐negative PTB is related to the lower bacillary burden and higher associated C T value compared to individuals with AFB smear‐positive PTB. Individuals with PTB and HIV co‐infection are more likely to have smear‐negative tuberculosis, which implies a lower bacillary burden and higher mean C T values on Xpert testing ( Beynon 2018 ; Lange 2017 ), and this is the likely mechanism for the lower sensitivity of Xpert MTB/RIF for the diagnosis of tuberculosis in people living with HIV.…”
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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