Performance of Xpert MTB/RIF, Xpert Ultra, and Abbott RealTi m e MTB for Diagnosis of Pulmonary Tuberculosis in a High-HIV-Burden Setting

Abstract

More sensitive tests are needed for the diagnosis of smear-negative and HIV-associated tuberculosis. This study compares the sensitivities and specificities of three molecular tests, namely, the Xpert MTB/RIF test, the Xpert Ultra (Ultra), and RealTime MTB (RT-MTB), in a high HIV prevalence setting. Symptomatic adults were recruited from three outpatient sites, and each provided 4 sputum specimens. The diagnostic performance of Xpert MTB/RIF, Ultra, and RT-MTB was evaluated, with culture as a reference standard. HIV infection occurred in 62% of patients, with a median CD4 count of 220 cells/l. The Ultra test had the highest sensitivity of 89.3% (95% confidence interval [CI], 78.1 to 96) compared to those of the Xpert MTB/RIF at 82.1% (95% CI, 69.6 to 91.1; P ϭ 0.12) and RT-MTB at 78.6% (95% CI, 65.6 to 88.4; P ϭ 0.68). The specificity was highest with the Xpert MTB/RIF at 100% (95% CI, 98 to 100), followed by RealTime MTB at 96.7% (95% CI, 92.9 to 98.8; P ϭ 0.03) and the Ultra at 95.6% (95% CI, 91.5 to 98.1; P ϭ 0.08). In patients with smear-negative disease, the Ultra was more sensitive than the Xpert MTB/RIF (64.7% [95% CI, 38.3 to 85.8] versus 41.2% [95% CI, 18.4 to 67.1], respectively; P ϭ 0.12), and RT-MTB performed equally to Xpert MTB/RIF. In a comparison of the Ultra and RT-MTB on the same sputum specimen pellets, the Ultra was more sensitive than RT-MTB in the overall cohort (88.9% [95% CI, 77.4 to 95.8] versus 77.8% [95% CI, 64.4 to 88], respectively; P ϭ 0.03) and among people with HIV (87.5% [95% CI, 71 to 96.5] versus 68.6% [95% CI, 50 to 83.9], respectively; P ϭ 0.03). Although these results did not reach statistical significance, they suggest that the Ultra is more sensitive than the Xpert MTB/RIF and RT-MTB, most prominently in smear-negative disease. This was accompanied by a loss of specificity.

The rapid molecular test Xpert MTB/RIF ultra: towards improved tuberculosis diagnosis and rifampicin resistance detection

“…1) [13]. Similar results have been obtained in a high-HIV-burden setting reporting a gain in sensitivity for Ultra of þ11.7% in adult HIV patients whereas no gain was observed in HIV-negative patients [19].…”

“…For instance, Berhanu and colleagues compared the performance of Ultra with the Real-Time MTB assay (RT-MTB) (Abbott, Des Plaines, USA) [43]. Sensitivity of Ultra and RT-MTB on the same specimens were 88.9% and 77.8%, respectively [19]; in contrast, Xpert and RT-MTB displayed similar performances [44]. It would be beneficial to have more studies that compare the performance of Xpert and Ultra with the other tests that target the same DNA sequences, in particular for the diagnosis of extrapulmonary tuberculosis.…”

Xpert MTB/RIF and Xpert MTB/RIF Ultra for pulmonary tuberculosis and rifampicin resistance in adults

“…On 11 October 2018, we performed a literature search specifically for studies that evaluated Xpert Ultra, but did not identify any additional studies. Following this search and after the end date for data analysis, we identified one additional study ( Berhanu 2018 ). Although not included in the main sections of this review, we provide a brief summary of this study here.…”

“…Although not included in the main sections of this review, we provide a brief summary of this study here. Berhanu 2018 compared Xpert MTB/RIF and Xpert Ultra in 237 participants with presumptive tuberculosis who were evaluated at three outpatient clinics in South Africa. Similar to the results in Dorman 2018 , this multicentre study found that Xpert Ultra yielded higher sensitivity at 89% (78% to 96%), compared to Xpert MTB/RIF sensitivity of 82% (70% to 91%), but lower specificity at 96% (92% to 98%) compared to Xpert MTB/RIF specificity of 100% (98% to 100%).…”

Potential of host serum protein biosignatures in the diagnosis of tuberculous meningitis in children

“…GeneXpert Ultra (the next generation assay) has been shown to overcome some of the shortcomings of GeneXpert MTB/RIF as it showed improved sensitivity of 95% and negative predictive value of 99% in a more recent study on HIV positive adults with TBM (16). However, concerns over lowered specificity and positive predictive value compared to GeneXpert MTB/RIF need to be allayed by prospective testing in a large population including children and those that are HIV-uninfected (16,18,19). The main common limitation to the above-described tests is the difficulty in obtaining the diagnostic sample (CSF) due to the need for more invasive sampling methods and low yields of mycobacteria obtained from childhood CSF samples, as a result of the paucibacillary nature of the disease.…”