More In-Flight TB Exposure: Passenger Screening With New Blood Test Recommended

In mid-December 2006, another individual (albeit unnamed) infected with MDR TB made headlines by catching a 16-hour flight from New Delhi, India, to Chicago, Illinois (American Airlines #293). However, a major difference between this 30-year-old native Nepalese woman* and the infamous Andrew Speaker is that the woman was actively coughing on the overseas flight, thereby increasing the risk of TB transmission to her fellow travelers. The CDC has been attempting to track down the passengers sitting near the woman, who was hospitalized approximately 1 week after the flight for active disease, according to a USA Today/ABC news report.

The part of this story that caught my eye (and I’ll admit that it’s possible that I’m woefully out of it) is that the CDC is recommending testing of passengers with either the standard PPD skin test—which is as old as the hills^†—or the new-to-me QuantiFERON TB Gold blood test (QFT-G; Cellestis)—which was FDA approved in December 2004 for in vitro diagnosis.

As pretty much everybody knows, ye olde PPD (or Mantoux) test requires the intradermal injection of 5 tuberculin units (0.1 mL) of purified protein derived (hence “PPD”) from Mycobacterium tuberculosis. At 48-72 hours, induration (as an indicator of cell-mediated immunity against TB) is measured at the injection site—the trick being (if there is a trick) that induration, not erythema, should be assessed. The diameter of induration is gauged to interpret positivity, depending on patient-related risk factors—for instance, TB exposure in the line of known healthcare work. An induration diameter of 15 mm or greater is typically interpreted as meaning that the individual has been infected with TB at some point in time, if there are no known risk factors for exposure. Smaller indurations are interpreted on the basis of an individual’s potential exposure history and immune status.

The longtime major drawbacks of the PPD test are false negatives associated with immunocompromise (eg, HIV infection) or active TB infection and false positives associated with the previous administration of the bacille Calmette-Guérin (BCG) vaccine, often given in booster fashion to infants and children where TB is endemic.

The new QFT-G test requires the collection and testing of whole blood and detects interferon-γ released from lymphocytes in response to the simulated antigens esat-6 and cfp-10,^‡ which are secreted from all strains of M. tuberculosis. These antigens are also secreted by pathogenic M. bovis but not BCG vaccine strains or common non–TB mycobacteria. In its 2005 TB-testing guideline report, the CDC recommends that “QFT-G can be used in all circumstances in which the [PPD test] is currently used, including contact investigations.” Testing using sequenced PPD and QFT-G tests is not recommended; although this method, as a means of testing confirmation, appears to be performed with some frequency in Europe.

The specificity of a similar blood test, ELISPOT or T-SPOT-TB, is close to that of the QFT-G; however, the former test has not yet been approved for use in the United States. The average cost of a single QFT-G test, including personnel costs, is estimated at $35-$120, and that for a PPD skin test is approximately $13. Published cost-effectiveness studies, at least those performed in Germany, include not only test expenses but the costs of follow-up testing because of initial, indeterminate results and unnecessary treatment or prophylaxis owing to false-positive PPD test results.

*Presumably the woman, who resides in northern California, also traveled by plane from O’Hare to San Francisco; however, testing of fellow plane passengers is only recommended by WHO if the flight duration is 8 hours or longer, because the risk of TB transmission on shorter flights is believed to be minimal.

†Hills being approximately 90 years of age.

‡6- and 10-kD antigens, respectively, which form a heterodimer and are associated with TB virulence.