Simple, accurate test now available for latent TB

A new blood test for tuberculosis infection could revolutionize the method for screening health care workers and lead to a reduction in false positive results.

"It’s tremendous. It’s a 100-year upgrade of the tuberculin skin test," says Gerald Mazurek, MD, medical epidemiologist with the Division of Tuberculosis Elimination at the Centers for Disease Control and Prevention (CDC) and the principal investigator for CDC’s Phase III trials of the test. "Diagnosing tuberculosis infections is difficult, especially when the infections are asymptomatic. We have relied on the tuberculin skin test for years despite its limitations," he says.

While the Food and Drug Administration approved QuantiFERON-TB in November 2001, hospitals and other facilities with high-risk populations are just beginning to conduct pilot programs with the new test, says Mark Boyle, senior vice president, sales and marketing at Cellestis of Valencia, CA, which is manufacturing and marketing the test in the United States.

In guidelines published in December, the CDC recommends confirming some positive Quanti-FERON-TB test results with a skin test.1

But Mazurek and other researchers say the blood test improves upon and eventually could replace the skin test. QuantiFERON-TB is produced by the Australian medical diagnostic firm Cellestis Limited. It costs $10 per patient for the diagnostic kit.

"I think it’s the future of testing for latent tuberculosis infection," says Lee Reichman, MD, MPH, executive director of the National Tuberculosis Center at the University of Medicine and Dentistry of New Jersey in Newark and author of Time Bomb: The Global Epidemic of Multi-Drug Resistant TB (McGraw Hill, 2001).

The current TB skin test presents a host of potential problems for hospital employee health. Health care workers must return for follow-up within 48 to 72 hours for an evaluation of the reaction, and redness or erythema is sometimes mistaken for a positive reaction. Infection with other mycobacteria or previous BCG vaccination also can produce false positive results.

The blood test works by measuring a component of the cell mediated immune response to tuberculin purified protein derivative (PPD). It identifies gamma interferon, a protein produced by white blood cells as a reaction to TB infection. Mazurek and colleagues compared the two tests in 1,226 subjects and found that the QuantiFERON was comparable to the skin test in its ability to detect latent TB but was less affected by previous vaccination with BCG or by other nontuberculous mycobacteria.2 And while the PPD skin test sometimes provokes an immune response that can impact future test results, the blood test can be repeated as often as needed.

How much will the convenience of a TB blood test be worth to hospitals?

The skin test is currently less expensive (about $2 per test for the reagent) than QuantiFERON. But Boyle contends that the extra staff time used to track down employees, read their reactions, and follow up on questionable reactions makes the two tests roughly comparable in cost. The blood test requires some additional lab time, but it is still much more efficient, he says. "Just by having only a single contact with the employee, you cut down on a lot of money."

The objectivity of QuantiFERON also is appealing. For those with a known risk of exposure to tuberculosis, which includes hospital and nursing home workers, the response to a PPD antigen must be at least 15% of the response to a positive control antigen. In subjects judged to be at low risk for TB exposure, the response must be at least 30% that of the control. The blood test also can compare the reaction to Mycobacterium tuberculosis with other mycobacteria antigens to rule out false positives.

"The results can be available the next day," Mazurek notes. "There’s much more versatility in its ability to give you a result."

If the QuantiFERON test is negative, CDC does not recommend any further evaluation. But people with positive results should have a chest X-ray and possibly a TB skin test to confirm the QuantiFERON test results. People with no identified risk for TB infection should have a positive QuantiFERON result confirmed with a skin test before therapy is advised, Mazurek says.

For people at increased risk of infection, including health care workers, the confirmatory skin test is optional. In contrast, TB skin tests should not be confirmed with the QuantiFERON-TB because the injected PPD could affect the blood test results, he adds.

"We think this will increase the accuracy of detecting latent tuberculosis infection," he says. "We think this methodology will probably be more accurate than just getting the TB skin test alone."

Further research is under way, but currently QuantiFERON is not recommended for people with active TB, contacts of people with active TB, children under the age of 17, pregnant women, and immunosuppressed individuals.

Eventually, the blood test itself will offer an even greater ability to detect latent TB. "We can improve the specificity or sensitivity of the test by looking at multiple antigens," Mazurek says. The CDC is collaborating with the manufacturer and others to identify more sensitive and specific antigens for the test. "We need to develop collaborations and encourage others to evaluate the assay," he says. "The tuberculin skin test has been evaluated and improved over the last 100 years. The QuantiFERON also needs [more] evaluation."

[Editor’s note: More information on QuantiFERON-TB is available from mark_boyle@cellestis.com. Telephone: (800) 519-4627.]

References

1. Mazurek GH, Villarino ME. Guidelines for using the QuantiFERON-TB test for diagnosing latent Mycobacterium tuberculosis infection. MMWR Dispatch 2002; 51:1-5.

2. Mazurek GH, LoBue PA, Daley CL, et al. Comparison of whole-blood interferon assay with tuberculin skin testing for detecting latent Mycobacterium tuberculosis infection. JAMA 2001; 286:1,740-1,747.