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

Summary Background Identification 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... Full description

Journal Title: The Lancet (British edition) 2016, Vol.387 (10035), p.2312-2322
Main Author: Zak, Daniel E, PhD
Other Authors: Penn-Nicholson, Adam, PhD , Scriba, Thomas J, PhD , Thompson, Ethan, PhD , Suliman, Sara, PhD , Amon, Lynn M, PhD , Mahomed, Hassan, MD , Erasmus, Mzwandile, BSc , Whatney, Wendy, BScHons , Hussey, Gregory D, Prof , Abrahams, Deborah, DipMT , Kafaar, Fazlin, DipNur , Hawkridge, Tony, FCPHM , Verver, Suzanne, PhD , Hughes, E Jane, BScHons , Ota, Martin, MD , Sutherland, Jayne, PhD , Howe, Rawleigh, MD , Dockrell, Hazel M, Prof , Boom, W Henry, Prof , Thiel, Bonnie, MS , Ottenhoff, Tom H M, Prof , Mayanja-Kizza, Harriet, Prof , Crampin, Amelia C, FFPHM , Downing, Katrina, PhD , Hatherill, Mark, MD , Valvo, Joe, BS , Shankar, Smitha, MS , Parida, Shreemanta K, MD , Kaufmann, Stefan H E, Prof , Walzl, Gerhard, Prof , Aderem, Alan, PhD , Hanekom, Willem A, Prof
Format: Electronic Article Electronic Article
Language: English
Subjects:
HIV
RNA
Quelle: Alma/SFX Local Collection
Publisher: England: Elsevier Ltd
ID: ISSN: 0140-6736
Link: https://www.ncbi.nlm.nih.gov/pubmed/27017310
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title: A blood RNA signature for tuberculosis disease risk: a prospective cohort study
format: Article
creator:
  • Zak, Daniel E, PhD
  • Penn-Nicholson, Adam, PhD
  • Scriba, Thomas J, PhD
  • Thompson, Ethan, PhD
  • Suliman, Sara, PhD
  • Amon, Lynn M, PhD
  • Mahomed, Hassan, MD
  • Erasmus, Mzwandile, BSc
  • Whatney, Wendy, BScHons
  • Hussey, Gregory D, Prof
  • Abrahams, Deborah, DipMT
  • Kafaar, Fazlin, DipNur
  • Hawkridge, Tony, FCPHM
  • Verver, Suzanne, PhD
  • Hughes, E Jane, BScHons
  • Ota, Martin, MD
  • Sutherland, Jayne, PhD
  • Howe, Rawleigh, MD
  • Dockrell, Hazel M, Prof
  • Boom, W Henry, Prof
  • Thiel, Bonnie, MS
  • Ottenhoff, Tom H M, Prof
  • Mayanja-Kizza, Harriet, Prof
  • Crampin, Amelia C, FFPHM
  • Downing, Katrina, PhD
  • Hatherill, Mark, MD
  • Valvo, Joe, BS
  • Shankar, Smitha, MS
  • Parida, Shreemanta K, MD
  • Kaufmann, Stefan H E, Prof
  • Walzl, Gerhard, Prof
  • Aderem, Alan, PhD
  • Hanekom, Willem A, Prof
subjects:
  • Adolescent
  • Adolescents
  • Adult
  • Antitubercular agents
  • Biomarkers
  • Blood
  • Case-Control Studies
  • Charities
  • Child
  • Communicable diseases
  • Development and progression
  • Disease
  • Disease control
  • Epidemics
  • Gene Expression
  • Gene sequencing
  • Grants
  • Health risks
  • HIV
  • Human immunodeficiency virus
  • Humans
  • Identification methods
  • Infections
  • Internal Medicine
  • Lung diseases
  • Medical research
  • Medicine(all)
  • Medicine, Experimental
  • Middle Aged
  • Molecular biology
  • Mycobacterium
  • Mycobacterium tuberculosis
  • Mycobacterium tuberculosis - genetics
  • Prospective Studies
  • Reverse Transcriptase Polymerase Chain Reaction
  • Ribonucleic acid
  • Risk
  • Risk Assessment
  • Risk Factors
