N C Bahr1, L Tugume2, R Rajasingham3, R Kiggundu2, D A Williams4, B Morawski5, D Alland6, D B Meya7, J Rhein8, D R Boulware5. 1. Division of Infectious Diseases and International Medicine, Department of Medicine, University of Minnesota, Minneapolis, USA; Center for Infectious Diseases & Microbiology Translational Research, University of Minnesota, Minneapolis, Minnesota, USA; Infectious Disease Institute, Makerere University, Kampala, Uganda. 2. Infectious Disease Institute, Makerere University, Kampala, Uganda. 3. Division of Infectious Diseases and International Medicine, Department of Medicine, University of Minnesota, Minneapolis, USA. 4. Division of Infectious Diseases and International Medicine, Department of Medicine, University of Minnesota, Minneapolis, USA; Infectious Disease Institute, Makerere University, Kampala, Uganda. 5. Division of Infectious Diseases and International Medicine, Department of Medicine, University of Minnesota, Minneapolis, USA; Center for Infectious Diseases & Microbiology Translational Research, University of Minnesota, Minneapolis, Minnesota, USA. 6. Center for Infectious Disease, New Jersey Medical School, Rutgers Biomedical and Health Sciences, Newark, New Jersey, USA. 7. Division of Infectious Diseases and International Medicine, Department of Medicine, University of Minnesota, Minneapolis, USA; Infectious Disease Institute, Makerere University, Kampala, Uganda; School of Medicine, College of Health Sciences, Makerere University, Kampala, Uganda. 8. Division of Infectious Diseases and International Medicine, Department of Medicine, University of Minnesota, Minneapolis, USA; Center for Infectious Diseases & Microbiology Translational Research, University of Minnesota, Minneapolis, Minnesota, USA, Infectious Disease Institute, Makerere University, Kampala, Uganda.
Abstract
BACKGROUND: TB meningitis (TBM) diagnosis is difficult and novel diagnostic methods are needed. The World Health Organization recommends Xpert(®) MTB/RIF as the initial TBM diagnostic test based on two studies reporting suboptimal sensitivity (~50-60%). OBJECTIVE: To study the effect of cerebrospinal fluid (CSF) centrifugation on Xpert performance for TBM detection. DESIGN: A total of 107 predominantly human immunodeficiency virus (HIV) infected adults with presumed meningitis were screened prospectively in Kampala, Uganda. CSF was tested using 1) microscopy for acid-fast bacilli; 2) MGIT™ culture; 3) Xpert of 2 ml of unprocessed CSF; and 4) Xpert of centrifuged CSF. Diagnostic performance was measured against an a priori composite reference standard of any positive CSF tuberculosis test. RESULTS: Of 107 participants, 18 (17%) had definite TBM. When CSF was centrifuged, Xpert had better sensitivity (13/18, 72%) than when using 2 ml of unprocessed CSF (5/18, 28%; P = 0.008). The median centrifuged CSF volume was 6 ml (IQR 4-10). Mycobacterial culture yielded 71% (12/17) sensitivity at a median delay of 27 days. Only 39% were positive by both culture and centrifuged Xpert, with additional cases detected by Xpert and culture. CONCLUSIONS: CSF centrifugation optimizes the diagnostic performance of Xpert in the detection of TBM. A combination of culture and Xpert detected the largest number of cases.
BACKGROUND:TB meningitis (TBM) diagnosis is difficult and novel diagnostic methods are needed. The World Health Organization recommends Xpert(®) MTB/RIF as the initial TBM diagnostic test based on two studies reporting suboptimal sensitivity (~50-60%). OBJECTIVE: To study the effect of cerebrospinal fluid (CSF) centrifugation on Xpert performance for TBM detection. DESIGN: A total of 107 predominantly human immunodeficiency virus (HIV) infected adults with presumed meningitis were screened prospectively in Kampala, Uganda. CSF was tested using 1) microscopy for acid-fast bacilli; 2) MGIT™ culture; 3) Xpert of 2 ml of unprocessed CSF; and 4) Xpert of centrifuged CSF. Diagnostic performance was measured against an a priori composite reference standard of any positive CSF tuberculosis test. RESULTS: Of 107 participants, 18 (17%) had definite TBM. When CSF was centrifuged, Xpert had better sensitivity (13/18, 72%) than when using 2 ml of unprocessed CSF (5/18, 28%; P = 0.008). The median centrifuged CSF volume was 6 ml (IQR 4-10). Mycobacterial culture yielded 71% (12/17) sensitivity at a median delay of 27 days. Only 39% were positive by both culture and centrifuged Xpert, with additional cases detected by Xpert and culture. CONCLUSIONS: CSF centrifugation optimizes the diagnostic performance of Xpert in the detection of TBM. A combination of culture and Xpert detected the largest number of cases.
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