title: 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. 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.
authors.affiliation: Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium Infectious Diseases Institute, College of Health Sciences, Makerere University, Kampala, Uganda jannekecox@xs4all.nl.
authors.forename: Janneke A
authors.initials: JA
authors.lastname: Cox
authors.affiliation: Department of Pathology, College of Health Sciences, Makerere University, Kampala, Uganda.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Lukande
authors.affiliation: Department of Pathology, College of Health Sciences, Makerere University, Kampala, Uganda Department of Pathology, Mulago Hospital, Kampala, Uganda.
authors.forename: Sam
authors.initials: S
authors.lastname: Kalungi
authors.affiliation: Department of Pathology, University Hospital Antwerp, University of Antwerp, Antwerp, Belgium.
authors.forename: Eric
authors.initials: E
authors.lastname: Van Marck
authors.affiliation: Department of Pathology, University Hospital Antwerp, University of Antwerp, Antwerp, Belgium.
authors.forename: Martin
authors.initials: M
authors.lastname: Lammens
authors.affiliation: Department of Diagnostic Oncology & Molecular Pathology, Netherlands Cancer Institute-Antonie van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
authors.forename: Koen
authors.initials: K
authors.lastname: Van de Vijver
authors.affiliation: Infectious Diseases Institute, College of Health Sciences, Makerere University, Kampala, Uganda.
authors.forename: Andrew
authors.initials: A
authors.lastname: Kambugu
authors.affiliation: Joint Pathology Center, Silver Spring, Maryland, USA.
authors.forename: Ann M
authors.initials: AM
authors.lastname: Nelson
authors.affiliation: Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium Department of Epidemiology and Social Medicine, University of Antwerp, Antwerp, Belgium.
authors.forename: Robert
authors.initials: R
authors.lastname: Colebunders
authors.affiliation: Infectious Diseases Institute, College of Health Sciences, Makerere University, Kampala, Uganda Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Yukari C
authors.initials: YC
authors.lastname: Manabe
mesh_terms: D000328:Adult; D001344:Autopsy; D002555:Cerebrospinal Fluid / Q000737:chemistry*; D015331:Cohort Studies; D004269:DNA, Bacterial / Q000032:analysis* / Q000235:genetics; D003955:Diagnostic Tests, Routine / Q000379:methods; D005260:Female; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D007118:Immunoassay / Q000379:methods*; D008070:Lipopolysaccharides / Q000032:analysis*; D008297:Male; D025202:Molecular Diagnostic Techniques / Q000379:methods*; D019095:Point-of-Care Systems; D012680:Sensitivity and Specificity; D014390:Tuberculosis, Meningeal / Q000175:diagnosis*; D014454:Uganda
chemical_list: D004269:DNA, Bacterial; D008070:Lipopolysaccharides; C050016:lipoarabinomannan