Evidence map›Paper›PMID 30462176›Full record

ArticleClinical infectious diseases : an official publication of the Infectious Diseases Society of America2019

A Novel, 5-Transcript, Whole-blood Gene-expression Signature for Tuberculosis Screening Among People Living With Human Immunodeficiency Virus.

Jayant V Rajan, Fred C Semitala, Tejas Mehta, Mark Seielstad, Lani Montalvo, Alfred Andama, Lucy Asege, Martha Nakaye, Jane Katende, Sandra Mwebe and 3 more

Registry-linked trialAbstract read
In one paragraph

Article in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04557176 (TB Screening Improves Preventive Therapy Uptake Trial), which is not on this map. Cited by 21 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed, 3 pooled it
–field-weighted citation impact
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.

NCT04557176 naactive not recruitingnot on this mapstarted 2020, after this paper: background citation

TB Screening Improves Preventive Therapy Uptake Trial

TypeinterventionalSponsorUniversity of California, San FranciscoRan2020 to 2025Enrolled1,719ConditionsTuberculosis, Latent Tuberculosis, Tuberculosis Prevention, HIVArmsCRP, point-of-care assay
3 · Its place in the literature

Who cites it

21 citing papers in PubMed, 3 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Article
  5. Monocyte-Amplified Transcriptional Signatures of Human Diseases.bioRxiv : the preprint server for biology · 2026
    Article
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  9. Review
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  13. The Role of C-Reactive Protein as a Triage Tool for Pulmonary Tuberculosis in Children.Journal of the Pediatric Infectious Diseases Society · 2022
    Article
  14. Article
  15. Article
  16. Analysis of real-time PCRThe Egyptian journal of medical human genetics · 2022
    Article
  17. A systematic review of potential screening biomarkers for active TB disease.Journal of clinical tuberculosis and other mycobacterial diseases · 2021
    Review
  18. Article
  19. Article
  20. Article
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

13 authors.

Jayant V RajanDivision of Experimental Medicine, Department of Medicine, Zuckerberg San Francisco General Hospital, University of California, San Francisco.
Fred C SemitalaDepartment of Medicine, Makerere University School of Medicine, Kampala, Uganda.
Tejas MehtaDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Zuckerberg San Francisco General Hospital, San Francisco.
Mark SeielstadInstitute for Human Genetics, Department of Laboratory Medicine, Department of Epidemiology and Biostatistics, University of California, San Francisco.
Lani MontalvoBlood Systems Research Institute, San Francisco, California.
Alfred AndamaInfectious Diseases Research Collaboration, Kampala, Uganda.
Lucy AsegeInfectious Diseases Research Collaboration, Kampala, Uganda.
Martha NakayeInfectious Diseases Research Collaboration, Kampala, Uganda.
Jane KatendeInfectious Diseases Research Collaboration, Kampala, Uganda.
Sandra MwebeInfectious Diseases Research Collaboration, Kampala, Uganda.
Moses R KamyaDepartment of Medicine, Makerere University School of Medicine, Kampala, Uganda.
Christina YoonDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Zuckerberg San Francisco General Hospital, San Francisco.
Adithya CattamanchiDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Zuckerberg San Francisco General Hospital, San Francisco.

Funding

Virology CoreP30AI027763 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI STEVEN Grant DEEKS · 1988 to 2026
$93.6M
Evaluation of novel tuberculosis screening strategies for people living with HIVK23AI114363 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI YOON, CHRISTINA · 2014 to 2018
$943k
NHLBI NIH HHS L30 HL110240NIAID NIH HHS K23 AI114363NIAID NIH HHS P30 AI027763PEPFAR
6 · The paper itself

Abstract

backgroundGene-expression profiles have been reported to distinguish between patients with and without active tuberculosis (TB), but no prior study has been conducted in the context of TB screening.

methodsWe included all the patients (n = 40) with culture-confirmed TB and time-matched controls (n = 80) enrolled between July 2013 and April 2015 in a TB screening study among people living with human immunodeficiency virus (PLHIV) in Kampala, Uganda. We randomly split the patients into training (n = 80) and test (n = 40) datasets. We used the training dataset to derive candidate signatures that consisted of 1 to 5 differentially-expressed transcripts (P ≤ .10) and compared the performance of our candidate signatures with 4 published TB gene-expression signatures, both on the independent test dataset and in 2 external datasets.

resultsWe identified a novel, 5-transcript signature that met the accuracy thresholds recommended for a TB screening test. On the independent test dataset, our signature had an area under the curve (AUC) of 0.87 (95% confidence interval [CI] 0.72-0.98), with sensitivity of 94% and specificity of 75%. None of the 4 published TB signatures achieved desired accuracy thresholds. Our novel signature performed well in external datasets from both high (AUC 0.81, 95% CI 0.74-0.88) and low (0.81, 95% CI 0.77-0.85) TB burden settings.

conclusionsWe identified the first gene-expression signature for TB screening. Our signature has the potential to be translated into a point-of-care test to facilitate systematic TB screening among PLHIV and other high-risk populations.

Indexed as

TranscriptomeAdultArea Under CurveBiomarkersCase-Control StudiesFemaleHIV InfectionsHumansMaleMycobacterium tuberculosisOligonucleotide Array Sequence AnalysisPoint-of-Care TestingSensitivity and SpecificityTuberculosisUgandaBiomarkersHIVscreeningtuberculosis

Identifiers

PMID30462176
PMCPMC6579960

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Registered trials

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.