"Like a smoldering ember that can catch fire again"
What’s the best way to deal with TB?
Dr. Fukushima: Early detection and early treatment. From my point of view, we should employ IGRA and low-dose computerized tomography scans to detect both latent TB infections in high-risk populations and patients with early, active TB. For developing countries with limited healthcare resources, I would recommend a combination of x-rays and IGRA. Treatment is the same worldwide. If done properly – meaning not stopping treatment mid-way – we can cure ninety-some percent of the cases.
What’s the advantage of IGRA versus TST in latent TB testing?
Dr. Fukushima: Several factors favor IGRAs. The biggest is that IGRAs aren’t affected by BCG vaccination, which leads to false positive results with the tuberculin skin test. IGRAs also have a higher specificity and sensitivity, allowing to find 90 % of the true positives. They’re also highly objective, so they’re not affected by the person analyzing the results, and patients only have to come in once. For TST, in contrast, you are supposed to have specialized training to accurately assess them. Even I haven’t had that.
For example, at my hospital, I tested 36 TB patients with the second generation of QuantiFERON ten years ago. That had 86 % sensitivity and tuberculin's was 86 % too. But for healthy people, 78 staff at my hospital, QFT produced only 9 % positive test results in contrast to 94 % false positives with TST. That means the specificity for tuberculin was only 6 %, and 91 % for QFT.
What’s the main difference between QFT-Plus and the former test generations in your view?
Dr. Fukushima: The biggest difference between QFT-Plus and former generations is the incorporation of CD8+ T-cell response data in addition to the measurement of CD4 T-cell response. This allows the test to measure a broader range of immune response.
What are the technology’s potential benefits?
Dr. Fukushima: When we test someone positive for LTBI, at this point nobody knows whether we are facing a recent or older infection. Early research suggests that, thanks to the CD8+ data, going forward it might be possible to differentiate this. Meanwhile, we might be able to identify individuals who have a higher risk to progress to active TB.
Another point is that the CD8+ technology promises to deliver higher sensitivity and specificity in patients at greatest risk for TB infection, particularly individuals co-infected with HIV and elderly patients with lower levels of CD4, i.e. a weaker immune system. About 30 % to 40 % of elderly patients have non-functioning immune systems and will thus likely test negative for LTBI even if infected. And the older a patient gets, the lower the CD4 level, which makes it more difficult to detect TB infection regardless of the method used.
Is this also reflected in your research results?
Dr. Fukushima: If a person is 80 years or younger, I found the test results generated with QFT and QFT-Plus to be comparable. They had a sensitivity of 91 % and 94 %, respectively. But for those 80 years or older, QFT-Plus seems to provide better performance. Here, QFT-Plus shows a sensitivity of 83 % compared to 74 % for the third-generation – and I think the difference would be more pronounced in a larger patient sample with several thousand over 80.
What’s the difference between QFT-Plus and other IGRAs?
Dr. Fukushima: It’s obvious. I’ve found both QFT and QFT-Plus to be significantly more sensitive both in the overall patient population and in individuals over 80.