Figure 1. Breaking the cycle of TB transmission with improved vaccination regimens.

The TB bacillus is transmitted by inhalation of aerosolized microdroplets that are released by coughing of infected individuals, usually those with advanced cavitary lung lesions that erode into the bronchi. Infants and young children exposed to such infectious aerosols are highly susceptible to infection and have a high risk of developing severe, progressive disease with dissemination beyond the lungs to other organs. Cumulative deaths from TB currently total approximately 1.5 million globally per year. The yellow boxes indicate key points in the infectious cycle where vaccination could have the greatest impact. Neonatal BCG vaccination is already well established in most countries with high prevalence of TB, and improvements at this stage will likely involve introduction of modified BCG strains with better safety and immunogenicity profiles. Vaccination of uninfected or latently infected adults or older children may involve a more diverse array of new vaccine candidates. Recent reports suggest benefit from revaccinating adults with BCG, and one trial has shown significant efficacy of the M72 subunit vaccine in prevention of disease in adults with latent TB infection.