  • RNA
  • RNA, Bacterial - metabolism
  • Sensitivity
  • Studies
  • Teenagers
  • Tuberculosis
  • Tuberculosis - blood
  • Tuberculosis - diagnosis
  • Tuberculosis - genetics
  • Tuberculosis vaccines
  • Vaccines
  • Young Adult
ispartof: The Lancet (British edition), 2016, Vol.387 (10035), p.2312-2322
description: Summary Background Identification 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. Methods In 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. Findings Between 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
language: eng
source: Alma/SFX Local Collection
identifier: ISSN: 0140-6736
fulltext: fulltext
issn:
  • 0140-6736
  • 1474-547X
url: Link


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titleA blood RNA signature for tuberculosis disease risk: a prospective cohort study
sourceAlma/SFX Local Collection
creatorZak, Daniel E, PhD ; Penn-Nicholson, Adam, PhD ; Scriba, Thomas J, PhD ; Thompson, Ethan, PhD ; Suliman, Sara, PhD ; Amon, Lynn M, PhD ; Mahomed, Hassan, MD ; Erasmus, Mzwandile, BSc ; Whatney, Wendy, BScHons ; Hussey, Gregory D, Prof ; Abrahams, Deborah, DipMT ; Kafaar, Fazlin, DipNur ; Hawkridge, Tony, FCPHM ; Verver, Suzanne, PhD ; Hughes, E Jane, BScHons ; Ota, Martin, MD ; Sutherland, Jayne, PhD ; Howe, Rawleigh, MD ; Dockrell, Hazel M, Prof ; Boom, W Henry, Prof ; Thiel, Bonnie, MS ; Ottenhoff, Tom H M, Prof ; Mayanja-Kizza, Harriet, Prof ; Crampin, Amelia C, FFPHM ; Downing, Katrina, PhD ; Hatherill, Mark, MD ; Valvo, Joe, BS ; Shankar, Smitha, MS ; Parida, Shreemanta K, MD ; Kaufmann, Stefan H E, Prof ; Walzl, Gerhard, Prof ; Aderem, Alan, PhD ; Hanekom, Willem A, Prof
creatorcontribZak, Daniel E, PhD ; Penn-Nicholson, Adam, PhD ; Scriba, Thomas J, PhD ; Thompson, Ethan, PhD ; Suliman, Sara, PhD ; Amon, Lynn M, PhD ; Mahomed, Hassan, MD ; Erasmus, Mzwandile, BSc ; Whatney, Wendy, BScHons ; Hussey, Gregory D, Prof ; Abrahams, Deborah, DipMT ; Kafaar, Fazlin, DipNur ; Hawkridge, Tony, FCPHM ; Verver, Suzanne, PhD ; Hughes, E Jane, BScHons ; Ota, Martin, MD ; Sutherland, Jayne, PhD ; Howe, Rawleigh, MD ; Dockrell, Hazel M, Prof ; Boom, W Henry, Prof ; Thiel, Bonnie, MS ; Ottenhoff, Tom H M, Prof ; Mayanja-Kizza, Harriet, Prof ; Crampin, Amelia C, FFPHM ; Downing, Katrina, PhD ; Hatherill, Mark, MD ; Valvo, Joe, BS ; Shankar, Smitha, MS ; Parida, Shreemanta K, MD ; Kaufmann, Stefan H E, Prof ; Walzl, Gerhard, Prof ; Aderem, Alan, PhD ; Hanekom, Willem A, Prof ; ACS and GC6-74 cohort study groups
descriptionSummary Background Identification 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. Methods In 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. Findings Between 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. Interpretation The whole blood tuberculosis risk signature prospectively identified people at risk of developing active tuberculosis, opening the possibility for targeted intervention to prevent the disease. Funding Bill & Melinda Gates Foundation, the National Institutes of Health, Aeras, the European Union, and the South African Medical Research Council.
