Comparison of Xpert MTB/RIF (G4) and Xpert Ultra, including trace readouts, for the diagnosis of pulmonary tuberculosis in a TB and HIV endemic setting

Abstract

Background: There are limited data about Xpert-Ultra performance in different settings, in HIV-infected persons, in those with a history of previous TB, and with trace readouts. Methods: We evaluated the relative accuracy of Xpert-MTB/RIF and Xpert-Ultra in 272 selected but wellcharacterized archived sputum samples. Of these, 168 were culture-positive (64/168 smear-positive and 104/168 smear-negative), and 104 were culture-negative (102/104 from patients with previous TB and 2/ 104 from patients without a TB history). Assay-specific limit-of-detection (LOD) experiments were conducted using serial dilutions of Mycobacterium tuberculosis H37Rv. Results: Overall sensitivity (95%CI) in smear-negative culture-positive samples for Xpert-MTB/RIF and Xpert-Ultra were 71.2% (62.5-79.9) and 77% (68.9-85.1), respectively (and in HIV-infected persons: 63.5% (50-76.1) and 73.1% (61.1-85.2), respectively). The LOD for Xpert-Ultra was lower (9 versus 184 CFU/ml). There were a total of 9/272 (3.3%) Xpert Ultra trace readouts (6/104 [5.8%]) in smear-negative culturepositive persons, and 3/102 (3%) in culture-negative non-TB persons with a history of previous TB). Conclusions: Xpert-Ultra had a lower LOD compared to Xpert-MTB/RIF. A small proportion of samples (<5%) from culture-negative patients but with a history of previous TB had a likely false-positive trace readout. These data inform the management of patients with suspected TB in endemic settings.

The transition to Xpert MTB/RIF ultra: diagnostic accuracy for pulmonary tuberculosis in Kampala, Uganda

“…Among HIV-positive patients, we also found a similar Ultra sensitivity to other studies in HIV-endemic settings that found an 87-90% sensitivity without significant difference compared to HIV-negative patients [3,13]. Some studies have found that a previous history of TB reduced Ultra specificity [3,14,15], whereas we did not perhaps because we excluded patients who had TB in the past 1 year. The role of hospitalization has not been previously evaluated and we did not find a significant difference in inpatients vs. outpatients.…”

Lymphocyte Non-Specific Function Detection Facilitating the Stratification of Mycobacterium tuberculosis Infection

“…Nevertheless, each approach has additional limitations, such as the poor sensitivity of microscopy, time-consuming of culture, the high cost of molecular tests (5). Even in the era of the GeneXpert MTB/RIF Ultra, challenge remains due to unsatisfactory sensitivity for clinical requirement (6,7), which highlights the fact that better diagnostics might have to be achieved based on host factors rather than pathogen detection. However, the current use of blood-based available immunological tests including T-SPOT.TB (T-SPOT) and QuantiFERON-TB Gold In-Tube (QFT-GIT) was limited by their poor ability to reliably stratify ATB from LTBI especially in TB endemic areas (8,9).…”

HIV-associated tuberculosis

“…65 Xpert Ultra incorporated a semiquantitative "trace" category to identify paucibacillary TB, which is more common in HIV-positive individuals. 66 The WHO recommends that "trace results" should be interpreted as true positive in people living with HIV. 65 According to a UNAIDS survey in 2020, WHOrecommended rapid tests for TB were available in most facilities providing HIV testing and care in 12 out of 30 high TB/HIV burden countries.…”

“…65 Xpert Ultra incorporated a semiquantitative “trace” category to identify paucibacillary TB, which is more common in HIV-positive individuals. 66 The WHO recommends that “trace results” should be interpreted as true positive in people living with HIV. 65…”