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.


OBJECTIVE
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.


METHODS
Cohort study.


METHODS
Midwestern urban university.


METHODS
69 healthy adults.


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


METHODS
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.
Division of Infectious Diseases and Immunology, Saint Louis University Health Sciences Center, Missouri 63110, USA. hoftdf@slu.edu
D F
DF
Hoft
J M
JM
Tennant
D000328:Adult; D001500:BCG Vaccine / Q000276:immunology*; D015331:Cohort Studies; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology*; D007371:Interferon-gamma / Q000032:analysis; D008214:Lymphocytes / Q000276:immunology; D008403:Mass Screening / Q000592:standards*; D008875:Middle Aged; D011237:Predictive Value of Tests; D012016:Reference Values; D012882:Skin Tests; D014376:Tuberculosis / Q000517:prevention & control*
D001500:BCG Vaccine; D007371:Interferon-gamma