Interventions for Tuberculosis Control and Elimination 2002

• Differences in virulence of M. tuberculosis strains;
• Differences in risk attributable to exogenous reinfection tuberculosis;
• Differences in genetic make-up of vaccinees;
• Differences in nutritional status of vaccinees;
• Differences in prevalence of infection with environmental mycobacteria;
• Other factors.
Differences in methodological stringency
Quite obviously, not every study can be methodologically as rigorously conducted
as ideal standards of study design and conduct call for. 731,734 Among
the clinical trials, several have been excluded from major reviews and metaanalyses
such as those conducted by Colditz and collaborators. 791,792 These
authors found that study validity score explained 66% of the variation in
prospective clinical trials and 36% in retrospective case-control studies, 791
and only 15% in case-control studies on BCG protection against infant
tuberculosis. 792 Nevertheless, perhaps the most relevant trial showing no
protection against bacteriologically confirmed tuberculosis, conducted in
Chingleput, India, was judged to be of high scientific quality by a WHO
expert committee specifically charged to ascertain the trial’s validity. 793
It must be kept in mind that the range of protection cannot be taken
at face value, but must also be seen in the context of what the study in
question sought to address. BCG trials (be they prospective or retrospective)
ascertained protection against various outcomes such as morbid state
(tuberculosis or death from tuberculosis) and site of disease, e.g., pulmonary,
extrapulmonary single site, and disseminated tuberculosis, taking into account
such things as bacteriologic certainty of the case, age of the patients, and
time elapsed since vaccination. What seems apparent from the studies is
the tendency of BCG to provide its greatest protection within the few years
following vaccination, against death from tuberculosis, disseminated disease
manifestations, and bacteriologically unconfirmed tuberculosis. In summarizing
these effects, BCG is generally most effective against serious forms
of tuberculosis occurring shortly after infection acquired at an early age.
Thus, any evaluation of the protective efficacy of BCG vaccination should
be stratified according to these variables.
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