Tuberculosis (TB) remains a significant challenge globally. Even in lowprevalence countries like Germany, vulnerable groups like immunosuppressed patients remain at risk. For patients with compromised immune systems, such as those undergoing chemotherapy or living with conditions like HIV or autoimmune diseases, effective screening and testing are crucial to prevent the progression of latent TB infection (LTBI) to active TB disease.

Dr Martin Obermeier and his team at MIB perform around 30 TB tests daily, the vast majority of samples coming from immunosuppressed patients. “We see a lot of patients, especially those with HIV or under immunosuppressive therapy, who are at high risk of developing active TB,” explains Obermeier. In these groups, early detection is key: “If you can diagnose and treat LTBI before developing into active disease, it’s much easier, especially if you’re comparing it to treating extensively drug-resistant tuberculosis. Early detection and intervention are key to preventing active disease.”

Reliable detection in patients

Traditionally, TB testing has been challenging in immunosuppressed patients as a result of low lymphocyte counts, often leading to false-negative results or inconclusive tests. Revvity’s T-SPOT.TB test, a highly sensitive blood test based on ELISPOT technology, offers a robust solution for detecting LTBI in immunosuppressed patients.

One of the standout advantages of the T-SPOT.TB test is the high level of sample standardisation, mitigating for low lymphocyte counts. “The real advantage of the T-SPOT.TB test is its ability to standardise the number of peripheral blood mononuclear cells (PBMCs) used, ensuring consistent and accurate results even in patients with low CD4 counts,” Obermeier explains. “We’ve used T-SPOT.TB for over 15 years in our lab, and its reliability and reproducibility, especially in difficult cases, have been remarkable. The number of tests where we can’t report a result was below 2.5% in 2023 which is remarkably low for an assay based on stimulating cells.”

Since MIB adopted the T-SPOT.TB test 15 years ago, Revvity has made strides to innovate an automated workflow for the test, integrating technologies like its T-Cell Select magnetic bead-based PBMC isolation, liquid handling and spot counting. Adopting automation has had a transformative effect on the MIB lab: “With the semi-automated workflow we now have, we’ve reduced handson time by at least 50% or more compared to the manual process,” Obermeier explains.

“With automation, and based on our findings, we see more cells being successfully isolated from the samples, and the quality of these cells seems to be better compared to the manual process,” Obermeier notes. Furthermore, automation in PBMC cell isolation enables samples to be processed up to 54 hours following collection, which is particularly valuable in samples that have been in transit for extended periods.

Barriers to wider TB testing

Despite the vast clinical benefits of performing regular TB testing in immunosuppressed patients, challenges remain in expanding its use. “The biggest challenge,” Obermeier explains, “is convincing healthcare providers of the necessity of testing.”

The reluctance of healthcare providers to initiate testing due to concerns about the subsequent steps if a test comes back positive is a significant issue. “In Germany, the treatment strategies for latent TB can be quite complex, which makes some providers hesitant to test,” he explains. Newer treatment options, such as shorter antibiotic courses like the 1HP (one-month rifapentine and isoniazid) option endorsed by WHO, could alleviate some of these concerns.

As the TB threat continues, particularly with rising migration from high-prevalence regions and the potential spread of drug resistant strains, the role of accurate, reliable testing becomes ever more critical, and education will be an important factor in expanding testing.

“We need to be prepared for the challenges ahead. With tools like T-SPOT. TB and new automation technologies, we are better equipped to identify and manage TB infections in even the most vulnerable patients.”