Can you trust the TB blood test? Questions linger
Hospitals slow to warn to switch
After years of struggling with the vagaries of the tuberculosis skin test, you might think that hospitals would embrace a new technology. But the blood test has been slow to catch on.
Cost and laboratory barriers likely will be resolved as new versions of the test obtain wider distribution. But TB experts want to know: Would you put more faith in this test than the skin test to detect seroconversions without producing false-positives?
A study is under way that may provide the convincing evidence to increase use of the TB blood test. The Tuberculosis Epidemiologic Studies Consortium will compare two new blood tests with the skin test as tools for detecting seroconversions in health care workers. More than 3,000 health care workers will be enrolled at the Texas Department of Health, Columbia University, the Maryland Department of Health and Mental Hygiene, and the Denver Health and Hospitals Authority.
There still are many lingering questions about the blood tests and the transition from skin tests to blood tests, notes Charles Daley, MD, principal investigator and chief of the Division of Mycobacterial and Respiratory Infections at the National Jewish Medical and Research Center in Denver.
"This [blood] test is better than the skin test," says Daley. "When it finally gets out there, we want people to trust it. The problem with the skin test is that no one trusted it."
In fact, questions about the skin test create potential problems for the blood test. Should you retest health care workers who tested positive with the skin test in past years? How do you respond to a previous positive that now is negative? Will health care workers who have received treatment for latent tuberculosis infection become negative on a blood test?
"This is going to create a lot of controversy at every facility about how they're going to do this [transition]," says Daley. "If you decide to retest everyone with this blood test, it's going to cost money. Most places are just going to switch over [without retesting]."
New tests emerge
The study will focus on two new blood tests that are expected to be approved in the United States in 2007. FDA approval is pending on the QuantiFERON-TB Gold In-Tube, a new version of the blood test manufactured by Cellestis Ltd., of Carnegie, Australia. The blood is collected in tubes containing the antigens (as well as positive and negative control tubes).
It uses three antigens instead of two, which may improve its specificity, and after incubation, it is stable and can be refrigerated for up to 28 days, according to company information information (www.cellestis.com). With the current Quanti-FERON-TB Gold test, samples must be processed within 12 hours of collection, which causes logistical issues for some hospitals and laboratories.
The T-Spot TB test, produced by Oxford Immunotec, of Oxford, UK, is touted for its sensitivity and is able to "identify a single effector T cell when it is activated by M. tuberculosis antigens," according to the company literature (www.oxfordimmunotec.com/products_services/tspottb.html). That could be a benefit when testing immunosuppressed patients. The blood samples must be processed within eight hours of collection.
Both tests detect the production of interferon gamma in response to Mycobacterium tuberculosis antigens. The QuantiFERON test measures the interferon gamma directly, while the T-Spot measures the interferon-producing T cells. Unlike the skin test, the reaction is not affected by the presence of non-TB mycobacterium or BCG vaccination.
As the blood tests begin to replace the skin tests, health care facilities will have questions about how to interpret the results, says Daley. For example, treatment for latent tuberculosis infection may cause health care workers to shift to a negative blood test result. The blood test will need clear definitions — for example, how much change in interferon represents a positive?
"We're going to look at the variation in results over time, with the goal of defining a conversion cut point and to see how many people might go from a positive result to a negative result," he says. "We'll also be able to compare these two tests head to head and see which one performs better."
Researchers also will evaluate the issue of indeterminate test results. A study conducted in U.S. Navy recruits resulted in a level of indeterminate QFT-G results of about 2%, but among immunosuppressed populations, the rates may be as high as 13% to 20%, according to the CDC. Cellestis recommended using lithium heparin tubes rather than sodium heparin tubes to address the problem, the CDC reported.
"If you test HIV-infected people, you would expect to have a greater number of people who are indeterminate, although that has not been proven," says Gerald Mazurek, MD, medical officer with the CDC's Division of TB Elimination. "There have not been many studies done in HIV-infected people."
The CDC also noted that there have been two reports of expectedly high positive results with the QuantiFERON test. Using both the skin test and blood test could help facilities compare the information they receive, he notes.
By comparing the tests, the consortium's study will shed light on important questions, notes Mazurek: "What percentage of people have discordant results between TST [tuberculin skin test], QuantiFERON, and Elispot [T-Spot]? What factors are associated with discordance with various tests?"
