Blood test vs. skin test: Are hospitals ready for the TB 'gold standard'?

Hospitals consider secondary use of Quantiferon

After years of frustration with tuberculin skin tests, hospitals have a chance to revolutionize their TB screening with a new blood test. But even as the Centers for Disease Control and Prevention (CDC) issued guidelines for its use, few seem poised to take that step.

For the foreseeable future, the tuberculin skin test remains the predominant screening method. Because of cost and other concerns, many hospitals view Quantiferon-TB Gold as just an extra tool to be used on a selective basis.

That stance puzzles public health authorities, who view Quantiferon-TB Gold as the first significant advance in a century of TB testing and the new "gold standard."

In fact, the tuberculin skin test has posed a host of problems for employee health professionals: the subjective nature of the readings, false positives, two-step baseline testing, and the need for employees to show up twice to have the test placed and then interpreted. TB skin tests also may register a positive result if the employee has had a BCG vaccine or a different mycobacterial infection. The blood test works by measuring a component of the cell-mediated immune response to two proteins in the cell wall of M. tuberculosis.

"There's a lack of faith in the tuberculin skin test," says Michael Iademarco, MD, MPH, associate director for science in the division of tuberculosis elimination at the CDC in Atlanta. "When you get a positive with the Quantiferon test, you'll be getting fewer of them. It is more specific. When you get that positive, the infection control program will be able to focus on these true positives and get them to the needed treatment [for latent TB infection]."

CDC's draft updated TB guidelines tout the advantages of Quantiferon-TB, citing a study stating that the blood test "may be more efficient and cost-effective than TSTs [tuberculin skin tests]." (The final publication of the TB guidelines was pending at HEH presstime.)

The blood test offers reassurance to health care workers, particularly those foreign-born workers who have a history of BCG vaccination, says Rachel Stricof, MPH, chair of the TB task force of the Association for Professionals in Infection Control and Epidemiology (APIC). She is also APIC's liason to the Advisory Council for the Elimination of TB.

"If I had an exposure, I would prefer having the Quantiferon-TB Gold test rather than the tuberculin skin test because I believe the results are more likely to be reliable," she says.

Employee health professionals recognize the benefits of Quantiferon-TB Gold. It is an administrative relief, eliminating the need to follow up with employees within 48 to 72 hours after the placement of the test. Quality control is a major issue with the tuberculin skin test, as test readers sometime mistake erythema, or redness, for a positive reaction. CDC's new TB guidelines call for greater training requirements for the employees who place and read the tests, including six hours of lecture and demonstration and 16 hours of supervised practical work by a TST reader.

But Quantiferon-TB Gold also poses challenges:

• Cost. Quantiferon may eventually become the "gold standard," but for now many hospitals are viewing it as a golden luxury. "Actually, it's a money saver," contends Mark Boyle, senior vice president for sales and marketing at Cellestis Inc., of Valencia, CA, the manufacturer of Quantiferon-TB Gold. "There's a lot of lost productivity [when employees leave their posts to have their skin test placed or read]. Those are real costs for hospitals."

False positives from the skin test also lead to costly follow up, including chest X-rays, and even unnecessary treatment for latent TB.

But the Quantiferon reagent is significantly more expensive — about $15 a test for Quantiferon-TB Gold compared to about $3 per test for the tuberculin skin test. The savings throughout the hospital in less staff time are harder to quantify. Meanwhile, Quantiferon-TB Gold also involves greater lab costs.

"The cost factor on Quantiferon is going to make it a questionable test as far as whether it can be used for routine screenings," says Bruce Cunha, RN, MS, COHN-S, manager of employee health and safety at the Marshfield (WI) Clinic. At least for now, Cunha plans to use the blood test as a secondary test when the tuberculin skin test produces a questionable result.

The Mayo Clinic in Rochester, MN, is taking a similar, staged approach. In a pilot project, the Mayo Clinic will use both Quantiferon-TB Gold and the regular two-step TB skin test for baseline testing of new employees. "We're going to do a cost analysis and see if Quantiferon would actually be cheaper in the long run," says William Buchta, MD, MPH, medical director of the Employee Occupational Health Service at Mayo.

Quantiferon also will be used as a confirmatory test after a positive skin test if it is equivocal, he says.

Iademarco notes that there are no data evaluating the use of Quantiferon in conjunction with annual skin testing, and that the CDC doesn't recommend using both tests. "We don't have any specific recommendations coming out in that regard. I don't really see a place for that," he says.

The University of Texas Health Center at Tyler switched to Quantiferon-TB Gold this past year. The cost was mitigated by a reduction in serial testing that also occurred last year.

"As part of our 2005 TB risk assessment, we looked at our risk classifications and determined that we could reduce the frequency of testing in some cases," says Marian Crawford, RN, COHN, nursing coordinator of the Occupational Health Clinic. "Employees who work in non-clinical settings and do not share air space with TB patients will be tested at hire and upon exposure, but do not receive serial testing." The frequency of most serial testing was reduced from every six months to annually, she says.

"We did a cost analysis and looked at the cost of Quantiferon-TB Gold compared to a skin test. The cost saving is in employee time and administrative issues," she says. "For our new employees, it ended up being pretty much the same cost because you went from four visits [with two-step baseline skin testing] to one visit. For our serial visits, it's a little more expensive to use the Quantiferon."

Quantiferon is especially useful with employees who may have had BCG vaccination, she notes.

• Laboratory expertise. To use Quantiferon, hospitals need easy access to a laboratory with the capability to perform the test. The lab also must develop its own quality assurance system; Cellestis does not provide a proficiency panel.

Timing is an important issue, as the blood sample must be processed by a lab within 12 hours of the blood draw. The next version of Quantiferon, which awaits Food and Drug Administration approval, would allow a longer time period between the blood draw and the lab processing, Boyle says.

Quantiferon is an ELISA-based test that is not difficult for labs to incorporate, says Boyle. But it may take time before use of the test becomes widespread. In some parts of the country, it may be difficult to find a lab that is prepared to run the Quantiferon test.

Recently, Cunha tried to find a lab in Michigan to test the blood of a soldier who had returned from Iraq. (Cunha is serving in the Army reserve, but based in Wisconsin.) He could not find a lab that could perform a Quantiferon test in the state.

• Employee attitudes. Will employees embrace the new test? Many of them may appreciate the efficiency of the blood test and its specificity. But others may find the blood draw to be more invasive than a simple prick of the skin.

"I think people understand the reticence a lot of employees are going to have to being phlebotomized every year," says Mark Russi, MD, MPH, associate professor of medicine and public health at the Yale University School of Medicine and director of occupational health at Yale-New Haven (CT) Hospital.

It may simply be a matter of time before Quantiferon gains favor in hospitals. The updated TB guidelines give hospitals more flexibility in TB screening, enabling settings at low risk for tuberculosis to eliminate TB screening unless there is an exposure.

In low-risk settings, positive results on the skin test are also more likely to be false positives, notes Iademarco. "In the health care setting, false positives are a big burden," he says. A more specific test may be just what those hospitals need.