Evidence map›Paper›PMID 31924549›Full record

ArticleThe Lancet. Infectious diseases2020

Xpert MTB/RIF Ultra for the diagnosis of HIV-associated tuberculous meningitis: a prospective validation study.

Fiona V Cresswell, Lillian Tugume, Nathan C Bahr, Richard Kwizera, Ananta S Bangdiwala, Abdu K Musubire, Morris Rutakingirwa, Enock Kagimu, Edwin Nuwagira, Edward Mpoza and 8 more

Open access · hybridAbstract readValidation Study
PubMed Full text at PMC Publisher
In one paragraph

Article in The Lancet. Infectious diseases, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers, 10 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
70citing papers in PubMed, 10 pooled it
17.8field-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

70 citing papers in PubMed, 10 syntheses or guidelines pooled it, 117 citations in OpenAlex.

  1. A clinical practice guideline for tuberculous meningitis.The Lancet. Infectious diseases · 2026
    Guideline
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  6. Evaluating the efficacy of stool sample on Xpert MTB/RIF Ultra and its comparison with other sample types by meta-analysis for TB diagnostics.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2022
    Pooled it
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  11. Trial
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  20. Construction and verification of early diagnosis model of tuberculous meningitis.Frontiers in cellular and infection microbiology · 2026
    Article

10 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors at 6 institutions in 3 countries.

Fiona V CresswellClinical Research Department, London School of Hygiene & Tropical Medicine, London, UK; Infectious Diseases Institute, College of Health Sciences, Makerere University, Kampala, Uganda; Medical Research Council/Uganda Virus Research Institute and London School of Hygiene & Tropical Medicine Uganda Research Unit, Entebbe, Uganda. Electronic address: fiona.cresswell@lshtm.ac.uk.
Lillian TugumeInfectious Diseases Institute, College of Health Sciences, Makerere University, Kampala, Uganda.
Nathan C BahrDivision of Infectious Diseases, Department of Medicine, University of Kansas, Kansas City, KS, USA.
Richard KwizeraInfectious Diseases Institute, College of Health Sciences, Makerere University, Kampala, Uganda.
Ananta S BangdiwalaDivision of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, MN, USA.
Abdu K MusubireInfectious Diseases Institute, College of Health Sciences, Makerere University, Kampala, Uganda.
Morris RutakingirwaInfectious Diseases Institute, College of Health Sciences, Makerere University, Kampala, Uganda.
Enock KagimuInfectious Diseases Institute, College of Health Sciences, Makerere University, Kampala, Uganda.
Edwin NuwagiraMbarara University of Science and Technology, Mbarara, Uganda.
Edward MpozaClinical Research Department, London School of Hygiene & Tropical Medicine, London, UK.
Joshua RheinInfectious Diseases Institute, College of Health Sciences, Makerere University, Kampala, Uganda; Division of Infectious Diseases and International Medicine, Department of Medicine, University of Minnesota, Minneapolis, MN, USA.
Darlisha A WilliamsInfectious Diseases Institute, College of Health Sciences, Makerere University, Kampala, Uganda.
Conrad MuzooraMbarara University of Science and Technology, Mbarara, Uganda.
Daniel GrintTropical Epidemiology Group, London School of Hygiene & Tropical Medicine, London, UK.
Alison M ElliottClinical Research Department, London School of Hygiene & Tropical Medicine, London, UK; Medical Research Council/Uganda Virus Research Institute and London School of Hygiene & Tropical Medicine Uganda Research Unit, Entebbe, Uganda.
David B MeyaInfectious Diseases Institute, College of Health Sciences, Makerere University, Kampala, Uganda.
David R BoulwareDivision of Infectious Diseases and International Medicine, Department of Medicine, University of Minnesota, Minneapolis, MN, USA.
ASTRO-CM team
Makerere University · UGInfectious Diseases Institute · UGLondon School of Hygiene & Tropical Medicine · GBUniversity of Minnesota · USMbarara University of Science and Technology · UGUniversity of Kansas · US

