According to the World Health Organization (WHO), tuberculosis (TB) is the leading cause of death by a single infectious disease worldwide. In 2023, TB caused approximately 1.25 million deaths, including 161,000 among people with HIV. More than 10 million individuals contract TB annually, including 1.3 million children.1 Given its impact, there is a strong focus on improving TB detection, and identifying LTBI before it becomes active and contagious to others.1,2 Two types of diagnostic tests are predominantly used for detection of LTBI, the traditional tuberculin skin test (TST) and interferon-gamma release assays (IGRAs).
Comparing TST and IGRA tests
In a recent presentation, Professor Juzar Ali closely examined the differences between IGRA tests and TST methodologies for detecting LTBI. When referring to TST, he comments: “TST sensitivity is limited in immunocompromised individuals, and the specificity can be affected by other factors such as environmental mycobacteria or prior BCG vaccination.” He also remarks that the TST can provide “false positive results due to cross-reactivity of antigens within the PPD to both BCG and nontuberculous mycobacteria.”
When presenting IGRAs he mentions “the antigens used – ESAT-6 or CFP10 – are not present in M. bovis BCG or in most environmental mycobacteria, so the specificity is not so much of a problem,” he adds. “There is no cross-reactivity with BCG and in most nontuberculous mycobacteria (NTM), so IGRAs are a good way to exclude other NTM infections.”
IGRA tests, such as Revvity’s T-SPOT.TB test and Qiagen’s QuantiFERON-TB Gold Plus (QFT-Plus), detect TB infection using a blood sample to measure IFN-gamma released from T cells responding to TB antigen stimulation, offering a more accurate way of detecting TB infection compared to TST.
Key differences among IGRAs
Available IGRA tests have important differences. T-SPOT.TB requires a single tube, eliminating the need for shaking, incubation, refrigeration, or on-site processing. In contrast, QFT-Plus requires four tubes and on-site incubation. T-SPOT. TB also washes cells, enabling removal of potentially interfering substances, which QFT-Plus does not. A unique feature of T-SPOT.TB is its “borderline” result category, which preserves the test’s overall reliability. Professor Ali presents data from a study by King et al. highlighting the clinical utility of the borderline range. This study found that 79.8% of borderline results were resolved as positive or negative upon retesting, suggesting the borderline range is useful in maintaining the performance of the test.3
He comments, “a borderline result is an important differentiation in clinical practice, which is why I am a big fan of this category of result, as it tells us to retest, and nearly 80% of the time I get a conclusive answer”.
Why choose T-SPOT.TB?
T-SPOT.TB offers high sensitivity and specificity, making it particularly effective in immunosuppressed patients. Its low rate of indeterminate results reduces the need for costly retests, improving diagnostic reliability and reducing delays to diagnosis. As Professor Ali says: “T-SPOT.TB is slightly superior in certain conditions, and its borderline result category is a valuable tool in clinical practice.”
While diagnosing active TB follows a clear protocol, LTBI testing benefits from IGRAs due to their enhanced accuracy and reliability. For clinicians, selecting the right IGRA test can improve TB detection and management, ultimately aiding in global TB control efforts.