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languageeng
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subjectAdolescent ; Adolescents ; Adult ; Antitubercular agents ; Biomarkers ; Blood ; Case-Control Studies ; Charities ; Child ; Communicable diseases ; Development and progression ; Disease ; Disease control ; Epidemics ; Gene Expression ; Gene sequencing ; Grants ; Health risks ; HIV ; Human immunodeficiency virus ; Humans ; Identification methods ; Infections ; Internal Medicine ; Lung diseases ; Medical research ; Medicine(all) ; Medicine, Experimental ; Middle Aged ; Molecular biology ; Mycobacterium ; Mycobacterium tuberculosis ; Mycobacterium tuberculosis - genetics ; Prospective Studies ; Reverse Transcriptase Polymerase Chain Reaction ; Ribonucleic acid ; Risk ; Risk Assessment ; Risk Factors ; RNA ; RNA, Bacterial - metabolism ; Sensitivity ; Studies ; Teenagers ; Tuberculosis ; Tuberculosis - blood ; Tuberculosis - diagnosis ; Tuberculosis - genetics ; Tuberculosis vaccines ; Vaccines ; Young Adult
ispartofThe Lancet (British edition), 2016, Vol.387 (10035), p.2312-2322
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1Penn-Nicholson, Adam, PhD
2Scriba, Thomas J, PhD
3Thompson, Ethan, PhD
4Suliman, Sara, PhD
5Amon, Lynn M, PhD
6Mahomed, Hassan, MD
7Erasmus, Mzwandile, BSc
8Whatney, Wendy, BScHons
9Hussey, Gregory D, Prof
10Abrahams, Deborah, DipMT
11Kafaar, Fazlin, DipNur
12Hawkridge, Tony, FCPHM
13Verver, Suzanne, PhD
14Hughes, E Jane, BScHons
15Ota, Martin, MD
16Sutherland, Jayne, PhD
17Howe, Rawleigh, MD
18Dockrell, Hazel M, Prof
19Boom, W Henry, Prof
20Thiel, Bonnie, MS
21Ottenhoff, Tom H M, Prof
22Mayanja-Kizza, Harriet, Prof
23Crampin, Amelia C, FFPHM
24Downing, Katrina, PhD
25Hatherill, Mark, MD
26Valvo, Joe, BS
27Shankar, Smitha, MS
28Parida, Shreemanta K, MD
29Kaufmann, Stefan H E, Prof
30Walzl, Gerhard, Prof
31Aderem, Alan, PhD
32Hanekom, Willem A, Prof
33ACS and GC6-74 cohort study groups
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descriptionSummary Background Identification 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. Methods In 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. Findings Between 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. Interpretation The whole blood tuberculosis risk signature prospectively identified people at risk of developing active tuberculosis, opening the possibility for targeted intervention to prevent the disease. Funding Bill & Melinda Gates Foundation, the National Institutes of Health, Aeras, the European Union, and the South African Medical Research Council.
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1Adolescents
2Adult
3Antitubercular agents
4Biomarkers
5Blood
6Case-Control Studies
7Charities
8Child
9Communicable diseases
10Development and progression
11Disease
12Disease control
13Epidemics
14Gene Expression
15Gene sequencing
16Grants
17Health risks
18HIV
19Human immunodeficiency virus
20Humans
21Identification methods
22Infections
23Internal Medicine
24Lung diseases
25Medical research
26Medicine(all)
27Medicine, Experimental
28Middle Aged
29Molecular biology
30Mycobacterium
31Mycobacterium tuberculosis
32Mycobacterium tuberculosis - genetics
33Prospective Studies
34Reverse Transcriptase Polymerase Chain Reaction
35Ribonucleic acid
36Risk
37Risk Assessment
38Risk Factors
39RNA
40RNA, Bacterial - metabolism
41Sensitivity
42Studies
43Teenagers
44Tuberculosis
45Tuberculosis - blood
46Tuberculosis - diagnosis
47Tuberculosis - genetics
48Tuberculosis vaccines
49Vaccines
50Young Adult
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titleA blood RNA signature for tuberculosis disease risk: a prospective cohort study
authorZak, Daniel E, PhD ; Penn-Nicholson, Adam, PhD ; Scriba, Thomas J, PhD ; Thompson, Ethan, PhD ; Suliman, Sara, PhD ; Amon, Lynn M, PhD ; Mahomed, Hassan, MD ; Erasmus, Mzwandile, BSc ; Whatney, Wendy, BScHons ; Hussey, Gregory D, Prof ; Abrahams, Deborah, DipMT ; Kafaar, Fazlin, DipNur ; Hawkridge, Tony, FCPHM ; Verver, Suzanne, PhD ; Hughes, E Jane, BScHons ; Ota, Martin, MD ; Sutherland, Jayne, PhD ; Howe, Rawleigh, MD ; Dockrell, Hazel M, Prof ; Boom, W Henry, Prof ; Thiel, Bonnie, MS ; Ottenhoff, Tom H M, Prof ; Mayanja-Kizza, Harriet, Prof ; Crampin, Amelia C, FFPHM ; Downing, Katrina, PhD ; Hatherill, Mark, MD ; Valvo, Joe, BS ; Shankar, Smitha, MS ; Parida, Shreemanta K, MD ; Kaufmann, Stefan H E, Prof ; Walzl, Gerhard, Prof ; Aderem, Alan, PhD ; Hanekom, Willem A, Prof
