Evidence map›Paper›PMID 27017310›Full record

ArticleLancet (London, England)2016

A blood RNA signature for tuberculosis disease risk: a prospective cohort study.

Daniel E Zak, Adam Penn-Nicholson, Thomas J Scriba, Ethan Thompson, Sara Suliman, Lynn M Amon, Hassan Mahomed, Mzwandile Erasmus, Wendy Whatney, Gregory D Hussey and 24 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Lancet (London, England), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 494 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
494citing papers in PubMed, 5 pooled it
70.7field-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

494 citing papers in PubMed, 5 syntheses or guidelines pooled it, 806 citations in OpenAlex.

  1. Biomarker tests of progression from tuberculosis infection to disease: a systematic review.European respiratory review : an official journal of the European Respiratory Society · 2026
    Pooled it
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  6. Trial
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  10. Compartment-specific inflammation in tuberculous lymphadenitis: a case-control study.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026
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  16. Restricted MHC-II trafficking inbioRxiv : the preprint server for biology · 2026
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  17. Monocyte-Amplified Transcriptional Signatures of Human Diseases.bioRxiv : the preprint server for biology · 2026
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434 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

34 authors at 13 institutions in 9 countries.

Daniel E ZakThe Center for Infectious Disease Research, Seattle, WA, USA.
Adam Penn-NicholsonSouth African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine & Department of Paediatrics and Child Health, University of Cape Town, Cape Town, South Africa.
Thomas J ScribaSouth African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine & Department of Paediatrics and Child Health, University of Cape Town, Cape Town, South Africa.
Ethan ThompsonThe Center for Infectious Disease Research, Seattle, WA, USA.
Sara SulimanSouth African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine & Department of Paediatrics and Child Health, University of Cape Town, Cape Town, South Africa.
Lynn M AmonThe Center for Infectious Disease Research, Seattle, WA, USA.
Hassan MahomedSouth African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine & Department of Paediatrics and Child Health, University of Cape Town, Cape Town, South Africa.
Mzwandile ErasmusSouth African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine & Department of Paediatrics and Child Health, University of Cape Town, Cape Town, South Africa.
Wendy WhatneySouth African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine & Department of Paediatrics and Child Health, University of Cape Town, Cape Town, South Africa.
Gregory D HusseySouth African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine & Department of Paediatrics and Child Health, University of Cape Town, Cape Town, South Africa.
Deborah AbrahamsSouth African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine & Department of Paediatrics and Child Health, University of Cape Town, Cape Town, South Africa.
Fazlin KafaarSouth African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine & Department of Paediatrics and Child Health, University of Cape Town, Cape Town, South Africa.
Tony HawkridgeSouth African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine & Department of Paediatrics and Child Health, University of Cape Town, Cape Town, South Africa.
Suzanne VerverKNCV Tuberculosis Foundation, The Hague, Netherlands.
E Jane HughesSouth African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine & Department of Paediatrics and Child Health, University of Cape Town, Cape Town, South Africa.
Martin OtaVaccines & Immunity, Medical Research Council Unit, Fajara, The Gambia.
Jayne SutherlandVaccines & Immunity, Medical Research Council Unit, Fajara, The Gambia.
Rawleigh HoweImmunology Unit, Armauer Hansen Research Institute, Addis Ababa, Ethiopia.
Hazel M DockrellDepartment of Immunology and Infection, London School of Hygiene & Tropical Medicine, London, UK.
W Henry BoomTuberculosis Research Unit, Case Western Reserve University, Cleveland, OH, USA.
Bonnie ThielTuberculosis Research Unit, Case Western Reserve University, Cleveland, OH, USA.
Tom H M OttenhoffDepartment of Infectious Diseases, Leiden University Medical Center, Leiden, Netherlands.
Harriet Mayanja-KizzaDepartment of Medicine and Department of Microbiology, Makerere University, Kampala, Uganda.
Amelia C CrampinDepartment of Immunology and Infection, London School of Hygiene & Tropical Medicine, London, UK; Karonga Prevention Study, Chilumba, Malawi.
Katrina DowningSouth African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine & Department of Paediatrics and Child Health, University of Cape Town, Cape Town, South Africa.
Mark HatherillSouth African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine & Department of Paediatrics and Child Health, University of Cape Town, Cape Town, South Africa.
Joe ValvoThe Center for Infectious Disease Research, Seattle, WA, USA.
Smitha ShankarThe Center for Infectious Disease Research, Seattle, WA, USA.
Shreemanta K ParidaDepartment of Immunology, Max Planck Institute for Infection Biology, Berlin, Germany.
Stefan H E KaufmannDepartment of Immunology, Max Planck Institute for Infection Biology, Berlin, Germany.
Gerhard WalzlDST/NRF Centre of Excellence for Biomedical TB Research and MRC Centre for TB Research, Division of Molecular Biology and Human Genetics, Stellenbosch University, Tygerberg, South Africa.
Alan AderemThe Center for Infectious Disease Research, Seattle, WA, USA.
Willem A HanekomSouth African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine & Department of Paediatrics and Child Health, University of Cape Town, Cape Town, South Africa. Electronic address: willem.hanekom@gatesfoundation.org.
ACS and GC6-74 cohort study groups
University of Cape Town · ZASouth African Tuberculosis Vaccine Initiative · ZACenter for Infectious Disease Research · USInfectious Disease Research Institute · USCase Western Reserve University · USLondon School of Hygiene & Tropical Medicine · GBMax Planck Institute for Infection Biology · DEMRC Unit the Gambia · GMArmauer Hansen Research Institute · ETLeiden University Medical Center · NLMakerere University · UGStellenbosch University · ZATuBerculosis Vaccine Initiative · NL

