Diagnostic information from a negative QuantiFERON-TB Gold Plus result in adults evaluated for tuberculosis in Brazil and South Africa
- 1Universidade do Estado do Amazonas
Abstract
Interferon-gamma release assays detect Mycobacterium tuberculosis infection but cannot distinguish infection from active tuberculosis (TB). We evaluated the diagnostic information provided by QuantiFERON-TB Gold Plus (QFT-Plus) among adults investigated for active TB in Brazil and South Africa. Adults with presumptive TB were prospectively enrolled by convenience sampling. QFT-Plus was the index test, and diagnostic classification required microbiological confirmation of TB or an established alternative diagnosis. QFT-Plus results did not inform diagnostic classification. Accuracy was assessed among participants with determinate results, primarily using likelihood ratios. Of 723 participants tested, 48 (6.6%) had indeterminate results, all due to low mitogen responses. Among 675 participants with determinate results, 147 (21.8%) had confirmed TB. Sensitivity was 68.0% (95% CI, 60.1-75.0), specificity was 59.3% (95% CI, 55.0-63.4), and the negative likelihood ratio was 0.54 (95% CI, 0.42- 0.69). At the observed prevalence, a negative result left a 13.1% probability of active TB. Negative likelihood ratio confidence intervals included 1 in both South African HIV strata. Specificity was higher among participants with HIV in both countries. Adding TB2 to TB1 alone identified 15 additional TB cases and generated 18 additional positive results among participants without active TB. HIV and active TB were independently associated with indeterminate results in exploratory regression. A negative QFT-Plus result provided insufficient information to exclude active TB. Higher negative predictive values among participants with HIV reflected lower disease prevalence and higher specificity rather than greater sensitivity. Negative or indeterminate results should not terminate diagnostic evaluation.
IMPORTANCEBlood tests that detect immune responses to Mycobacterium tuberculosis can yield negative results in people with active tuberculosis. Understanding how much reassurance a negative result provides is therefore important when these tests are encountered during diagnostic investigation. Among symptomatic adults in Brazil and South Africa, a negative QuantiFERON-TB Gold Plus result left a substantial probability of active disease. Differences between populations showed why apparently reassuring negative predictive values can be misleading. The additional antigen tube detected more cases but did not overcome the tests limited ability to exclude disease. Indeterminate results were associated with human immunodeficiency virus infection and active tuberculosis. These findings support laboratory reporting and clinical interpretation that clearly communicate the limitations of negative and indeterminate results and the need for continued investigation when active tuberculosis remains suspected.
Related
- Optimizing diagnosis of Mycobacterium tuberculosis latent infection: ELISpot as a technique of choice for samples with high negative control values in QuantiFERON assay
- Performance of ultra-sensitive electrochemiluminescence LAM assay for diagnosing tuberculosis in HIV-negative individuals: a multicentre, prospective diagnostic study
- From armed-conflict to care: clinical outcomes, diagnostic challenges, and psychosocial burden in children evaluated for suspected cancer displaced from Gaza and treated at a regional center of excellence
- Laryngeal tuberculosis mimicking a vallecular cyst: a diagnostic pitfall.
- Beyond diagnostic accuracy: defining the role of tongue swabs in decentralised tuberculosis screening
BibTeX
@misc{costa2026diagnostic,
title = {{Diagnostic information from a negative QuantiFERON-TB Gold Plus result in adults evaluated for tuberculosis in Brazil and South Africa}},
author = {A. G. da Costa and A. Trajman and M. C. Borges-Cabral and A. Esmail and B. K. S. Carvalho and B. P. Loiola and A. B. Souza and R. Spener-Gomes and J. s. Jesus and V. S. Sampaio and D. B. d. Castro and K. Dheda and M. Cordeiro-Santos},
howpublished = {medRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.25.26363952},
url = {https://www.medrxiv.org/content/10.64898/2026.09.25.26363952v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Diagnostic information from a negative QuantiFERON-TB Gold Plus result in adults evaluated for tuberculosis in Brazil and South Africa
AU - A. G. da Costa
AU - A. Trajman
AU - M. C. Borges-Cabral
AU - A. Esmail
AU - B. K. S. Carvalho
AU - B. P. Loiola
AU - A. B. Souza
AU - R. Spener-Gomes
AU - J. s. Jesus
AU - V. S. Sampaio
AU - D. B. d. Castro
AU - K. Dheda
AU - M. Cordeiro-Santos
PY - 2026
DA - 2026/09/25
PB - medRxiv
DO - 10.64898/2026.09.25.26363952
UR - https://www.medrxiv.org/content/10.64898/2026.09.25.26363952v1
AB - Interferon-gamma release assays detect Mycobacterium tuberculosis infection but cannot distinguish infection from active tuberculosis (TB). We evaluated the diagnostic information provided by QuantiFERON-TB Gold Plus (QFT-Plus) among adults investigated for active TB in Brazil and South Africa. Adults with presumptive TB were prospectively enrolled by convenience sampling. QFT-Plus was the index test, and diagnostic classification required microbiological confirmation of TB or an established alternative diagnosis. QFT-Plus results did not inform diagnostic classification. Accuracy was assessed among participants with determinate results, primarily using likelihood ratios. Of 723 participants tested, 48 (6.6%) had indeterminate results, all due to low mitogen responses. Among 675 participants with determinate results, 147 (21.8%) had confirmed TB. Sensitivity was 68.0% (95% CI, 60.1-75.0), specificity was 59.3% (95% CI, 55.0-63.4), and the negative likelihood ratio was 0.54 (95% CI, 0.42- 0.69). At the observed prevalence, a negative result left a 13.1% probability of active TB. Negative likelihood ratio confidence intervals included 1 in both South African HIV strata. Specificity was higher among participants with HIV in both countries. Adding TB2 to TB1 alone identified 15 additional TB cases and generated 18 additional positive results among participants without active TB. HIV and active TB were independently associated with indeterminate results in exploratory regression. A negative QFT-Plus result provided insufficient information to exclude active TB. Higher negative predictive values among participants with HIV reflected lower disease prevalence and higher specificity rather than greater sensitivity. Negative or indeterminate results should not terminate diagnostic evaluation. IMPORTANCEBlood tests that detect immune responses to Mycobacterium tuberculosis can yield negative results in people with active tuberculosis. Understanding how much reassurance a negative result provides is therefore important when these tests are encountered during diagnostic investigation. Among symptomatic adults in Brazil and South Africa, a negative QuantiFERON-TB Gold Plus result left a substantial probability of active disease. Differences between populations showed why apparently reassuring negative predictive values can be misleading. The additional antigen tube detected more cases but did not overcome the tests limited ability to exclude disease. Indeterminate results were associated with human immunodeficiency virus infection and active tuberculosis. These findings support laboratory reporting and clinical interpretation that clearly communicate the limitations of negative and indeterminate results and the need for continued investigation when active tuberculosis remains suspected.
ER -