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1Adolescents
2Adult
3Antitubercular agents
4Biomarkers
5Blood
6Case-Control Studies
7Charities
8Child
9Communicable diseases
10Development and progression
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14Gene Expression
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16Grants
17Health risks
18HIV
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20Humans
21Identification methods
22Infections
23Internal Medicine
24Lung diseases
25Medical research
26Medicine(all)
27Medicine, Experimental
28Middle Aged
29Molecular biology
30Mycobacterium
31Mycobacterium tuberculosis
32Mycobacterium tuberculosis - genetics
33Prospective Studies
34Reverse Transcriptase Polymerase Chain Reaction
35Ribonucleic acid
36Risk
37Risk Assessment
38Risk Factors
39RNA
40RNA, Bacterial - metabolism
41Sensitivity
42Studies
43Teenagers
44Tuberculosis
45Tuberculosis - blood
46Tuberculosis - diagnosis
47Tuberculosis - genetics
48Tuberculosis vaccines
49Vaccines
50Young Adult
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0Zak, Daniel E, PhD
1Penn-Nicholson, Adam, PhD
2Scriba, Thomas J, PhD
3Thompson, Ethan, PhD
4Suliman, Sara, PhD
5Amon, Lynn M, PhD
6Mahomed, Hassan, MD
7Erasmus, Mzwandile, BSc
8Whatney, Wendy, BScHons
9Hussey, Gregory D, Prof
10Abrahams, Deborah, DipMT
11Kafaar, Fazlin, DipNur
12Hawkridge, Tony, FCPHM
13Verver, Suzanne, PhD
14Hughes, E Jane, BScHons
15Ota, Martin, MD
16Sutherland, Jayne, PhD
17Howe, Rawleigh, MD
18Dockrell, Hazel M, Prof
19Boom, W Henry, Prof
20Thiel, Bonnie, MS
21Ottenhoff, Tom H M, Prof
22Mayanja-Kizza, Harriet, Prof
23Crampin, Amelia C, FFPHM
24Downing, Katrina, PhD
25Hatherill, Mark, MD
26Valvo, Joe, BS
27Shankar, Smitha, MS
28Parida, Shreemanta K, MD
29Kaufmann, Stefan H E, Prof
30Walzl, Gerhard, Prof
31Aderem, Alan, PhD
32Hanekom, Willem A, Prof
33ACS and GC6-74 cohort study groups
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jtitleThe Lancet (British edition)
delivery
delcategoryRemote Search Resource
fulltextfulltext
addata
au
0Zak, Daniel E, PhD
1Penn-Nicholson, Adam, PhD
2Scriba, Thomas J, PhD
3Thompson, Ethan, PhD
4Suliman, Sara, PhD
5Amon, Lynn M, PhD
6Mahomed, Hassan, MD
7Erasmus, Mzwandile, BSc
8Whatney, Wendy, BScHons
9Hussey, Gregory D, Prof
10Abrahams, Deborah, DipMT
11Kafaar, Fazlin, DipNur
12Hawkridge, Tony, FCPHM
13Verver, Suzanne, PhD
14Hughes, E Jane, BScHons
15Ota, Martin, MD
16Sutherland, Jayne, PhD
17Howe, Rawleigh, MD
18Dockrell, Hazel M, Prof
19Boom, W Henry, Prof
20Thiel, Bonnie, MS
21Ottenhoff, Tom H M, Prof
22Mayanja-Kizza, Harriet, Prof
23Crampin, Amelia C, FFPHM
24Downing, Katrina, PhD
25Hatherill, Mark, MD
26Valvo, Joe, BS
27Shankar, Smitha, MS
28Parida, Shreemanta K, MD
29Kaufmann, Stefan H E, Prof
30Walzl, Gerhard, Prof
31Aderem, Alan, PhD
32Hanekom, Willem A, Prof
aucorpACS and GC6-74 cohort study groups
formatjournal
genrearticle
ristypeJOUR
atitleA blood RNA signature for tuberculosis disease risk: a prospective cohort study
jtitleThe Lancet (British edition)
addtitleLancet
date2016
risdate2016
volume387
issue10035
spage2312
epage2322
pages2312-2322
issn0140-6736
eissn1474-547X
codenLANCAO
abstractSummary Background Identification 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. Methods In 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. Findings Between 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. Interpretation The whole blood tuberculosis risk signature prospectively identified people at risk of developing active tuberculosis, opening the possibility for targeted intervention to prevent the disease. Funding Bill & Melinda Gates Foundation, the National Institutes of Health, Aeras, the European Union, and the South African Medical Research Council.
copEngland
pubElsevier Ltd
pmid27017310
doi10.1016/S0140-6736(15)01316-1
oafree_for_read