Accuracy of Lipoarabinomannan and Xpert MTB/RIF Testing in Cerebrospinal Fluid To Diagnose Tuberculous Meningitis in an Autopsy Cohort of HIV-Infected Adults

• Published in: Journal of clinical microbiology Vol. 53; no. 8; pp. 2667 - 2673
• Main Authors: Cox, Janneke A, Lukande, Robert L, Kalungi, Sam, Van Marck, Eric, Lammens, Martin, Van de Vijver, Koen, Kambugu, Andrew, Nelson, Ann M, Colebunders, Robert, Manabe, Yukari C
• Format: Journal Article
• Language: English
• Published: United States American Society for Microbiology 01.08.2015
• Subjects: Adult; Autopsy; Cerebrospinal Fluid - chemistry; Cohort Studies; Diagnostic Tests, Routine - methods; DNA, Bacterial - analysis; DNA, Bacterial - genetics; Female; HIV Infections - complications; Humans; Immunoassay - methods; Lentivirus; Lipopolysaccharides - analysis; Male; Molecular Diagnostic Techniques - methods; Mycobacteriology and Aerobic Actinomycetes; Point-of-Care Systems; Retroviridae; Sensitivity and Specificity; Tuberculosis, Meningeal - diagnosis; Uganda; Uganda
• ISSN: 0095-1137; 1098-660X
• DOI: 10.1128/JCM.00624-15

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. Point-of-care tests have high accuracy in diagnosis of TBM in deceased HIV-infected adults. LAM LFA in CSF is a useful additional diagnostic tool.