Clinical Inquiries

How should we manage a patient with a positive PPD and prior BCG vaccination?

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Prior bacille Calmette-Guérin (BCG) vaccination increases the likelihood of a positive tuberculosis (TB) 5TU purified protein derivative (PPD) skin test. The PPD response following BCG vaccine varies with age at vaccination, number of years since the BCG vaccination, number of times vaccinated, and number of PPDs performed. An induration of greater than 14 mm is unlikely to be due to prior BCG vaccination (strength of recommendation [SOR]: A, based on meta-analysis of validation cohort studies).

The variable reaction after BCG vaccination, along with the desire to detect all cases of TB, has led to recommendations that all patients with a positive PPD test be treated as true positives. These patients should undergo chest radiography and appropriate treatment, regardless of history of BCG vaccine (SOR: B, extrapolation from level 1 study).

A recently developed alternative is the interferon-gamma assay (QuantiFERON-TB Gold test), which may be used in place of, or in addition to, the PPD skin test for patients who are known to have received a BCG vaccine (SOR: B, extrapolation from a validation cohort study).


Disregard history of BCG immunization when evaluating positive PPDs among immigrants
Drew Malloy, MD
University of California Santa Cruz Student Health Service, Santa Cruz, Calif

When I was in residency in Seattle, the experts at the King County TB clinic advised disregarding the history of BCG immunization when evaluating positive PPDs among immigrants. The authors of this review provide evidence confirming this policy. The only new option for helping your patients in weighing the pros and cons of chemoprophylaxis for latent TB is the new interferon-gamma assay. While 3 times the cost of a PPD, it is a reasonable option for patients who want more specific evidence of latent infection before taking 6 to 9 months of a potentially toxic therapy.

I can think of many situations where the specificity of this test may have persuaded some patients to undertake treatment and spared others the risks and inconvenience of isoniazid.

Evidence summary

In areas where tuberculosis is prevalent, the World Health Organization recommends BCG vaccination at birth, without booster doses, to prevent childhood complications of TB infection;1 however, the vaccine’s efficacy is known to be inconsistent. Though BCG vaccine given at birth can decrease the risk of miliary TB and TB meningitis among children, estimates of its effectiveness in preventing adult pulmonary TB range widely from 0% to 80%.1

Though prior BCG vaccination increases the risk of a reactive PPD, this effect is also known to be inconsistent. A 2002 meta-analysis showed that the person’s age at the time of their BCG vaccination and the years since vaccination influence the relative risk of a positive PPD (TABLE). The highest relative risk of a positive PPD occurred among patients who received BCG vaccination after infancy and within 15 years of the PPD testing. This same meta-analysis also examined the significance of the size of the PPD response; a subset of 4 studies showed that equal proportions of BCG vaccinated and unvaccinated patients had indurations of 14 mm or more.2


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