Prospective multicentre head-to-head validation of host blood transcriptomic biomarkers for pulmonary tuberculosis by real-time PCR.

Journal

Communications medicine
ISSN: 2730-664X
Titre abrégé: Commun Med (Lond)
Pays: England
ID NLM: 9918250414506676

Informations de publication

Date de publication:
2022
Historique:
entrez: 28 3 2022
pubmed: 29 3 2022
medline: 29 3 2022
Statut: ppublish

Résumé

Sensitive point-of-care screening tests are urgently needed to identify individuals at highest risk of tuberculosis. We prospectively tested performance of host-blood transcriptomic tuberculosis signatures. Adults without suspicion of tuberculosis were recruited from five endemic South African communities. Eight parsimonious host-blood transcriptomic tuberculosis signatures were measured by microfluidic RT-qPCR at enrolment. Upper respiratory swab specimens were tested with a multiplex bacterial-viral RT-qPCR panel in a subset of participants. Diagnostic and prognostic performance for microbiologically confirmed prevalent and incident pulmonary tuberculosis was tested in all participants at baseline and during active surveillance through 15 months follow-up, respectively. Among 20,207 HIV-uninfected and 963 HIV-infected adults screened; 2923 and 861 were enroled. There were 61 HIV-uninfected (weighted prevalence 1.1%) and 10 HIV-infected (prevalence 1.2%) tuberculosis cases at baseline. Parsimonious signature diagnostic performance was superior among symptomatic (AUCs 0.85-0.98) as compared to asymptomatic (AUCs 0.61-0.78) HIV-uninfected participants. Thereafter, 24 HIV-uninfected and 9 HIV-infected participants progressed to incident tuberculosis (1.1 and 1.0 per 100 person-years, respectively). Among HIV-uninfected individuals, prognostic performance for incident tuberculosis occurring within 6-12 months was higher relative to 15 months. 1000 HIV-uninfected participants were tested for respiratory microorganisms and 413 HIV-infected for HIV plasma viral load; 7/8 signature scores were higher ( Several parsimonious tuberculosis transcriptomic signatures met triage test targets among symptomatic participants, and incipient test targets within 6 months. However, the signatures were upregulated with viral infection and offered poor specificity for diagnosing sub-clinical tuberculosis.

Sections du résumé

Background
Sensitive point-of-care screening tests are urgently needed to identify individuals at highest risk of tuberculosis. We prospectively tested performance of host-blood transcriptomic tuberculosis signatures.
Methods
Adults without suspicion of tuberculosis were recruited from five endemic South African communities. Eight parsimonious host-blood transcriptomic tuberculosis signatures were measured by microfluidic RT-qPCR at enrolment. Upper respiratory swab specimens were tested with a multiplex bacterial-viral RT-qPCR panel in a subset of participants. Diagnostic and prognostic performance for microbiologically confirmed prevalent and incident pulmonary tuberculosis was tested in all participants at baseline and during active surveillance through 15 months follow-up, respectively.
Results
Among 20,207 HIV-uninfected and 963 HIV-infected adults screened; 2923 and 861 were enroled. There were 61 HIV-uninfected (weighted prevalence 1.1%) and 10 HIV-infected (prevalence 1.2%) tuberculosis cases at baseline. Parsimonious signature diagnostic performance was superior among symptomatic (AUCs 0.85-0.98) as compared to asymptomatic (AUCs 0.61-0.78) HIV-uninfected participants. Thereafter, 24 HIV-uninfected and 9 HIV-infected participants progressed to incident tuberculosis (1.1 and 1.0 per 100 person-years, respectively). Among HIV-uninfected individuals, prognostic performance for incident tuberculosis occurring within 6-12 months was higher relative to 15 months. 1000 HIV-uninfected participants were tested for respiratory microorganisms and 413 HIV-infected for HIV plasma viral load; 7/8 signature scores were higher (
Conclusions
Several parsimonious tuberculosis transcriptomic signatures met triage test targets among symptomatic participants, and incipient test targets within 6 months. However, the signatures were upregulated with viral infection and offered poor specificity for diagnosing sub-clinical tuberculosis.

Identifiants

DOI: 10.1038/s43856-022-00086-8 PMID: 35342900 PMC: PMC8954216
pubmed: 35342900
doi: 10.1038/s43856-022-00086-8
pmc: PMC8954216
mid: NIHMS1787893
pii:
doi:

Types de publication

Journal Article

Langues

eng

Subventions

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

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Auteurs

Simon C Mendelsohn (SC)

South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, and Division of Immunology, Department of Pathology, University of Cape Town, 7925 Cape Town, South Africa.
ORCID: 0000-0002-4054-2766

Stanley Kimbung Mbandi (SK)

South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, and Division of Immunology, Department of Pathology, University of Cape Town, 7925 Cape Town, South Africa.
ORCID: 0000-0001-6121-9039

Andrew Fiore-Gartland (A)

Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.

Adam Penn-Nicholson (A)

South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, and Division of Immunology, Department of Pathology, University of Cape Town, 7925 Cape Town, South Africa.
ORCID: 0000-0002-1883-0059

Munyaradzi Musvosvi (M)

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

Humphrey Mulenga (H)

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

Michelle Fisher (M)

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

Katie Hadley (K)

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

Mzwandile Erasmus (M)

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

Onke Nombida (O)

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

Michèle Tameris (M)

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

Gerhard Walzl (G)

DST/NRF Centre of Excellence for Biomedical TB Research; South African Medical Research Council Centre for TB Research; Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, 7505 Cape Town, South Africa.
ORCID: 0000-0003-2487-125X

Kogieleum Naidoo (K)

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

Gavin Churchyard (G)

The Aurum Institute, 2194 Johannesburg, South Africa.
School of Public Health, University of Witwatersrand, 2193 Johannesburg, South Africa.
Department of Medicine, Vanderbilt University, Nashville, TN 37232, USA.

Mark Hatherill (M)

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

Thomas J Scriba (TJ)

South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, and Division of Immunology, Department of Pathology, University of Cape Town, 7925 Cape Town, South Africa.
ORCID: 0000-0002-0641-1359

Classifications MeSH