Funding

Improving Diagnostics and Neurocognitive Outcomes in HIV/AIDS-related MeningitisR01NS086312 · NINDS · UNIVERSITY OF MINNESOTA · PI David R Boulware, David Bisagaya Meya · 2013 to 2026
$8.3M
Infectious Disease Training in Clinical InvestigationT32AI055433 · NIAID · UNIVERSITY OF MINNESOTA TWIN CITIES · PI David R Boulware · 2003 to 2026
$6.1M
Novel Diagnostic Development for TB Meningitis and HistoplasmosisK23NS110470 · NINDS · UNIVERSITY OF MINNESOTA · PI BAHR, NATHAN · 2019 to 2023
$1.0M
Improving Outcomes of HIV-Associated Cryptococcosis in Resource-Limited SettingsK01TW010268 · FIC · UNIVERSITY OF MINNESOTA · PI RHEIN, JOSHUA R · 2016 to 2020
$703k
Epidemiology, Immunopathogenesis, and Outcomes of Non-traumatic Spinal Cord Injury in UgandaK43TW010718 · FIC · INFECTIOUS DISEASES INSTITUTE · PI MUSUBIRE, ABDU KISEKKA · 2017 to 2021
$514k
FIC NIH HHS K01 TW010268FIC NIH HHS K43 TW010718Medical Research Council MC_UU_00027/5Medical Research Council MR/R010161/1NIAID NIH HHS T32 AI055433NINDS NIH HHS K23 NS110470NINDS NIH HHS R01 NS086312Wellcome TrustWellcome Trust 107743Wellcome Trust 210772/Z/18/Z
6 · The paper itself

Abstract

introductionTuberculous meningitis accounts for 1-5% of tuberculosis cases. Diagnostic delay contributes to poor outcomes. We evaluated the performance of the new Xpert MTB/RIF Ultra (Xpert Ultra) for tuberculous meningitis diagnosis.

methodsIn this prospective validation study, we tested the cerebrospinal fluid (CSF) of adults presenting with suspected meningitis (ie, headache or altered mental status with clinical signs of meningism) to the Mulago National Referral Hospital and Mbarara Regional Referral Hospital in Uganda. We centrifuged the CSF, resuspended the cell pellet in 2 mL CSF, and tested 0·5 mL aliquots with Xpert Ultra, Xpert MTB/RIF (Xpert), and mycobacterial growth indicator tube (MGIT) culture. We quantified diagnostic performance against the uniform case definition of probable or definite tuberculous meningitis and a composite microbiological reference standard.

findingsFrom Nov 25, 2016, to Jan 24, 2019, we screened 466 adults with suspected meningitis and tested 204 for tuberculous meningitis. Uniform clinical case definition classified 51 participants as having probable or definite tuberculous meningitis. Against this uniform case definition, Xpert Ultra had 76·5% sensitivity (95% CI 62·5-87·2; 39 of 51 patients) and a negative predictive value of 92·7% (87·6-96·2; 153 of 165), compared with 55·6% sensitivity (44·0-70·4; 25 of 45; p=0·0010) and a negative predictive value of 85·8% (78·9-91·1; 121 of 141) for Xpert and 61·4% sensitivity (45·5-75·6; 27 of 44; p=0·020) and negative predictive value of 85·2% (77·4-91·1; 98 of 115) for MGIT culture. Against the composite microbiological reference standard, Xpert Ultra had sensitivity of 92·9% (80·5-98·5; 39 of 42), higher than Xpert at 65·8% (48·6-80·4; 25 of 38; p=0·0063) and MGIT culture at 72·2% (55·9-86·2; 27 of 37; p=0·092). Xpert Ultra detected nine tuberculous meningitis cases missed by Xpert and MGIT culture.

interpretationXpert Ultra detected tuberculous meningitis with higher sensitivity than Xpert and MGIT culture in this HIV-positive population. However, with a negative predictive value of 93%, Xpert Ultra cannot be used as a rule-out test. Clinical judgment and novel highly sensitive point-of-care tests are still required.

fundingWellcome Trust, National Institute of Health, National Institute of Neurologic Diseases and Stroke, Fogarty International Center, and National Institute of Allergy and Infectious Diseases.

Indexed as

Cerebrospinal FluidHIV InfectionsHospitalsHumansMolecular Diagnostic TechniquesMycobacterium tuberculosisPredictive Value of TestsSensitivity and SpecificityTuberculosis, MeningealTuberculosis, Multidrug-ResistantUganda

Identifiers

PMID31924549
PMCPMC7045085
OpenAlexW2998865775

What OpenQuestion holds

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LicenceTDM
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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.