Evaluation of a transcriptomic signature of tuberculosis risk in combination with an interferon gamma release assay: A diagnostic test accuracy study.

Combination Mycobacterium tuberculosis Performance QuantiFERON Signature Transcriptomic

Journal

EClinicalMedicine
ISSN: 2589-5370
Titre abrégé: EClinicalMedicine
Pays: England
ID NLM: 101733727

Informations de publication

Date de publication:
May 2022
Historique:
received: 24 01 2022
revised: 25 03 2022
accepted: 29 03 2022
entrez: 2 5 2022
pubmed: 3 5 2022
medline: 3 5 2022
Statut: epublish

Résumé

We evaluated the diagnostic and prognostic performance of a transcriptomic signature of tuberculosis (TB) risk (RISK11) and QuantiFERON-TB Gold-plus (QFTPlus) as combination biomarkers of TB risk. Healthy South Africans who were HIV-negative aged 18-60 years with baseline RISK11 and QFTPlus results were evaluated in a prospective cohort study conducted between Sept 20, 2016 and Dec 20, 2019. Prevalence and incidence-rate ratios were used to evaluate risk of TB. Positive (LR+) and negative (LR-) likelihood ratios were used to compare individual tests versus Both-Positive (RISK11+/QFTPlus+) and Either-Positive (RISK11+ or QFTPlus+) combinations. Among 2912 participants, prevalent TB in RISK11+/QFTPlus+ participants was 13·3-fold (95% CI 4·2-42·7) higher than RISK11-/QFTPlus-; 2·4-fold (95% CI 1·2-4·8) higher than RISK11+/QFTPlus-; and 4·5-fold (95% CI 2·5-8·0) higher than RISK11-/QFTPlus+ participants. Risk of incident TB in RISK11+/QFTPlus+ participants was 8·3-fold (95% CI 2·5-27·0) higher than RISK11-/QFTPlus-; 2·5-fold (95% CI 1·0-6·6) higher than RISK11+/QFTPlus-; and 2·1-fold (95% CI 1·2-3·4) higher than RISK11-/QFTPlus+ participants, respectively. Compared to QFTPlus, the Both-Positive test combination increased diagnostic LR+ from 1·3 (95% CI 1·2-1·5) to 4·7 (95% CI 3·2-7·0), and prognostic LR+ from 1·4 (95% CI 1·2-1·5) to 2·8 (95% CI 1·5-5·1), but did not improve upon RISK11 alone. Compared with RISK11, the Either-Positive test combination decreased diagnostic LR- from 0·7 (95% CI 0·6-0·9) to 0·3 (95% CI 0·2-0·6), and prognostic LR- from 0·9 (95% CI 0·8-1·0) to 0·3 (0·1-0·7), but did not improve upon QFTPlus alone. Combining two tests such as RISK11 and QFTPlus, with discordant individual performance characteristics does not improve overall discriminatory performance, relative to the individual tests. Bill and Melinda Gates Foundation, South African Medical Research Council.

Sections du résumé

Background UNASSIGNED
We evaluated the diagnostic and prognostic performance of a transcriptomic signature of tuberculosis (TB) risk (RISK11) and QuantiFERON-TB Gold-plus (QFTPlus) as combination biomarkers of TB risk.
Methods UNASSIGNED
Healthy South Africans who were HIV-negative aged 18-60 years with baseline RISK11 and QFTPlus results were evaluated in a prospective cohort study conducted between Sept 20, 2016 and Dec 20, 2019. Prevalence and incidence-rate ratios were used to evaluate risk of TB. Positive (LR+) and negative (LR-) likelihood ratios were used to compare individual tests versus Both-Positive (RISK11+/QFTPlus+) and Either-Positive (RISK11+ or QFTPlus+) combinations.
Findings UNASSIGNED
Among 2912 participants, prevalent TB in RISK11+/QFTPlus+ participants was 13·3-fold (95% CI 4·2-42·7) higher than RISK11-/QFTPlus-; 2·4-fold (95% CI 1·2-4·8) higher than RISK11+/QFTPlus-; and 4·5-fold (95% CI 2·5-8·0) higher than RISK11-/QFTPlus+ participants. Risk of incident TB in RISK11+/QFTPlus+ participants was 8·3-fold (95% CI 2·5-27·0) higher than RISK11-/QFTPlus-; 2·5-fold (95% CI 1·0-6·6) higher than RISK11+/QFTPlus-; and 2·1-fold (95% CI 1·2-3·4) higher than RISK11-/QFTPlus+ participants, respectively. Compared to QFTPlus, the Both-Positive test combination increased diagnostic LR+ from 1·3 (95% CI 1·2-1·5) to 4·7 (95% CI 3·2-7·0), and prognostic LR+ from 1·4 (95% CI 1·2-1·5) to 2·8 (95% CI 1·5-5·1), but did not improve upon RISK11 alone. Compared with RISK11, the Either-Positive test combination decreased diagnostic LR- from 0·7 (95% CI 0·6-0·9) to 0·3 (95% CI 0·2-0·6), and prognostic LR- from 0·9 (95% CI 0·8-1·0) to 0·3 (0·1-0·7), but did not improve upon QFTPlus alone.
Interpretation UNASSIGNED
Combining two tests such as RISK11 and QFTPlus, with discordant individual performance characteristics does not improve overall discriminatory performance, relative to the individual tests.
Funding UNASSIGNED
Bill and Melinda Gates Foundation, South African Medical Research Council.

