Evidence map›Paper›PMID 30217659›Full record

ArticleThe Journal of infection2018

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.

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 and 13 more

Open access · hybridAbstract readComparative StudyMulticenter Study
In one paragraph

Article in The Journal of infection, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers, 9 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
58citing papers in PubMed, 9 pooled it
13.3field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

58 citing papers in PubMed, 9 syntheses or guidelines pooled it, 109 citations in OpenAlex.

  1. A clinical practice guideline for tuberculous meningitis.The Lancet. Infectious diseases · 2026
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

23 authors at 6 institutions in 6 countries.

A Dorothee HeemskerkOxford University Clinical Research Unit, Ho Chi Minh City, Vietnam; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom. Electronic address: a.heemskerk@vumc.nl.
Joseph DonovanOxford University Clinical Research Unit, Ho Chi Minh City, Vietnam; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom. Electronic address: jdonovan@oucru.org.
Do Dang Anh ThuOxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.
Suzaan MaraisWellcome Center for Infectious Diseases Research in Africa and Department of Medicine, University of Cape Town, Observatory 7925, South Africa; Department of Neurology, Inkosi Albert Luthuli Central Hospital and University of KwaZulu-Natal, Durban, South Africa.
Lidya ChaidirInfectious Disease Research Center, Faculty of Medicine, Universitas Padjadjaran/Hasan Sadikin Hospital, Bandung, Indonesia.
Vu Thi Mong DungOxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.
Chad M CentnerDivision of Medical Microbiology, University of Cape Town and National Health Laboratory Service, Groote Schuur Hospital, Cape Town, South Africa.
Vu Thi Ngoc HaOxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.
Jessi AnnisaInfectious Disease Research Center, Faculty of Medicine, Universitas Padjadjaran/Hasan Sadikin Hospital, Bandung, Indonesia.
Sofiati DianInfectious Disease Research Center, Faculty of Medicine, Universitas Padjadjaran/Hasan Sadikin Hospital, Bandung, Indonesia; Department of Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands.
Louise BovijnWellcome Center for Infectious Diseases Research in Africa and Department of Medicine, University of Cape Town, Observatory 7925, South Africa.
Nguyen Thi Hoang MaiOxford University Clinical Research Unit, Ho Chi Minh City, Vietnam; Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam.
Nguyen Hoan PhuOxford University Clinical Research Unit, Ho Chi Minh City, Vietnam; Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam.
Nguyen Van Vinh ChauOxford University Clinical Research Unit, Ho Chi Minh City, Vietnam; Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam.
Ahmad Rizal GaniemInfectious Disease Research Center, Faculty of Medicine, Universitas Padjadjaran/Hasan Sadikin Hospital, Bandung, Indonesia.
Cao Thao VanOxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.
Ronald B GeskusOxford University Clinical Research Unit, Ho Chi Minh City, Vietnam; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
Nguyen Thuy Thuong ThuongOxford University Clinical Research Unit, Ho Chi Minh City, Vietnam; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
Rovina RuslamiInfectious Disease Research Center, Faculty of Medicine, Universitas Padjadjaran/Hasan Sadikin Hospital, Bandung, Indonesia.
Graeme MeintjesWellcome Center for Infectious Diseases Research in Africa and Department of Medicine, University of Cape Town, Observatory 7925, South Africa.
Reinout van CrevelCentre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom; Department of Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands.
Robert J WilkinsonWellcome Center for Infectious Diseases Research in Africa and Department of Medicine, University of Cape Town, Observatory 7925, South Africa; Department of Medicine, Imperial College London, W2 1PG, United Kingdom; Francis Crick Institute, NW1 1AT, United Kingdom.
Guy E ThwaitesOxford University Clinical Research Unit, Ho Chi Minh City, Vietnam; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
Oxford University Clinical Research Unit · VNAngkor Hospital for Children · KHDr. Hasan Sadikin General Hospital · IDUniversity of Cape Town · ZARadboud University Nijmegen · NLNational Health Laboratory Service · ZA

Funding

Medical Research Council MC_U117588499Wellcome Trust 104803Wellcome Trust 106680/Z/14/ZWellcome Trust 203135Wellcome Trust 206724/Z/17/Z
6 · The paper itself

Abstract

objectivesTuberculous 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.

methodsIn 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.

resultsA 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.

conclusionsModified 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.

Indexed as

Bacteriological TechniquesMolecular Diagnostic TechniquesAdultCerebrospinal FluidColoring AgentsDiagnostic Tests, RoutineFemaleHumansIndonesiaInternationalityMaleMiddle AgedMycobacterium tuberculosisProspective StudiesSensitivity and SpecificitySouth AfricaColoring AgentsCytospinDiagnosisTuberculous meningitisXpert MTB/RIFZiehl–Neelsen stain

Identifiers

PMID30217659
PMCPMC6293313
OpenAlexW2892187955

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.