Accuracy of lipoarabinomannan and xpert MTB/RIF testing in cerebrospinal fluid to diagnose tuberculous meningitis in an autopsy cohort of HIV-infected adults

Abstract

Point-of-care tests for tuberculous meningitis (TBM) are needed. We studied the diagnostic accuracy of the lipoarabinomannan (LAM) lateral flow assay (LFA), LAM enzyme-linked immunosorbent assay (ELISA), and Xpert MTB/RIF in cerebrospinal fluid (CSF) in an autopsy cohort of Ugandan HIV-infected adults. We obtained written informed consent postmortem from the next of kin. A complete autopsy was done and CSF obtained. We performed LAM LFA (on unprepared and supernatant CSF after heating and spinning), LAM ELISA, and Xpert MTB/RIF on the CSF samples. Accuracy parameters were calculated for histopathological TBM and also for the composite standard, including Xpert MTB/RIF-positive cases. We tested CSF of 91 patients. LAM LFA had a sensitivity of 75% for definite histopathological TBM, ELISA a sensitivity of 43%, and Xpert MTB/RIF a sensitivity of 100% and specificities of 87%, 91%, and 87%, respectively. LAM LFA had a sensitivity of 50% for definite and probable histopathological TBM, ELISA a sensitivity of 38%, and Xpert MTB/RIF a sensitivity of 86% and specificities of 70%, 91%, and 87%, respectively. LAM LFA had a sensitivity of 68% for the composite standard and ELISA a sensitivity of 48% and specificities of 78% and 98%, respectively. The rapid diagnostic tests detected TBM in 22% to 78% of patients not on anti-TB treatment. Pointof-care tests have high accuracy in diagnosis of TBM in deceased HIV-infected adults. LAM LFA in CSF is a useful additional diagnostic tool.