New technologies improve the diagnosis of tuberculosis infection

IDC New York 2011

NEW YORK — Recent advances in detecting tuberculosis (TB) infection have significantly improved the specificity of testing and should change the way children are tested, according to a presentation during the 24th Annual Infectious Diseases in Children Symposium.

Jeffrey R. Starke, MD, an infectious disease specialist at Baylor College of Medicine in Houston, said the interferon-gamma release assay (IGRA) tests, QuantiFERON and T.Spot TB, do not cross-react with the bacille Calmette-Guérin (BCG) vaccine and Mycobacterium avium complex the way the tuberculin skin test (TST) does, so their results are more specific for TB infection.

Many false positives

More than 60% of TB disease cases in the United States are in those who are foreign-born, according to Starke. Although 50% of infants who receive the BCG vaccine will not develop a TST, most infants who do will have a negative skin test by 5 years post-vaccination.

Jeffrey R. Starke

“Some will have a boost-able skin test. In other words, if we do more than one skin test, we may actually bring out a positive because of the BCG, not because of TB infection,” Starke said. “But if you just do a single test, it is likely that 90% of the kids will have a negative skin test 5 years after BCG.”

For that reason, he added, the previous dogma was that all skin tests should be interpreted “exactly the same way regardless of whether the child had received BCG vaccine.” However, because hundreds of millions of children get BCG vaccine, 5% to 10% of children with a falsely positive skin test is still a very high number, according to Starke.

IGRA vs. TST

There has not been a significant advance in the diagnostic techniques of TB in the past 100 years, and all existing diagnostic tests for children have shortcomings, according to Starke. All available tests for TB infection are more accurate when used in children with a high index of suspicion, which includes symptoms or contact with a person with TB. In addition, repeat TST skin tests only become more difficult to interpret, he explained to the audience.

However, the IGRAs do offer some advantages over TST, especially in foreign-born children. For example, IGRAs do not cross-react with BCG, and therefore result in significantly fewer false positive results.

Starke recommends one of the following two strategies for children who have received BCG vaccine: 1) forego the TST and test first with an IGRA to avoid false-positive results; or 2) do the TST, but follow up with an IGRA to confirm or refute the positive TST results.

IGRAs should be used with caution in children younger than 5 years and in children who are immunocompromised “because there are relatively few data concerning their performance characteristics in these groups that have a high rate of developing TB disease if they have untreated TB infection,” Starke advised.

According to the Updated Guidelines for Using Interferon Gamma Release Assays to Detect Mycobacterium tuberculosis Infection published in 2010 in Morbidity and Mortality Weekly Report, TST is the preferred test, and IGRAs are acceptable in children younger than 5 years. For patients who have received BCG vaccine, IGRA is preferred and TST is acceptable. The 2009 AAP Red Book includes similar recommendations, stating that IGRAs can be used in any situation that a TST would be used in children aged 4 years and older, as long as they are immunocompetent.

“Neither IGRAs nor the TST are perfect, so clinical judgment is also needed,” Stake said.

Improvements still to come

“Huge improvements in the diagnosis of tuberculosis infection and disease are on the horizon,” Starke said.

However, because most techniques are studied only in adults before they become available, and TB is fundamentally different in children, Starke said more pediatric-specific studies are “critical” to shifting the gold standards, although it is likely that all tests will have to be considered according to how cases present clinically and epidemiologically.

Disclosure: Dr. Starke reports no relevant financial disclosures.

For more information:

• Starke J. Tuberculosis diagnostics: using the new technologies. Presented at: the 24th Annual Infectious Diseases in Children Symposium; Nov. 18-20, 2011; New York.

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