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
<strong>Objectives</strong> 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...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
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Elsevier
2018
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| _version_ | 1826304052489617408 |
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| author | Heemskerk, AD Donovan, JT Thu, DDA Marais, S Chaidir, L Dung, VTM Centner, CM Ha, VTN Annisa, J Dian, S Bovijn, L Mai, NTH Phu, NH Chau, NVV Ganiem, AR Van, CT Geskus, RB Thuong, NTT Ruslami, R Meintjes, G Van Crevel, R Wilkinson, RJ Thwaites, GE |
| author_facet | Heemskerk, AD Donovan, JT Thu, DDA Marais, S Chaidir, L Dung, VTM Centner, CM Ha, VTN Annisa, J Dian, S Bovijn, L Mai, NTH Phu, NH Chau, NVV Ganiem, AR Van, CT Geskus, RB Thuong, NTT Ruslami, R Meintjes, G Van Crevel, R Wilkinson, RJ Thwaites, GE |
| author_sort | Heemskerk, AD |
| collection | OXFORD |
| description | <strong>Objectives</strong> 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. <strong>Methods</strong> 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. <strong>Results</strong> 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. <strong>Conclusions</strong> 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. |
| first_indexed | 2024-03-07T06:11:58Z |
| format | Journal article |
| id | oxford-uuid:efd3664f-1868-4e6b-b9ae-bd150be39816 |
| institution | University of Oxford |
| last_indexed | 2024-03-07T06:11:58Z |
| publishDate | 2018 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | oxford-uuid:efd3664f-1868-4e6b-b9ae-bd150be398162022-03-27T11:43:11ZImproving the microbiological diagnosis of tuberculous meningitis: A prospective, international, multicentre comparison of conventional and modified Ziehl–Neelsen stain, GeneXpert, and culture of cerebrospinal fluidJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:efd3664f-1868-4e6b-b9ae-bd150be39816Symplectic Elements at OxfordElsevier2018Heemskerk, ADDonovan, JTThu, DDAMarais, SChaidir, LDung, VTMCentner, CMHa, VTNAnnisa, JDian, SBovijn, LMai, NTHPhu, NHChau, NVVGaniem, ARVan, CTGeskus, RBThuong, NTTRuslami, RMeintjes, GVan Crevel, RWilkinson, RJThwaites, GE <strong>Objectives</strong> 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. <strong>Methods</strong> 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. <strong>Results</strong> 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. <strong>Conclusions</strong> 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. |
| spellingShingle | Heemskerk, AD Donovan, JT Thu, DDA Marais, S Chaidir, L Dung, VTM Centner, CM Ha, VTN Annisa, J Dian, S Bovijn, L Mai, NTH Phu, NH Chau, NVV Ganiem, AR Van, CT Geskus, RB Thuong, NTT Ruslami, R Meintjes, G Van Crevel, R Wilkinson, RJ Thwaites, GE 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 |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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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