Incremental Yield of Xpert MTB/RIF Ultra over Xpert MTB/RIF in the diagnosis of extra-pulmonary tuberculosis

Abstract

Introduction: The next-generation Xpert MTB/RIF Ultra(Ultra) was introduced recently and has proven to have higher yield than Xpert MTB/RIF(Xpert) in the diagnosis of pulmonary tuberculosis(PTB). However, there is paucity of data on the yield of Ultra in the diagnosis of extra-pulmonary tuberculosis(EPTB) especially from high prevalence countries. Materials and Methods: The primary objective is to determine the performance characteristics such as sensitivity, specificity, and predictive values of Ultra and Xpert in the diagnosis of EPTB. The yield of Ultra and Xpert were compared against MGIT culture and against composite reference standard(CRS). CRS is defined as either culture positive for mycobacterium tuberculosis or histopathology showing granulomatous inflammation suggestive of TB with clinical decision to start anti-TB treatment(ATT). Results: We tested 250 samples from suspected EPTB patients with Ultra, Xpert, MGIT culture, Histopathology & other tests as required. There were 123(49%)lymph nodes, 44(17.6%)pleural biopsies, 80(32%)pleural fluid and others. The sensitivity of Ultra and Xpert were 72.1%(CI 56,85) and 51.2%(CI 36,67) against MGIT culture positivity and 45.5%(CI 35,56) and 25.3%(CI 17,35) against CRS respectively. The specificity of Ultra and Xpert were 87.8%(CI 83,92) and 95.1%(CI 36,67) against MGIT culture positivity and 98.2%(CI 94,99.8) and 99.1%(CI 95,100) against CRS. Conclusions: Ultra has higher sensitivity in diagnosis of EPTB as compared to Xpert. The specificity is maintained when diagnosis of EPTB is based on CRS. The study confirms that replacement of Xpert with Ultra would improve diagnostic confirmation of EPTB, without much loss of specificity.