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Improving the microbiological diagnosis of tuberculous meningitis: A prospective, international, multicentre comparison of conventional and modified Ziehl-Neelsen stain, GeneXpert, and culture of cerebrospinal fluid

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journal contribution
posted on 12.08.2020 by A Dorothee Heemskerk, Joseph Donovan, Do Dang Anh Thu, Suzaan Marais, Lidya Chaidir, Vu Thi Mong Dung, Chad M Centner, Vu Thi Ngoc Ha, Jessi Annisa, Sofiati Dian, Louise Bovijn, Nguyen Thi Hoang Mai, Nguyen Hoan Phu, Nguyen Van Vinh Chau, Ahmad Rizal Ganiem, Cao Thao Van, Ronald B Geskus, Nguyen Thuy Thuong Thuong, Rovina Ruslami, Graeme Meintjes, Reinout van Crevel, Robert J Wilkinson, Guy E Thwaites
OBJECTIVES: Tuberculous meningitis (TBM) is the severest form of tuberculosis, but current diagnostic tests are insensitive. Recent reports suggest simple modifications to conventional cerebrospinal fluid (CSF) Ziehl-Neelsen (ZN) staining may greatly improve sensitivity. We sought to define the performance of modified and conventional ZN stain for TBM diagnosis. METHODS: In hospitals in Vietnam, South Africa and Indonesia we conducted a prospective study of modified ZN with or without cytospin, conventional ZN smear, GeneXpert, and culture on CSF in adults with suspected TBM. RESULTS: A total of 618 individuals were enrolled across 3 sites. Compared with the TBM clinical diagnostic gold standard for research (definite probable or possible TBM), sensitivity of conventional ZN and modified ZN with cytospin were 33.9% and 34.5% respectively (p = 1.0 for the difference between tests), compared with culture 31.8% and Xpert 25.1%. Using culture as a reference, sensitivities of conventional ZN, modified ZN with cytospin, and Xpert were 66.4%, 67.5%, and 72.3%, respectively. Higher CSF volume and lactate, and lower CSF:blood glucose ratio were independently associated with microbiologically confirmed TBM. CONCLUSIONS: Modified ZN stain does not improve diagnosis of TBM. Currently available tests are insensitive, but testing large CSF volumes improves performance. New diagnostic tests for TBM are urgently required.