Interventions for Tuberculosis Control and Elimination 2002

However, an effect is difficult to demonstrate in the case of fully drugsusceptible
tuberculosis, which responds superbly to chemotherapy. What
is perhaps needed is to study its value in the treatment of multiple drugresistant
tuberculosis, where the unequivocal outcome of death is a frequent
enough event to permit a more definitive evaluation of the claims for
improved immunologic response.
Vaccination with saprophytic (environmental) mycobacteria
The experiments by Palmer and Long have shown that various species of
environmental mycobacteria provide some protection against experimental
tuberculosis, but to different degrees and never exceeding that of BCG. 826
As mentioned above, the trial in the United Kingdom and the observations
in Malawi have lent further credibility to the hypothesis that certain environmental
species might offer some protection against tuberculosis. This
line of experimentation has been further pursued and evidence accumulated
that animals vaccinated with environmental mycobacteria have an increased
resistance to a subsequent challenge with virulent tubercle bacilli compared
to non-vaccinated animals. 828 So far, none of these vaccinations have been
superior to BCG vaccination.
Auxotrophs
Another approach has been the development of so-called auxotrophic vaccines,
where BCG and M. tuberculosis have been used to generate selected
auxotrophs by insertional mutagenesis. 1185 The advantage of such a vaccine
might be that it would gradually die in the host (an advantage in
immunocompromised hosts) and that a weakened auxotrophic M. tuberculosis
might be more immunogenic than BCG. 1185 However, survival time
of the vaccine might be critical and has not yet been characterized sufficiently
well to demonstrate superiority over BCG vaccination in experimental
models, 1193 but certain mutations in genes involved in amino-acid
biosynthesis have been promising in experimental models. 1194
DNA vaccines
Most efforts currently being undertaken are in the development of a DNA
vaccine, 1195-1204 but none of the experimental models has yet shown superiority
to BCG vaccine. There is, however, some experimental evidence that
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