Elitza Theel, Ph.D., and Team Talk TB Testing with CAP Today
Elitza Theel, Ph.D., Director of the Infectious Diseases Serology Laboratory, Co-Director of the Vector-Borne Diseases Laboratory, and Associate Professor of Laboratory Medicine and Pathology at Mayo Clinic in Rochester, was recently interviewed by CAP Today about tuberculosis (TB) testing. The standard skin-reaction test, widely adopted by the early 1940s, is still in use today. The goal of testing is to break the transmission cycle.
According to Dr. Theel, “From the clinician perspective and the laboratory perspective, because of its infectious nature, we want to identify people with latent tuberculosis. The ultimate goal is to treat them, so they don’t progress to active TB.”
However, latent TB cannot be detected directly. Further, an estimated 13 million residents in the U.S. have latent TB infection. Among those, about 5 to 10% will develop TB if they don’t receive treatment. Because of this, several changes have been made, including:
- A recently updated treatment guideline from the American Thoracic Society, Infectious Diseases Society of America, and Centers for Disease Control and Prevention (CDC) calls for stratifying patients into three groups based on risk of progression: high risk, low to intermediate risk, and unlikely to progress or to have TB.
- Qiagen’s fourth-generation assay. Like other earlier interferon gamma release assays (IGRAs), the Plus test detects CD4 T-cell response and detects CD8 T-cell response.
- The CDC plans to change medical screening guidelines for immigrants, effective October 1, calling for the use of an FDA-approved IGRA for TB screening, including children under age five.
However, even before the above changes, some health care providers had begun to move away from the skin test. Dr. Theel notes that specificity can be a problem with the skin test, and it can be falsely positive in individuals who have undergone Bacillus Calmette-Guerin (BCG) vaccination or if the test was administered or interpreted incorrectly. And sensitivity, particularly in patients who are immunosuppressed or in very young children, can be lower.
For annual health care employee screening, many institutions are making the switch from skin testing to an IGRA as well, says Dr. Theel, who reports seeing this among Mayo’s reference lab clients. Collectively, she says, referring to Mayo’s reference lab testing and its own patient population, which includes a large number of patients from TB endemic areas, “we performed more than 90,0000 QuantiFeron tests last year.”
Though Mayo has already switched from the QuantiFeron Gold test to the Plus test, Dr. Theel says she’d like to see more peer-reviewed literature showing the advantage of using the newer assay. The addition of CD8-positive T-cell stimulation offers the potential for increased sensitivity in the case of active TB, she says, but her own literature search hasn’t yielded enough data to convince her yet. Ditto for studies that show the Plus test is more sensitive in HIV-positive patients with low CD4 T-cell counts. “I think the potential is there,” she says.
Mayo began offering the Plus test on February 13. For Lori Misner, CLS, and Heather Hilgart, BS, two technical specialists at Mayo, the switch created a few headaches. Single-tube collection might be helpful for smaller labs and clinics that don’t have the ability or resources to perform incubation and centrifugation, they acknowledge. But Mayo, a large international reference laboratory, requires clients to send the completely processed tubes containing plasma ready to be placed onto an automated instrument. “We do not accept the single lithium heparin tube with whole blood,” Hilgart says.
According to Dr. Theel, the verification process was also a challenge. She cited two factors. “One, you need fresh whole blood, so you essentially have to enroll individuals. And you need patients who have latent TB, so you need to have a good positive and negative pool.” The lab enrolled low-risk, skin-test-negative Mayo employees for the negative controls, but had to look elsewhere for positive samples.
“We started by enrolling skin-test-reactive employees. However, they didn’t always yield a positive QuantiFeron result,” Hilgart says. “So we had to expand our search, and we collaborated with our local TB clinic” to obtain positive QuantiFeron specimens.
The switch involved some logistical juggling, says Misner, since the lab also builds QuantiFeron collection tubes as kits for its clients. Adding the fourth tube meant giving a 60-day notice about the switch and required numerous conversations with clients about using up older kits in a timely fashion. “That was tricky,” she recalls. “How do you get clients to stop drawing the three tubes and start sending the four tubes?” Overall the switch went fairly well, she says. “But you still have those people who are ordering the correct test but using the wrong tubes.”
When they first learned of the impending change, Hilgart says, it sounded simple: We’re just adding this extra tube. She laughs. “Given the reality of lab workflows, it’s more like, Oh my gosh, they’re bringing in an extra tube! It really did change things for us. We went from running 25 patients at a time to 21 patients at a time. It affects your laboratory information system. And it affects our postanalytic—when we’re done with the tubes, we have to make more room to store them until we’re able to dispose of them. We’re using more reagents, more plates, each day now, and we have to make more space in the refrigerators to do all that. So, there were a lot of workflow changes we had to make just for our one extra tube.”
Dr. Theel says, “We did do a lot of education for internal and external providers.” That communication was critical in making the switch, she continues. “Pay attention to all impacted areas,” she advises, including phlebotomy.