New Blood-Based TB Test More Accurate at Detecting Recent Exposure

UTRECHT, The Netherlands, March 15 -- Tuberculosis tests based on interferon-gamma responses detected exposure to a TB-infected store employee, setting off a contact investigation among more than 20,000 customers.

On the other hand, a positive result on the standard tuberculin skin test was not associated with exposure to the infected employee, according to Ailko Bossink, Ph.D., of the Hospital Diakonessenhuis here.

In a large cross-sectional study -- conducted as part of an investigation of the store worker's contacts -- a positive tuberculin skin test was only significantly associated with age, Dr. Bossink and colleagues reported in the second March issue of the American Journal of Respiratory and Critical Care Medicine.

The researcher concluded that the interferon-gamma tests reflected exposure to the employee, who was smear-positive for TB and had been infectious for 11 months before the contact investigation in January, 2005.

The tuberculin skin test, they said, was probably reflecting earlier exposure to TB, possibly in countries with a higher prevalence of the disease than Holland.

"Among the 785 study participants, tuberculin skin test results were associated with age, whereas positive interferon-gamma blood test assay results were significantly associated with cumulative shopping time," Dr. Bossink and colleagues said. "Tuberculin skin test results were not associated with any measure of exposure to the index case in the supermarket."

All told, more than 20,000 customers of the store were tested, using the tuberculin skin test. Dr. Bossink and colleagues recruited 469 of them on the day of the tuberculin skin tests and administered the two commercially available interferon-gamma blood tests.

The two blood tests are QuantiFERON-TB Gold (QFT-G), a whole-blood assay that uses an enzyme-linked immunoabsorbent assay (ELISA) for detection of interferon-gamma responses, and T-SPOT.TB, which is based on the enzyme-linked immunospot technique.

Another 316 customers with a positive tuberculin skin test were recruited on the day the skin tests were read. The researchers excluded people who had previously had a bacillus Calmette-Gurin vaccination, which can give a false-positive result to the tuberculin skin test.

The researchers analyzed the tuberculin skin test responses at a cut-off of 10 millimeters and 15 millimeters. At both cut-offs, the tuberculin skin test was significantly associated only with age.

Specifically, for every 10-year increase in age, the likelihood of an induration greater than 15 millimeters increased 40%. (The odds ratio was 1.40, with a 95% confidence interval from 1.13 to 1.74, which was significant at P<0.002.)

Similarly, the likelihood of an induration greater than 10 millimeters increased 34% for every 10-year step in age, which was also significant, at P<0.008.

The 15-millimeter level was regarded as reliably indicating latent TB infection.

On the other hand, the probability of a positive QFT-G increased significantly in association with the frequency of shopping as well as with the cumulative shopping time (at P=0.009 and P=0.007, respectively).

Meanwhile, the probability of a positive T-SPOT.TB test was significantly associated only with the monthly number of visits to the supermarket, at P=0.04.

"It was not possible to document actual face-to-face contact with the source case," the researchers said, so frequency of shopping and cumulative shopping time was used as proxies.

The two interferon-gamma tests were in agreement 89.6% of the time, while agreement with the tuberculin skin test varied depending on the induration level. But when the tuberculin skin test induration was 15 millimeters or greater, the QFT-G test was positive 86.5 % of the time, while the T-SPOT.TB agreed 81.8% of the time.

"Positive interferon-gamma blood assays were observed in a significant proportion of recently exposed contacts with a negative tuberculin skin test result," Dr. Bossink and colleagues noted. "The clinical significance of this finding merits further study if the blood tests are to replace the tuberculin skin test and be used for therapeutic decisions."

The discordance among the tests "raises several intriguing questions," said Madhukar Pai, M.D., Ph.D., and Dick Menzies, M.D., both of McGill University in Montreal.

Among the questions, they wrote in an accompanying editorial, are:

• What host, biologic, or environmental factors explain the discordance?
• Can interferon-gamma tests have lower sensitivity for remote TB infection but better sensitivity for recent infection?

But the key question, they said, is whether interferon-gamma tests are better at predicting TB disease than the tuberculin skin test. Answers to that question will have to come from longitudinal studies, rather than the cross-sectional design used by Dr. Bossink and colleagues, they said.