Interventions for Tuberculosis Control and Elimination 2002

Differences in vaccine strains
The available BCG vaccine strains differ widely in phenotype and genotype.
660,661,685,686 It has been proposed 794 that differences in vaccine strains
may account for observed variations in vaccine efficacy. In the rabbit
model, not all BCG (and M. microti) strains provided the same level of
protection. 795 However, the most powerful argument against this hypothesis
arises from the Chingleput study, where two vaccine strains were
used 763-765 that had documented high efficacy in other settings but were not
shown to be efficacious in Chingleput. Furthermore, one of the studies (a
case-control study from Indonesia) cited for evidence of differential effectiveness
of strains, examined successive vaccination policies, and was thus
by necessity a non-concurrent study which additionally failed to adjust for
time elapsed since vaccination. 796
Differences in vaccine dose
BCG has been administered through various routes, initially orally, then
parenterally. The latter administration may have been given intradermally
or transdermally via multipuncture devices. The dosage reaching the target
thus may well have varied. Nevertheless, the following observations
seem to contradict the argument of an influence of differential dosage effect.
Three controlled clinical trials with low efficacy used multipuncture administration,
768,785,786 and one with high efficacy did so too. 742 Furthermore,
the trial in Chingleput specifically considered in its design the possibility
of deterioration of vaccine potency in the field, and allocated vaccinees also
to two arms receiving a ten-fold difference in dose, with no difference in
effect. 763-765
Differences in virulence of M. tuberculosis strains
That not all tubercle bacilli are equally virulent has been demonstrated
repeatedly both for M. bovis BCG 797 and M. tuberculosis in general, 798,799
and for isoniazid-resistant strains in particular. 38,800-802
The hypothesis that the relative frequency of more or less virulent
tubercle bacilli affects the observed protective efficacy of BCG vaccination
is based on the argument that tubercle bacilli of lower virulence might also
cause tuberculin skin test reactions of smaller size. Such persons then
might be classified as “non-reactors”, i.e., persons not infected with tubercle
bacilli, thus becoming eligible for vaccination. Vaccination of actually
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