Is the PPD obsolete?

May 1, 2007

PPDIn February of this year the New York City Department of Health released a new policy paper indicating that they will no longer use the PPD as a screening tool for tuberculosis in their clinics.They have switched to the QuantiFERON-TB Gold, (QFT-G), a blood test. This test is an ELISA, which measures interferon-gamma secretion by t-lymphocytes in response to tuberculosis specific antigens. The test requires heparinized whole blood and must be processed within 12 hours of the blood draw.

The test exposes the patients t-lymphocytes to two proteins. The first is ESAT-6, or early secretory antigenic target-6. The second is CFP10, or culture filtrate protein 10. These two antigens are highly specific to m. tuberculosis. They are NOT found in BCG or in MAC. Therefore, the test has a much higher specificity for exposure to TB than PPD.

Like the PPD, it does not distinguish between latent or active infection. Unlike the PPD, it does differentiate BCG exposure. It also decreases the uncertainty we often find when a patient appears to have active TB but his/her PPD is negative. The CDC reports on three studies looking at sensitivity and specificity of the test. In composite, they describe the specificity between 67% in an immuno-compromised population to 98.1% in a healthy population. Sensitivity ranged 81 to 98% in these same populations. The only documented false positives are prior exposures to M. Kansasii, M. Marinum, or M. szulgai.

In contrast, the PPD has a documented specificity of 49% and sensitivity of 33%.

From a practical and economic point of view, the QFT-G is a huge advance beyond PPD. The test offers a positive or negative result and is not reader dependent. There is never a need for second, or booster, test. The patient does not have to return on a specific date to get the results, and the patient can learn the results over the phone. This will halve the number of necessary clinic appointments in the screened population. The only disappointing factor is the lack of specificity for the immunocompromised population. Still, the results are a vast improvement over those for PPD.

Please refer to the web-site below for the CDC guideline.

http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5415a4.htm

-Deborah Shapiro, MD, Attending Physician, Division of General Internal Medicine

Image courtesy of wikimedia commons

2 Responses to Is the PPD obsolete?

  1. Neal H. Steigbigel, M.D. on May 4, 2007 at 10:01 am

    Although the new Quantaferon Gold test has a number of advantages over the PPD skin test ,it so far has, as regards current data and intelligent estimate, the major problems of senstivity and specificty of the skin test. That is: 1) the new test does more likely reflect previous experience with M. tbc (and not BCG or MAC), but it cannot differentiate between latent and active tbc; so that a patient with the positive test and a given clinical problem may not have active tbc as an explanation for that problem, but merely have prior latent tbc infection and an unrealted clinical probem at hand. 2) It has been known for decades (and prior to the HIV epidemic) that 20-25% of individuals with proven active tbc of all kinds will have a negative skin test; so far there is no strong evidence that such frequent false negatives will be absent with the new test, until large series of patients with proven active tbc are tested with it and compared to their skin test results and show much fewer false negatives. I doubt that the results with the new test will show substantially high false negative rate to be much lower, but we must wait for the results of such good studies. The most valuable way to use either of these tests now (and the new test is preferred for its specificity for M.tbc infection, even if only latent) is to have a baseline result and if the test later becomes positive (conversion) there is a substantial risk of active tbc developing over the next several years–therefore, the value of treating the latent tbc infection in that period of high vulnerability.

  2. Frank Jones on December 20, 2008 at 2:13 am

    in response to mr. Steigbigel’s post, 20-25% false negative? i thought the generally accepted number for false negatives for immunocompetent people not in a state of acute (severe) tb was around 5%. i think your number of 20-25% “even before hiv existed” is an incorrect exaggeration. if PPD was as inaccurate as you state, how would the US have managed to all but stamp out TB using only this simple test? (since the US does not use BCG vaccination). therefore, i believe PPD is better than you give it credit for, and if this new quantaferon-gold test is even a little better than PPD, that is great news.

Leave a Reply

Your email address will not be published. Required fields are marked *

*