A re-examination of the variations in the efficacy of BCG vaccination against tuberculosis in clinical trials.
METHODS
The findings of the principal controlled trials of BCG vaccination against tuberculosis are reviewed.


OBJECTIVE
To investigate possible reasons for the wide variations in vaccine efficacy in different trials, and in particular for the apparent adverse effect in the first few years in the trial in Chingleput, South India.


METHODS
(1) A substantial reduction, or even a reversal, of overall efficacy could result if the assessment of vaccine efficacy included a subgroup adversely affected by vaccination. (2) Several trials include in the assessment many subjects with weak initial tuberculin sensitivity, due either to environmental mycobacterial infection or to Mycobacterium tuberculosis infection. It is accepted that vaccine efficacy may be moderately reduced in the former subgroup. It is postulated that the latter subgroup may be at risk of reactivation of tuberculosis soon after vaccination, perhaps from focal reactions due to enhancement of their weak sensitivity. (3) The low levels of efficacy in several trials, and the early adverse effect in Chingleput, are broadly consistent with this hypothesis.


CONCLUSIONS
Clinical tuberculosis due to BCG vaccination of subjects with weak tuberculin sensitivity following M. tuberculosis infection may make an important contribution to the variations in efficacy found in clinical trials.
Springett
V H
VH
Medical Research Council Biostatistics Unit, Institute of Public Health, Cambridge, UK.
Sutherland
I
I
D000293:Adolescent; D001500:BCG Vaccine / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D002986:Clinical Trials as Topic; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D016896:Treatment Outcome; D014373:Tuberculin / Q000276:immunology; D014374:Tuberculin Test; D014376:Tuberculosis / Q000276:immunology / Q000517:prevention & control*
D001500:BCG Vaccine; D014373:Tuberculin