Interventions for Tuberculosis Control and Elimination 2002

Petroff’s concerns about a reversion to virulence of BCG have never
been confirmed, and his observation of different colony morphology with
virulent and avirulent colonies 673 have not been confirmed elsewhere. 676
The BCG strain family
Until the introduction of freeze-drying in Japan in 1943, 683 the only means
of maintaining a viable strain was through sub-culturing. With the distribution
of the vaccine strain to multiple laboratories in the world, each using
slightly different techniques for strain maintenance, it is not surprising that
the BCG family shows large diversity. 660 The first freeze-dried French
strain (1949) from the Pasteur Institute in Paris was strain 1173-P2 , from
which the Glaxo and Danish strains descended. 684
Recent work based on molecular characterization of the various substrains
points to various mutations that have occurred at different points in
time (figure 57), 685-687 and indicates that the various BCG sub-strains are
morphologically and genetically different from each other.
Safety record of BCG vaccination
A large review has shown BCG to be one of the safest vaccines. 688,689 The
demarcation between a normal reaction and an adverse reaction is not always
clear. 690 The normal reaction is a red indurated area measuring five to
15 mm. A crust is formed around this induration, which is soft at the center
for three to four weeks. At six to ten weeks, the crust falls off, leaving
a flat scar measuring three to seven millimeters. 690 Regional lymphadenopathy
in the absence of erythema or vesicle formation should also
be considered a normal reaction to the vaccine. 691 Complications include
cutaneous lesions and regional suppurative lymphadenitis; more severe localized
or multiple lesions (such as musculo-skeletal lesions); 692-694 and nonfatal
and fatal complications resulting from hypersensitivity reactions or
mycobacterial dissemination. 688,689,695-702 The risk of complications varies
with the type of vaccine and with the age at vaccination. The risk of
osteomyelitis ranged from 0.01 to 50 per 1 million vaccinations, that of
multiple or generalized lesions from 0.01 to 2 and that of fatal cases from
0.01 to 1 per million vaccinated individuals. 688,689 The lowest complication
rates were reported with the Tokyo strain, and the highest with the
Gothenburg strain produced in Denmark. 692,703
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