Funding

TUBERCULOSIS SUPPLEMENTD43TW000231 · FIC · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI ABDOOL KARIM, QUARRAISHA · 1993 to 2014
$13.1M
Host determinants of protection against tuberculosis in adolescentsR01AI087915 · NIAID · UNIVERSITY OF CAPE TOWN · PI SCRIBA, THOMAS JENS · 2011 to 2015
$3.3M
FIC NIH HHS 5 D43 TW000231FIC NIH HHS D43 TW000231Medical Research Council MC_U190071468Medical Research Council MC_U190074190Medical Research Council MC_U190081991Medical Research Council MC_UP_A900_1122NIAID NIH HHS R01 AI087915NIAID NIH HHS R01-AI087915
6 · The paper itself

Abstract

backgroundIdentification of blood biomarkers that prospectively predict progression of Mycobacterium tuberculosis infection to tuberculosis disease might lead to interventions that combat the tuberculosis epidemic. We aimed to assess whether global gene expression measured in whole blood of healthy people allowed identification of prospective signatures of risk of active tuberculosis disease.

methodsIn this prospective cohort study, we followed up healthy, South African adolescents aged 12-18 years from the adolescent cohort study (ACS) who were infected with M tuberculosis for 2 years. We collected blood samples from study participants every 6 months and monitored the adolescents for progression to tuberculosis disease. A prospective signature of risk was derived from whole blood RNA sequencing data by comparing participants who developed active tuberculosis disease (progressors) with those who remained healthy (matched controls). After adaptation to multiplex quantitative real-time PCR (qRT-PCR), the signature was used to predict tuberculosis disease in untouched adolescent samples and in samples from independent cohorts of South African and Gambian adult progressors and controls. Participants of the independent cohorts were household contacts of adults with active pulmonary tuberculosis disease.

findingsBetween July 6, 2005, and April 23, 2007, we enrolled 6363 participants from the ACS study and 4466 from independent South African and Gambian cohorts. 46 progressors and 107 matched controls were identified in the ACS cohort. A 16 gene signature of risk was identified. The signature predicted tuberculosis progression with a sensitivity of 66·1% (95% CI 63·2-68·9) and a specificity of 80·6% (79·2-82·0) in the 12 months preceding tuberculosis diagnosis. The risk signature was validated in an untouched group of adolescents (p=0·018 for RNA sequencing and p=0·0095 for qRT-PCR) and in the independent South African and Gambian cohorts (p values <0·0001 by qRT-PCR) with a sensitivity of 53·7% (42·6-64·3) and a specificity of 82·8% (76·7-86) in the 12 months preceding tuberculosis.

interpretationThe whole blood tuberculosis risk signature prospectively identified people at risk of developing active tuberculosis, opening the possibility for targeted intervention to prevent the disease.

fundingBill & Melinda Gates Foundation, the National Institutes of Health, Aeras, the European Union, and the South African Medical Research Council.

Indexed as

AdolescentAdultCase-Control StudiesChildGene ExpressionHumansMiddle AgedMycobacterium tuberculosisProspective StudiesReverse Transcriptase Polymerase Chain ReactionRisk AssessmentRisk FactorsRNA, BacterialTuberculosisYoung AdultRNA, Bacterial

Identifiers

PMID27017310
PMCPMC5392204
OpenAlexW2310773425

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

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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.