1. Case–control diagnostic accuracy study of a non-sputum CD38-based TAM-TB test from a single milliliter of blood
- Author
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Hellen Hiza, Sebastien Gagneux, Mohamed Sasamalo, Damien Portevin, Jerry Hella, Ainhoa Arbués, Beatrice Magani, and Klaus Reither
- Subjects
Adult ,CD4-Positive T-Lymphocytes ,Male ,medicine.medical_specialty ,Tuberculosis ,Adolescent ,Science ,HIV Infections ,Lymphocyte Activation ,Sensitivity and Specificity ,Turnaround time ,Article ,Cigarette Smoking ,Translational Research, Biomedical ,Mycobacterium tuberculosis ,Interferon-gamma ,Young Adult ,Applied immunology ,Antigen ,Computer Systems ,Internal medicine ,medicine ,Humans ,Membrane Glycoproteins ,biology ,Receiver operating characteristic ,medicine.diagnostic_test ,Tumor Necrosis Factor-alpha ,business.industry ,Diagnostic markers ,Liter ,Middle Aged ,Translational research ,biology.organism_classification ,medicine.disease ,ADP-ribosyl Cyclase 1 ,ROC Curve ,Area Under Curve ,Case-Control Studies ,Immunoassay ,Sputum ,Medicine ,Female ,medicine.symptom ,business - Abstract
BackgroundCD4 T cell phenotyping-based blood assays have the potential to meet WHO target product profiles (TPP) of non-sputum-biomarker-based tests to diagnose tuberculosis (TB). Yet, substantial refinements are required to allow their implementation in clinical settings. This study assessed the real time performance of a simplified T cell activation marker (TAM)-TB assay to detect TB in adults from one millilitre of blood with a 24h turnaround time.MethodsWe recruited 479 GeneXpert® positive cases and 108 symptomatic but GeneXpert® negative controls from presumptive adult TB patients in the Temeke District of Dar-es-Salaam, Tanzania. TAM-TB assay accuracy was assessed by comparison with a composite reference standard comprising GeneXpert® and solid culture. A single millilitre of fresh blood was processed to measure expression of CD38 or CD27 by CD4 T cells producing INF-γ and/or TNF-α in response to a synthetic peptide pool covering the sequences of Mycobacterium tuberculosis (Mtb) ESAT-6, CFP-10 and TB10.4 antigens on a 4-color FACSCalibur apparatus.ResultsSignificantly superior to CD27 in accurately diagnosing TB, the CD38-based TAM-TB assay specificity reached 93.4% for a sensitivity of 82.2% with an area under the receiver operating characteristics curve of 0.87 (95% CI 0.84-0.91). The assay performance was not significantly affected by HIV status.ConclusionsWe successfully implemented TAM-TB immunoassay routine testing with a 24h turnaround time at district level in a resource limited setting. Starting from one millilitre of fresh blood and being not influenced by HIV status, TAM-TB assay format and performance appears closely compatible with the optimal TPP accuracy criteria defined by WHO for a non-sputum confirmatory TB test.
- Published
- 2021