The Value of Lateral Flow Urine Lipoarabinomannan Assay and Empirical Treatment in the Xpert MTB/RIF Ultra Era: a Prospective Cohort Study

Abstract Introduction: The value of Lateral Flow urine Lipoarabinomannan (LF-LAM) assay and the role of empiric tuberculosis (TB) treatment in the era of the highly sensitive Xpert MTB/RIF Ultra (Xpert Ultra) assay is unclear. This study aimed to assess the additional yield of Xpert Ultra compared to Xpert MTB/RIF, the yield of LF-LAM assay when used in combination with Xpert Ultra, and the role of empiric TB treatment in the Xpert Ultra era among patients with symptoms of TB admitted to a tertiary hospital in Ethiopia. Methods: We performed a secondary analysis of a cohort of hospitalized Xpert MTB/RIF-negative patients. Sputum samples were examined for Mycobacterium tuberculosis by culture and Xpert Ultra. In HIV positive and severely ill patients, a urine sample was collected for the LF-LAM assay. Treatment outcome was assessed six months after enrollment. Logistic regression was used to identify factors predictive of deaths among Xpert Ultra negative patients. Results: Of the 250 hospitalized Xpert MTB/RIF-negative patients, 35 (14.0%) had culture-confirmed TB. The Xpert Ultra assay diagnosed 31 of the 35 culture positive cases that had been missed by Xpert MTB/RIF. The LF-LAM assay did not identify any case that was not detected by Xpert Ultra. Empiric treatment did not improve survival among Xpert Ultra negative patients (OR 1.28, 95% CI: 0.3-5.3). Low body mass index (< 18.5kg/m2) was the only significant predictor of death in Xpert Ultra negative patients (OR 4.0, 95% CI: 1.12-16.5).Conclusions: In this prospective cohort, we observed that LF-LAM did not improve the diagnostic yield when used in combination with Xpert Ultra and did not find a survival benefit of empiric treatment among Xpert Ultra negative individuals. Research is needed to determine the optimal management of patients with presumptive TB and a negative Xpert Ultra assay in high TB burden settings.