Many hospitals have taken a wait-and-see approach as the newer blood tests evolve. But some have begun incorporating the tests into their screening program.
For example, the San Francisco TB control program has been using the QuantiFERON-TB Gold test for about two years. A more accurate test means fewer unneeded diagnostic X-rays or unnecessary treatment for latent tuberculosis infection, says director Masae Kawamura, MD.
About two-thirds of her health care workers are foreign-born, and many of them have already tested positive to the skin test. They have an option of being retested with the blood test, says Kawamura. Some who previously were positive with the skin test have tested negative, she says.
"The results are different [than with the skin test], and that's what makes everyone feel uncomfortable," she says. "This tells me how wrong we've been with the skin test all along. In fact, the blood test may turn out to be a much better surveillance tool in the end."
The TB program uses the blood test with its high-risk patient population because it can be accomplished in one visit. Blood test results also are objective measures that can be compared from one facility to another, whereas the measurement of a skin test may depend on the test reader's training and ability, Kawamura notes.
"As a busy health care worker, would you prefer to get a one-time blood test or to have to go back twice to place and to read, and knowing it is less accurate? I would prefer the blood test," she says.
Kawamura says she would like to see more health care facilities switching to the blood test. "I think we are our own worst enemy in public health," she says. "Now that we have this new technology, we're holding on to this [old] technology we know so well. We need to embrace the new technology, study it, and operationalize it. We've needed a more accurate test all this time."
Hospitals find partial uses
The transition to the blood test has been gradual. At Tampa (FL) General Hospital, for example, employees who have received the BCG vaccine or who test positive after an exposure or in an annual screen will be retested with the blood test, says JoAnn Shea, MSN, ARNP, director of employee health and wellness.
The hospital also may use the blood test in pre-placement exams, she says. In fact, the training that the Centers for Disease Control and Prevention recommends as a "model" for skin test placers and readers would be time-consuming and costly — and adds to the appeal of the blood test, she says. "I think down the road we will use it more and more," she says.
The National Jewish Medical and Research Center also is converting its screening program to the blood test, says Daley. Non-BCG-vaccinated health care workers who have documented positive skin tests don't need to be tested again, he says, but the hospital may retest those who have a history of BCG vaccine.
Daley cautions against combining the use of the two tests by using the blood test instead of a two-step baseline but then switching to annual screening with a skin test. "I don't think you can flip back and forth between these tests," he says. "They measure different things. They're not equivalent."
Meanwhile, he predicts that health care workers will request the blood test as it becomes available. "They hated the skin test. They didn't trust it," he says. "They just never believed the results. If they think there's a better test, they'll probably go with a better test."
Should You Use QuantiFERON-TB Gold?
What are the advantages?
- Requires a single patient visit to draw a blood sample.
- Results can be available within 24 hours.
- Does not boost responses measured by subsequent tests, which can happen with tuberculin skin tests (TST).
- Is not subject to reader bias that can occur with TST.
- Is not affected by prior BCG (bacille Calmette-Guérin) vaccination.
What are the disadvantages and limitations?
- Blood samples must be processed within 12 hours after collection while white blood cells are still viable.
- There are limited data on the use of QFT-G in children younger than 17 years of age, among persons recently exposed to M. tuberculosis, and in immunocompromised persons (e.g., impaired immune function caused by HIV infection or AIDS, current treatment with immunosuppressive drugs, selected hematological disorders, specific malignancies, diabetes, silicosis, or chronic renal failure).
- Errors in collecting or transporting blood specimens or in running and interpreting the assay can decrease the accuracy of QFT-G.
- Limited data on the use of QFT-G to determine who is at risk for developing TB disease.
When should you use the test?
- QFT-G can be used in all circumstances in which the tuberculin skin test (TST) is currently used, including contact investigations, evaluation of recent immigrants who have had BCG vaccination, and TB screening of health care workers and others undergoing serial evaluation for M. tuberculosis. However, caution should be used when testing certain populations because of limited data on the use of QFT-G.
Source: Centers for Disease Control and Prevention, Division of Tuberculosis Elimination, Atlanta.
After years of struggling with the vagaries of the tuberculosis skin test, you might think that hospitals would embrace a new technology. But the blood test has been slow to catch on.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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