Out With the Old
Could second generation interferon-γ release assays replace existing tests and transform TB diagnosis through improved sensitivity?
Tuberculosis (TB) testing is big business: tens of thousands of patients that display suggestive symptoms are tested in the UK alone. In countries where TB incidence is relatively low, interferon-γ release assays (IGRAs) are commonly used for diagnosis – but new research has found that these blood tests cannot accurately rule out the disease. In addition, second-generation IGRAs showed much higher sensitivity than existing tests (1), potentially heralding their replacement.
Early diagnosis is essential in suspected TB cases, both to speed patient treatment and to prevent the spread of disease. But a study by Ajit Lalvani, Chair in Infectious Diseases at the National Heart and Lung Institute, and colleagues highlights the issues with current testing. From 845 adults enrolled in the study – including 363 who had TB – the sensitivity readings of the T-SPOT.TB and QFT-GIT tests were 81.4 and 67.3 percent, respectively. “There is a huge unmet clinical need for better diagnostic tests for active TB,” Lalvani says – and a highly sensitive test that could rapidly rule out the disease soon after initial clinical presentation might be just what the doctor ordered.
In the same patient population, second-generation IGRAs detected TB with 94 percent sensitivity, a substantial increase on currently available tests. “The enhanced sensitivity is conferred by the inclusion of a novel Mycobacterium tuberculosis antigen, Rv3615c, which is recognized by T cells in most TB patients, but not in uninfected individuals,” explains Lalvani. “Many patients who do not respond to existing IGRAs have T cells that recognize this new antigen, making it more suitable for use in suspected cases.”
Lalvani hopes that more accurate tests will save time and resources, ensuring that patients who require treatment receive it promptly. “Current methods are expensive and time-consuming – in our cohort, 28 percent of patients who were treated for TB didn’t actually have positive cultures once the laboratory results came back.” Before it can enter the clinic, the new IGRA must go through regulatory approval, but its creators hope to achieve a quality-assured commercial diagnostic kit within two years. “It will transform the diagnostic process in developed countries with low-to-moderate TB burden,” says Lalvani, anticipating a future where suspected TB patients have a definitive answer within 24 hours of presentation.
- HS Whitworth et al., “Clinical utility of existing and second-generation interferon-γ release assays for diagnostic evaluation of tuberculosis: an observational cohort study”, Lancet Infect Dis, 19, 193–202 (2019). PMID: 30655049.
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