Diagnostic Accuracy of Early Secretory Antigenic Target-6-Free Interferon-gamma Release Assay Compared to QuantiFERON-TB Gold In-tube.

Adolescent Antigens, Bacterial / immunology Bacterial Proteins / immunology Child Cohort Studies Female Humans Interferon-gamma / blood Interferon-gamma Release Tests Male Mycobacterium tuberculosis / immunology ROC Curve Reagent Kits, Diagnostic Reproducibility of Results Tuberculosis / blood Tuberculosis Vaccines / administration & dosage

IFN-γ release assay diagnosis qualification tuberculosis infection

Journal

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

ISSN: 1537-6591

Titre abrégé: Clin Infect Dis

Pays: United States

ID NLM: 9203213

Informations de publication

Date de publication:
30 10 2019

Historique:

received: 04 10 2018

accepted: 16 01 2019

pubmed: 23 1 2019

medline: 26 9 2020

entrez: 23 1 2019

Statut: ppublish

Résumé

Early secretory antigenic target-6 (ESAT-6) is an immunodominant Mycobacterium tuberculosis (M.tb) antigen included in novel vaccines against tuberculosis (TB) and in interferon-gamma (IFN-γ) release assays (IGRAs). Therefore, the availability of an ESAT-6-free IGRA is essential to determine M.tb infection status following vaccination with ESAT-6-containing vaccines. We aimed to qualify a recently developed ESAT-6-free IGRA and to assess its diagnostic performance in comparison to QuantiFERON-TB Gold In-tube (QFT). Participants with different levels of M.tb exposure and TB disease were enrolled to determine the ESAT-6-free IGRA cutoff, test assay performance in independent cohorts compared to standard QFT, and perform a technical qualification of antigen-coated blood collection tubes. ESAT-6-free IGRA antigen recognition was evaluated in QFT-positive and QFT-negative South African adolescents. The ESAT-6-free IGRA cutoff was established at 0.61 IU/mL, based on receiver operating characteristic analysis in M.tb-unexposed controls and microbiologically confirmed pulmonary TB patients. In an independent cohort of healthy adolescents, levels of IFN-γ released in QFT and ESAT-6-free IGRA were highly correlated (P < .0001, r = 0.83) and yielded comparable positivity rates, 41.5% and 43.5%, respectively, with 91% concordance between the tests (kappa = 0.82; 95% confidence interval, 0.74-0.90; McNemar test P = .48). ESAT-6-free IGRA blood collection tubes had acceptable lot-to-lot variability, precision, and stability. The novel ESAT-6-free IGRA had diagnostic accuracy comparable to QFT and is suitable for use in clinical trials to assess efficacy of candidate TB vaccines to prevent established M.tb infection.

Sections du résumé

BACKGROUND

METHODS

Participants with different levels of M.tb exposure and TB disease were enrolled to determine the ESAT-6-free IGRA cutoff, test assay performance in independent cohorts compared to standard QFT, and perform a technical qualification of antigen-coated blood collection tubes.

RESULTS

ESAT-6-free IGRA antigen recognition was evaluated in QFT-positive and QFT-negative South African adolescents. The ESAT-6-free IGRA cutoff was established at 0.61 IU/mL, based on receiver operating characteristic analysis in M.tb-unexposed controls and microbiologically confirmed pulmonary TB patients. In an independent cohort of healthy adolescents, levels of IFN-γ released in QFT and ESAT-6-free IGRA were highly correlated (P < .0001, r = 0.83) and yielded comparable positivity rates, 41.5% and 43.5%, respectively, with 91% concordance between the tests (kappa = 0.82; 95% confidence interval, 0.74-0.90; McNemar test P = .48). ESAT-6-free IGRA blood collection tubes had acceptable lot-to-lot variability, precision, and stability.

CONCLUSIONS

The novel ESAT-6-free IGRA had diagnostic accuracy comparable to QFT and is suitable for use in clinical trials to assess efficacy of candidate TB vaccines to prevent established M.tb infection.

Identifiants

DOI: 10.1093/cid/ciz034 PMID: 30668657 PMC: PMC6821223

pubmed: 30668657

pii: 5298338

doi: 10.1093/cid/ciz034

pmc: PMC6821223

doi:

Substances chimiques

Antigens, Bacterial 0

Bacterial Proteins 0

ESAT-6 protein, Mycobacterium tuberculosis 0

Reagent Kits, Diagnostic 0

Tuberculosis Vaccines 0

Interferon-gamma 82115-62-6

Types de publication

Comparative Study Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

Pagination

1724-1730

Subventions

Organisme : NIAID NIH HHS

ID : U01 AI115619

Pays : United States

Commentaires et corrections

Type : CommentIn

Informations de copyright

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