Diagnostic accuracy of Xpert ultra for childhood tuberculosis: A preliminary systematic review and meta‐analysis

Abstract

Diagnosis of childhood tuberculosis (TB) is challenging. Xpert MTB/RIF and the new version Xpert MTB/RIF Ultra (Ultra) are molecular tests currently used to rapidly identify the infection. We reviewed the literature for the accuracy of Ultra assay in the diagnosis of tuberculosis and rifampicin resistance in children. We conducted a full search in PubMed, Web of Science (WOS), Embase, and Scopus, up to April 2021. A bivariate random‐effects model was used to determine the pooled sensitivity and specificity of Ultra, with a 95% confidence interval (CI), compared with culturing and the composite reference standard (CRS). In the ten included studies (2,427 participants), the pooled Ultra sensitivity and specificity, in diagnosing pulmonary tuberculosis (PTB), were 78% (95% CI, 73–82) and 92% (95% CI, 91–94), respectively, against culture. Since a high heterogeneity was found between studies, we created subgroups based on different samples and ages. Ultra‐pooled sensitivity was consistently lower against CRS (95% CI, 35%, 32–38). Compared to Xpert MTB/RIF, Ultra sensitivity tended toward higher values (Ultra: 73%, 67%–78% vs. Xpert MTB/RIF: 66%, 60%–72%), but specificity was lower (Ultra: 95%, 94%–96% vs. Xpert MTB/RIF: 99%, 98%–99%). Ultra has improved the definitive diagnosis of PTB, particularly in subjects with paucibacillary TB, including children. The lower specificity could be due to the fact that culture is an imperfect reference standard. Further studies are needed to evaluate the accuracy of Ultra in the diagnosis of childhood TB.

Clinical Characteristics of Pulmonary Tuberculosis in Children Tested by Xpert MTB/RIF Ultra

“…4 The recently released Xpert Ultra cartridge was developed for increased sensitivity and should provide added value in children with paucibacillary TB. 17 As previously reported, 18 the Xpert Ultra showed a high sensitivity (84.9%) in patients with confirmed TB in the present study, which is consistent with the comparable LOD for liquid culture. However, the low positive rates of MTB culture (26.0%) and Xpert Ultra (31.0%) in all of the enrolled subjects with active TB in the present study suggested a low bacterial load in the samples of the children.…”

Evaluation of Xpert MTB/RIF Ultra for the Diagnosis of Extrapulmonary Tuberculosis: A Retrospective Analysis in Saudi Arabia

“…Another study by Signorino et al . suggested that the reason for the low specificity of the Xpert Ultra may be attributed to the unsatisfactory quality of the culture method, as a reference test, and needs further investigation [ 47 ]. Donovan et al .…”

Recent advances in microbiological and molecular biological detection techniques of tuberculous meningitis

“…Recent research has shown that Xpert Ultra is a potential gamechanger with more advantages than Xpert in TBM diagnosis. Xpert Ultra has increased sensitivity (including accuracy of RIF resistance testing), and detection of MTB in smear-negative, paucibacillary, paediatric, CSF, and other specimens of extrapulmonary TB ( Kaswala et al, 2022 ; Signorino et al, 2022 ; Sun et al, 2022 ). In 2017, WHO recommended the use of Xpert Ultra to replace Xpert in diagnosing TBM ( Bahr et al, 2018 ; Rindi, 2022 ).…”