Identifiants

DOI: 10.1016/j.eclinm.2022.101396 PMID: 35497063 PMC: PMC9046130
pubmed: 35497063
doi: 10.1016/j.eclinm.2022.101396
pii: S2589-5370(22)00126-2
pmc: PMC9046130
doi:

Types de publication

Journal Article

Langues

eng

Pagination

101396

Subventions

Organisme : FIC NIH HHS
ID : D43 TW010559
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI154463
Pays : United States

Informations de copyright

© 2022 The Authors.

Déclaration de conflit d'intérêts

AP-N, GW, GC, TJS, and MH report grants from the Bill & Melinda Gates Foundation, during the conduct of the study; AP-N and GW report grants from the South African Medical Research Council, during the conduct of the study; GW and TJS report grants from the South African National Research Foundation, during the conduct of the study. In addition, AP-N and TJS have a patent of the RISK11 and RISK6 signatures issued; GW has a patent “TB diagnostic markers” (PCT/IB2013/054377) issued and a patent “Method for diagnosing TB” (PCT/IB2017/052142) pending. All other authors had nothing to disclose.

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Auteurs

Humphrey Mulenga (H)

South African Tuberculosis Vaccine Initiative, Department of Pathology, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, University of Cape Town, Anzio Road, Observatory 7925, South Africa.

Andrew Fiore-Gartland (A)

Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Fairview Ave. N., Seattle, WA 98109-1024, USA.

Simon C Mendelsohn (SC)

South African Tuberculosis Vaccine Initiative, Department of Pathology, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, University of Cape Town, Anzio Road, Observatory 7925, South Africa.

Adam Penn-Nicholson (A)

South African Tuberculosis Vaccine Initiative, Department of Pathology, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, University of Cape Town, Anzio Road, Observatory 7925, South Africa.

Stanley Kimbung Mbandi (SK)

South African Tuberculosis Vaccine Initiative, Department of Pathology, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, University of Cape Town, Anzio Road, Observatory 7925, South Africa.

Elisa Nemes (E)

South African Tuberculosis Vaccine Initiative, Department of Pathology, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, University of Cape Town, Anzio Road, Observatory 7925, South Africa.

Bhavesh Borate (B)

Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Fairview Ave. N., Seattle, WA 98109-1024, USA.

Munyaradzi Musvosvi (M)

South African Tuberculosis Vaccine Initiative, Department of Pathology, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, University of Cape Town, Anzio Road, Observatory 7925, South Africa.

Michèle Tameris (M)

South African Tuberculosis Vaccine Initiative, Department of Pathology, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, University of Cape Town, Anzio Road, Observatory 7925, South Africa.

Gerhard Walzl (G)

DST/NRF Centre of Excellence for Biomedical TB Research and SAMRC Centre for TB Research, Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, Francie Van Zijl Drive, Parow 7505, South Africa.

Kogieleum Naidoo (K)

Centre for the AIDS Programme of Research in South Africa (CAPRISA), Doris Duke Medical Research Institute, University of KwaZulu-Natal, 719 Umbilo Road, Durban 4001, South Africa.
MRC-CAPRISA HIV-TB Pathogenesis and Treatment Research Unit, Doris Duke Medical Research Institute, University of KwaZulu-Natal, 719 Umbilo Road, Durban 4001, South Africa.

Gavin Churchyard (G)

The Aurum Institute, 29 Queens Rd, Parktown, Johannesburg, Gauteng 2194, South Africa.
School of Public Health, University of Witwatersrand, 27 St Andrews Road, Parktown, Johannesburg 2193, South Africa.
Department of Medicine, Vanderbilt University, Nashville, TN, USA.

Thomas J Scriba (TJ)

South African Tuberculosis Vaccine Initiative, Department of Pathology, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, University of Cape Town, Anzio Road, Observatory 7925, South Africa.

Mark Hatherill (M)

South African Tuberculosis Vaccine Initiative, Department of Pathology, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, University of Cape Town, Anzio Road, Observatory 7925, South Africa.

Classifications MeSH