Accuracy of Xpert Ultra in the diagnosis of pulmonary tuberculosis among children in Uganda: a sub-study from the SHINE trial.

Background: Childhood tuberculosis presents significant diagnostic challenges associated with paucibacillary disease, and requires a more sensitive test. We evaluated the diagnostic accuracy of XpertMTB/Rif Ultra (Ultra) compared to other microbiological tests using respiratory samples from Ugandan children in the SHINE trial.Design/Methods: SHINE is a randomized trial evaluating shorter treatment in 1204 children with minimal TB disease in Africa/India. Among 352 samples and one cervical lymph node fine needle aspirate, one sample was randomly selected per patient and tested with Xpert MTB/Rif (Xpert), Lowenstein Jensen (LJ) and liquid (MGIT) cultures. We selected only uncontaminated stored sample pellet for Ultra testing. We estimated sensitivity of Xpert and Ultra against culture and a composite microbiological reference standard (any positive result).Results: Of 398 children, 353 (89%) had culture, Xpert and Ultra results. Median age was 2.8-years (IQR 1.3-5.3); 8.5% (30/353) HIV-infected, 54.4% (192/353) male. 31/353 (9%) were positive by LJ and/or MGIT; 36 (10%) by Ultra and 16 (5%) by Xpert. Sensitivities were (%; 95% CI), 58% (39-65% (18/31)) for Ultra and 45% (27-64% (14/31)) for Xpert against any culture-positive, with false-positives of <1% and 5.5% for Xpert and Ultra. Against a composite microbiological reference, sensitives were 72% (58-84% (36/50) for Ultra, and 32% (20-47% (16/50)) for Xpert. However, there were 17 samples that are positive only on Ultra (majority trace).Conclusions: Among children screened for minimal TB in Uganda, Ultra has higher sensitivity than Xpert. This represents an important advance for a condition which has posed a diagnostic challenge for decades.