@article{Heemskerk2018,
abstract = {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.},
author = {Heemskerk, A. Dorothee and Donovan, Joseph and Thu, Do Dang Anh and Marais, Suzaan and Chaidir, Lidya and Dung, Vu Thi Mong and Centner, Chad M and Ha, Vu Thi Ngoc and Annisa, Jessi and Dian, Sofiati and Bovijn, Louise and Mai, Nguyen Thi Hoang and Phu, Nguyen Hoan and Chau, Nguyen Van Vinh and Ganiem, Ahmad Rizal and Van, Cao Thao and Geskus, Ronald B and Thuong, Nguyen Thuy Thuong and Ruslami, Rovina and Meintjes, Graeme A and van Crevel, Reinout and Wilkinson, Robert J and Thwaites, Guy E},
doi = {10.1016/j.jinf.2018.09.003},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Heemskerk et al. - 2018 - Improving the microbiological diagnosis of tuberculous meningitis a prospective, international, multicentre co.pdf:pdf},
issn = {15322742},
journal = {Journal of Infection},
keywords = {Cytospin,Diagnosis,OA,Tuberculous meningitis,Xpert MTB/RIF,Ziehl–Neelsen stain,fund{\_}ack,original},
mendeley-tags = {OA,fund{\_}ack,original},
month = {sep},
number = {6},
pages = {509--515},
pmid = {30217659},
publisher = {W.B. Saunders},
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}},
url = {https://www.sciencedirect.com/science/article/pii/S0163445318302767?via{\%}3Dihub},
volume = {77},
year = {2018}
}

{"_id":"uA6JKXfhkoKpxhxTq","bibbaseid":"heemskerk-donovan-thu-marais-chaidir-dung-centner-ha-etal-improvingthemicrobiologicaldiagnosisoftuberculousmeningitisaprospectiveinternationalmulticentrecomparisonofconventionalandmodifiedziehlneelsenstaingenexpertandcultureofcerebrospinalfluid-2018","author_short":["Heemskerk, A. D.","Donovan, J.","Thu, D. D. A.","Marais, S.","Chaidir, L.","Dung, V. T. M.","Centner, C. M","Ha, V. T. N.","Annisa, J.","Dian, S.","Bovijn, L.","Mai, N. T. H.","Phu, N. H.","Chau, N. V. V.","Ganiem, A. R.","Van, C. T.","Geskus, R. B","Thuong, N. T. T.","Ruslami, R.","Meintjes, G. A","van Crevel, R.","Wilkinson, R. J","Thwaites, G. E"],"bibdata":{"bibtype":"article","type":"article","abstract":"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.","author":[{"propositions":[],"lastnames":["Heemskerk"],"firstnames":["A.","Dorothee"],"suffixes":[]},{"propositions":[],"lastnames":["Donovan"],"firstnames":["Joseph"],"suffixes":[]},{"propositions":[],"lastnames":["Thu"],"firstnames":["Do","Dang","Anh"],"suffixes":[]},{"propositions":[],"lastnames":["Marais"],"firstnames":["Suzaan"],"suffixes":[]},{"propositions":[],"lastnames":["Chaidir"],"firstnames":["Lidya"],"suffixes":[]},{"propositions":[],"lastnames":["Dung"],"firstnames":["Vu","Thi","Mong"],"suffixes":[]},{"propositions":[],"lastnames":["Centner"],"firstnames":["Chad","M"],"suffixes":[]},{"propositions":[],"lastnames":["Ha"],"firstnames":["Vu","Thi","Ngoc"],"suffixes":[]},{"propositions":[],"lastnames":["Annisa"],"firstnames":["Jessi"],"suffixes":[]},{"propositions":[],"lastnames":["Dian"],"firstnames":["Sofiati"],"suffixes":[]},{"propositions":[],"lastnames":["Bovijn"],"firstnames":["Louise"],"suffixes":[]},{"propositions":[],"lastnames":["Mai"],"firstnames":["Nguyen","Thi","Hoang"],"suffixes":[]},{"propositions":[],"lastnames":["Phu"],"firstnames":["Nguyen","Hoan"],"suffixes":[]},{"propositions":[],"lastnames":["Chau"],"firstnames":["Nguyen","Van","Vinh"],"suffixes":[]},{"propositions":[],"lastnames":["Ganiem"],"firstnames":["Ahmad","Rizal"],"suffixes":[]},{"propositions":[],"lastnames":["Van"],"firstnames":["Cao","Thao"],"suffixes":[]},{"propositions":[],"lastnames":["Geskus"],"firstnames":["Ronald","B"],"suffixes":[]},{"propositions":[],"lastnames":["Thuong"],"firstnames":["Nguyen","Thuy","Thuong"],"suffixes":[]},{"propositions":[],"lastnames":["Ruslami"],"firstnames":["Rovina"],"suffixes":[]},{"propositions":[],"lastnames":["Meintjes"],"firstnames":["Graeme","A"],"suffixes":[]},{"propositions":["van"],"lastnames":["Crevel"],"firstnames":["Reinout"],"suffixes":[]},{"propositions":[],"lastnames":["Wilkinson"],"firstnames":["Robert","J"],"suffixes":[]},{"propositions":[],"lastnames":["Thwaites"],"firstnames":["Guy","E"],"suffixes":[]}],"doi":"10.1016/j.jinf.2018.09.003","file":":C$\\$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Heemskerk