Evaluation of the QuantiFERON-Tuberculosis Gold Plus Assay in Children with Tuberculosis Disease or Following Household Exposure to Tuberculosis

Kay, Alexander; DiNardo, Andrew; Dlamini, Qiniso; Kahari, Jaqueline; Mndzebele, Temhlanga; Mtetwa, Godwin; Ustero, Pilar; Maphalala, Gugu; Mandalakas, Anna M.

doi:10.4269/ajtmh.18-0674

Cited by 24 publications

(34 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…TB effectiveness for diagnosing pediatric tuberculosis as only adults were studied; substantial differences have been reported between immune responses to MTB in children versus adults. [ 41 , 42 ] Third, the impact of nontuberculous mycobacterial (NTM) infection was not considered here even though patients infected with M. kansasii, M. szulgai or M. marinum may also have positive IGRA results, since NTM also harbor genes encoding ESAT-6 and CFP-10 antigens. [ 7 ]…”

Section: Discussionmentioning

confidence: 99%

Factors associated with differential T cell responses to antigens ESAT-6 and CFP-10 in pulmonary tuberculosis patients

Liu

Wu²,

Ertai³

et al. 2021

Medicine

View full text Add to dashboard Cite

The T-SPOT.TB assay detects cellular immune responses to 2 core Mycobacterium tuberculosis antigens, early secreted antigenic target of 6-kDa protein (ESAT-6) and culture filtrate protein-10 (CFP-10). T-SPOT.TB has been recently used for auxiliary diagnosis of active pulmonary tuberculosis (PTB). However, testing can produce inconsistent results due to differential PTB patient immune responses to these antigens, prompting us to identify factors underlying inconsistent results. Data were retrospectively analyzed from 1225 confirmed PTB patients who underwent T-SPOT.TB testing at 5 specialized tuberculosis hospitals in China between December 2012 and November 2015. Numbers of spot-forming cells (SFCs) reflecting T cell responses to ESAT-6 and CFP-10 antigens were recorded then analyzed via multivariable logistic regression to reveal factors underlying discordant T cell responses to these antigens. The agreement rate of 84.98% (82.85%–86.94%) between PTB patient ESAT-6 and CFP-10 responses demonstrated high concordance. Additionally, positivity rates were higher for ESAT-6 than for CFP-10 (84.8% vs 80.7%, P < .001), with ESAT-6 and CFP-10 microwell SFC numbers for each single positive group not differing significantly (P > .99), while spot numbers of the single positive group were lower than numbers for the double positive group (P < .001). Elderly patients (aged ≥66 years) and patients receiving retreatment were most likely to have discordance results. ESAT-6 promoted significantly more positive T-SPOT.TB results than did CFP-10 in PTB patients. Advanced age and retreatment status were correlated with discordant ESAT-6 and CFP-10 results. Assessment of factors underlying discordance may lead to improved PTB diagnosis using T-SPOT.TB.

show abstract

Section: Discussionmentioning

confidence: 99%

Factors associated with differential T cell responses to antigens ESAT-6 and CFP-10 in pulmonary tuberculosis patients

Liu

Wu²,

Ertai³

et al. 2021

Medicine

View full text Add to dashboard Cite

show abstract

“…Blood transcriptional markers and cell-free DNA in urine constitute promising additional candidates for non-sputum triage or confirmatory TB tests 6 , 7 . Tuberculin skin test (TST) and interferon-gamma (IFN-γ) release assays cannot differentiate latent infection from active disease and a decreased sensitivity has been reported in children living with HIV 8 , 9 . In contrast, we and others demonstrated that T cell activation markers (TAM), notably CD27, but also CD38, Ki-67, CD153, CD161 and HLA-DR, can distinguish active from latent TB, monitor patient response to treatment and retrospectively diagnose TB with unprecedented accuracy 10 – 14 .…”

Section: Introductionmentioning

confidence: 99%

Case–control diagnostic accuracy study of a non-sputum CD38-based TAM-TB test from a single milliliter of blood

Hiza

Hella

Arbués

et al. 2021

Sci Rep

View full text Add to dashboard Cite

CD4 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 24 h turnaround time. We 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 IFN-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. Significantly 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. To conclude, we successfully implemented TAM-TB immunoassay routine testing with a 24 h 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.

show abstract

“…Blood transcriptional markers and cell-free DNA in urine constitute promising additional candidates for non-sputum triage or confirmatory TB tests [6] [7]. Tuberculin skin test (TST) and interferon-gamma release assays cannot differentiate latent infection from active disease and a decreased sensitivity has been reported in children living with HIV [8,9]. In contrast, we and others demonstrated that T cell activation markers (TAM), notably CD27, but also CD38, Ki-67, CD153, CD161 and HLA-DR, can distinguish active from latent TB, monitor patient response to treatment and retrospectively diagnose TB in children with unprecedented accuracy [10][11][12][13].…”

Section: Introductionmentioning

confidence: 99%

Case-control, diagnostic accuracy study of a non-sputum CD38-based TAM-TB test from a single milliliter of blood

Hiza

Hella

Arbués

et al. 2021

Preprint

View full text Add to dashboard Cite

Background: CD4 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. Methods: We 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-gamma; and/or TNF-alpha; 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. Results: Significantly 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. Conclusions: We successfully implemented TAM-TB immunoassay routine testing with a 24h turnaround time at district level in a resource limited setting. Starting from one milliliter 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.

show abstract

Evaluation of the QuantiFERON-Tuberculosis Gold Plus Assay in Children with Tuberculosis Disease or Following Household Exposure to Tuberculosis

Cited by 24 publications

References 13 publications

Factors associated with differential T cell responses to antigens ESAT-6 and CFP-10 in pulmonary tuberculosis patients

Factors associated with differential T cell responses to antigens ESAT-6 and CFP-10 in pulmonary tuberculosis patients

Case–control diagnostic accuracy study of a non-sputum CD38-based TAM-TB test from a single milliliter of blood

Case-control, diagnostic accuracy study of a non-sputum CD38-based TAM-TB test from a single milliliter of blood

Contact Info

Product

Resources

About