Illustration from Scientific Research

In current designs of phase 3 vaccine trials, the direct effect of the vaccine is calculated by comparing the proportion of unvaccinated (pink) and vaccinated (blue) groups who develop clinical tuberculosis (dashed areas). Individuals who develop tuberculosis (dashed) could cause secondary tuberculosis infections (arrows), which could be prevented if the vaccine has indirect effects. A vaccine could reduce infectiousness and onward transmission in vaccinated individuals who develop tuberculosis, or prevent secondary transmission that would have otherwise occurred (dotted arrows) in the absence of a vaccine programme.

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