Comparing QuantiFERON-TB Gold Plus with QuantiFERON-TB Gold in-tube for diagnosis of latent tuberculosis infection among highly TB exposed gold miners in South Africa

Thobani Ntshiqa; Violet Chihota; Raoul Mansukhani; Lindiwe Nhlangulela; Kavindhran Velen; Salome Charalambous; Pholo Maenetje; Thomas R Hawn; Robert Wallis; Alison D Grant; Katherine Fielding; Gavin Churchyard

doi:10.12688/gatesopenres.13191.3

Comparing QuantiFERON-TB Gold Plus with QuantiFERON-TB Gold in-tube for diagnosis of latent tuberculosis infection among highly TB exposed gold miners in South Africa

Gates Open Res. 2022 Aug 18:5:66. doi: 10.12688/gatesopenres.13191.3. eCollection 2021.

Authors

Thobani Ntshiqa¹, Violet Chihota^{1

2}, Raoul Mansukhani³, Lindiwe Nhlangulela¹, Kavindhran Velen¹, Salome Charalambous^{1

2}, Pholo Maenetje¹, Thomas R Hawn⁴, Robert Wallis¹, Alison D Grant^{2

3

5}, Katherine Fielding^{2

3}, Gavin Churchyard^{1

2}

Affiliations

¹ Implementation Research Division, The Aurum Institute, Johannesburg, Gauteng, 2193, South Africa.
² School of Public Health, University of the Witwatersrand, Johannesburg, Gauteng, 2193, South Africa.
³ Department of Infectious Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, United Kingdom, WC1E 7HT, UK.
⁴ Department of Medicine, University of Washington, Seattle, Seattle, New York, 98195, USA.
⁵ Africa Health Research Institute, Laboratory Medicine & Medical Sciences, College of Health Sciences, University of KwaZulu-Natal, Durban, KwaZulu-Natal, 4041, South Africa.

Abstract

Background: QuantiFERON-TB-Gold-in-tube (QFT-GIT) is an interferon-gamma release assay (IGRA) used to diagnose latent tuberculosis infection. Limited data exists on performance of QuantiFERON-TB Gold-Plus (QFT-Plus), a next generation of IGRA that includes an additional antigen tube 2 (TB2) while excluding TB7.7 from antigen tube 1 (TB1), to measure TB specific CD4+ and CD8+ T lymphocytes responses. We compared agreement between QFT-Plus and QFT-GIT among highly TB exposed goldminers in South Africa. Methods: We enrolled HIV-negative goldminers in South Africa, aged ≥33 years with no prior history of TB disease or evidence of silicosis. Blood samples were collected for QFT-GIT and QFT-Plus. QFT-GIT was considered positive if TB1 tested positive; while QFT-Plus was positive if both or either TB1 or TB2 tested positive, as per manufacturer's recommendations. We compared the agreement between QFT-Plus and QFT-GIT using Cohen's Kappa. To assess the specific contribution of CD8+ T-cells, we used TB2-TB1 differential values as an indirect estimate. A cut-off value was set at 0.6. Logistic regression was used to identify factors associated with having TB2-TB1>0.6 difference on QFT-Plus. Results: Of 349 enrolled participants, 304 had QFT-Plus and QFT-GIT results: 205 (68%) were positive on both assays; 83 (27%) were negative on both assays while 16 (5%) had discordant results. Overall, there was 94.7% (288/304) agreement between QFT-Plus and QFT-GIT (Kappa = 0.87). 214 had positive QFT-Plus result, of whom 202 [94.4%, median interquartile range (IQR): 3.06 (1.31, 7.00)] were positive on TB1 and 205 [95.8%, median (IQR): 3.25 (1.53, 8.02)] were positive on TB2. A TB2-TB1>0.6 difference was observed in 16.4% (35/214), with some evidence of a difference by BMI; 14.9% (7/47), 9.8% (9/92) and 25.3% (19/75) for BMI of 18.5-24.9, 18.5-25 and >30 kg/m 2, respectively (P=0.03). Conclusion: In a population of HIV-negative goldminers, QFT-Plus showed high agreement with QFT-GIT, suggesting similar performance.

Keywords: Goldmines; Latent Tuberculosis Infection; Performance; QFT-GIT; QFT-Plus; South Africa; TST.

Grants and funding

This study was funded by the Bill & Melinda Gates Foundation [OPP1116635].