et al. - 2018 - Improving the microbiological diagnosis of tuberculous meningitis a prospective, international, multicentre co.pdf:pdf","issn":"15322742","journal":"Journal of Infection","keywords":"Cytospin,Diagnosis,OA,Tuberculous meningitis,Xpert MTB/RIF,Ziehl–Neelsen stain,fund_ack,original","mendeley-tags":"OA,fund_ack,original","month":"sep","number":"6","pages":"509–515","pmid":"30217659","publisher":"W.B. Saunders","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","url":"https://www.sciencedirect.com/science/article/pii/S0163445318302767?via\\%3Dihub","volume":"77","year":"2018","bibtex":"@article{Heemskerk2018,\r\nabstract = {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.},\r\nauthor = {Heemskerk, A. Dorothee and Donovan, Joseph and Thu, Do Dang Anh and Marais, Suzaan and Chaidir, Lidya and Dung, Vu Thi Mong and Centner, Chad M and Ha, Vu Thi Ngoc and Annisa, Jessi and Dian, Sofiati and Bovijn, Louise and Mai, Nguyen Thi Hoang and Phu, Nguyen Hoan and Chau, Nguyen Van Vinh and Ganiem, Ahmad Rizal and Van, Cao Thao and Geskus, Ronald B and Thuong, Nguyen Thuy Thuong and Ruslami, Rovina and Meintjes, Graeme A and van Crevel, Reinout and Wilkinson, Robert J and Thwaites, Guy E},\r\ndoi = {10.1016/j.jinf.2018.09.003},\r\nfile = {:C$\\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Heemskerk et al. - 2018 - Improving the microbiological diagnosis of tuberculous meningitis a prospective, international, multicentre co.pdf:pdf},\r\nissn = {15322742},\r\njournal = {Journal of Infection},\r\nkeywords = {Cytospin,Diagnosis,OA,Tuberculous meningitis,Xpert MTB/RIF,Ziehl–Neelsen stain,fund{\\_}ack,original},\r\nmendeley-tags = {OA,fund{\\_}ack,original},\r\nmonth = {sep},\r\nnumber = {6},\r\npages = {509--515},\r\npmid = {30217659},\r\npublisher = {W.B. Saunders},\r\ntitle = {{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}},\r\nurl = {https://www.sciencedirect.com/science/article/pii/S0163445318302767?via{\\%}3Dihub},\r\nvolume = {77},\r\nyear = {2018}\r\n}\r\n","author_short":["Heemskerk, A. D.","Donovan, J.","Thu, D. D. A.","Marais, S.","Chaidir, L.","Dung, V. T. M.","Centner, C. M","Ha, V. T. N.","Annisa, J.","Dian, S.","Bovijn, L.","Mai, N. T. H.","Phu, N. H.","Chau, N. V. V.","Ganiem, A. R.","Van, C. T.","Geskus, R. B","Thuong, N. T. T.","Ruslami, R.","Meintjes, G. A","van Crevel, R.","Wilkinson, R. J","Thwaites, G. E"],"key":"Heemskerk2018","id":"Heemskerk2018","bibbaseid":"heemskerk-donovan-thu-marais-chaidir-dung-centner-ha-etal-improvingthemicrobiologicaldiagnosisoftuberculousmeningitisaprospectiveinternationalmulticentrecomparisonofconventionalandmodifiedziehlneelsenstaingenexpertandcultureofcerebrospinalfluid-2018","role":"author","urls":{"Paper":"https://www.sciencedirect.com/science/article/pii/S0163445318302767?via\\%3Dihub"},"keyword":["Cytospin","Diagnosis","OA","Tuberculous meningitis","Xpert MTB/RIF","Ziehl–Neelsen stain","fund_ack","original"],"metadata":{"authorlinks":{}}},"bibtype":"article","biburl":"https://drive.google.com/uc?export=download&id=1-JLqZ7RwZ3VC2d6ErLGHAtOeMRS_7GCz","dataSources":["Krmt6gt9ktB2s6ARh"],"keywords":["cytospin","diagnosis","oa","tuberculous meningitis","xpert mtb/rif","ziehl–neelsen stain","fund_ack","original"],"search_terms":["improving","microbiological","diagnosis","tuberculous","meningitis","prospective","international","multicentre","comparison","conventional","modified","ziehl","neelsen","stain","genexpert","culture","cerebrospinal","fluid","heemskerk","donovan","thu","marais","chaidir","dung","centner","ha","annisa","dian","bovijn","mai","phu","chau","ganiem","van","geskus","thuong","ruslami","meintjes","van crevel","wilkinson","thwaites"],"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","year":2018}