Interventions for Tuberculosis Control and Elimination 2002

Following these early experiments in humans, BCG was distributed to
a large number of laboratories, largely in Europe, and given to hundreds
of thousands of children within a decade after its introduction. 664-667 Trials
to evaluate its impact began in Europe 668-670 and North America. 671,672
Controlled assessment of the vaccine’s efficacy was conspicuously
absent, and one of its most violent opponents was Petroff in the USA, who
doubted both the vaccine’s innocuousness and efficacy. 673,674 Despite the
justified concerns about the quality of the data on efficacy given all the
methodological problems (such as selection bias), it seemed apparent that
BCG reduced case fatality from tuberculosis among exposed children in a
variety of settings (figure 54). 666 It also seemed to protect adult student
nurses heavily exposed to tuberculosis both from death and disease (figure
55). 668-670,675
Deaths per 100 infants
(log scale)
35
20
10
5
3
Not vaccinated Vaccinated
Figure 54. Early, non-controlled comparisons in crude infant mortality before and
after introduction of BCG vaccination in 16 countries, reported up to 1932. 666
The assumption of the safety of BCG vaccination was severely challenged
when 72 of 251 children who were presumably vaccinated with BCG
between December 10, 1929, and April 30, 1930, died from tuberculosis
in Lübeck, Germany. 676-678 While not all circumstances surrounding this
disaster have ever become public, 679 it soon became apparent that BCG was
not the cause. The preliminary epidemiologic analysis in July 1930 already
showed large differences in case fatality by week of vaccination (figure 56),
indicating that strains with different virulence had been mixed. 680 This was
bacteriologically confirmed by demonstrating that virulent tubercle bacilli,
but not BCG, were consistently isolated on autopsy. 676 The epidemiologic
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