Persistence and boosting of bacille Calmette-Guérin-induced delayed-type hypersensitivity.

BACKGROUND

Bacille Calmette-Guérin (BCG) vaccination may induce persistent and booster purified protein derivative (PPD) responses that complicate tuberculosis screening efforts.

OBJECTIVES

To investigate the effects of BCG vaccination on serial PPD tests and to study correlations between persistent delayed-type hypersensitivity and other potential surrogate markers of protective immunity.

DESIGN

Cohort study.

SETTING

Midwestern urban university.

PARTICIPANTS

69 healthy adults.

INTERVENTIONS: BCG vaccination, blood samples drawn for immunologic studies, and PPD tests done sequentially over 1 to 3 years.

MEASUREMENTS: Serial PPD induration, lymphoproliferation, and interferon-gamma responses.

RESULTS

10% of participants (95% CI, 4% to 20%) had persistent PPD responses of 15 mm or greater, and 3% (CI, 0% to 10%) demonstrated PPD boosting of 15 mm or greater 1 to 3 years after BCG vaccination. Intradermal BCG vaccination induced a larger number of persistent responses that were 10 mm or greater than did percutaneous BCG vaccination (12 of 46 participants compared with 1 of 23 participants; P = 0.05). Persistent and boosted delayed-type hypersensitivity correlated with mycobacterial-specific lymphoproliferation and interferon-gamma responses.

CONCLUSIONS

Previous BCG vaccination reduces the predictive value of serial PPD testing. The lowest PPD predictive values will occur in persons without known tuberculosis exposure who were vaccinated recently or many times with intradermal BCG. In addition, BCG-related persistence and boosting of delayed-type hypersensitivity responses correlate with other potential surrogate markers of protective mycobacterial immunity.